Pituitary, Thyroid & Adrenal Disorders

BALTIMORE – Tumor size and the presence of mutations of the succinate dehydrogenase complex subunit B (SDHB) gene may be reliable indicators of prognosis after surgery for pheochromocytoma and abdominal paraganglioma, investigators in a National Cancer Institute–funded study have reported.

“The staging of pheochromocytoma and abdominal paraganglioma can be difficult, but it is critical for optimal patient care,” Yasmine Assadipour, MD, of the National Cancer Institute, Bethesda, Md., and the George Washington University Hospital, Washington, reported at the annual meeting of the American Association of Endocrine Surgeons.

“Any clinically relevant grading or prognostic system should include SDHB mutation status and primary tumor size as prime features of scoring,” Dr. Assadipour said. “Histologic features such as Ki-67 or mitotic index may not be as useful for prognostic information in patients with pheochromocytoma and abdominal paraganglioma, particularly in the setting of SDHB mutation.”

Dr. Assadipour and her coinvestigators focused their investigation on mutations of the SDHB (succinate dehydrogenase complex subunit B) gene, which codes for one of four subunits comprising a mitochondrial protein.

They also considered primary tumor size, functionality, pathology, surgical approach, and histologic features including Ki-67 index and mitotic index. The study was a retrospective analysis of 84 patients who had surgery for PC [pheochromocytoma] or PGL [paraganglioma] and had germ line genetic testing. Of the 84 patients, 35 patients had sporadic disease and 49 had germ line SDHB mutation. The study analyzed tumor samples for Ki-67/MIB-1 staining and mitotic index.

“In a univariate analysis, SDHB mutation, tumor size and surgical approach were associated with local regional recurrence,” Dr. Assadipour said. “In a multivariate analysis, the only independent risk factors were SDHB mutation status and tumor size; Ki-67 and mitotic index did not have any association with recurrence.”

The researchers found similar results when they looked at distant metastasis. “SDHB mutation, tumor size, abdominal paraganglioma and surgical approach were associated with distant metastasis,” Dr. Assadipour said. “Again, Ki-67 and mitotic index were not.”

In the multivariate analysis, again, only patient SDHB status and tumor size were independently associated with metastasis.”

Dr. Yasmine Assadipour

The incidence of local recurrence in patients with the SDHB mutation was 47.6% vs. 9.1% in those without the gene mutation, Dr. Assadipour said. The rates of distant metastasis showed a similar disparity: 56.5% and 9.1%, respectively.

Patients with the SDHB mutation presented at a younger age than those without the mutation, 33 vs. 49.6 years old. Among the 65 patients who underwent R0 primary tumor resection, those with the SDHB mutation, paraganglioma, and larger tumor size had a shorter disease-free survival, Dr. Assadipour said.

In analyzing tumor size, Dr. Assadipour said two stratifications were studied: evaluating tumors sized 0-3 cm, 3-6 cm and 6 cm and larger; and 0-5 cm and 5 cm and larger. “Tumors over 6 cm had the shortest disease-free survival, and even when we applied the under-5 cm and over-5 cm scale, we clearly saw a difference in disease-free survival,” she said. Ki-67 and mitotic index were not related to disease-free survival.

The presence of a SDHB mutation had a hazard ratio of 16.2, while tumor diameter greater than 6 cm had a HR of 15.4, Dr. Assadipour said. These were the only independent risk factors for local recurrence, distant metastases and shorter disease-free interval found in the study.

During the discussion, Lawrence T. Kim, MD, of the University of North Carolina asked if the researchers found any differences in outcomes related to the surgical approach. “We were unable to identify whether any surgical approach improved or worsened outcomes on multivariate analysis” Dr. Assadipour said.

Thomas J. Fahey, MD, of New York asked what she would recommend for surgical approaches for patients with PC and PGL.

“Our general recommendation is that an adrenal pheochromocytoma that is over 6 cm carries a higher risk of recurrence and distant metastasis so an open approach with lymph node dissection ensuring negative surgical margins should be considered,” Dr. Assadipour said. “For abdominal paragangliomas, unless they are quite small and in a favorable location, we would generally recommend an open approach.”

The study was supported by the intramural program of the Center for Cancer Research, National Cancer Institute, National Institutes of Health. Dr. Assadipour and her coauthors had no financial relationships to disclose.

BALTIMORE – Tumor size and the presence of mutations of the succinate dehydrogenase complex subunit B (SDHB) gene may be reliable indicators of prognosis after surgery for pheochromocytoma and abdominal paraganglioma, investigators in a National Cancer Institute–funded study have reported.

“The staging of pheochromocytoma and abdominal paraganglioma can be difficult, but it is critical for optimal patient care,” Yasmine Assadipour, MD, of the National Cancer Institute, Bethesda, Md., and the George Washington University Hospital, Washington, reported at the annual meeting of the American Association of Endocrine Surgeons.

“Any clinically relevant grading or prognostic system should include SDHB mutation status and primary tumor size as prime features of scoring,” Dr. Assadipour said. “Histologic features such as Ki-67 or mitotic index may not be as useful for prognostic information in patients with pheochromocytoma and abdominal paraganglioma, particularly in the setting of SDHB mutation.”

Dr. Assadipour and her coinvestigators focused their investigation on mutations of the SDHB (succinate dehydrogenase complex subunit B) gene, which codes for one of four subunits comprising a mitochondrial protein.

They also considered primary tumor size, functionality, pathology, surgical approach, and histologic features including Ki-67 index and mitotic index. The study was a retrospective analysis of 84 patients who had surgery for PC [pheochromocytoma] or PGL [paraganglioma] and had germ line genetic testing. Of the 84 patients, 35 patients had sporadic disease and 49 had germ line SDHB mutation. The study analyzed tumor samples for Ki-67/MIB-1 staining and mitotic index.

“In a univariate analysis, SDHB mutation, tumor size and surgical approach were associated with local regional recurrence,” Dr. Assadipour said. “In a multivariate analysis, the only independent risk factors were SDHB mutation status and tumor size; Ki-67 and mitotic index did not have any association with recurrence.”

The researchers found similar results when they looked at distant metastasis. “SDHB mutation, tumor size, abdominal paraganglioma and surgical approach were associated with distant metastasis,” Dr. Assadipour said. “Again, Ki-67 and mitotic index were not.”

In the multivariate analysis, again, only patient SDHB status and tumor size were independently associated with metastasis.”

Dr. Yasmine Assadipour

The incidence of local recurrence in patients with the SDHB mutation was 47.6% vs. 9.1% in those without the gene mutation, Dr. Assadipour said. The rates of distant metastasis showed a similar disparity: 56.5% and 9.1%, respectively.

Patients with the SDHB mutation presented at a younger age than those without the mutation, 33 vs. 49.6 years old. Among the 65 patients who underwent R0 primary tumor resection, those with the SDHB mutation, paraganglioma, and larger tumor size had a shorter disease-free survival, Dr. Assadipour said.

In analyzing tumor size, Dr. Assadipour said two stratifications were studied: evaluating tumors sized 0-3 cm, 3-6 cm and 6 cm and larger; and 0-5 cm and 5 cm and larger. “Tumors over 6 cm had the shortest disease-free survival, and even when we applied the under-5 cm and over-5 cm scale, we clearly saw a difference in disease-free survival,” she said. Ki-67 and mitotic index were not related to disease-free survival.

The presence of a SDHB mutation had a hazard ratio of 16.2, while tumor diameter greater than 6 cm had a HR of 15.4, Dr. Assadipour said. These were the only independent risk factors for local recurrence, distant metastases and shorter disease-free interval found in the study.

During the discussion, Lawrence T. Kim, MD, of the University of North Carolina asked if the researchers found any differences in outcomes related to the surgical approach. “We were unable to identify whether any surgical approach improved or worsened outcomes on multivariate analysis” Dr. Assadipour said.

Thomas J. Fahey, MD, of New York asked what she would recommend for surgical approaches for patients with PC and PGL.

“Our general recommendation is that an adrenal pheochromocytoma that is over 6 cm carries a higher risk of recurrence and distant metastasis so an open approach with lymph node dissection ensuring negative surgical margins should be considered,” Dr. Assadipour said. “For abdominal paragangliomas, unless they are quite small and in a favorable location, we would generally recommend an open approach.”

The study was supported by the intramural program of the Center for Cancer Research, National Cancer Institute, National Institutes of Health. Dr. Assadipour and her coauthors had no financial relationships to disclose.

BALTIMORE – Tumor size and the presence of mutations of the succinate dehydrogenase complex subunit B (SDHB) gene may be reliable indicators of prognosis after surgery for pheochromocytoma and abdominal paraganglioma, investigators in a National Cancer Institute–funded study have reported.

“The staging of pheochromocytoma and abdominal paraganglioma can be difficult, but it is critical for optimal patient care,” Yasmine Assadipour, MD, of the National Cancer Institute, Bethesda, Md., and the George Washington University Hospital, Washington, reported at the annual meeting of the American Association of Endocrine Surgeons.

“Any clinically relevant grading or prognostic system should include SDHB mutation status and primary tumor size as prime features of scoring,” Dr. Assadipour said. “Histologic features such as Ki-67 or mitotic index may not be as useful for prognostic information in patients with pheochromocytoma and abdominal paraganglioma, particularly in the setting of SDHB mutation.”

Dr. Assadipour and her coinvestigators focused their investigation on mutations of the SDHB (succinate dehydrogenase complex subunit B) gene, which codes for one of four subunits comprising a mitochondrial protein.

They also considered primary tumor size, functionality, pathology, surgical approach, and histologic features including Ki-67 index and mitotic index. The study was a retrospective analysis of 84 patients who had surgery for PC [pheochromocytoma] or PGL [paraganglioma] and had germ line genetic testing. Of the 84 patients, 35 patients had sporadic disease and 49 had germ line SDHB mutation. The study analyzed tumor samples for Ki-67/MIB-1 staining and mitotic index.

“In a univariate analysis, SDHB mutation, tumor size and surgical approach were associated with local regional recurrence,” Dr. Assadipour said. “In a multivariate analysis, the only independent risk factors were SDHB mutation status and tumor size; Ki-67 and mitotic index did not have any association with recurrence.”

The researchers found similar results when they looked at distant metastasis. “SDHB mutation, tumor size, abdominal paraganglioma and surgical approach were associated with distant metastasis,” Dr. Assadipour said. “Again, Ki-67 and mitotic index were not.”

In the multivariate analysis, again, only patient SDHB status and tumor size were independently associated with metastasis.”

Dr. Yasmine Assadipour

The incidence of local recurrence in patients with the SDHB mutation was 47.6% vs. 9.1% in those without the gene mutation, Dr. Assadipour said. The rates of distant metastasis showed a similar disparity: 56.5% and 9.1%, respectively.

Patients with the SDHB mutation presented at a younger age than those without the mutation, 33 vs. 49.6 years old. Among the 65 patients who underwent R0 primary tumor resection, those with the SDHB mutation, paraganglioma, and larger tumor size had a shorter disease-free survival, Dr. Assadipour said.

In analyzing tumor size, Dr. Assadipour said two stratifications were studied: evaluating tumors sized 0-3 cm, 3-6 cm and 6 cm and larger; and 0-5 cm and 5 cm and larger. “Tumors over 6 cm had the shortest disease-free survival, and even when we applied the under-5 cm and over-5 cm scale, we clearly saw a difference in disease-free survival,” she said. Ki-67 and mitotic index were not related to disease-free survival.

The presence of a SDHB mutation had a hazard ratio of 16.2, while tumor diameter greater than 6 cm had a HR of 15.4, Dr. Assadipour said. These were the only independent risk factors for local recurrence, distant metastases and shorter disease-free interval found in the study.

During the discussion, Lawrence T. Kim, MD, of the University of North Carolina asked if the researchers found any differences in outcomes related to the surgical approach. “We were unable to identify whether any surgical approach improved or worsened outcomes on multivariate analysis” Dr. Assadipour said.

Thomas J. Fahey, MD, of New York asked what she would recommend for surgical approaches for patients with PC and PGL.

“Our general recommendation is that an adrenal pheochromocytoma that is over 6 cm carries a higher risk of recurrence and distant metastasis so an open approach with lymph node dissection ensuring negative surgical margins should be considered,” Dr. Assadipour said. “For abdominal paragangliomas, unless they are quite small and in a favorable location, we would generally recommend an open approach.”

The study was supported by the intramural program of the Center for Cancer Research, National Cancer Institute, National Institutes of Health. Dr. Assadipour and her coauthors had no financial relationships to disclose.

The Endocrine Society’s updated Clinical Practice Guideline for managing primary aldosteronism is “a clarion call” for physicians to recognize the impact of this substantial public health problem and dramatically ramp up their screening and treatment efforts and was published in the Journal of Clinical Endocrinology and Metabolism.

This update differs from the previous (2008) version of the guideline in “the explicit recognition of primary aldosteronism as a major public health issue and not merely a matter of case detection, diagnosis, and treatment of individual patients,” wrote John W. Funder, MD, and his associates on the task force that compiled the guideline.

Many physicians in current practice were taught that the disorder “is a rare and benign cause of hypertension, [and] thus merely a footnote to the management of hypertension as a whole. Cardiologists usually write guidelines for hypertension with some input from nephrologists and clinical pharmacologists [but] little or none from endocrinologists,” they noted.

As a result, most patients with hypertension and occult aldosteronism are never screened for the disorder and receive suboptimal care. Primary care providers must be “made keenly aware” that the proportion of people with hypertension who have aldosteronism is much higher than previously thought (at roughly 10%), that another 20% of hypertensive people have “inappropriate aldosterone secretion,” and that both groups respond remarkably well to medical therapy, particularly to mineralocorticoid-receptor antagonists. This is critical because hypertensive patients with aldosteronism are at much greater risk for cardiovascular morbidity and mortality than their age-, sex-, and BP-matched counterparts who don’t have aldosteronism, said Dr. Funder of the Hudson Institute of Medical Research, Clayton (VIC), Australia, and his associates.

In addition to recommendations regarding screening and treatment and summaries of the evidence on which those recommendations are based, the new guideline offers a remarks section for each recommendation, which includes technical suggestions to help clinicians implement them in real-world practice.

Among the Guideline’s recommendations:

• Screen for primary aldosteronism all patients who have sustained BP above 150/100 mm Hg, hypertension resistant to three conventional antihypertensive drugs, hypertension that requires four or more drugs to control it, hypertension plus hypokalemia, hypertension plus adrenal incidentaloma, hypertension plus sleep apnea, hypertension plus a family history of early-onset hypertension or stroke at a young age, and hypertension plus a first-degree relative with primary aldosteronism.

Use the plasma aldosterone/renin ratio for this screening.

• Do one or more confirmatory tests to definitively confirm the diagnosis before proceeding to subtype classification. The exception to this recommendation is patients who develop spontaneous hypokalemia.

• Do adrenal CT as the initial step in subtype classification, to exclude large masses that may signal adrenocortical carcinoma and to help interventional radiologists and surgeons make anatomic assessments.

Before surgery, an experienced radiologist should determine whether adrenal disease is unilateral or bilateral using adrenal venous sampling.

Order genetic testing for patients with disease onset before age 20 years and for those who have a family history of either aldosteronism or early stroke.

• Laparoscopic adrenalectomy is the surgery of choice for most patients with unilateral adrenal disease. For patients unwilling or unable to undergo surgery or further investigations, prescribe a mineralocorticoid-receptor antagonist.

Medical therapy is the treatment of choice for bilateral adrenal disease. Spironolactone is the first-line agent, and eplerenone is an alternative agent to offer. This guideline is intended to be revised further as management evolves over the next 5 years. It is likely that by then, a rapid, inexpensive confirmatory test will be available to definitively establish the diagnosis and that third- and perhaps fourth-generation mineralocorticoid-receptor antagonists will be available for treatment. Simpler and more accurate methods of measuring plasma aldosterone concentration and direct renin concentration, which “would be a game changer for the primary care physician,” are currently being developed, Dr. Funder and his associates said (J. Clin. Endocrinol. Metab. 2016 May;101:1889-916).

In the meantime, “the main strategy is to convince primary-care physicians to screen for primary aldosteronism in all at-risk hypertensive patients,” they noted.

Copies of the full Guideline are available at societyservices@endocrine.org or by calling 202-971-3636.

The Endocrine Society’s updated Clinical Practice Guideline for managing primary aldosteronism is “a clarion call” for physicians to recognize the impact of this substantial public health problem and dramatically ramp up their screening and treatment efforts and was published in the Journal of Clinical Endocrinology and Metabolism.

This update differs from the previous (2008) version of the guideline in “the explicit recognition of primary aldosteronism as a major public health issue and not merely a matter of case detection, diagnosis, and treatment of individual patients,” wrote John W. Funder, MD, and his associates on the task force that compiled the guideline.

Many physicians in current practice were taught that the disorder “is a rare and benign cause of hypertension, [and] thus merely a footnote to the management of hypertension as a whole. Cardiologists usually write guidelines for hypertension with some input from nephrologists and clinical pharmacologists [but] little or none from endocrinologists,” they noted.

As a result, most patients with hypertension and occult aldosteronism are never screened for the disorder and receive suboptimal care. Primary care providers must be “made keenly aware” that the proportion of people with hypertension who have aldosteronism is much higher than previously thought (at roughly 10%), that another 20% of hypertensive people have “inappropriate aldosterone secretion,” and that both groups respond remarkably well to medical therapy, particularly to mineralocorticoid-receptor antagonists. This is critical because hypertensive patients with aldosteronism are at much greater risk for cardiovascular morbidity and mortality than their age-, sex-, and BP-matched counterparts who don’t have aldosteronism, said Dr. Funder of the Hudson Institute of Medical Research, Clayton (VIC), Australia, and his associates.

In addition to recommendations regarding screening and treatment and summaries of the evidence on which those recommendations are based, the new guideline offers a remarks section for each recommendation, which includes technical suggestions to help clinicians implement them in real-world practice.

Among the Guideline’s recommendations:

• Screen for primary aldosteronism all patients who have sustained BP above 150/100 mm Hg, hypertension resistant to three conventional antihypertensive drugs, hypertension that requires four or more drugs to control it, hypertension plus hypokalemia, hypertension plus adrenal incidentaloma, hypertension plus sleep apnea, hypertension plus a family history of early-onset hypertension or stroke at a young age, and hypertension plus a first-degree relative with primary aldosteronism.

Use the plasma aldosterone/renin ratio for this screening.

• Do one or more confirmatory tests to definitively confirm the diagnosis before proceeding to subtype classification. The exception to this recommendation is patients who develop spontaneous hypokalemia.

• Do adrenal CT as the initial step in subtype classification, to exclude large masses that may signal adrenocortical carcinoma and to help interventional radiologists and surgeons make anatomic assessments.

Before surgery, an experienced radiologist should determine whether adrenal disease is unilateral or bilateral using adrenal venous sampling.

Order genetic testing for patients with disease onset before age 20 years and for those who have a family history of either aldosteronism or early stroke.

• Laparoscopic adrenalectomy is the surgery of choice for most patients with unilateral adrenal disease. For patients unwilling or unable to undergo surgery or further investigations, prescribe a mineralocorticoid-receptor antagonist.

Medical therapy is the treatment of choice for bilateral adrenal disease. Spironolactone is the first-line agent, and eplerenone is an alternative agent to offer. This guideline is intended to be revised further as management evolves over the next 5 years. It is likely that by then, a rapid, inexpensive confirmatory test will be available to definitively establish the diagnosis and that third- and perhaps fourth-generation mineralocorticoid-receptor antagonists will be available for treatment. Simpler and more accurate methods of measuring plasma aldosterone concentration and direct renin concentration, which “would be a game changer for the primary care physician,” are currently being developed, Dr. Funder and his associates said (J. Clin. Endocrinol. Metab. 2016 May;101:1889-916).

In the meantime, “the main strategy is to convince primary-care physicians to screen for primary aldosteronism in all at-risk hypertensive patients,” they noted.

Copies of the full Guideline are available at societyservices@endocrine.org or by calling 202-971-3636.

The Endocrine Society’s updated Clinical Practice Guideline for managing primary aldosteronism is “a clarion call” for physicians to recognize the impact of this substantial public health problem and dramatically ramp up their screening and treatment efforts and was published in the Journal of Clinical Endocrinology and Metabolism.

This update differs from the previous (2008) version of the guideline in “the explicit recognition of primary aldosteronism as a major public health issue and not merely a matter of case detection, diagnosis, and treatment of individual patients,” wrote John W. Funder, MD, and his associates on the task force that compiled the guideline.

Many physicians in current practice were taught that the disorder “is a rare and benign cause of hypertension, [and] thus merely a footnote to the management of hypertension as a whole. Cardiologists usually write guidelines for hypertension with some input from nephrologists and clinical pharmacologists [but] little or none from endocrinologists,” they noted.

As a result, most patients with hypertension and occult aldosteronism are never screened for the disorder and receive suboptimal care. Primary care providers must be “made keenly aware” that the proportion of people with hypertension who have aldosteronism is much higher than previously thought (at roughly 10%), that another 20% of hypertensive people have “inappropriate aldosterone secretion,” and that both groups respond remarkably well to medical therapy, particularly to mineralocorticoid-receptor antagonists. This is critical because hypertensive patients with aldosteronism are at much greater risk for cardiovascular morbidity and mortality than their age-, sex-, and BP-matched counterparts who don’t have aldosteronism, said Dr. Funder of the Hudson Institute of Medical Research, Clayton (VIC), Australia, and his associates.

In addition to recommendations regarding screening and treatment and summaries of the evidence on which those recommendations are based, the new guideline offers a remarks section for each recommendation, which includes technical suggestions to help clinicians implement them in real-world practice.

Among the Guideline’s recommendations:

• Screen for primary aldosteronism all patients who have sustained BP above 150/100 mm Hg, hypertension resistant to three conventional antihypertensive drugs, hypertension that requires four or more drugs to control it, hypertension plus hypokalemia, hypertension plus adrenal incidentaloma, hypertension plus sleep apnea, hypertension plus a family history of early-onset hypertension or stroke at a young age, and hypertension plus a first-degree relative with primary aldosteronism.

Use the plasma aldosterone/renin ratio for this screening.

• Do one or more confirmatory tests to definitively confirm the diagnosis before proceeding to subtype classification. The exception to this recommendation is patients who develop spontaneous hypokalemia.

• Do adrenal CT as the initial step in subtype classification, to exclude large masses that may signal adrenocortical carcinoma and to help interventional radiologists and surgeons make anatomic assessments.

Before surgery, an experienced radiologist should determine whether adrenal disease is unilateral or bilateral using adrenal venous sampling.

Order genetic testing for patients with disease onset before age 20 years and for those who have a family history of either aldosteronism or early stroke.

• Laparoscopic adrenalectomy is the surgery of choice for most patients with unilateral adrenal disease. For patients unwilling or unable to undergo surgery or further investigations, prescribe a mineralocorticoid-receptor antagonist.

Medical therapy is the treatment of choice for bilateral adrenal disease. Spironolactone is the first-line agent, and eplerenone is an alternative agent to offer. This guideline is intended to be revised further as management evolves over the next 5 years. It is likely that by then, a rapid, inexpensive confirmatory test will be available to definitively establish the diagnosis and that third- and perhaps fourth-generation mineralocorticoid-receptor antagonists will be available for treatment. Simpler and more accurate methods of measuring plasma aldosterone concentration and direct renin concentration, which “would be a game changer for the primary care physician,” are currently being developed, Dr. Funder and his associates said (J. Clin. Endocrinol. Metab. 2016 May;101:1889-916).

In the meantime, “the main strategy is to convince primary-care physicians to screen for primary aldosteronism in all at-risk hypertensive patients,” they noted.

Copies of the full Guideline are available at societyservices@endocrine.org or by calling 202-971-3636.

Patients who survived pediatric-onset cancer are at increased risk for developing or experiencing endocrine abnormalities.

Risk was significantly higher in survivors who underwent high-risk therapeutic exposures compared with survivors not so exposed. Moreover, the incidence and prevalence of endocrine abnormalities increased across the lifespan of survivors, reported Sogol Mostoufi-Moab, MD, of University of Pennsylvania, Philadelphia, and his associates (J Clin Oncol. 2016 Jul. doi: 10.1200/JCO.2016.66.6545).

A total of 14,290 patients met the study’s eligibility requirements, which included a diagnosis of cancer before age 21 years and 5-year survival following diagnosis. Cancer diagnoses included leukemia, Hodgkin and non-Hodgkin lymphoma, Wilms tumor, neuroblastoma, sarcoma, bone malignancy, and central nervous system malignancy. Baseline and follow-up questionnaires collected endocrine-related outcomes of interest, demographic information, and medical histories for both cancer survivors and their siblings (n = 4,031). For survivors, median age at diagnosis was 6 years and median age at last follow-up was 32 years. For siblings, median age at last follow-up was 34 years.

Overall 44% of cancer survivors had at least one endocrinopathy, 16.7% had at least two, and 6.6% had three or more. Survivors of Hodgkin lymphoma had the highest frequency of endocrine abnormality (60.1%) followed by survivors of CNS malignancy (54%), leukemia (45.6%), sarcoma (41.3%), non-Hodgkin lymphoma (39.7%), and neuroblastoma (31.9%).

Specifically, thyroid disorders were more frequent among cancer survivors than among their siblings: underactive thyroid (hazard ratio, 2.2; 95% confidence interval, 1.8-2.7), overactive thyroid (HR, 2.4; 95% CI, 1.7-3.3), thyroid nodules (HR, 3.9; 95% CI, 2.9-5.4), and thyroid cancer (HR 2.5; 95% CI, 1.2-5.3).

Compared to their siblings, cancer survivors showed increased risk of developing diabetes (RR, 1.8; 95% CI, 1.4-2.3).

Among survivors, those exposed to high-risk therapies (defined by the Children’s Oncology Group’s Long-Term Follow-Up Guidelinesfor Survivors of Childhood, Adolescent, and Young Adult Cancers) were at a greater risk of developing primary hypothyroidism (HR, 6.6; 95% CI, 5.6-7.8) central hypothyroidism (HR, 3.9; 95% CI, 2.9-5.2), an overactive thyroid (HR, 1.8; 95% CI, 1.2-2.8), thyroid nodules (HR, 6.3; 95% CI, 5.2-7.5), and thyroid cancer (HR, 9.2; 95% CI, 6.2-13.7) compared with survivors not so exposed.

The National Cancer Institute, the Cancer Center Support Grant, and the American Lebanese Syrian Associated Charities of St. Jude Children’s Research Hospital funded the study. Dr. Mostoufi-Moab and nine other investigators had no disclosures to report. Two investigators reported receiving financial compensation or honoraria from Merck or Sandoz.

jcraig@frontlinemedcom.com

On Twitter @jessnicolecraig

Patients who survived pediatric-onset cancer are at increased risk for developing or experiencing endocrine abnormalities.

Risk was significantly higher in survivors who underwent high-risk therapeutic exposures compared with survivors not so exposed. Moreover, the incidence and prevalence of endocrine abnormalities increased across the lifespan of survivors, reported Sogol Mostoufi-Moab, MD, of University of Pennsylvania, Philadelphia, and his associates (J Clin Oncol. 2016 Jul. doi: 10.1200/JCO.2016.66.6545).

A total of 14,290 patients met the study’s eligibility requirements, which included a diagnosis of cancer before age 21 years and 5-year survival following diagnosis. Cancer diagnoses included leukemia, Hodgkin and non-Hodgkin lymphoma, Wilms tumor, neuroblastoma, sarcoma, bone malignancy, and central nervous system malignancy. Baseline and follow-up questionnaires collected endocrine-related outcomes of interest, demographic information, and medical histories for both cancer survivors and their siblings (n = 4,031). For survivors, median age at diagnosis was 6 years and median age at last follow-up was 32 years. For siblings, median age at last follow-up was 34 years.

Overall 44% of cancer survivors had at least one endocrinopathy, 16.7% had at least two, and 6.6% had three or more. Survivors of Hodgkin lymphoma had the highest frequency of endocrine abnormality (60.1%) followed by survivors of CNS malignancy (54%), leukemia (45.6%), sarcoma (41.3%), non-Hodgkin lymphoma (39.7%), and neuroblastoma (31.9%).

Specifically, thyroid disorders were more frequent among cancer survivors than among their siblings: underactive thyroid (hazard ratio, 2.2; 95% confidence interval, 1.8-2.7), overactive thyroid (HR, 2.4; 95% CI, 1.7-3.3), thyroid nodules (HR, 3.9; 95% CI, 2.9-5.4), and thyroid cancer (HR 2.5; 95% CI, 1.2-5.3).

Compared to their siblings, cancer survivors showed increased risk of developing diabetes (RR, 1.8; 95% CI, 1.4-2.3).

Among survivors, those exposed to high-risk therapies (defined by the Children’s Oncology Group’s Long-Term Follow-Up Guidelinesfor Survivors of Childhood, Adolescent, and Young Adult Cancers) were at a greater risk of developing primary hypothyroidism (HR, 6.6; 95% CI, 5.6-7.8) central hypothyroidism (HR, 3.9; 95% CI, 2.9-5.2), an overactive thyroid (HR, 1.8; 95% CI, 1.2-2.8), thyroid nodules (HR, 6.3; 95% CI, 5.2-7.5), and thyroid cancer (HR, 9.2; 95% CI, 6.2-13.7) compared with survivors not so exposed.

The National Cancer Institute, the Cancer Center Support Grant, and the American Lebanese Syrian Associated Charities of St. Jude Children’s Research Hospital funded the study. Dr. Mostoufi-Moab and nine other investigators had no disclosures to report. Two investigators reported receiving financial compensation or honoraria from Merck or Sandoz.

jcraig@frontlinemedcom.com

On Twitter @jessnicolecraig

Patients who survived pediatric-onset cancer are at increased risk for developing or experiencing endocrine abnormalities.

Risk was significantly higher in survivors who underwent high-risk therapeutic exposures compared with survivors not so exposed. Moreover, the incidence and prevalence of endocrine abnormalities increased across the lifespan of survivors, reported Sogol Mostoufi-Moab, MD, of University of Pennsylvania, Philadelphia, and his associates (J Clin Oncol. 2016 Jul. doi: 10.1200/JCO.2016.66.6545).

A total of 14,290 patients met the study’s eligibility requirements, which included a diagnosis of cancer before age 21 years and 5-year survival following diagnosis. Cancer diagnoses included leukemia, Hodgkin and non-Hodgkin lymphoma, Wilms tumor, neuroblastoma, sarcoma, bone malignancy, and central nervous system malignancy. Baseline and follow-up questionnaires collected endocrine-related outcomes of interest, demographic information, and medical histories for both cancer survivors and their siblings (n = 4,031). For survivors, median age at diagnosis was 6 years and median age at last follow-up was 32 years. For siblings, median age at last follow-up was 34 years.

Overall 44% of cancer survivors had at least one endocrinopathy, 16.7% had at least two, and 6.6% had three or more. Survivors of Hodgkin lymphoma had the highest frequency of endocrine abnormality (60.1%) followed by survivors of CNS malignancy (54%), leukemia (45.6%), sarcoma (41.3%), non-Hodgkin lymphoma (39.7%), and neuroblastoma (31.9%).

Specifically, thyroid disorders were more frequent among cancer survivors than among their siblings: underactive thyroid (hazard ratio, 2.2; 95% confidence interval, 1.8-2.7), overactive thyroid (HR, 2.4; 95% CI, 1.7-3.3), thyroid nodules (HR, 3.9; 95% CI, 2.9-5.4), and thyroid cancer (HR 2.5; 95% CI, 1.2-5.3).

Compared to their siblings, cancer survivors showed increased risk of developing diabetes (RR, 1.8; 95% CI, 1.4-2.3).

Among survivors, those exposed to high-risk therapies (defined by the Children’s Oncology Group’s Long-Term Follow-Up Guidelinesfor Survivors of Childhood, Adolescent, and Young Adult Cancers) were at a greater risk of developing primary hypothyroidism (HR, 6.6; 95% CI, 5.6-7.8) central hypothyroidism (HR, 3.9; 95% CI, 2.9-5.2), an overactive thyroid (HR, 1.8; 95% CI, 1.2-2.8), thyroid nodules (HR, 6.3; 95% CI, 5.2-7.5), and thyroid cancer (HR, 9.2; 95% CI, 6.2-13.7) compared with survivors not so exposed.

The National Cancer Institute, the Cancer Center Support Grant, and the American Lebanese Syrian Associated Charities of St. Jude Children’s Research Hospital funded the study. Dr. Mostoufi-Moab and nine other investigators had no disclosures to report. Two investigators reported receiving financial compensation or honoraria from Merck or Sandoz.

jcraig@frontlinemedcom.com

On Twitter @jessnicolecraig

The benefits of treating subclinical hypothyroidism with low-dose levothyroxine may outweigh the harms of delaying treatment until the condition has become symptomatic, requiring higher doses, according to one of the authors of a “Beyond the Guidelines” assessment of this controversy.

Last year, the U.S. Preventive Services Task Force issued guidelines and updated its 2004 recommendations, which essentially stated that there is no evidence to support treating subclinical hypothyroidism. In their own guidelines, the American Association of Clinical Endocrinologists and American Thyroid Association have instead advocated aggressive case-finding and recommend screening individuals who may be a high risk. These societies also argue that subclinical hypothyroidism can have an adverse effect on cardiovascular outcomes and therefore it merits case-findings.

©jarun011/Thinkstock.com

In the June 6, 2016 issue of the Annals of Internal Medicine (doi: 10.7326/M16-0857), experts from Beth Israel Deaconess Medical Center in Boston offered differing perspectives on the issue, as to whether or not subclinical hypothyroidism should be treated.

They gave their viewpoints in the context of a case study:

Mrs. C is a 60-year-old woman who has experienced mild symptoms such as fatigue and constipation for about 10 years, and has a family history of “thyroid problems.” In 2012, her TSH level was slightly elevated (5.8 uIU/L), and in 2013, she reported fatigue, although her TSH level was similar (5.9 uIU/L) to the year before.

Her free thyroxine (T₄) was normal (0.93 ng/dL), and given the stability of her TSH level, treatment was not initiated. Recently, she reported weight gain, intermittent constipation, and persistent fatigue. Currently she is being treated for hyperlipidemia with atorvastatin 10 mg daily as well as for cervical radiculitis. Two of her three sisters receive thyroid medication, and recently, her blood pressure was 136/79 mm Hg with a heart rate of 77 beats per minute. Her weight had increased by 9 pounds, to 156 pounds (body mass index, 29.6 kg/m²). Her thyroid examination was normal, and her TSH measurement was 6.5 uIU/ML and free T₄ was 1 ng/dL.

Should she begin thyroid replacement therapy?

Dr. Pamela Hartzband noted that there is an “evidence base suggesting that patients like Ms. C may benefit with respect to both morbidity and mortality,” given her family history and elevated cholesterol levels. TSH is a sensitive indicator of primary hypothyroidism, and given that the patient’s levels have gradually increased, this is significant and suggests early thyroid failure. That said, in “reviewing the evidence for benefit of treatment, there are not only conflicting data but also conflicting interpretation[s] of the same data by different experts,” according to Dr. Hartzband.

However, subclinical hypothyroidism has been associated with a greater risk for both cardiovascular morbidity and mortality in some but not all prospective population-based studies.

Symptom relief is the primary goal for patients, and Mrs. C has described symptoms that are suggestive of hypothyroidism including fatigue, constipation, scalp hair loss, and weight gain and elevated TSH. There is a “paucity of evidence” demonstrating improvement with treatment of subclinical hypothyroidism. And while harms associated with treatment can also be a concern, there is remarkably limited evidence for harms related to the treatment of subclinical hypothyroidism, noted Dr. Hartzband of the division of endocrinology and metabolism and medical director of the Thyroid Biopsy Clinic at Beth Israel Deaconess Medical Center, Boston.

There is, however, speculation that patients might develop hyperthyroidism from being given excessive doses of levothyroxine, but this can be avoided by initiating treatment of subclinical hypothyroidism with low-dose levothyroxine (25-50 mcg).

Overall, when weighing the benefits and harms of treatment in this case, Dr. Hartzband would consider offering Ms. C a trial of levothyroxine. The reasoning is that based on family history, she is at increased risk for thyroid disease and was appropriately tested by measuring TSH. In addition, levothyroxine could lower her cholesterol levels and risk for heart disease, and she might be able to reduce or even discontinue her statin therapy.

“I believe that for Ms. C the potential for benefit outweighs potential risk,” wrote Dr. Hartzband. “If she does not feel better and if cholesterol is not improved, then levothyroxine could be stopped until her TSH rises further.”

Dr. Carol K. Bates of the division of general medicine and primary care at Beth Israel Deaconess Medical Center, Boston, leaned more toward holding back on treatment. For one thing, since there is a diurnal variation in TSH, the patient’s TSH values might have been normal if measured in the afternoon instead of the morning.

As far as the risk of heart disease, where much of the treatment debate is focused, she pointed out that while there is an association between congestive heart failure, coronary artery disease, and subclinical hypothyroidism, Mrs. C only has a mildly increased TSH.

There have also been arguments that treating subclinical hypothyroidism could lower cholesterol levels. Ms. C started on a statin in 2003 when her TSH was 3.5 and thus euthyroid. Any efforts to lower cholesterol might be done by adjusting her statin dose rather than adding levothyroxine.

Both over- and undertreatment with thyroid hormone replacement are common, she pointed out, and overtreatment has been associated with an increased risk for hip and major osteoporotic fracture, as well as increasing the risk for atrial fibrillation. She also noted that there is harm in medicalizing a normal condition, as the upper range of TSH is arbitrarily set based upon population data.

In the case of Mrs. C, Dr. Bates would explain that there is no risk for heart disease given the degree of thyroid dysfunction and, especially, that her goal of weight loss and symptom relief likely won’t happen.

If she did wish to be treated, Dr. Bates would also start her on a low dose. “If she were to embark on treatment, I would suggest monitoring her weight and symptoms,” she wrote. “While many authorities would recommend treatment at a calculated full replacement dose, my experience suggests that this risks overtreatment, and I would recommend starting at 25 to 50 mcg.”

The benefits of treating subclinical hypothyroidism with low-dose levothyroxine may outweigh the harms of delaying treatment until the condition has become symptomatic, requiring higher doses, according to one of the authors of a “Beyond the Guidelines” assessment of this controversy.

Last year, the U.S. Preventive Services Task Force issued guidelines and updated its 2004 recommendations, which essentially stated that there is no evidence to support treating subclinical hypothyroidism. In their own guidelines, the American Association of Clinical Endocrinologists and American Thyroid Association have instead advocated aggressive case-finding and recommend screening individuals who may be a high risk. These societies also argue that subclinical hypothyroidism can have an adverse effect on cardiovascular outcomes and therefore it merits case-findings.

©jarun011/Thinkstock.com

In the June 6, 2016 issue of the Annals of Internal Medicine (doi: 10.7326/M16-0857), experts from Beth Israel Deaconess Medical Center in Boston offered differing perspectives on the issue, as to whether or not subclinical hypothyroidism should be treated.

They gave their viewpoints in the context of a case study:

Mrs. C is a 60-year-old woman who has experienced mild symptoms such as fatigue and constipation for about 10 years, and has a family history of “thyroid problems.” In 2012, her TSH level was slightly elevated (5.8 uIU/L), and in 2013, she reported fatigue, although her TSH level was similar (5.9 uIU/L) to the year before.

Her free thyroxine (T₄) was normal (0.93 ng/dL), and given the stability of her TSH level, treatment was not initiated. Recently, she reported weight gain, intermittent constipation, and persistent fatigue. Currently she is being treated for hyperlipidemia with atorvastatin 10 mg daily as well as for cervical radiculitis. Two of her three sisters receive thyroid medication, and recently, her blood pressure was 136/79 mm Hg with a heart rate of 77 beats per minute. Her weight had increased by 9 pounds, to 156 pounds (body mass index, 29.6 kg/m²). Her thyroid examination was normal, and her TSH measurement was 6.5 uIU/ML and free T₄ was 1 ng/dL.

Should she begin thyroid replacement therapy?

Dr. Pamela Hartzband noted that there is an “evidence base suggesting that patients like Ms. C may benefit with respect to both morbidity and mortality,” given her family history and elevated cholesterol levels. TSH is a sensitive indicator of primary hypothyroidism, and given that the patient’s levels have gradually increased, this is significant and suggests early thyroid failure. That said, in “reviewing the evidence for benefit of treatment, there are not only conflicting data but also conflicting interpretation[s] of the same data by different experts,” according to Dr. Hartzband.

However, subclinical hypothyroidism has been associated with a greater risk for both cardiovascular morbidity and mortality in some but not all prospective population-based studies.

Symptom relief is the primary goal for patients, and Mrs. C has described symptoms that are suggestive of hypothyroidism including fatigue, constipation, scalp hair loss, and weight gain and elevated TSH. There is a “paucity of evidence” demonstrating improvement with treatment of subclinical hypothyroidism. And while harms associated with treatment can also be a concern, there is remarkably limited evidence for harms related to the treatment of subclinical hypothyroidism, noted Dr. Hartzband of the division of endocrinology and metabolism and medical director of the Thyroid Biopsy Clinic at Beth Israel Deaconess Medical Center, Boston.

There is, however, speculation that patients might develop hyperthyroidism from being given excessive doses of levothyroxine, but this can be avoided by initiating treatment of subclinical hypothyroidism with low-dose levothyroxine (25-50 mcg).

Overall, when weighing the benefits and harms of treatment in this case, Dr. Hartzband would consider offering Ms. C a trial of levothyroxine. The reasoning is that based on family history, she is at increased risk for thyroid disease and was appropriately tested by measuring TSH. In addition, levothyroxine could lower her cholesterol levels and risk for heart disease, and she might be able to reduce or even discontinue her statin therapy.

“I believe that for Ms. C the potential for benefit outweighs potential risk,” wrote Dr. Hartzband. “If she does not feel better and if cholesterol is not improved, then levothyroxine could be stopped until her TSH rises further.”

Dr. Carol K. Bates of the division of general medicine and primary care at Beth Israel Deaconess Medical Center, Boston, leaned more toward holding back on treatment. For one thing, since there is a diurnal variation in TSH, the patient’s TSH values might have been normal if measured in the afternoon instead of the morning.

As far as the risk of heart disease, where much of the treatment debate is focused, she pointed out that while there is an association between congestive heart failure, coronary artery disease, and subclinical hypothyroidism, Mrs. C only has a mildly increased TSH.

There have also been arguments that treating subclinical hypothyroidism could lower cholesterol levels. Ms. C started on a statin in 2003 when her TSH was 3.5 and thus euthyroid. Any efforts to lower cholesterol might be done by adjusting her statin dose rather than adding levothyroxine.

Both over- and undertreatment with thyroid hormone replacement are common, she pointed out, and overtreatment has been associated with an increased risk for hip and major osteoporotic fracture, as well as increasing the risk for atrial fibrillation. She also noted that there is harm in medicalizing a normal condition, as the upper range of TSH is arbitrarily set based upon population data.

In the case of Mrs. C, Dr. Bates would explain that there is no risk for heart disease given the degree of thyroid dysfunction and, especially, that her goal of weight loss and symptom relief likely won’t happen.

If she did wish to be treated, Dr. Bates would also start her on a low dose. “If she were to embark on treatment, I would suggest monitoring her weight and symptoms,” she wrote. “While many authorities would recommend treatment at a calculated full replacement dose, my experience suggests that this risks overtreatment, and I would recommend starting at 25 to 50 mcg.”

The benefits of treating subclinical hypothyroidism with low-dose levothyroxine may outweigh the harms of delaying treatment until the condition has become symptomatic, requiring higher doses, according to one of the authors of a “Beyond the Guidelines” assessment of this controversy.

Last year, the U.S. Preventive Services Task Force issued guidelines and updated its 2004 recommendations, which essentially stated that there is no evidence to support treating subclinical hypothyroidism. In their own guidelines, the American Association of Clinical Endocrinologists and American Thyroid Association have instead advocated aggressive case-finding and recommend screening individuals who may be a high risk. These societies also argue that subclinical hypothyroidism can have an adverse effect on cardiovascular outcomes and therefore it merits case-findings.

©jarun011/Thinkstock.com

In the June 6, 2016 issue of the Annals of Internal Medicine (doi: 10.7326/M16-0857), experts from Beth Israel Deaconess Medical Center in Boston offered differing perspectives on the issue, as to whether or not subclinical hypothyroidism should be treated.

They gave their viewpoints in the context of a case study:

Mrs. C is a 60-year-old woman who has experienced mild symptoms such as fatigue and constipation for about 10 years, and has a family history of “thyroid problems.” In 2012, her TSH level was slightly elevated (5.8 uIU/L), and in 2013, she reported fatigue, although her TSH level was similar (5.9 uIU/L) to the year before.

Her free thyroxine (T₄) was normal (0.93 ng/dL), and given the stability of her TSH level, treatment was not initiated. Recently, she reported weight gain, intermittent constipation, and persistent fatigue. Currently she is being treated for hyperlipidemia with atorvastatin 10 mg daily as well as for cervical radiculitis. Two of her three sisters receive thyroid medication, and recently, her blood pressure was 136/79 mm Hg with a heart rate of 77 beats per minute. Her weight had increased by 9 pounds, to 156 pounds (body mass index, 29.6 kg/m²). Her thyroid examination was normal, and her TSH measurement was 6.5 uIU/ML and free T₄ was 1 ng/dL.

Should she begin thyroid replacement therapy?

Dr. Pamela Hartzband noted that there is an “evidence base suggesting that patients like Ms. C may benefit with respect to both morbidity and mortality,” given her family history and elevated cholesterol levels. TSH is a sensitive indicator of primary hypothyroidism, and given that the patient’s levels have gradually increased, this is significant and suggests early thyroid failure. That said, in “reviewing the evidence for benefit of treatment, there are not only conflicting data but also conflicting interpretation[s] of the same data by different experts,” according to Dr. Hartzband.

However, subclinical hypothyroidism has been associated with a greater risk for both cardiovascular morbidity and mortality in some but not all prospective population-based studies.

Symptom relief is the primary goal for patients, and Mrs. C has described symptoms that are suggestive of hypothyroidism including fatigue, constipation, scalp hair loss, and weight gain and elevated TSH. There is a “paucity of evidence” demonstrating improvement with treatment of subclinical hypothyroidism. And while harms associated with treatment can also be a concern, there is remarkably limited evidence for harms related to the treatment of subclinical hypothyroidism, noted Dr. Hartzband of the division of endocrinology and metabolism and medical director of the Thyroid Biopsy Clinic at Beth Israel Deaconess Medical Center, Boston.

There is, however, speculation that patients might develop hyperthyroidism from being given excessive doses of levothyroxine, but this can be avoided by initiating treatment of subclinical hypothyroidism with low-dose levothyroxine (25-50 mcg).

Overall, when weighing the benefits and harms of treatment in this case, Dr. Hartzband would consider offering Ms. C a trial of levothyroxine. The reasoning is that based on family history, she is at increased risk for thyroid disease and was appropriately tested by measuring TSH. In addition, levothyroxine could lower her cholesterol levels and risk for heart disease, and she might be able to reduce or even discontinue her statin therapy.

“I believe that for Ms. C the potential for benefit outweighs potential risk,” wrote Dr. Hartzband. “If she does not feel better and if cholesterol is not improved, then levothyroxine could be stopped until her TSH rises further.”

Dr. Carol K. Bates of the division of general medicine and primary care at Beth Israel Deaconess Medical Center, Boston, leaned more toward holding back on treatment. For one thing, since there is a diurnal variation in TSH, the patient’s TSH values might have been normal if measured in the afternoon instead of the morning.

As far as the risk of heart disease, where much of the treatment debate is focused, she pointed out that while there is an association between congestive heart failure, coronary artery disease, and subclinical hypothyroidism, Mrs. C only has a mildly increased TSH.

There have also been arguments that treating subclinical hypothyroidism could lower cholesterol levels. Ms. C started on a statin in 2003 when her TSH was 3.5 and thus euthyroid. Any efforts to lower cholesterol might be done by adjusting her statin dose rather than adding levothyroxine.

Both over- and undertreatment with thyroid hormone replacement are common, she pointed out, and overtreatment has been associated with an increased risk for hip and major osteoporotic fracture, as well as increasing the risk for atrial fibrillation. She also noted that there is harm in medicalizing a normal condition, as the upper range of TSH is arbitrarily set based upon population data.

In the case of Mrs. C, Dr. Bates would explain that there is no risk for heart disease given the degree of thyroid dysfunction and, especially, that her goal of weight loss and symptom relief likely won’t happen.

If she did wish to be treated, Dr. Bates would also start her on a low dose. “If she were to embark on treatment, I would suggest monitoring her weight and symptoms,” she wrote. “While many authorities would recommend treatment at a calculated full replacement dose, my experience suggests that this risks overtreatment, and I would recommend starting at 25 to 50 mcg.”

ORLANDO – Radiofrequency (RF) ablation is a safe and effective procedure for treating focal adrenal tumors in patients who are poor surgical candidates or who refuse adrenalectomy. With a short treatment time and minimal hospital stay, RF ablation can provide rapid clinical and biochemical improvement.

Dr. Lima Lawrence, an internal medicine resident at the University of Illinois at Chicago/Advocate Christ Medical Center in Oak Lawn, presented a case report and a review of the literature during an oral abstract session at the annual meeting of the American Association of Clinical Endocrinologists. The patient was a 65-year-old woman who presented with weight gain, decreased energy, and muscle weakness. On physical exam, she was hypertensive, anxious, obese, and had prominent supraclavicular fat pads. Salivary cortisol and overnight dexamethasone suppression tests were both elevated, and ACTH levels were depressed, confirming the diagnosis of a cortisol-secreting tumor causing adrenal Cushing’s syndrome. Computed tomography (CT) surveillance showed a progressively enlarging right-sided adrenal mass. A peritoneal biopsy revealed a low-grade serous neoplasm of peritoneal origin.

Her medical history included type 2 diabetes, uncontrolled hypertension, mixed connective tissue disease, depression, and total abdominal hysterectomy with bilateral salpingo-oophorectomy for ovarian cancer.

Dr. Lawrence said the patient had been scheduled for adrenalectomy, but it was not performed because of an intraoperative finding of peritoneal studding from what turned out to be metastatic ovarian cancer. Therefore, she underwent CT-guided RF ablation of the adrenal mass using a 14-gauge probe that heated a 3.5-cm ablation zone to 50-60 C for 8-10 minutes to achieve complete tumor necrosis.

The patient showed dramatic “clinical and biochemical improvement,” Dr. Lawrence said. The patient had no procedural complications and no blood loss and was observed for 23 hours before being discharged to home. A CT scan 8 weeks later showed a slightly decreased mass with marked decreased radiographic attenuation post-contrast from 30.2 Hounsfield Units (HU) preoperatively to 17 HU on follow-up.

Potential adverse outcomes using RF ablation include a risk of pneumothorax, hemothorax, and tumor seeding along the catheter track, but this last possibility can be mitigated by continuing to heat the RF probe as it is withdrawn.

Published evidence supports use of RF ablation. “To date there have been no randomized clinical trials comparing the safety, efficacy, and survival benefits of adrenalectomy vs. radio frequency ablation,” she said. It may not be feasible to do a randomized trial. But a review of the literature generally supports the efficacy of the technique although the publications each involved a small series of patients, Dr. Lawrence said in an interview.

A 2003 series (Cancer. 2003;97:554-60) of 15 primary or metastatic adrenal cell carcinomas that were unresectable or were in patients who were not surgical candidates showed nonenhancement and no growth in 8 (53%) at a mean follow-up of 10.3 months. Eight of the 12 tumors of 5 cm or smaller had complete loss of radiographic enhancement and a decrease in size.

From a retrospective series of 13 patients with functional adrenal neoplasms over 7 years, there was 100% resolution of biochemical abnormalities and clinical symptoms at a mean follow-up of 21.2 months. One small pneumothorax and one limited hemothorax occurred, neither of which required hospital admission. There were two instances of transient, self-remitting hypertension associated with the procedures (Radiology. 2011;258:308-16).

In 2015, one group of investigators followed 11 patients for 12 weeks postprocedure. Eight of nine patients with Conn’s syndrome attained normal serum aldosterone levels. One with a nodule close to the inferior vena cava had incomplete ablation. Two of two Cushing’s patients had normal cortisol levels after the procedure (J Vasc Interv Radiol. 2015;26:1459-64).

A retrospective analysis of 16 adrenal metastases showed that 13 (81%) had no local progression over 14 months after ablation. In two of three functional adrenal neoplasms, clinical and biochemical abnormalities resolved (Eur J Radiol. 2012.81:1717-23).

A retrospective series of 10 adrenal metastases showed that one recurred at 7 months after image-guided thermal ablation, with no recurrence of the rest at 26.6 months. There was no tumor recurrence for any of the cases of metastatic disease localized to the RF ablation site (J Vasc Interv Radiol. 2014;25:593-8).

Results were somewhat less good in a retrospective evaluation of 35 patients with unresectable adrenal masses over 9 years. Although 33 of 35 (94%) lost tumor enhancement after the initial adrenal RF ablation, there was local tumor progression in 8 of 35 (23%) patients at a mean follow-up of 30.1 months (Radiology. 2015;277:584-93).

Finally, Dr. Lawrence discussed a systematic literature review on adrenalectomy vs. stereotactic ablative body radiotherapy (SABR) and percutaneous catheter ablation (PCA) in the treatment of adrenal metastases: 30 papers on adrenalectomy on 818 patients; 9 papers on SABR on 178 patients; and 6 papers on PCA, including RF ablation, on 51 patients. The authors concluded that there was “insufficient evidence to determine the best local treatment modality for isolated or limited adrenal metastases.” Adrenalectomy appeared to be a reasonable treatment for suitable patients. SABR was a valid alternative for nonsurgical candidates, but they did not recommend PCA until more long-term outcomes were available (Cancer Treat Rev. 2014;40:838-46).

Dr. Lawrence concurred, based on her case study and literature review. She said RF ablation “offers patients a minimally invasive option for treating focal adrenal tumors” and is a “safe and effective procedure … in patients who are poor surgical candidates or refuse adrenalectomy.” More long-term follow-up studies are needed before RF ablation could replace adrenalectomy, she noted.

ORLANDO – Radiofrequency (RF) ablation is a safe and effective procedure for treating focal adrenal tumors in patients who are poor surgical candidates or who refuse adrenalectomy. With a short treatment time and minimal hospital stay, RF ablation can provide rapid clinical and biochemical improvement.

Dr. Lima Lawrence, an internal medicine resident at the University of Illinois at Chicago/Advocate Christ Medical Center in Oak Lawn, presented a case report and a review of the literature during an oral abstract session at the annual meeting of the American Association of Clinical Endocrinologists. The patient was a 65-year-old woman who presented with weight gain, decreased energy, and muscle weakness. On physical exam, she was hypertensive, anxious, obese, and had prominent supraclavicular fat pads. Salivary cortisol and overnight dexamethasone suppression tests were both elevated, and ACTH levels were depressed, confirming the diagnosis of a cortisol-secreting tumor causing adrenal Cushing’s syndrome. Computed tomography (CT) surveillance showed a progressively enlarging right-sided adrenal mass. A peritoneal biopsy revealed a low-grade serous neoplasm of peritoneal origin.

Her medical history included type 2 diabetes, uncontrolled hypertension, mixed connective tissue disease, depression, and total abdominal hysterectomy with bilateral salpingo-oophorectomy for ovarian cancer.

Dr. Lawrence said the patient had been scheduled for adrenalectomy, but it was not performed because of an intraoperative finding of peritoneal studding from what turned out to be metastatic ovarian cancer. Therefore, she underwent CT-guided RF ablation of the adrenal mass using a 14-gauge probe that heated a 3.5-cm ablation zone to 50-60 C for 8-10 minutes to achieve complete tumor necrosis.

The patient showed dramatic “clinical and biochemical improvement,” Dr. Lawrence said. The patient had no procedural complications and no blood loss and was observed for 23 hours before being discharged to home. A CT scan 8 weeks later showed a slightly decreased mass with marked decreased radiographic attenuation post-contrast from 30.2 Hounsfield Units (HU) preoperatively to 17 HU on follow-up.

Potential adverse outcomes using RF ablation include a risk of pneumothorax, hemothorax, and tumor seeding along the catheter track, but this last possibility can be mitigated by continuing to heat the RF probe as it is withdrawn.

Published evidence supports use of RF ablation. “To date there have been no randomized clinical trials comparing the safety, efficacy, and survival benefits of adrenalectomy vs. radio frequency ablation,” she said. It may not be feasible to do a randomized trial. But a review of the literature generally supports the efficacy of the technique although the publications each involved a small series of patients, Dr. Lawrence said in an interview.

A 2003 series (Cancer. 2003;97:554-60) of 15 primary or metastatic adrenal cell carcinomas that were unresectable or were in patients who were not surgical candidates showed nonenhancement and no growth in 8 (53%) at a mean follow-up of 10.3 months. Eight of the 12 tumors of 5 cm or smaller had complete loss of radiographic enhancement and a decrease in size.

From a retrospective series of 13 patients with functional adrenal neoplasms over 7 years, there was 100% resolution of biochemical abnormalities and clinical symptoms at a mean follow-up of 21.2 months. One small pneumothorax and one limited hemothorax occurred, neither of which required hospital admission. There were two instances of transient, self-remitting hypertension associated with the procedures (Radiology. 2011;258:308-16).

In 2015, one group of investigators followed 11 patients for 12 weeks postprocedure. Eight of nine patients with Conn’s syndrome attained normal serum aldosterone levels. One with a nodule close to the inferior vena cava had incomplete ablation. Two of two Cushing’s patients had normal cortisol levels after the procedure (J Vasc Interv Radiol. 2015;26:1459-64).

A retrospective analysis of 16 adrenal metastases showed that 13 (81%) had no local progression over 14 months after ablation. In two of three functional adrenal neoplasms, clinical and biochemical abnormalities resolved (Eur J Radiol. 2012.81:1717-23).

A retrospective series of 10 adrenal metastases showed that one recurred at 7 months after image-guided thermal ablation, with no recurrence of the rest at 26.6 months. There was no tumor recurrence for any of the cases of metastatic disease localized to the RF ablation site (J Vasc Interv Radiol. 2014;25:593-8).

Results were somewhat less good in a retrospective evaluation of 35 patients with unresectable adrenal masses over 9 years. Although 33 of 35 (94%) lost tumor enhancement after the initial adrenal RF ablation, there was local tumor progression in 8 of 35 (23%) patients at a mean follow-up of 30.1 months (Radiology. 2015;277:584-93).

Finally, Dr. Lawrence discussed a systematic literature review on adrenalectomy vs. stereotactic ablative body radiotherapy (SABR) and percutaneous catheter ablation (PCA) in the treatment of adrenal metastases: 30 papers on adrenalectomy on 818 patients; 9 papers on SABR on 178 patients; and 6 papers on PCA, including RF ablation, on 51 patients. The authors concluded that there was “insufficient evidence to determine the best local treatment modality for isolated or limited adrenal metastases.” Adrenalectomy appeared to be a reasonable treatment for suitable patients. SABR was a valid alternative for nonsurgical candidates, but they did not recommend PCA until more long-term outcomes were available (Cancer Treat Rev. 2014;40:838-46).

Dr. Lawrence concurred, based on her case study and literature review. She said RF ablation “offers patients a minimally invasive option for treating focal adrenal tumors” and is a “safe and effective procedure … in patients who are poor surgical candidates or refuse adrenalectomy.” More long-term follow-up studies are needed before RF ablation could replace adrenalectomy, she noted.

ORLANDO – Radiofrequency (RF) ablation is a safe and effective procedure for treating focal adrenal tumors in patients who are poor surgical candidates or who refuse adrenalectomy. With a short treatment time and minimal hospital stay, RF ablation can provide rapid clinical and biochemical improvement.

Dr. Lima Lawrence, an internal medicine resident at the University of Illinois at Chicago/Advocate Christ Medical Center in Oak Lawn, presented a case report and a review of the literature during an oral abstract session at the annual meeting of the American Association of Clinical Endocrinologists. The patient was a 65-year-old woman who presented with weight gain, decreased energy, and muscle weakness. On physical exam, she was hypertensive, anxious, obese, and had prominent supraclavicular fat pads. Salivary cortisol and overnight dexamethasone suppression tests were both elevated, and ACTH levels were depressed, confirming the diagnosis of a cortisol-secreting tumor causing adrenal Cushing’s syndrome. Computed tomography (CT) surveillance showed a progressively enlarging right-sided adrenal mass. A peritoneal biopsy revealed a low-grade serous neoplasm of peritoneal origin.

Her medical history included type 2 diabetes, uncontrolled hypertension, mixed connective tissue disease, depression, and total abdominal hysterectomy with bilateral salpingo-oophorectomy for ovarian cancer.

Dr. Lawrence said the patient had been scheduled for adrenalectomy, but it was not performed because of an intraoperative finding of peritoneal studding from what turned out to be metastatic ovarian cancer. Therefore, she underwent CT-guided RF ablation of the adrenal mass using a 14-gauge probe that heated a 3.5-cm ablation zone to 50-60 C for 8-10 minutes to achieve complete tumor necrosis.

The patient showed dramatic “clinical and biochemical improvement,” Dr. Lawrence said. The patient had no procedural complications and no blood loss and was observed for 23 hours before being discharged to home. A CT scan 8 weeks later showed a slightly decreased mass with marked decreased radiographic attenuation post-contrast from 30.2 Hounsfield Units (HU) preoperatively to 17 HU on follow-up.

Potential adverse outcomes using RF ablation include a risk of pneumothorax, hemothorax, and tumor seeding along the catheter track, but this last possibility can be mitigated by continuing to heat the RF probe as it is withdrawn.

Published evidence supports use of RF ablation. “To date there have been no randomized clinical trials comparing the safety, efficacy, and survival benefits of adrenalectomy vs. radio frequency ablation,” she said. It may not be feasible to do a randomized trial. But a review of the literature generally supports the efficacy of the technique although the publications each involved a small series of patients, Dr. Lawrence said in an interview.

A 2003 series (Cancer. 2003;97:554-60) of 15 primary or metastatic adrenal cell carcinomas that were unresectable or were in patients who were not surgical candidates showed nonenhancement and no growth in 8 (53%) at a mean follow-up of 10.3 months. Eight of the 12 tumors of 5 cm or smaller had complete loss of radiographic enhancement and a decrease in size.

From a retrospective series of 13 patients with functional adrenal neoplasms over 7 years, there was 100% resolution of biochemical abnormalities and clinical symptoms at a mean follow-up of 21.2 months. One small pneumothorax and one limited hemothorax occurred, neither of which required hospital admission. There were two instances of transient, self-remitting hypertension associated with the procedures (Radiology. 2011;258:308-16).

In 2015, one group of investigators followed 11 patients for 12 weeks postprocedure. Eight of nine patients with Conn’s syndrome attained normal serum aldosterone levels. One with a nodule close to the inferior vena cava had incomplete ablation. Two of two Cushing’s patients had normal cortisol levels after the procedure (J Vasc Interv Radiol. 2015;26:1459-64).

A retrospective analysis of 16 adrenal metastases showed that 13 (81%) had no local progression over 14 months after ablation. In two of three functional adrenal neoplasms, clinical and biochemical abnormalities resolved (Eur J Radiol. 2012.81:1717-23).

A retrospective series of 10 adrenal metastases showed that one recurred at 7 months after image-guided thermal ablation, with no recurrence of the rest at 26.6 months. There was no tumor recurrence for any of the cases of metastatic disease localized to the RF ablation site (J Vasc Interv Radiol. 2014;25:593-8).

Results were somewhat less good in a retrospective evaluation of 35 patients with unresectable adrenal masses over 9 years. Although 33 of 35 (94%) lost tumor enhancement after the initial adrenal RF ablation, there was local tumor progression in 8 of 35 (23%) patients at a mean follow-up of 30.1 months (Radiology. 2015;277:584-93).

Finally, Dr. Lawrence discussed a systematic literature review on adrenalectomy vs. stereotactic ablative body radiotherapy (SABR) and percutaneous catheter ablation (PCA) in the treatment of adrenal metastases: 30 papers on adrenalectomy on 818 patients; 9 papers on SABR on 178 patients; and 6 papers on PCA, including RF ablation, on 51 patients. The authors concluded that there was “insufficient evidence to determine the best local treatment modality for isolated or limited adrenal metastases.” Adrenalectomy appeared to be a reasonable treatment for suitable patients. SABR was a valid alternative for nonsurgical candidates, but they did not recommend PCA until more long-term outcomes were available (Cancer Treat Rev. 2014;40:838-46).

Dr. Lawrence concurred, based on her case study and literature review. She said RF ablation “offers patients a minimally invasive option for treating focal adrenal tumors” and is a “safe and effective procedure … in patients who are poor surgical candidates or refuse adrenalectomy.” More long-term follow-up studies are needed before RF ablation could replace adrenalectomy, she noted.

BALTIMORE – Patients who have recurrent adrenocortical carcinoma appear to have one option to increase their survival: surgery that includes complete tumor resection – but it may a viable path only if the recurrence occurred a year or more after the initial resection and diagnosis, according to an retrospective study of patients at five French university hospitals. “Adrenocortical carcinoma (ACC) is a rare, malignant tumor that has a poor prognosis, and recurrence of the tumor is considerable with 75% recurrence at 5 years,” Dr. Claire Blanchard of the Digestive and Endocrine Surgery Clinic at the Central University Hospital, Nantes, France, reported at the annual meeting of the American Association of Endocrine Surgeons. “Complete resection of recurrence is the only curative treatment.”

The researchers conducted a retrospective study of patients with at least one recurrence, diagnosed between 1980 and 2014, after initial resection of ACC, comparing outcomes in 29 patients who underwent surgery with 30 who had non-operative treatment, mainly chemotherapy and radiation.

Patients who had an operation for recurrence more often had local recurrence, 75% vs. 10% in the nonoperative group, and more frequently had a unique site of recurrence, 97% vs. 45%, than the nonoperative patients, Dr. Blanchard said.

These other demographic and tumor characteristics were similar between the operative and nonoperative groups, respectively: age, 49 years and 53 years; gender, 63% and 79% female; Weiss score, 6 and 7; Ki-67 protein index, 23% and 24%; tumor size, 99.2 mm and 115.5 mm; ENSAT stage, 65% and 45% stages I and II; and R0 resection status of the primary tumor at initial surgery, 83% and 71%.

The univariate analysis showed that appearance of the first recurrence more than 12 months after the initial diagnosis increased a patient’s chance of survival after treatment for recurrence, Dr. Blanchard said.

“Recurrences occurred at median delay of 12 months after the initial surgery,” Dr. Blanchard said. “In the 59 patients, 24 had local recurrences and 35 had distant metastases.”

Overall median survival after the first recurrence was 91 months for patients who had surgery vs. 15 months for those who did not. Overall median survival after initial resection of the primary tumor was 133 months, with a range of 14 to 252 months, in operated patients vs. 32 months, ranging from 21 to 43 months, in those who had no surgery, Dr. Blanchard said.

Of the 29 surgery patients in the surgery group, 22 had local-regional resections, 6 of whom had adjunctive radiation of the tumor bed.

“The type of resection in recurrent ACC depends on the location of the recurrence,” senior coauthor Dr. Eric Mirallié said. “In the case of local recurrence, we resected the adrenalectomy bed and all the adjacent invaded organs.”

In this series, 6 patients had resection of the tumor bed and 16 had adjacent organ resections; 8 patients (28%) had two or more operations for recurrences. These operations involved eight splenectomies, seven resections for abdominal nodules, six nephrectomies, three distal pancreatectomies, three segmental colectomies, and two minor hepatectomies. All operations were by laparotomy.

“In cases of distant recurrence, complete metastasectomy was performed,” Dr. Mirallié said. The series reported two right hepatectomies, one liver tumorectomy, one lung tumorectomy, and one brain tumorectomy.

“Nonoperative management is reserved for nonresectable patients with recurrent adrenocortical carcinoma,” Dr. Mirallié said. “Oral chemotherapy like mitotane was always given when possible. In cases of nonresectable local recurrence, radiotherapy can be used.”

During the discussion, Dr. Bradford K. Mitchell of Michigan State University, East Lansing, said that the benefit of improved survival in surgical patients in the study may have been a function of selection bias as patients who were not operated on may have had more advanced disease.

Dr. Blanchard and her coauthors had no financial relationships to disclose.

BALTIMORE – Patients who have recurrent adrenocortical carcinoma appear to have one option to increase their survival: surgery that includes complete tumor resection – but it may a viable path only if the recurrence occurred a year or more after the initial resection and diagnosis, according to an retrospective study of patients at five French university hospitals. “Adrenocortical carcinoma (ACC) is a rare, malignant tumor that has a poor prognosis, and recurrence of the tumor is considerable with 75% recurrence at 5 years,” Dr. Claire Blanchard of the Digestive and Endocrine Surgery Clinic at the Central University Hospital, Nantes, France, reported at the annual meeting of the American Association of Endocrine Surgeons. “Complete resection of recurrence is the only curative treatment.”

The researchers conducted a retrospective study of patients with at least one recurrence, diagnosed between 1980 and 2014, after initial resection of ACC, comparing outcomes in 29 patients who underwent surgery with 30 who had non-operative treatment, mainly chemotherapy and radiation.

Patients who had an operation for recurrence more often had local recurrence, 75% vs. 10% in the nonoperative group, and more frequently had a unique site of recurrence, 97% vs. 45%, than the nonoperative patients, Dr. Blanchard said.

These other demographic and tumor characteristics were similar between the operative and nonoperative groups, respectively: age, 49 years and 53 years; gender, 63% and 79% female; Weiss score, 6 and 7; Ki-67 protein index, 23% and 24%; tumor size, 99.2 mm and 115.5 mm; ENSAT stage, 65% and 45% stages I and II; and R0 resection status of the primary tumor at initial surgery, 83% and 71%.

The univariate analysis showed that appearance of the first recurrence more than 12 months after the initial diagnosis increased a patient’s chance of survival after treatment for recurrence, Dr. Blanchard said.

“Recurrences occurred at median delay of 12 months after the initial surgery,” Dr. Blanchard said. “In the 59 patients, 24 had local recurrences and 35 had distant metastases.”

Overall median survival after the first recurrence was 91 months for patients who had surgery vs. 15 months for those who did not. Overall median survival after initial resection of the primary tumor was 133 months, with a range of 14 to 252 months, in operated patients vs. 32 months, ranging from 21 to 43 months, in those who had no surgery, Dr. Blanchard said.

Of the 29 surgery patients in the surgery group, 22 had local-regional resections, 6 of whom had adjunctive radiation of the tumor bed.

“The type of resection in recurrent ACC depends on the location of the recurrence,” senior coauthor Dr. Eric Mirallié said. “In the case of local recurrence, we resected the adrenalectomy bed and all the adjacent invaded organs.”

In this series, 6 patients had resection of the tumor bed and 16 had adjacent organ resections; 8 patients (28%) had two or more operations for recurrences. These operations involved eight splenectomies, seven resections for abdominal nodules, six nephrectomies, three distal pancreatectomies, three segmental colectomies, and two minor hepatectomies. All operations were by laparotomy.

“In cases of distant recurrence, complete metastasectomy was performed,” Dr. Mirallié said. The series reported two right hepatectomies, one liver tumorectomy, one lung tumorectomy, and one brain tumorectomy.

“Nonoperative management is reserved for nonresectable patients with recurrent adrenocortical carcinoma,” Dr. Mirallié said. “Oral chemotherapy like mitotane was always given when possible. In cases of nonresectable local recurrence, radiotherapy can be used.”

During the discussion, Dr. Bradford K. Mitchell of Michigan State University, East Lansing, said that the benefit of improved survival in surgical patients in the study may have been a function of selection bias as patients who were not operated on may have had more advanced disease.

Dr. Blanchard and her coauthors had no financial relationships to disclose.

BALTIMORE – Patients who have recurrent adrenocortical carcinoma appear to have one option to increase their survival: surgery that includes complete tumor resection – but it may a viable path only if the recurrence occurred a year or more after the initial resection and diagnosis, according to an retrospective study of patients at five French university hospitals. “Adrenocortical carcinoma (ACC) is a rare, malignant tumor that has a poor prognosis, and recurrence of the tumor is considerable with 75% recurrence at 5 years,” Dr. Claire Blanchard of the Digestive and Endocrine Surgery Clinic at the Central University Hospital, Nantes, France, reported at the annual meeting of the American Association of Endocrine Surgeons. “Complete resection of recurrence is the only curative treatment.”

The researchers conducted a retrospective study of patients with at least one recurrence, diagnosed between 1980 and 2014, after initial resection of ACC, comparing outcomes in 29 patients who underwent surgery with 30 who had non-operative treatment, mainly chemotherapy and radiation.

Patients who had an operation for recurrence more often had local recurrence, 75% vs. 10% in the nonoperative group, and more frequently had a unique site of recurrence, 97% vs. 45%, than the nonoperative patients, Dr. Blanchard said.

These other demographic and tumor characteristics were similar between the operative and nonoperative groups, respectively: age, 49 years and 53 years; gender, 63% and 79% female; Weiss score, 6 and 7; Ki-67 protein index, 23% and 24%; tumor size, 99.2 mm and 115.5 mm; ENSAT stage, 65% and 45% stages I and II; and R0 resection status of the primary tumor at initial surgery, 83% and 71%.

The univariate analysis showed that appearance of the first recurrence more than 12 months after the initial diagnosis increased a patient’s chance of survival after treatment for recurrence, Dr. Blanchard said.

“Recurrences occurred at median delay of 12 months after the initial surgery,” Dr. Blanchard said. “In the 59 patients, 24 had local recurrences and 35 had distant metastases.”

Overall median survival after the first recurrence was 91 months for patients who had surgery vs. 15 months for those who did not. Overall median survival after initial resection of the primary tumor was 133 months, with a range of 14 to 252 months, in operated patients vs. 32 months, ranging from 21 to 43 months, in those who had no surgery, Dr. Blanchard said.

Of the 29 surgery patients in the surgery group, 22 had local-regional resections, 6 of whom had adjunctive radiation of the tumor bed.

“The type of resection in recurrent ACC depends on the location of the recurrence,” senior coauthor Dr. Eric Mirallié said. “In the case of local recurrence, we resected the adrenalectomy bed and all the adjacent invaded organs.”

In this series, 6 patients had resection of the tumor bed and 16 had adjacent organ resections; 8 patients (28%) had two or more operations for recurrences. These operations involved eight splenectomies, seven resections for abdominal nodules, six nephrectomies, three distal pancreatectomies, three segmental colectomies, and two minor hepatectomies. All operations were by laparotomy.

“In cases of distant recurrence, complete metastasectomy was performed,” Dr. Mirallié said. The series reported two right hepatectomies, one liver tumorectomy, one lung tumorectomy, and one brain tumorectomy.

“Nonoperative management is reserved for nonresectable patients with recurrent adrenocortical carcinoma,” Dr. Mirallié said. “Oral chemotherapy like mitotane was always given when possible. In cases of nonresectable local recurrence, radiotherapy can be used.”

During the discussion, Dr. Bradford K. Mitchell of Michigan State University, East Lansing, said that the benefit of improved survival in surgical patients in the study may have been a function of selection bias as patients who were not operated on may have had more advanced disease.

Dr. Blanchard and her coauthors had no financial relationships to disclose.

BALTIMORE – Biopsy results from a commercially available genetic test for ruling out malignancy of thyroid nodules may not provide reliable answers to clinicians and patients.

When fine-needle aspiration biopsy of thyroid nodules comes back inconclusive, clinicians have increasingly utilized the Afirma gene expression classifier (GEC) to rule out malignancy, but a retrospective analysis of almost 200 patients with indeterminate biopsy results along with a pooled analysis of 11 previous studies has raised questions about the negative predictive value of the test.

©Sebastian Kaulitzki/Fotolia

“The Afirma GEC test has substantial variability in performance,” said Dr. Zaid Al-Qurayshi of Tulane University, New Orleans, who reported the results at the annual meeting of the American Association of Endocrine Surgeons. “This variability cannot be explained based on differences in prevalence alone, but may also be the result of intrinsic test properties.”

The Afirma GEC measures the expression of 167 genes to more precisely determine the cancer risk of an indeterminate biopsied thyroid nodule and avoid unnecessary surgery. The test costs approximately $4,800 per nodule.

The researchers undertook the study in light of an American Thyroid Association (ATA) statement last year that concluded that test results are predicated on the clinician knowing the prevalence of malignancy within each indeterminate cytologic category at his/her own institution. Without this information, the performance of the diagnostic tests may vary substantially (Thyroid. 2015;25:760-8).

The single-center, retrospective cohort analysis included 192 patients with 210 indeterminate biopsy results, 145 of whom had surgery with 154 thyroid nodules. With a malignancy prevalence of 45%, the expected negative predictive value (NPV) of the test was estimated to be 85%, Dr. Al-Qurayshi said. However, the actual observed NPV was 69%. “If the prevalence was assumed to be 25%, the expected NPV was estimated to be 94%, while the observed NPV would have been 85%,” Dr. Al-Qurayshi said.

The researchers calculated the expected NPV by adopting the sensitivity and specificity rates of the test as reported in previous studies, while they calculated the observed NPV based on the actual negative rate among the Tulane cohort, Dr. Al-Qurayshi said.

Dr. Al-Qurayshi and colleagues then compared their results with pooled data from 11 other studies of the Afirma GEC. The pooled data analysis included 1,303 patients and yielded a malignancy prevalence of 31.1%, with a range of 29%-35%, and a pooled NPV of 92%, with a range of 87%-96%, Dr. Al-Qurayshi said.

“A lot of previously published studies took the sensitivity and specificity that were previously reported for granted, and now we are showing this sensitivity is all over the place,” Dr. Al-Qurayshi said. “Now, we don’t know which is the true one, and we need a larger clinical trial first to determine the true properties. Then we can ask how the prevalence in one’s institution is affecting the performance of the test.”

In an interview, Dr. Emad Kandil, senior study coauthor, also of Tulane, said the 69% NPV of the Tulane cohort puts the diagnostic scenario “back to ground zero, which is similar to what we had prior to the use of the new commercially available genetic tests.” He added, “A larger, randomized trial of the Afirma GEC test should answer those questions.”

The seminal study for the Afirma GEC, authored by Dr. Erik Alexander of Brigham and Women’s Hospital, Boston, in 2012, reported a 92% NPV with the test (N Engl J Med. 2012;367:705-15).

“The first thought was that they had different results because their population was different,” Dr. Al-Qurayshi said. “The ATA statement noted that it is the clinician’s responsibility to determine if this test is appropriate for their population or not, but the performance of the test doesn’t just depend on the population property, but it also depends on the intrinsic testing properties.”

Dr. Kandil disclosed that he has been a primary investigator in the ENHANCE multicenter study of the Afirma GEC. The other coauthors had no financial disclosures.

BALTIMORE – Biopsy results from a commercially available genetic test for ruling out malignancy of thyroid nodules may not provide reliable answers to clinicians and patients.

When fine-needle aspiration biopsy of thyroid nodules comes back inconclusive, clinicians have increasingly utilized the Afirma gene expression classifier (GEC) to rule out malignancy, but a retrospective analysis of almost 200 patients with indeterminate biopsy results along with a pooled analysis of 11 previous studies has raised questions about the negative predictive value of the test.

©Sebastian Kaulitzki/Fotolia

“The Afirma GEC test has substantial variability in performance,” said Dr. Zaid Al-Qurayshi of Tulane University, New Orleans, who reported the results at the annual meeting of the American Association of Endocrine Surgeons. “This variability cannot be explained based on differences in prevalence alone, but may also be the result of intrinsic test properties.”

The Afirma GEC measures the expression of 167 genes to more precisely determine the cancer risk of an indeterminate biopsied thyroid nodule and avoid unnecessary surgery. The test costs approximately $4,800 per nodule.

The researchers undertook the study in light of an American Thyroid Association (ATA) statement last year that concluded that test results are predicated on the clinician knowing the prevalence of malignancy within each indeterminate cytologic category at his/her own institution. Without this information, the performance of the diagnostic tests may vary substantially (Thyroid. 2015;25:760-8).

The single-center, retrospective cohort analysis included 192 patients with 210 indeterminate biopsy results, 145 of whom had surgery with 154 thyroid nodules. With a malignancy prevalence of 45%, the expected negative predictive value (NPV) of the test was estimated to be 85%, Dr. Al-Qurayshi said. However, the actual observed NPV was 69%. “If the prevalence was assumed to be 25%, the expected NPV was estimated to be 94%, while the observed NPV would have been 85%,” Dr. Al-Qurayshi said.

The researchers calculated the expected NPV by adopting the sensitivity and specificity rates of the test as reported in previous studies, while they calculated the observed NPV based on the actual negative rate among the Tulane cohort, Dr. Al-Qurayshi said.

Dr. Al-Qurayshi and colleagues then compared their results with pooled data from 11 other studies of the Afirma GEC. The pooled data analysis included 1,303 patients and yielded a malignancy prevalence of 31.1%, with a range of 29%-35%, and a pooled NPV of 92%, with a range of 87%-96%, Dr. Al-Qurayshi said.

“A lot of previously published studies took the sensitivity and specificity that were previously reported for granted, and now we are showing this sensitivity is all over the place,” Dr. Al-Qurayshi said. “Now, we don’t know which is the true one, and we need a larger clinical trial first to determine the true properties. Then we can ask how the prevalence in one’s institution is affecting the performance of the test.”

In an interview, Dr. Emad Kandil, senior study coauthor, also of Tulane, said the 69% NPV of the Tulane cohort puts the diagnostic scenario “back to ground zero, which is similar to what we had prior to the use of the new commercially available genetic tests.” He added, “A larger, randomized trial of the Afirma GEC test should answer those questions.”

The seminal study for the Afirma GEC, authored by Dr. Erik Alexander of Brigham and Women’s Hospital, Boston, in 2012, reported a 92% NPV with the test (N Engl J Med. 2012;367:705-15).

“The first thought was that they had different results because their population was different,” Dr. Al-Qurayshi said. “The ATA statement noted that it is the clinician’s responsibility to determine if this test is appropriate for their population or not, but the performance of the test doesn’t just depend on the population property, but it also depends on the intrinsic testing properties.”

Dr. Kandil disclosed that he has been a primary investigator in the ENHANCE multicenter study of the Afirma GEC. The other coauthors had no financial disclosures.

BALTIMORE – Biopsy results from a commercially available genetic test for ruling out malignancy of thyroid nodules may not provide reliable answers to clinicians and patients.

When fine-needle aspiration biopsy of thyroid nodules comes back inconclusive, clinicians have increasingly utilized the Afirma gene expression classifier (GEC) to rule out malignancy, but a retrospective analysis of almost 200 patients with indeterminate biopsy results along with a pooled analysis of 11 previous studies has raised questions about the negative predictive value of the test.

©Sebastian Kaulitzki/Fotolia

“The Afirma GEC test has substantial variability in performance,” said Dr. Zaid Al-Qurayshi of Tulane University, New Orleans, who reported the results at the annual meeting of the American Association of Endocrine Surgeons. “This variability cannot be explained based on differences in prevalence alone, but may also be the result of intrinsic test properties.”

The Afirma GEC measures the expression of 167 genes to more precisely determine the cancer risk of an indeterminate biopsied thyroid nodule and avoid unnecessary surgery. The test costs approximately $4,800 per nodule.

The researchers undertook the study in light of an American Thyroid Association (ATA) statement last year that concluded that test results are predicated on the clinician knowing the prevalence of malignancy within each indeterminate cytologic category at his/her own institution. Without this information, the performance of the diagnostic tests may vary substantially (Thyroid. 2015;25:760-8).

The single-center, retrospective cohort analysis included 192 patients with 210 indeterminate biopsy results, 145 of whom had surgery with 154 thyroid nodules. With a malignancy prevalence of 45%, the expected negative predictive value (NPV) of the test was estimated to be 85%, Dr. Al-Qurayshi said. However, the actual observed NPV was 69%. “If the prevalence was assumed to be 25%, the expected NPV was estimated to be 94%, while the observed NPV would have been 85%,” Dr. Al-Qurayshi said.

The researchers calculated the expected NPV by adopting the sensitivity and specificity rates of the test as reported in previous studies, while they calculated the observed NPV based on the actual negative rate among the Tulane cohort, Dr. Al-Qurayshi said.

Dr. Al-Qurayshi and colleagues then compared their results with pooled data from 11 other studies of the Afirma GEC. The pooled data analysis included 1,303 patients and yielded a malignancy prevalence of 31.1%, with a range of 29%-35%, and a pooled NPV of 92%, with a range of 87%-96%, Dr. Al-Qurayshi said.

“A lot of previously published studies took the sensitivity and specificity that were previously reported for granted, and now we are showing this sensitivity is all over the place,” Dr. Al-Qurayshi said. “Now, we don’t know which is the true one, and we need a larger clinical trial first to determine the true properties. Then we can ask how the prevalence in one’s institution is affecting the performance of the test.”

In an interview, Dr. Emad Kandil, senior study coauthor, also of Tulane, said the 69% NPV of the Tulane cohort puts the diagnostic scenario “back to ground zero, which is similar to what we had prior to the use of the new commercially available genetic tests.” He added, “A larger, randomized trial of the Afirma GEC test should answer those questions.”

The seminal study for the Afirma GEC, authored by Dr. Erik Alexander of Brigham and Women’s Hospital, Boston, in 2012, reported a 92% NPV with the test (N Engl J Med. 2012;367:705-15).

“The first thought was that they had different results because their population was different,” Dr. Al-Qurayshi said. “The ATA statement noted that it is the clinician’s responsibility to determine if this test is appropriate for their population or not, but the performance of the test doesn’t just depend on the population property, but it also depends on the intrinsic testing properties.”

Dr. Kandil disclosed that he has been a primary investigator in the ENHANCE multicenter study of the Afirma GEC. The other coauthors had no financial disclosures.

Pediatric patients diagnosed with pheochromocytomas (PHEO) or paragangliomas (PGL) were nearly three times as likely to also carry a diagnosis of attention deficit hyperactivity disorder (ADHD), compared to pediatric patients without PHEO or PGL, investigators reported.

In addition, in 33% of the patients with PHEO and PGL, ADHD symptoms were resolved following surgical removal of the tumor.

PHEO and PGL are rare tumors of the adrenal gland. About 10% of PHEO and PGL cases occur in patients younger than 18 years. PHEOs form inside the adrenal gland in the adrenal medulla while PGLs form outside the adrenal gland. Both tumors cause excess secretion of epinephrine and norepinephrine resulting in high blood pressure, headaches, weight loss, excess sweating, anxiety, and depression. These tumors are most often surgically removed or treated with medication. Chemotherapy and radiation therapy have not been as effective in treating PHEO or PGL.

ADHD is a neurodevelopment disorder characterized by a pattern of inattention and hyperactivity or impulsivity. ADHD is associated with catecholamine dysregulation; the function of catecholamine receptors is impaired by either excess or deficient stimulation. ADHD has a prevalence of 7.2% in children aged 4-18.

©mik38/thinkstockphotos.com

In addition to the overlap in symptoms, “the stimulants used to treat ADHD may exacerbate the symptoms of the PHEO/PGL and potentially lead to a hypertensive crisis ... Amphetamines, the most widely used ADHD medication class, lead to release of stored catecholamines from vesicles, block reuptake of norepinephrine and dopamine, and block catecholamine degradation,” wrote Dr. M. Batsis of the Eunice Kennedy Shriver National Institute of Child Health and Human Development and her associates (Horm Metab Res. 2016 May 12. doi: 10.1055/s-0042-106725).

“I noticed that a lot of patients with the same story as follows: [parents] went to their pediatrician when their child started having feelings of anxiety or their heart was racing. And these symptoms were attributed to ADHD, and the child was started on medications. It wasn’t until later symptoms – an abdominal mass or a hypertensive crisis – that the patient was ultimately found out to have a pheochromocytoma,” Dr. Maya Lodish, a pediatric endocrinologist and coauthor of the paper, said in an interview.

“In hindsight, it just was not picked up. ADHD medications in no way affect tumor growth. The substances that these tumors release are stimulants. Endocrine tumors release catecholamine which are naturally occurring hormones we release under stress. When you add on top of that a stimulant medication [to treat ADHD] that may causes the nervous system to go into overdrive,” she said.

Due to the rarity of PHEO and PGL, their association with ADHD has not been well characterized. The purpose of this study was to therefore better assess the relationship between ADHD and PHEO/PGL development.

Investigators recruited 43 pediatric patients aged 6-17 who had been diagnosed with PHEO or PGL. Twenty-one percent (n = 9) of patients with PHEO/PGL carried a diagnosis of ADHD, compared to 7.2% in the general population (P = .0328).

Prior to the surgical removal of the tumors, eight of the nine patients had elevated levels of norepinephrine (n = 7), dopamine (n = 3), epinephrine (n = 1), metanephrine (n = 5) and/or normetanephrine (n = 7). In the remaining patient, levels were not measured.

Following the surgical removal of the tumors, three of the nine patients experienced both a resolution of their ADHD-related symptoms and a drop or normalization of their catecholamine and metanephrine levels. Two of those three patients showed no clinical signs of recurrent tumors while the third is under evaluation for a small pelvic lesion.

“These tumors are very rare and the vast majority of patients with ADHD are not affected by them, but they do occur. There are other organic conditions with the same symptoms – drug abuse, medications, Graves disease. If the child has symptoms attributed to ADHD and high blood pressure or family history of endocrine tumors then it is important to have a full organic workup to measure other causes of hypertension prior to starting stimulant medication,” Dr. Lodish said.

“My observation is that, and a lot of articles out there would agree, diagnoses of ADHD are on the rise and the prescribing of ADHD medication is also on the rise. I hope this is a bit of a wake-up call to practitioners that what’s common is common but there are some rare [conditions] to be aware of and so don’t have a knee jerk reaction to prescribing a medication for symptoms believed to be attributed to ADHD,” she said.

The Division of Intramural Research at the Eunice Kennedy Shriver National Institute of Child Health and Human Development supported the study. The investigators had no disclosures to report.

jcraig@frontlinemedcom.com

On Twitter @JessCraig_OP

Pediatric patients diagnosed with pheochromocytomas (PHEO) or paragangliomas (PGL) were nearly three times as likely to also carry a diagnosis of attention deficit hyperactivity disorder (ADHD), compared to pediatric patients without PHEO or PGL, investigators reported.

In addition, in 33% of the patients with PHEO and PGL, ADHD symptoms were resolved following surgical removal of the tumor.

PHEO and PGL are rare tumors of the adrenal gland. About 10% of PHEO and PGL cases occur in patients younger than 18 years. PHEOs form inside the adrenal gland in the adrenal medulla while PGLs form outside the adrenal gland. Both tumors cause excess secretion of epinephrine and norepinephrine resulting in high blood pressure, headaches, weight loss, excess sweating, anxiety, and depression. These tumors are most often surgically removed or treated with medication. Chemotherapy and radiation therapy have not been as effective in treating PHEO or PGL.

ADHD is a neurodevelopment disorder characterized by a pattern of inattention and hyperactivity or impulsivity. ADHD is associated with catecholamine dysregulation; the function of catecholamine receptors is impaired by either excess or deficient stimulation. ADHD has a prevalence of 7.2% in children aged 4-18.

©mik38/thinkstockphotos.com

In addition to the overlap in symptoms, “the stimulants used to treat ADHD may exacerbate the symptoms of the PHEO/PGL and potentially lead to a hypertensive crisis ... Amphetamines, the most widely used ADHD medication class, lead to release of stored catecholamines from vesicles, block reuptake of norepinephrine and dopamine, and block catecholamine degradation,” wrote Dr. M. Batsis of the Eunice Kennedy Shriver National Institute of Child Health and Human Development and her associates (Horm Metab Res. 2016 May 12. doi: 10.1055/s-0042-106725).

“I noticed that a lot of patients with the same story as follows: [parents] went to their pediatrician when their child started having feelings of anxiety or their heart was racing. And these symptoms were attributed to ADHD, and the child was started on medications. It wasn’t until later symptoms – an abdominal mass or a hypertensive crisis – that the patient was ultimately found out to have a pheochromocytoma,” Dr. Maya Lodish, a pediatric endocrinologist and coauthor of the paper, said in an interview.

“In hindsight, it just was not picked up. ADHD medications in no way affect tumor growth. The substances that these tumors release are stimulants. Endocrine tumors release catecholamine which are naturally occurring hormones we release under stress. When you add on top of that a stimulant medication [to treat ADHD] that may causes the nervous system to go into overdrive,” she said.

Due to the rarity of PHEO and PGL, their association with ADHD has not been well characterized. The purpose of this study was to therefore better assess the relationship between ADHD and PHEO/PGL development.

Investigators recruited 43 pediatric patients aged 6-17 who had been diagnosed with PHEO or PGL. Twenty-one percent (n = 9) of patients with PHEO/PGL carried a diagnosis of ADHD, compared to 7.2% in the general population (P = .0328).

Prior to the surgical removal of the tumors, eight of the nine patients had elevated levels of norepinephrine (n = 7), dopamine (n = 3), epinephrine (n = 1), metanephrine (n = 5) and/or normetanephrine (n = 7). In the remaining patient, levels were not measured.

Following the surgical removal of the tumors, three of the nine patients experienced both a resolution of their ADHD-related symptoms and a drop or normalization of their catecholamine and metanephrine levels. Two of those three patients showed no clinical signs of recurrent tumors while the third is under evaluation for a small pelvic lesion.

“These tumors are very rare and the vast majority of patients with ADHD are not affected by them, but they do occur. There are other organic conditions with the same symptoms – drug abuse, medications, Graves disease. If the child has symptoms attributed to ADHD and high blood pressure or family history of endocrine tumors then it is important to have a full organic workup to measure other causes of hypertension prior to starting stimulant medication,” Dr. Lodish said.

“My observation is that, and a lot of articles out there would agree, diagnoses of ADHD are on the rise and the prescribing of ADHD medication is also on the rise. I hope this is a bit of a wake-up call to practitioners that what’s common is common but there are some rare [conditions] to be aware of and so don’t have a knee jerk reaction to prescribing a medication for symptoms believed to be attributed to ADHD,” she said.

The Division of Intramural Research at the Eunice Kennedy Shriver National Institute of Child Health and Human Development supported the study. The investigators had no disclosures to report.

jcraig@frontlinemedcom.com

On Twitter @JessCraig_OP

Pediatric patients diagnosed with pheochromocytomas (PHEO) or paragangliomas (PGL) were nearly three times as likely to also carry a diagnosis of attention deficit hyperactivity disorder (ADHD), compared to pediatric patients without PHEO or PGL, investigators reported.

In addition, in 33% of the patients with PHEO and PGL, ADHD symptoms were resolved following surgical removal of the tumor.

PHEO and PGL are rare tumors of the adrenal gland. About 10% of PHEO and PGL cases occur in patients younger than 18 years. PHEOs form inside the adrenal gland in the adrenal medulla while PGLs form outside the adrenal gland. Both tumors cause excess secretion of epinephrine and norepinephrine resulting in high blood pressure, headaches, weight loss, excess sweating, anxiety, and depression. These tumors are most often surgically removed or treated with medication. Chemotherapy and radiation therapy have not been as effective in treating PHEO or PGL.

ADHD is a neurodevelopment disorder characterized by a pattern of inattention and hyperactivity or impulsivity. ADHD is associated with catecholamine dysregulation; the function of catecholamine receptors is impaired by either excess or deficient stimulation. ADHD has a prevalence of 7.2% in children aged 4-18.

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In addition to the overlap in symptoms, “the stimulants used to treat ADHD may exacerbate the symptoms of the PHEO/PGL and potentially lead to a hypertensive crisis ... Amphetamines, the most widely used ADHD medication class, lead to release of stored catecholamines from vesicles, block reuptake of norepinephrine and dopamine, and block catecholamine degradation,” wrote Dr. M. Batsis of the Eunice Kennedy Shriver National Institute of Child Health and Human Development and her associates (Horm Metab Res. 2016 May 12. doi: 10.1055/s-0042-106725).

“I noticed that a lot of patients with the same story as follows: [parents] went to their pediatrician when their child started having feelings of anxiety or their heart was racing. And these symptoms were attributed to ADHD, and the child was started on medications. It wasn’t until later symptoms – an abdominal mass or a hypertensive crisis – that the patient was ultimately found out to have a pheochromocytoma,” Dr. Maya Lodish, a pediatric endocrinologist and coauthor of the paper, said in an interview.

“In hindsight, it just was not picked up. ADHD medications in no way affect tumor growth. The substances that these tumors release are stimulants. Endocrine tumors release catecholamine which are naturally occurring hormones we release under stress. When you add on top of that a stimulant medication [to treat ADHD] that may causes the nervous system to go into overdrive,” she said.

Due to the rarity of PHEO and PGL, their association with ADHD has not been well characterized. The purpose of this study was to therefore better assess the relationship between ADHD and PHEO/PGL development.

Investigators recruited 43 pediatric patients aged 6-17 who had been diagnosed with PHEO or PGL. Twenty-one percent (n = 9) of patients with PHEO/PGL carried a diagnosis of ADHD, compared to 7.2% in the general population (P = .0328).

Prior to the surgical removal of the tumors, eight of the nine patients had elevated levels of norepinephrine (n = 7), dopamine (n = 3), epinephrine (n = 1), metanephrine (n = 5) and/or normetanephrine (n = 7). In the remaining patient, levels were not measured.

Following the surgical removal of the tumors, three of the nine patients experienced both a resolution of their ADHD-related symptoms and a drop or normalization of their catecholamine and metanephrine levels. Two of those three patients showed no clinical signs of recurrent tumors while the third is under evaluation for a small pelvic lesion.

“These tumors are very rare and the vast majority of patients with ADHD are not affected by them, but they do occur. There are other organic conditions with the same symptoms – drug abuse, medications, Graves disease. If the child has symptoms attributed to ADHD and high blood pressure or family history of endocrine tumors then it is important to have a full organic workup to measure other causes of hypertension prior to starting stimulant medication,” Dr. Lodish said.

“My observation is that, and a lot of articles out there would agree, diagnoses of ADHD are on the rise and the prescribing of ADHD medication is also on the rise. I hope this is a bit of a wake-up call to practitioners that what’s common is common but there are some rare [conditions] to be aware of and so don’t have a knee jerk reaction to prescribing a medication for symptoms believed to be attributed to ADHD,” she said.

The Division of Intramural Research at the Eunice Kennedy Shriver National Institute of Child Health and Human Development supported the study. The investigators had no disclosures to report.

jcraig@frontlinemedcom.com

On Twitter @JessCraig_OP

The recent reclassification of encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC) as noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) – an action taken to better reflect the very low risk of adverse events associated with these tumors – has important clinical and psychological implications for patients.

“Even though physicians know that most thyroid cancers have an excellent prognosis, the impact on a patient of being given a diagnosis of cancer should not be underestimated,” Dr. Peter Angelos, professor of surgery and chief of endocrine surgery at the University of Chicago, said in an interview. “It is, however, critical for doctors and patients to understand that this change from ‘thyroid cancer’ to a ‘benign thyroid nodule,’ is not something that can be determined prior to surgery. Patients will still need thyroid operations to determine if their indeterminate nodules have cancer in them or not.”

The change in nomenclature followed an international, multidisciplinary, retrospective study of patients with thyroid nodules diagnosed as EFVPTC. Such patients are usually treated as having conventional thyroid cancer. The study included 109 patients with noninvasive EFVPTC who were followed for 10-26 years, and 101 with invasive EFVPTC who were followed for 1-18 years. At median follow-up of 13 years, all of the 109 patients with noninvasive EFVPTC were alive, and based on consensus diagnostic criteria developed by an Endocrine Pathology Society working group – a multinational panel of 24 thyroid pathologists – they had no evidence of disease, reported Dr. Yuri E. Nikiforov of the University of Pittsburgh and colleagues (JAMA Oncol. 2016 April 14. doi: 10.1001/jamaoncol.2016.0386).

Most of those patients (67%) were treated only with lobectomy, and none received radioiodine (RAI) treatment.

Of the 101 with invasive EFVPTC, 12 experienced an adverse event, including 5 who developed distant (lung and/or bone) metastases. Two died from the disease, one had a lymph node recurrence, one had persistent disease, and five had detectable serum thyroglobulin and were considered to have indeterminate or biochemically incomplete response to therapy, the investigators said.

Based on the findings in the noninvasive EFVPTC patients, the recommended nomenclature change was adopted to reflect the main morphological features of, and lack of invasion of, the benign tumors as well as their very low risk of adverse outcome. To assist in the diagnosis of NIFTP in routine pathology practice, a simplified three-point diagnostic nuclear scoring scheme based on the six main consensus nuclear features of the tumors was developed and validated; the scoring scheme yielded sensitivity of 98.6%, specificity of 90.1%, and overall classification accuracy of 94.3% for NIFTP.

The study involved a review of digitized histologic slides collected at 13 sites in 5 countries. The pathologists who composed the working group conducted the review and consulted in a series of teleconferences and face-to-face meetings to establish the consensus criteria. They measured the frequency of adverse outcomes, including death from disease, distant or locoregional metastases, and structural or biochemical recurrence.

The findings suggest that “clinical management of patients with NIFTP can be deescalated because they are unlikely to benefit from immediate completion thyroidectomy and RAI therapy,” the investigators said.

“Staging would be unnecessary. In addition to eliminating the psychological impact of the diagnosis of cancer, this would reduce complications of total thyroidectomy, risk of secondary tumors following RAI therapy, and the overall cost of health care. Avoidance of RAI treatment alone would save between $5,000 and $8,500 per patient (based on U.S. cost),” they wrote, adding that an estimated 45,000 patients worldwide each year will be affected by this reclassification, resulting in significant reduction in “psychological burden, medical overtreatment and expense, and other clinical consequences associated with a cancer diagnosis.”

Dr. Martha A. Zeiger, professor of surgery at Johns Hopkins University, Baltimore, agreed that the change has important implications for patients.

“With the advent of new nomenclature for encapsulated follicular variant of papillary thyroid cancer, namely that it is now considered a benign tumor, thousands of patients who have carried this original diagnosis of cancer can breathe a sigh of relief. Our new understanding will also decrease the number of patients undergoing more extensive surgery and many can now be treated with a thyroid lobectomy only,” she said in an interview.

One thing the new nomenclature doesn’t do, however, is solve the problem of the suspicious or indeterminate thyroid fine needle aspiration diagnosis, she noted.

“Clouding the landscape even further is the fact that many of our commonly used molecular diagnostics were based on studies in which encapsulated follicular variant of papillary thyroid cancer was considered malignant, and were included in the analysis. Because of this, diagnostic molecular tools will likely now require a renewed scrutiny as to their true efficacy in differentiating benign from malignant tumors,” she said.

Dr. Nikiforov is a consultant for Quest Diagnostics. A coauthor, Dr. Sylvia Asa, is a member of the medical advisory board of Leica Aperio, and another coauthor, Dr. Virginia LiVolsi, is a consultant for Veracyte Inc. The project used a facility supported by the National Cancer Institute, and molecular analysis was supported in part by funds from the University of Pittsburgh Cancer Institute and the University of Pittsburgh Medical Center. The Endocrine Pathology Society working group conference was supported by a grant from CBLPath Inc. Dr. Angelos and Dr. Zeiger reported having no disclosures.

sworcester@frontlinemedcom.com

The recent reclassification of encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC) as noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) – an action taken to better reflect the very low risk of adverse events associated with these tumors – has important clinical and psychological implications for patients.

“Even though physicians know that most thyroid cancers have an excellent prognosis, the impact on a patient of being given a diagnosis of cancer should not be underestimated,” Dr. Peter Angelos, professor of surgery and chief of endocrine surgery at the University of Chicago, said in an interview. “It is, however, critical for doctors and patients to understand that this change from ‘thyroid cancer’ to a ‘benign thyroid nodule,’ is not something that can be determined prior to surgery. Patients will still need thyroid operations to determine if their indeterminate nodules have cancer in them or not.”

The change in nomenclature followed an international, multidisciplinary, retrospective study of patients with thyroid nodules diagnosed as EFVPTC. Such patients are usually treated as having conventional thyroid cancer. The study included 109 patients with noninvasive EFVPTC who were followed for 10-26 years, and 101 with invasive EFVPTC who were followed for 1-18 years. At median follow-up of 13 years, all of the 109 patients with noninvasive EFVPTC were alive, and based on consensus diagnostic criteria developed by an Endocrine Pathology Society working group – a multinational panel of 24 thyroid pathologists – they had no evidence of disease, reported Dr. Yuri E. Nikiforov of the University of Pittsburgh and colleagues (JAMA Oncol. 2016 April 14. doi: 10.1001/jamaoncol.2016.0386).

Most of those patients (67%) were treated only with lobectomy, and none received radioiodine (RAI) treatment.

Of the 101 with invasive EFVPTC, 12 experienced an adverse event, including 5 who developed distant (lung and/or bone) metastases. Two died from the disease, one had a lymph node recurrence, one had persistent disease, and five had detectable serum thyroglobulin and were considered to have indeterminate or biochemically incomplete response to therapy, the investigators said.

Based on the findings in the noninvasive EFVPTC patients, the recommended nomenclature change was adopted to reflect the main morphological features of, and lack of invasion of, the benign tumors as well as their very low risk of adverse outcome. To assist in the diagnosis of NIFTP in routine pathology practice, a simplified three-point diagnostic nuclear scoring scheme based on the six main consensus nuclear features of the tumors was developed and validated; the scoring scheme yielded sensitivity of 98.6%, specificity of 90.1%, and overall classification accuracy of 94.3% for NIFTP.

The study involved a review of digitized histologic slides collected at 13 sites in 5 countries. The pathologists who composed the working group conducted the review and consulted in a series of teleconferences and face-to-face meetings to establish the consensus criteria. They measured the frequency of adverse outcomes, including death from disease, distant or locoregional metastases, and structural or biochemical recurrence.

The findings suggest that “clinical management of patients with NIFTP can be deescalated because they are unlikely to benefit from immediate completion thyroidectomy and RAI therapy,” the investigators said.

“Staging would be unnecessary. In addition to eliminating the psychological impact of the diagnosis of cancer, this would reduce complications of total thyroidectomy, risk of secondary tumors following RAI therapy, and the overall cost of health care. Avoidance of RAI treatment alone would save between $5,000 and $8,500 per patient (based on U.S. cost),” they wrote, adding that an estimated 45,000 patients worldwide each year will be affected by this reclassification, resulting in significant reduction in “psychological burden, medical overtreatment and expense, and other clinical consequences associated with a cancer diagnosis.”

Dr. Martha A. Zeiger, professor of surgery at Johns Hopkins University, Baltimore, agreed that the change has important implications for patients.

“With the advent of new nomenclature for encapsulated follicular variant of papillary thyroid cancer, namely that it is now considered a benign tumor, thousands of patients who have carried this original diagnosis of cancer can breathe a sigh of relief. Our new understanding will also decrease the number of patients undergoing more extensive surgery and many can now be treated with a thyroid lobectomy only,” she said in an interview.

One thing the new nomenclature doesn’t do, however, is solve the problem of the suspicious or indeterminate thyroid fine needle aspiration diagnosis, she noted.

“Clouding the landscape even further is the fact that many of our commonly used molecular diagnostics were based on studies in which encapsulated follicular variant of papillary thyroid cancer was considered malignant, and were included in the analysis. Because of this, diagnostic molecular tools will likely now require a renewed scrutiny as to their true efficacy in differentiating benign from malignant tumors,” she said.

Dr. Nikiforov is a consultant for Quest Diagnostics. A coauthor, Dr. Sylvia Asa, is a member of the medical advisory board of Leica Aperio, and another coauthor, Dr. Virginia LiVolsi, is a consultant for Veracyte Inc. The project used a facility supported by the National Cancer Institute, and molecular analysis was supported in part by funds from the University of Pittsburgh Cancer Institute and the University of Pittsburgh Medical Center. The Endocrine Pathology Society working group conference was supported by a grant from CBLPath Inc. Dr. Angelos and Dr. Zeiger reported having no disclosures.

sworcester@frontlinemedcom.com

The recent reclassification of encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC) as noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) – an action taken to better reflect the very low risk of adverse events associated with these tumors – has important clinical and psychological implications for patients.

“Even though physicians know that most thyroid cancers have an excellent prognosis, the impact on a patient of being given a diagnosis of cancer should not be underestimated,” Dr. Peter Angelos, professor of surgery and chief of endocrine surgery at the University of Chicago, said in an interview. “It is, however, critical for doctors and patients to understand that this change from ‘thyroid cancer’ to a ‘benign thyroid nodule,’ is not something that can be determined prior to surgery. Patients will still need thyroid operations to determine if their indeterminate nodules have cancer in them or not.”

The change in nomenclature followed an international, multidisciplinary, retrospective study of patients with thyroid nodules diagnosed as EFVPTC. Such patients are usually treated as having conventional thyroid cancer. The study included 109 patients with noninvasive EFVPTC who were followed for 10-26 years, and 101 with invasive EFVPTC who were followed for 1-18 years. At median follow-up of 13 years, all of the 109 patients with noninvasive EFVPTC were alive, and based on consensus diagnostic criteria developed by an Endocrine Pathology Society working group – a multinational panel of 24 thyroid pathologists – they had no evidence of disease, reported Dr. Yuri E. Nikiforov of the University of Pittsburgh and colleagues (JAMA Oncol. 2016 April 14. doi: 10.1001/jamaoncol.2016.0386).

Most of those patients (67%) were treated only with lobectomy, and none received radioiodine (RAI) treatment.

Of the 101 with invasive EFVPTC, 12 experienced an adverse event, including 5 who developed distant (lung and/or bone) metastases. Two died from the disease, one had a lymph node recurrence, one had persistent disease, and five had detectable serum thyroglobulin and were considered to have indeterminate or biochemically incomplete response to therapy, the investigators said.

Based on the findings in the noninvasive EFVPTC patients, the recommended nomenclature change was adopted to reflect the main morphological features of, and lack of invasion of, the benign tumors as well as their very low risk of adverse outcome. To assist in the diagnosis of NIFTP in routine pathology practice, a simplified three-point diagnostic nuclear scoring scheme based on the six main consensus nuclear features of the tumors was developed and validated; the scoring scheme yielded sensitivity of 98.6%, specificity of 90.1%, and overall classification accuracy of 94.3% for NIFTP.

The study involved a review of digitized histologic slides collected at 13 sites in 5 countries. The pathologists who composed the working group conducted the review and consulted in a series of teleconferences and face-to-face meetings to establish the consensus criteria. They measured the frequency of adverse outcomes, including death from disease, distant or locoregional metastases, and structural or biochemical recurrence.

The findings suggest that “clinical management of patients with NIFTP can be deescalated because they are unlikely to benefit from immediate completion thyroidectomy and RAI therapy,” the investigators said.

“Staging would be unnecessary. In addition to eliminating the psychological impact of the diagnosis of cancer, this would reduce complications of total thyroidectomy, risk of secondary tumors following RAI therapy, and the overall cost of health care. Avoidance of RAI treatment alone would save between $5,000 and $8,500 per patient (based on U.S. cost),” they wrote, adding that an estimated 45,000 patients worldwide each year will be affected by this reclassification, resulting in significant reduction in “psychological burden, medical overtreatment and expense, and other clinical consequences associated with a cancer diagnosis.”

Dr. Martha A. Zeiger, professor of surgery at Johns Hopkins University, Baltimore, agreed that the change has important implications for patients.

“With the advent of new nomenclature for encapsulated follicular variant of papillary thyroid cancer, namely that it is now considered a benign tumor, thousands of patients who have carried this original diagnosis of cancer can breathe a sigh of relief. Our new understanding will also decrease the number of patients undergoing more extensive surgery and many can now be treated with a thyroid lobectomy only,” she said in an interview.

One thing the new nomenclature doesn’t do, however, is solve the problem of the suspicious or indeterminate thyroid fine needle aspiration diagnosis, she noted.

“Clouding the landscape even further is the fact that many of our commonly used molecular diagnostics were based on studies in which encapsulated follicular variant of papillary thyroid cancer was considered malignant, and were included in the analysis. Because of this, diagnostic molecular tools will likely now require a renewed scrutiny as to their true efficacy in differentiating benign from malignant tumors,” she said.

Dr. Nikiforov is a consultant for Quest Diagnostics. A coauthor, Dr. Sylvia Asa, is a member of the medical advisory board of Leica Aperio, and another coauthor, Dr. Virginia LiVolsi, is a consultant for Veracyte Inc. The project used a facility supported by the National Cancer Institute, and molecular analysis was supported in part by funds from the University of Pittsburgh Cancer Institute and the University of Pittsburgh Medical Center. The Endocrine Pathology Society working group conference was supported by a grant from CBLPath Inc. Dr. Angelos and Dr. Zeiger reported having no disclosures.

sworcester@frontlinemedcom.com

BALTIMORE – Performing a parathyroidectomy in kidney transplant patients before their transplant can reduce the risk of graft failure and provide other benefits, the findings of a retrospective study of 913 patients suggest.

Uremic hyperparathyroidism (UHPT) is common in patients with end-stage kidney disease, and elevated parathyroid hormone (PTH) levels have been linked with delayed graft function after kidney transplants, but current guidelines for PTH levels may not go far enough to reduce the risk of graft failure and other post–kidney transplant complications in people with elevated PTH before transplant, according to Dr. Glenda G. Callender of Yale University, New Haven, Conn., and her colleagues.

“Uremic hyperparathyroidism was associated with an increased risk of complications in the first year post kidney transplant,” Dr. Callender said at the annual meeting of the American Association of Endocrine Surgeons. “Pre–kidney transplant parathyroidectomy was associated with a decreased risk of post–kidney transplant graft failure. This implies that pre–kidney transplant reduction of PTH levels should be considered in patients with UPHT.”

The Yale researchers reviewed outcomes of 913 patients at their institution who had a kidney transplant from 2005 to 2014. They analyzed biochemical values before kidney transplant and at three intervals post transplant: at 1 month, 6 months, and 1 year. Among the outcomes they evaluated were calcium and PTH levels, estimated glomerular filtration rate, complications, delayed graft function, and graft failure. The overall graft survival rate was 97.8% 1 year after kidney transplantation.

Overall, 49.4% of patients (451) had a diagnosis with UHPT before kidney transplant; 6.2% of all patients (57) had parathyroidectomy before kidney transplant and another 2% (18) had parathyroidectomy at some point after their kidney transplant operations. Median baseline PTH levels were higher in the UHPT patients: 206 pg/mL vs. 159 pg/mL for the non-UHPT group, Dr. Callender reported.

The researchers captured complete data on 37 of the 57 patients who had pretransplant parathyroidectomy. Twenty-four (65% of the group) had subtotal parathyroidectomy in which 3.5 glands were removed, and 12 (32%) had fewer than 3.5 glands removed. One patient had total parathyroidectomy, she said.

Among the patients with UHPT, the median pre–kidney transplant PTH was similar between the pretransplant parathyroidectomy and the no-parathyroidectomy groups: 218 pg/mL and 180 pg/mL, respectively, Dr. Callender said.

Pre–kidney transplant diagnosis of UHPT had an odds ratio of 1.44 for complications in the first year after transplant surgery, but not necessarily a greater risk for graft function or graft failure, she said. However, those relative risks changed with the degree of PTH above normal. Patients with UHPT who had pretransplant parathyroidectomy had a lower risk of graft failure, with an odds ratio of 0.547.

Current Kidney Disease Improving Global Outcomes (KDIGO) guidelines recommend maintaining PTH levels in patients with UHPT before they have kidney transplant surgery at no more than nine times normal. To test the optimal PTH levels before kidney transplant, the researchers analyzed thresholds ranging from two to nine times the normal limit.

“A pre–kidney transplant [PTH] level greater than or equal to six times normal was associated with post-transplant graft failure but not with delayed graft function or complications in the first year post kidney transplant,” Dr. Callender said. “Although the thresholds at two and four times normal were statistically significant, there was a continued risk significant for graft failure above six times normal.”

This finding “suggests that perhaps the current KDIGO guideline of maintaining patient PTH at up to nine times normal is too liberal,” Dr. Callender said.

She acknowledged several limitations of the study: its retrospective nature, small sample size, and “many missing data points” because a wide variety of dialysis centers with varying documentation standards collected information.

“However,” Dr. Callender said, “we believe these findings support the design and implementation of a multi-institutional, prospective, randomized control trial to evaluate whether a change in management of patients with uremic hyperparathyroidism is warranted.”

Dr. Callender and her coauthors had no financial relationships to disclose.

BALTIMORE – Performing a parathyroidectomy in kidney transplant patients before their transplant can reduce the risk of graft failure and provide other benefits, the findings of a retrospective study of 913 patients suggest.

Uremic hyperparathyroidism (UHPT) is common in patients with end-stage kidney disease, and elevated parathyroid hormone (PTH) levels have been linked with delayed graft function after kidney transplants, but current guidelines for PTH levels may not go far enough to reduce the risk of graft failure and other post–kidney transplant complications in people with elevated PTH before transplant, according to Dr. Glenda G. Callender of Yale University, New Haven, Conn., and her colleagues.

“Uremic hyperparathyroidism was associated with an increased risk of complications in the first year post kidney transplant,” Dr. Callender said at the annual meeting of the American Association of Endocrine Surgeons. “Pre–kidney transplant parathyroidectomy was associated with a decreased risk of post–kidney transplant graft failure. This implies that pre–kidney transplant reduction of PTH levels should be considered in patients with UPHT.”

The Yale researchers reviewed outcomes of 913 patients at their institution who had a kidney transplant from 2005 to 2014. They analyzed biochemical values before kidney transplant and at three intervals post transplant: at 1 month, 6 months, and 1 year. Among the outcomes they evaluated were calcium and PTH levels, estimated glomerular filtration rate, complications, delayed graft function, and graft failure. The overall graft survival rate was 97.8% 1 year after kidney transplantation.

Overall, 49.4% of patients (451) had a diagnosis with UHPT before kidney transplant; 6.2% of all patients (57) had parathyroidectomy before kidney transplant and another 2% (18) had parathyroidectomy at some point after their kidney transplant operations. Median baseline PTH levels were higher in the UHPT patients: 206 pg/mL vs. 159 pg/mL for the non-UHPT group, Dr. Callender reported.

The researchers captured complete data on 37 of the 57 patients who had pretransplant parathyroidectomy. Twenty-four (65% of the group) had subtotal parathyroidectomy in which 3.5 glands were removed, and 12 (32%) had fewer than 3.5 glands removed. One patient had total parathyroidectomy, she said.

Among the patients with UHPT, the median pre–kidney transplant PTH was similar between the pretransplant parathyroidectomy and the no-parathyroidectomy groups: 218 pg/mL and 180 pg/mL, respectively, Dr. Callender said.

Pre–kidney transplant diagnosis of UHPT had an odds ratio of 1.44 for complications in the first year after transplant surgery, but not necessarily a greater risk for graft function or graft failure, she said. However, those relative risks changed with the degree of PTH above normal. Patients with UHPT who had pretransplant parathyroidectomy had a lower risk of graft failure, with an odds ratio of 0.547.

Current Kidney Disease Improving Global Outcomes (KDIGO) guidelines recommend maintaining PTH levels in patients with UHPT before they have kidney transplant surgery at no more than nine times normal. To test the optimal PTH levels before kidney transplant, the researchers analyzed thresholds ranging from two to nine times the normal limit.

“A pre–kidney transplant [PTH] level greater than or equal to six times normal was associated with post-transplant graft failure but not with delayed graft function or complications in the first year post kidney transplant,” Dr. Callender said. “Although the thresholds at two and four times normal were statistically significant, there was a continued risk significant for graft failure above six times normal.”

This finding “suggests that perhaps the current KDIGO guideline of maintaining patient PTH at up to nine times normal is too liberal,” Dr. Callender said.

She acknowledged several limitations of the study: its retrospective nature, small sample size, and “many missing data points” because a wide variety of dialysis centers with varying documentation standards collected information.

“However,” Dr. Callender said, “we believe these findings support the design and implementation of a multi-institutional, prospective, randomized control trial to evaluate whether a change in management of patients with uremic hyperparathyroidism is warranted.”

Dr. Callender and her coauthors had no financial relationships to disclose.

BALTIMORE – Performing a parathyroidectomy in kidney transplant patients before their transplant can reduce the risk of graft failure and provide other benefits, the findings of a retrospective study of 913 patients suggest.

Uremic hyperparathyroidism (UHPT) is common in patients with end-stage kidney disease, and elevated parathyroid hormone (PTH) levels have been linked with delayed graft function after kidney transplants, but current guidelines for PTH levels may not go far enough to reduce the risk of graft failure and other post–kidney transplant complications in people with elevated PTH before transplant, according to Dr. Glenda G. Callender of Yale University, New Haven, Conn., and her colleagues.

“Uremic hyperparathyroidism was associated with an increased risk of complications in the first year post kidney transplant,” Dr. Callender said at the annual meeting of the American Association of Endocrine Surgeons. “Pre–kidney transplant parathyroidectomy was associated with a decreased risk of post–kidney transplant graft failure. This implies that pre–kidney transplant reduction of PTH levels should be considered in patients with UPHT.”

The Yale researchers reviewed outcomes of 913 patients at their institution who had a kidney transplant from 2005 to 2014. They analyzed biochemical values before kidney transplant and at three intervals post transplant: at 1 month, 6 months, and 1 year. Among the outcomes they evaluated were calcium and PTH levels, estimated glomerular filtration rate, complications, delayed graft function, and graft failure. The overall graft survival rate was 97.8% 1 year after kidney transplantation.

Overall, 49.4% of patients (451) had a diagnosis with UHPT before kidney transplant; 6.2% of all patients (57) had parathyroidectomy before kidney transplant and another 2% (18) had parathyroidectomy at some point after their kidney transplant operations. Median baseline PTH levels were higher in the UHPT patients: 206 pg/mL vs. 159 pg/mL for the non-UHPT group, Dr. Callender reported.

The researchers captured complete data on 37 of the 57 patients who had pretransplant parathyroidectomy. Twenty-four (65% of the group) had subtotal parathyroidectomy in which 3.5 glands were removed, and 12 (32%) had fewer than 3.5 glands removed. One patient had total parathyroidectomy, she said.

Among the patients with UHPT, the median pre–kidney transplant PTH was similar between the pretransplant parathyroidectomy and the no-parathyroidectomy groups: 218 pg/mL and 180 pg/mL, respectively, Dr. Callender said.

Pre–kidney transplant diagnosis of UHPT had an odds ratio of 1.44 for complications in the first year after transplant surgery, but not necessarily a greater risk for graft function or graft failure, she said. However, those relative risks changed with the degree of PTH above normal. Patients with UHPT who had pretransplant parathyroidectomy had a lower risk of graft failure, with an odds ratio of 0.547.

Current Kidney Disease Improving Global Outcomes (KDIGO) guidelines recommend maintaining PTH levels in patients with UHPT before they have kidney transplant surgery at no more than nine times normal. To test the optimal PTH levels before kidney transplant, the researchers analyzed thresholds ranging from two to nine times the normal limit.

“A pre–kidney transplant [PTH] level greater than or equal to six times normal was associated with post-transplant graft failure but not with delayed graft function or complications in the first year post kidney transplant,” Dr. Callender said. “Although the thresholds at two and four times normal were statistically significant, there was a continued risk significant for graft failure above six times normal.”

This finding “suggests that perhaps the current KDIGO guideline of maintaining patient PTH at up to nine times normal is too liberal,” Dr. Callender said.

She acknowledged several limitations of the study: its retrospective nature, small sample size, and “many missing data points” because a wide variety of dialysis centers with varying documentation standards collected information.

“However,” Dr. Callender said, “we believe these findings support the design and implementation of a multi-institutional, prospective, randomized control trial to evaluate whether a change in management of patients with uremic hyperparathyroidism is warranted.”

Dr. Callender and her coauthors had no financial relationships to disclose.