Pituitary, Thyroid & Adrenal Disorders

Total thyroidectomy can be performed more safely than many clinicians realize, and offers more durable results for people with Grave's disease than do antithyroid drugs or radioiodine, according to Dr. Kaare J. Weber of Mount Sinai School of Medicine, New York, and his associates.

The researchers reviewed the records of all 48 patients who underwent total thyroidectomy for Grave's disease at their hospital between 1993 and 2005. All but 7 of the patients were women, and the mean age was 40 years. All had typical symptoms including palpitations, eye disturbances, anxiety, weight loss, heat intolerance, and tremor.

Of this group, 24 patients had failed on medical therapy with or without radioiodine. Another 12 had refused radioiodine because of concerns about radiation exposure. The remaining 12 chose surgery for assessment of thyroid nodules that were presumed to be related to their disease.

After thyroidectomy and a mean of 40 months of follow-up, there were no recurrences of hyperthyroidism. In contrast, relapse rates of 20%–75% are cited in the literature for medical therapy, Dr. Weber and his associates said (Am. J. Surg. 2006;191:400–5).

Of the 20 patients who had mild or severe ophthalmopathy before surgery, 11 showed marked improvement or resolution of eye disorders and the remaining 9 showed either improvement or stabilization. In contrast, radioiodine treatment has been associated with the onset or exacerbation of ophthalmopathy, they said.

Eight patients (17%) were found to have papillary cancer of the thyroid at surgery. “These patients would not have received appropriate treatment for their coexisting cancer if they were treated only with antithyroid drugs and/or radioiodine,” the investigators noted.

No patients suffered permanent laryngeal nerve injury from the procedure. Complications included three cases of transient hypocalcemia and one case of temporary right vocal cord paralysis. Only one patient developed permanent hypoparathyroidism, and that case “followed a previous failed [thyroid] exploration at another institution,” they said.

“Despite today's methods for a safe thyroidectomy, concern over permanent recurrent laryngeal nerve injury and permanent hypoparathyroidism as a result of the hypervascularity of the thyroid gland prevents some physicians from recommending surgical therapy for Grave's disease,” Dr. Weber and his associates said.

These results demonstrate that total thyroidectomy now can be performed safely, with little of the morbidity and mortality that occurred when the procedure was first developed years ago. In addition, thyroidectomy addresses potentially cancerous nodules, as medical and radioiodine therapies do not, they said.

Total thyroidectomy can be performed more safely than many clinicians realize, and offers more durable results for people with Grave's disease than do antithyroid drugs or radioiodine, according to Dr. Kaare J. Weber of Mount Sinai School of Medicine, New York, and his associates.

The researchers reviewed the records of all 48 patients who underwent total thyroidectomy for Grave's disease at their hospital between 1993 and 2005. All but 7 of the patients were women, and the mean age was 40 years. All had typical symptoms including palpitations, eye disturbances, anxiety, weight loss, heat intolerance, and tremor.

Of this group, 24 patients had failed on medical therapy with or without radioiodine. Another 12 had refused radioiodine because of concerns about radiation exposure. The remaining 12 chose surgery for assessment of thyroid nodules that were presumed to be related to their disease.

After thyroidectomy and a mean of 40 months of follow-up, there were no recurrences of hyperthyroidism. In contrast, relapse rates of 20%–75% are cited in the literature for medical therapy, Dr. Weber and his associates said (Am. J. Surg. 2006;191:400–5).

Of the 20 patients who had mild or severe ophthalmopathy before surgery, 11 showed marked improvement or resolution of eye disorders and the remaining 9 showed either improvement or stabilization. In contrast, radioiodine treatment has been associated with the onset or exacerbation of ophthalmopathy, they said.

Eight patients (17%) were found to have papillary cancer of the thyroid at surgery. “These patients would not have received appropriate treatment for their coexisting cancer if they were treated only with antithyroid drugs and/or radioiodine,” the investigators noted.

No patients suffered permanent laryngeal nerve injury from the procedure. Complications included three cases of transient hypocalcemia and one case of temporary right vocal cord paralysis. Only one patient developed permanent hypoparathyroidism, and that case “followed a previous failed [thyroid] exploration at another institution,” they said.

“Despite today's methods for a safe thyroidectomy, concern over permanent recurrent laryngeal nerve injury and permanent hypoparathyroidism as a result of the hypervascularity of the thyroid gland prevents some physicians from recommending surgical therapy for Grave's disease,” Dr. Weber and his associates said.

These results demonstrate that total thyroidectomy now can be performed safely, with little of the morbidity and mortality that occurred when the procedure was first developed years ago. In addition, thyroidectomy addresses potentially cancerous nodules, as medical and radioiodine therapies do not, they said.

Total thyroidectomy can be performed more safely than many clinicians realize, and offers more durable results for people with Grave's disease than do antithyroid drugs or radioiodine, according to Dr. Kaare J. Weber of Mount Sinai School of Medicine, New York, and his associates.

The researchers reviewed the records of all 48 patients who underwent total thyroidectomy for Grave's disease at their hospital between 1993 and 2005. All but 7 of the patients were women, and the mean age was 40 years. All had typical symptoms including palpitations, eye disturbances, anxiety, weight loss, heat intolerance, and tremor.

Of this group, 24 patients had failed on medical therapy with or without radioiodine. Another 12 had refused radioiodine because of concerns about radiation exposure. The remaining 12 chose surgery for assessment of thyroid nodules that were presumed to be related to their disease.

After thyroidectomy and a mean of 40 months of follow-up, there were no recurrences of hyperthyroidism. In contrast, relapse rates of 20%–75% are cited in the literature for medical therapy, Dr. Weber and his associates said (Am. J. Surg. 2006;191:400–5).

Of the 20 patients who had mild or severe ophthalmopathy before surgery, 11 showed marked improvement or resolution of eye disorders and the remaining 9 showed either improvement or stabilization. In contrast, radioiodine treatment has been associated with the onset or exacerbation of ophthalmopathy, they said.

Eight patients (17%) were found to have papillary cancer of the thyroid at surgery. “These patients would not have received appropriate treatment for their coexisting cancer if they were treated only with antithyroid drugs and/or radioiodine,” the investigators noted.

No patients suffered permanent laryngeal nerve injury from the procedure. Complications included three cases of transient hypocalcemia and one case of temporary right vocal cord paralysis. Only one patient developed permanent hypoparathyroidism, and that case “followed a previous failed [thyroid] exploration at another institution,” they said.

“Despite today's methods for a safe thyroidectomy, concern over permanent recurrent laryngeal nerve injury and permanent hypoparathyroidism as a result of the hypervascularity of the thyroid gland prevents some physicians from recommending surgical therapy for Grave's disease,” Dr. Weber and his associates said.

These results demonstrate that total thyroidectomy now can be performed safely, with little of the morbidity and mortality that occurred when the procedure was first developed years ago. In addition, thyroidectomy addresses potentially cancerous nodules, as medical and radioiodine therapies do not, they said.

High-dose external beam radiotherapy controlled locally advanced, differentiated thyroid cancer in a retrospective study of 42 patients.

There is little information on the efficacy of external beam radiotherapy (EBRT) as adjuvant therapy in such patients. “The relatively low incidence of this malignancy, coupled with its long natural history, has precluded study of various treatment methods in the context of a prospective clinical trial,” said Dr. Kenyon M. Meadows and his associates at the University of Florida, Gainesville.

“Retrospective outcome studies remain the most reliable way of assessing therapeutic efficacy but are hampered by significant heterogeneity in diagnostic evaluation, staging, and treatment strategies that have evolved over time. Accordingly, the indications for EBRT for differentiated thyroid cancer remain poorly defined,” they said.

The 10% of thyroid cancer patients presenting with locally advanced disease are at high risk for local or regional recurrence. Five-year survival is 50%.

The investigators reviewed the records and assessed outcomes in all 42 patients who were treated for advanced or recurrent thyroid cancer with adjuvant high-dose EBRT at their university since April 1962. Median patient age was 58 (Am. J. Otolaryngol. 2006;27:24–8).

Ten patients died from thyroid cancer during a mean follow-up of 7 years and 16 died from unrelated causes. There were no local or regional recurrences at 5 years for patients with no gross residual disease at EBRT and 30% recurrence for those with gross residual disease at EBRT. No recurrences were seen with doses over 64 Gy.

Five-year survival free of distant metastases was 82% in those without metastasis at EBRT.

High-dose external beam radiotherapy controlled locally advanced, differentiated thyroid cancer in a retrospective study of 42 patients.

There is little information on the efficacy of external beam radiotherapy (EBRT) as adjuvant therapy in such patients. “The relatively low incidence of this malignancy, coupled with its long natural history, has precluded study of various treatment methods in the context of a prospective clinical trial,” said Dr. Kenyon M. Meadows and his associates at the University of Florida, Gainesville.

“Retrospective outcome studies remain the most reliable way of assessing therapeutic efficacy but are hampered by significant heterogeneity in diagnostic evaluation, staging, and treatment strategies that have evolved over time. Accordingly, the indications for EBRT for differentiated thyroid cancer remain poorly defined,” they said.

The 10% of thyroid cancer patients presenting with locally advanced disease are at high risk for local or regional recurrence. Five-year survival is 50%.

The investigators reviewed the records and assessed outcomes in all 42 patients who were treated for advanced or recurrent thyroid cancer with adjuvant high-dose EBRT at their university since April 1962. Median patient age was 58 (Am. J. Otolaryngol. 2006;27:24–8).

Ten patients died from thyroid cancer during a mean follow-up of 7 years and 16 died from unrelated causes. There were no local or regional recurrences at 5 years for patients with no gross residual disease at EBRT and 30% recurrence for those with gross residual disease at EBRT. No recurrences were seen with doses over 64 Gy.

Five-year survival free of distant metastases was 82% in those without metastasis at EBRT.

High-dose external beam radiotherapy controlled locally advanced, differentiated thyroid cancer in a retrospective study of 42 patients.

There is little information on the efficacy of external beam radiotherapy (EBRT) as adjuvant therapy in such patients. “The relatively low incidence of this malignancy, coupled with its long natural history, has precluded study of various treatment methods in the context of a prospective clinical trial,” said Dr. Kenyon M. Meadows and his associates at the University of Florida, Gainesville.

“Retrospective outcome studies remain the most reliable way of assessing therapeutic efficacy but are hampered by significant heterogeneity in diagnostic evaluation, staging, and treatment strategies that have evolved over time. Accordingly, the indications for EBRT for differentiated thyroid cancer remain poorly defined,” they said.

The 10% of thyroid cancer patients presenting with locally advanced disease are at high risk for local or regional recurrence. Five-year survival is 50%.

The investigators reviewed the records and assessed outcomes in all 42 patients who were treated for advanced or recurrent thyroid cancer with adjuvant high-dose EBRT at their university since April 1962. Median patient age was 58 (Am. J. Otolaryngol. 2006;27:24–8).

Ten patients died from thyroid cancer during a mean follow-up of 7 years and 16 died from unrelated causes. There were no local or regional recurrences at 5 years for patients with no gross residual disease at EBRT and 30% recurrence for those with gross residual disease at EBRT. No recurrences were seen with doses over 64 Gy.

Five-year survival free of distant metastases was 82% in those without metastasis at EBRT.

Nearly 60 years after exposure to radiation from the atomic bomb explosions in Hiroshima and Nagasaki, survivors remain at increased risk for both malignant and benign thyroid tumors, reported Dr. Misa Imaizumi of Nagasaki (Japan) University, and associates.

There is a significant, linear dose-response relationship: The prevalence of thyroid tumors rises as radiation dose increases. And the dose effects are significantly stronger in people who were exposed as children or adolescents in 1945 than they are in people who were 20 years old or older at that time.

These findings show that “careful examination of the thyroid is still important long after radiation exposure, especially for people exposed at younger ages,” Dr. Imaizumi and associates said (JAMA 2006;295:1011–22).

The researchers conducted what they described as the first comprehensive examinations for thyroid disease in 4,091 survivors of the Hiroshima and Nagasaki bombings. The 1,352 men and 2,739 women had a mean age of 70 years. About half had been within 2 kilometers of the hypocenters of the explosions.

Thyroid diseases were diagnosed at this examination or had been diagnosed previously in 1,833 subjects (44.8%). The prevalence of thyroid disease was significantly higher in women (51.0%) than in men (32.2%).

Malignant thyroid tumors were found in 87 subjects (2.1%), and benign nodules were detected in 207 subjects (5.1%). Another 71 subjects had previously had malignant tumors removed, whereas 43 had previously had benign nodules removed. Thyroid cysts were noted in an additional 324 subjects (7.9%), whereas 589 (14.4%) had mixed-type solid nodules and 321 (7.8%) had nodules for which cytology results were unavailable.

For all of these lesions, the prevalence increased in direct proportion to the degree of radiation exposure. Moreover, the prevalence was highest in people who had been exposed to the atomic bombs' radiation as children or adolescents. The exact reason for this is unknown, but it is likely that children's organs are more sensitive to radiation because of their higher rates of cell proliferation associated with growth, the investigators said.

Autoimmune thyroid diseases were not associated with radiation dose. A total of 1,127 subjects (27.5%) had antithyroid antibodies, 230 (5.6%) had hypothyroidism, and 62 (1.5%) had hyperthyroidism.

In an editorial comment, John D. Boice Jr., Sc.D., of Vanderbilt University in Nashville, Tenn. said, “It is remarkable that a biological effect from a single brief environmental exposure nearly 60 years in the past is still present and can be detected.”

The findings of Dr. Imaizumi and associates show that after radiation exposure, the risk of both malignant and benign thyroid disease “apparently lasts for life,” Dr. Boice said (JAMA 2006;295:1060–2).

Nearly 60 years after exposure to radiation from the atomic bomb explosions in Hiroshima and Nagasaki, survivors remain at increased risk for both malignant and benign thyroid tumors, reported Dr. Misa Imaizumi of Nagasaki (Japan) University, and associates.

There is a significant, linear dose-response relationship: The prevalence of thyroid tumors rises as radiation dose increases. And the dose effects are significantly stronger in people who were exposed as children or adolescents in 1945 than they are in people who were 20 years old or older at that time.

These findings show that “careful examination of the thyroid is still important long after radiation exposure, especially for people exposed at younger ages,” Dr. Imaizumi and associates said (JAMA 2006;295:1011–22).

The researchers conducted what they described as the first comprehensive examinations for thyroid disease in 4,091 survivors of the Hiroshima and Nagasaki bombings. The 1,352 men and 2,739 women had a mean age of 70 years. About half had been within 2 kilometers of the hypocenters of the explosions.

Thyroid diseases were diagnosed at this examination or had been diagnosed previously in 1,833 subjects (44.8%). The prevalence of thyroid disease was significantly higher in women (51.0%) than in men (32.2%).

Malignant thyroid tumors were found in 87 subjects (2.1%), and benign nodules were detected in 207 subjects (5.1%). Another 71 subjects had previously had malignant tumors removed, whereas 43 had previously had benign nodules removed. Thyroid cysts were noted in an additional 324 subjects (7.9%), whereas 589 (14.4%) had mixed-type solid nodules and 321 (7.8%) had nodules for which cytology results were unavailable.

For all of these lesions, the prevalence increased in direct proportion to the degree of radiation exposure. Moreover, the prevalence was highest in people who had been exposed to the atomic bombs' radiation as children or adolescents. The exact reason for this is unknown, but it is likely that children's organs are more sensitive to radiation because of their higher rates of cell proliferation associated with growth, the investigators said.

Autoimmune thyroid diseases were not associated with radiation dose. A total of 1,127 subjects (27.5%) had antithyroid antibodies, 230 (5.6%) had hypothyroidism, and 62 (1.5%) had hyperthyroidism.

In an editorial comment, John D. Boice Jr., Sc.D., of Vanderbilt University in Nashville, Tenn. said, “It is remarkable that a biological effect from a single brief environmental exposure nearly 60 years in the past is still present and can be detected.”

The findings of Dr. Imaizumi and associates show that after radiation exposure, the risk of both malignant and benign thyroid disease “apparently lasts for life,” Dr. Boice said (JAMA 2006;295:1060–2).

Nearly 60 years after exposure to radiation from the atomic bomb explosions in Hiroshima and Nagasaki, survivors remain at increased risk for both malignant and benign thyroid tumors, reported Dr. Misa Imaizumi of Nagasaki (Japan) University, and associates.

There is a significant, linear dose-response relationship: The prevalence of thyroid tumors rises as radiation dose increases. And the dose effects are significantly stronger in people who were exposed as children or adolescents in 1945 than they are in people who were 20 years old or older at that time.

These findings show that “careful examination of the thyroid is still important long after radiation exposure, especially for people exposed at younger ages,” Dr. Imaizumi and associates said (JAMA 2006;295:1011–22).

The researchers conducted what they described as the first comprehensive examinations for thyroid disease in 4,091 survivors of the Hiroshima and Nagasaki bombings. The 1,352 men and 2,739 women had a mean age of 70 years. About half had been within 2 kilometers of the hypocenters of the explosions.

Thyroid diseases were diagnosed at this examination or had been diagnosed previously in 1,833 subjects (44.8%). The prevalence of thyroid disease was significantly higher in women (51.0%) than in men (32.2%).

Malignant thyroid tumors were found in 87 subjects (2.1%), and benign nodules were detected in 207 subjects (5.1%). Another 71 subjects had previously had malignant tumors removed, whereas 43 had previously had benign nodules removed. Thyroid cysts were noted in an additional 324 subjects (7.9%), whereas 589 (14.4%) had mixed-type solid nodules and 321 (7.8%) had nodules for which cytology results were unavailable.

For all of these lesions, the prevalence increased in direct proportion to the degree of radiation exposure. Moreover, the prevalence was highest in people who had been exposed to the atomic bombs' radiation as children or adolescents. The exact reason for this is unknown, but it is likely that children's organs are more sensitive to radiation because of their higher rates of cell proliferation associated with growth, the investigators said.

Autoimmune thyroid diseases were not associated with radiation dose. A total of 1,127 subjects (27.5%) had antithyroid antibodies, 230 (5.6%) had hypothyroidism, and 62 (1.5%) had hyperthyroidism.

In an editorial comment, John D. Boice Jr., Sc.D., of Vanderbilt University in Nashville, Tenn. said, “It is remarkable that a biological effect from a single brief environmental exposure nearly 60 years in the past is still present and can be detected.”

The findings of Dr. Imaizumi and associates show that after radiation exposure, the risk of both malignant and benign thyroid disease “apparently lasts for life,” Dr. Boice said (JAMA 2006;295:1060–2).

DENVER — Up to half of all patients become hypothyroid within 5 years following radiotherapy for head and neck cancer in which the thyroid remains outside the primary field of radiation but is included in the low-neck field, Dr. Anna A. Norris reported at the annual meeting of the American Society for Therapeutic Radiology and Oncology.

As a result, such patients should undergo TSH screening. A good regimen is to check the TSH levels every 6 months for the first 2 years after radiotherapy and annually thereafter, said Dr. Norris of the University of Florida, Gainesville.

She reported on 390 consecutive patients who underwent radiotherapy for oropharyngeal cancer during the 1990s at the university. None had a history of thyroid disease or surgery. All received radiotherapy with a standard low-neck field that covered the area—including the entire thyroid—with a dose of 50 Gy, with boosts bringing the total dose to selected portions of the field up to 70 Gy. Median follow-up was 6.1 years.

During the 1990s, the practice at the university was to not routinely monitor TSH levels in such patients. But in the subset of 169 patients in whom TSH was monitored, the 5-year incidence of hypothyroidism—as defined by a TSH greater than 4.5 ng/mL—was 54%.

In a retrospective study, it's impossible to know how many patients had their TSH measured because of symptoms or physician preference. But even if it is assumed none of the 221 untested patients had hypothyroidism, the 5-year rate following radiotherapy was still 31%, she noted.

DENVER — Up to half of all patients become hypothyroid within 5 years following radiotherapy for head and neck cancer in which the thyroid remains outside the primary field of radiation but is included in the low-neck field, Dr. Anna A. Norris reported at the annual meeting of the American Society for Therapeutic Radiology and Oncology.

As a result, such patients should undergo TSH screening. A good regimen is to check the TSH levels every 6 months for the first 2 years after radiotherapy and annually thereafter, said Dr. Norris of the University of Florida, Gainesville.

She reported on 390 consecutive patients who underwent radiotherapy for oropharyngeal cancer during the 1990s at the university. None had a history of thyroid disease or surgery. All received radiotherapy with a standard low-neck field that covered the area—including the entire thyroid—with a dose of 50 Gy, with boosts bringing the total dose to selected portions of the field up to 70 Gy. Median follow-up was 6.1 years.

During the 1990s, the practice at the university was to not routinely monitor TSH levels in such patients. But in the subset of 169 patients in whom TSH was monitored, the 5-year incidence of hypothyroidism—as defined by a TSH greater than 4.5 ng/mL—was 54%.

In a retrospective study, it's impossible to know how many patients had their TSH measured because of symptoms or physician preference. But even if it is assumed none of the 221 untested patients had hypothyroidism, the 5-year rate following radiotherapy was still 31%, she noted.

DENVER — Up to half of all patients become hypothyroid within 5 years following radiotherapy for head and neck cancer in which the thyroid remains outside the primary field of radiation but is included in the low-neck field, Dr. Anna A. Norris reported at the annual meeting of the American Society for Therapeutic Radiology and Oncology.

As a result, such patients should undergo TSH screening. A good regimen is to check the TSH levels every 6 months for the first 2 years after radiotherapy and annually thereafter, said Dr. Norris of the University of Florida, Gainesville.

She reported on 390 consecutive patients who underwent radiotherapy for oropharyngeal cancer during the 1990s at the university. None had a history of thyroid disease or surgery. All received radiotherapy with a standard low-neck field that covered the area—including the entire thyroid—with a dose of 50 Gy, with boosts bringing the total dose to selected portions of the field up to 70 Gy. Median follow-up was 6.1 years.

During the 1990s, the practice at the university was to not routinely monitor TSH levels in such patients. But in the subset of 169 patients in whom TSH was monitored, the 5-year incidence of hypothyroidism—as defined by a TSH greater than 4.5 ng/mL—was 54%.

In a retrospective study, it's impossible to know how many patients had their TSH measured because of symptoms or physician preference. But even if it is assumed none of the 221 untested patients had hypothyroidism, the 5-year rate following radiotherapy was still 31%, she noted.

CHICAGO — Routine concurrent breast and thyroid sonographic examinations are useful in detecting small thyroid cancers, Dr. Jeong Seon Park said at the annual meeting of the Radiological Society of North America.

The two tests were combined in a prospective study conducted between January 2003 and March 2004 of 5,549 women.

The findings were so convincing that thyroid testing is now routine practice when a breast ultrasound is ordered at the Korean Cancer Center in Koyang, where the study was conducted.

Breast ultrasounds are added to mammography for women with dense breasts, and detect additional cancers in about 1 in 1,000 cases, she said.

All participants, aged 13–83 years, underwent breast and thyroid screening sonography (4,864 women) or sonography for diagnosis or follow-up of breast cancer (685 women).

Ultrasound-guided fine needle aspiration was performed when a thyroid lesion was suspicious for malignancy based on hypoechogenicity, irregular shape, or poorly defined margins.

A total of 42 (0.75%) cases of thyroid cancer were detected and confirmed pathologically. All were papillary carcinomas.

The incidence of thyroid cancer was significantly higher in women with breast cancer, reported Dr. Park and colleagues.

There were 13 (1.9%) thyroid cancers among the patients with breast cancer, compared with 29 (0.6%) thyroid cancers among patients with negative or benign breast disease.

The mean diameter of the thyroid masses was 9.9 mm in the breast cancer group and 8.6 mm in the noncancer group.

A total of 28 (66%) thyroid cancers were less than 1 cm in diameter. There were no metastases.

In the breast cancer group, 6 of the 13 cases were detected as having concurrent breast and thyroid cancers; the remaining 7 thyroid cancers were diagnosed after 6–14 months of follow-up.

“Sonographic screening to detect thyroid cancer in women is effective, but the survival benefit of early detection needs to be studied further,” she said.

Patients were offered the thyroid test free of charge during the study but are now charged and willing to pay for the additional test, she said.

CHICAGO — Routine concurrent breast and thyroid sonographic examinations are useful in detecting small thyroid cancers, Dr. Jeong Seon Park said at the annual meeting of the Radiological Society of North America.

The two tests were combined in a prospective study conducted between January 2003 and March 2004 of 5,549 women.

The findings were so convincing that thyroid testing is now routine practice when a breast ultrasound is ordered at the Korean Cancer Center in Koyang, where the study was conducted.

Breast ultrasounds are added to mammography for women with dense breasts, and detect additional cancers in about 1 in 1,000 cases, she said.

All participants, aged 13–83 years, underwent breast and thyroid screening sonography (4,864 women) or sonography for diagnosis or follow-up of breast cancer (685 women).

Ultrasound-guided fine needle aspiration was performed when a thyroid lesion was suspicious for malignancy based on hypoechogenicity, irregular shape, or poorly defined margins.

A total of 42 (0.75%) cases of thyroid cancer were detected and confirmed pathologically. All were papillary carcinomas.

The incidence of thyroid cancer was significantly higher in women with breast cancer, reported Dr. Park and colleagues.

There were 13 (1.9%) thyroid cancers among the patients with breast cancer, compared with 29 (0.6%) thyroid cancers among patients with negative or benign breast disease.

The mean diameter of the thyroid masses was 9.9 mm in the breast cancer group and 8.6 mm in the noncancer group.

A total of 28 (66%) thyroid cancers were less than 1 cm in diameter. There were no metastases.

In the breast cancer group, 6 of the 13 cases were detected as having concurrent breast and thyroid cancers; the remaining 7 thyroid cancers were diagnosed after 6–14 months of follow-up.

“Sonographic screening to detect thyroid cancer in women is effective, but the survival benefit of early detection needs to be studied further,” she said.

Patients were offered the thyroid test free of charge during the study but are now charged and willing to pay for the additional test, she said.

CHICAGO — Routine concurrent breast and thyroid sonographic examinations are useful in detecting small thyroid cancers, Dr. Jeong Seon Park said at the annual meeting of the Radiological Society of North America.

The two tests were combined in a prospective study conducted between January 2003 and March 2004 of 5,549 women.

The findings were so convincing that thyroid testing is now routine practice when a breast ultrasound is ordered at the Korean Cancer Center in Koyang, where the study was conducted.

Breast ultrasounds are added to mammography for women with dense breasts, and detect additional cancers in about 1 in 1,000 cases, she said.

All participants, aged 13–83 years, underwent breast and thyroid screening sonography (4,864 women) or sonography for diagnosis or follow-up of breast cancer (685 women).

Ultrasound-guided fine needle aspiration was performed when a thyroid lesion was suspicious for malignancy based on hypoechogenicity, irregular shape, or poorly defined margins.

A total of 42 (0.75%) cases of thyroid cancer were detected and confirmed pathologically. All were papillary carcinomas.

The incidence of thyroid cancer was significantly higher in women with breast cancer, reported Dr. Park and colleagues.

There were 13 (1.9%) thyroid cancers among the patients with breast cancer, compared with 29 (0.6%) thyroid cancers among patients with negative or benign breast disease.

The mean diameter of the thyroid masses was 9.9 mm in the breast cancer group and 8.6 mm in the noncancer group.

A total of 28 (66%) thyroid cancers were less than 1 cm in diameter. There were no metastases.

In the breast cancer group, 6 of the 13 cases were detected as having concurrent breast and thyroid cancers; the remaining 7 thyroid cancers were diagnosed after 6–14 months of follow-up.

“Sonographic screening to detect thyroid cancer in women is effective, but the survival benefit of early detection needs to be studied further,” she said.

Patients were offered the thyroid test free of charge during the study but are now charged and willing to pay for the additional test, she said.

Elderly patients with subclinical hypothyroidism have a higher rate of congestive heart failure than do those who are euthyroid, according to Dr. Nicolas Rodondi of the University of California, San Francisco, and his associates.

Overt hypothyroidism is known to be associated with cardiovascular disease (CVD), but studies evaluating a possible link between subclinical hypothyroidism and CVD have produced conflicting results. Dr. Rodondi and his associates conducted what they described as the first prospective study to assess the risk of heart failure (HF) events in subjects with subclinical hypothyroidism.

The investigators assessed thyrotropin levels in 2,730 men and women aged 70–79 years who were participating in a large cohort study of aging. The subjects were followed for 4 years to determine whether these hormone levels were related to HF or other cardiovascular disease events.

A total of 338 subjects (12.4%) were found to have subclinical hypothyroidism, defined as an elevated level of thyrotropin and a normal level of free thyroxine (T₄). During follow-up, 178 subjects had HF events (Arch. Intern. Med. 2005;165:2460–6).

Subjects with moderately to severely elevated thyrotropin levels (7.0 mIU/L or greater) had more HF events (35 per 1,000 person-years) than did those who were euthyroid (17 per 1,000 person-years). Each standard deviation increase of 4.0 mIU/L was associated with a 30% increase in HF events.

This link was stronger among subjects known to have previous HF events. The rate of recurrent HF events was seven times higher in those with subclinical hypothyroidism than in those who were euthyroid.

In contrast, subjects with mildly elevated thyrotropin (4.5–6.9 mIU/L) did not have higher HF event rates. Subclinical hypothyroidism was not found to be associated with other coronary heart disease events, stroke, peripheral arterial disease, CVD-related mortality, or total mortality.

These results suggest that further study is warranted to determine whether subclinical hypothyroidism causes heart failure or worsens existing heart failure, Dr. Rodondi and his associates said.

In an editorial that accompanied the article, Dr. Lawrence M. Crapo of Santa Clara Valley Medical Center, San Jose, Calif., noted these findings “certainly support the idea that the treatment of severe subclinical hypothyroidism with levothyroxine in patients younger than 80 years may be beneficial, but this remains to be proved in a randomized prospective therapeutic trial.”

The results further indicate that patients with mild hypothyroidism probably would not benefit from levothyroxine treatment, Dr. Crapo said (Arch. Intern. Med. 2005;165:2451–2).

Elderly patients with subclinical hypothyroidism have a higher rate of congestive heart failure than do those who are euthyroid, according to Dr. Nicolas Rodondi of the University of California, San Francisco, and his associates.

Overt hypothyroidism is known to be associated with cardiovascular disease (CVD), but studies evaluating a possible link between subclinical hypothyroidism and CVD have produced conflicting results. Dr. Rodondi and his associates conducted what they described as the first prospective study to assess the risk of heart failure (HF) events in subjects with subclinical hypothyroidism.

The investigators assessed thyrotropin levels in 2,730 men and women aged 70–79 years who were participating in a large cohort study of aging. The subjects were followed for 4 years to determine whether these hormone levels were related to HF or other cardiovascular disease events.

A total of 338 subjects (12.4%) were found to have subclinical hypothyroidism, defined as an elevated level of thyrotropin and a normal level of free thyroxine (T₄). During follow-up, 178 subjects had HF events (Arch. Intern. Med. 2005;165:2460–6).

Subjects with moderately to severely elevated thyrotropin levels (7.0 mIU/L or greater) had more HF events (35 per 1,000 person-years) than did those who were euthyroid (17 per 1,000 person-years). Each standard deviation increase of 4.0 mIU/L was associated with a 30% increase in HF events.

This link was stronger among subjects known to have previous HF events. The rate of recurrent HF events was seven times higher in those with subclinical hypothyroidism than in those who were euthyroid.

In contrast, subjects with mildly elevated thyrotropin (4.5–6.9 mIU/L) did not have higher HF event rates. Subclinical hypothyroidism was not found to be associated with other coronary heart disease events, stroke, peripheral arterial disease, CVD-related mortality, or total mortality.

These results suggest that further study is warranted to determine whether subclinical hypothyroidism causes heart failure or worsens existing heart failure, Dr. Rodondi and his associates said.

In an editorial that accompanied the article, Dr. Lawrence M. Crapo of Santa Clara Valley Medical Center, San Jose, Calif., noted these findings “certainly support the idea that the treatment of severe subclinical hypothyroidism with levothyroxine in patients younger than 80 years may be beneficial, but this remains to be proved in a randomized prospective therapeutic trial.”

The results further indicate that patients with mild hypothyroidism probably would not benefit from levothyroxine treatment, Dr. Crapo said (Arch. Intern. Med. 2005;165:2451–2).

Elderly patients with subclinical hypothyroidism have a higher rate of congestive heart failure than do those who are euthyroid, according to Dr. Nicolas Rodondi of the University of California, San Francisco, and his associates.

Overt hypothyroidism is known to be associated with cardiovascular disease (CVD), but studies evaluating a possible link between subclinical hypothyroidism and CVD have produced conflicting results. Dr. Rodondi and his associates conducted what they described as the first prospective study to assess the risk of heart failure (HF) events in subjects with subclinical hypothyroidism.

The investigators assessed thyrotropin levels in 2,730 men and women aged 70–79 years who were participating in a large cohort study of aging. The subjects were followed for 4 years to determine whether these hormone levels were related to HF or other cardiovascular disease events.

A total of 338 subjects (12.4%) were found to have subclinical hypothyroidism, defined as an elevated level of thyrotropin and a normal level of free thyroxine (T₄). During follow-up, 178 subjects had HF events (Arch. Intern. Med. 2005;165:2460–6).

Subjects with moderately to severely elevated thyrotropin levels (7.0 mIU/L or greater) had more HF events (35 per 1,000 person-years) than did those who were euthyroid (17 per 1,000 person-years). Each standard deviation increase of 4.0 mIU/L was associated with a 30% increase in HF events.

This link was stronger among subjects known to have previous HF events. The rate of recurrent HF events was seven times higher in those with subclinical hypothyroidism than in those who were euthyroid.

In contrast, subjects with mildly elevated thyrotropin (4.5–6.9 mIU/L) did not have higher HF event rates. Subclinical hypothyroidism was not found to be associated with other coronary heart disease events, stroke, peripheral arterial disease, CVD-related mortality, or total mortality.

These results suggest that further study is warranted to determine whether subclinical hypothyroidism causes heart failure or worsens existing heart failure, Dr. Rodondi and his associates said.

In an editorial that accompanied the article, Dr. Lawrence M. Crapo of Santa Clara Valley Medical Center, San Jose, Calif., noted these findings “certainly support the idea that the treatment of severe subclinical hypothyroidism with levothyroxine in patients younger than 80 years may be beneficial, but this remains to be proved in a randomized prospective therapeutic trial.”

The results further indicate that patients with mild hypothyroidism probably would not benefit from levothyroxine treatment, Dr. Crapo said (Arch. Intern. Med. 2005;165:2451–2).

CHANTILLY, VA. — Thyroid cancer patients who have received radioactive iodine ablation after thyroidectomy and who later have a negative whole body scan for thyroid cancer probably do not need to receive radioactive iodine therapy if their stimulated thyroglobulin levels stay below 10 ng/mL, Dr. R. Michael Tuttle said at the annual meeting of the Mid-Atlantic Chapter of the American Association of Clinical Endocrinologists.

Whether a patient with a very low stimulated thyroglobulin level should be treated again with radioactive iodine (RAI) “is probably one of the most common phone calls I get from around the country,” said Dr. Tuttle of Memorial Sloan-Kettering Cancer Center, New York.

The way thyroid cancer is treated today is “so remarkably different now than it was 10 or 15 years ago,” he said, adding that the detection of persistent thyroid cancer has improved to the point where thyroglobulin (Tg) levels of 1, 0.5, or 0.2 ng/mL can be detected and 3-mm lymph nodes in the tracheal-esophageal groove can be seen with ultrasound in patients who were thought to be cured 20 years ago.

“I can't tell you the number of patients who leave my office mad at me because I've explained to them that I cannot cure their thyroid cancer. Their thyroglobulin level of 0.3 ng/mL is probably going to be there for awhile and taking out that 2-mm lymph node beside their recurrent laryngeal nerve is probably only going to help the surgeon and pathologist because they can bill and code for it, and it is unlikely to help our patient.”

About 80% of full body scans after repeat administration of therapeutic RAI appear to show some uptake by thyroid cells in the neck, but about 40% of these may be lung metastases, based on experience with all forms of thyroid cancer. If physicians give 100–150 mCi of RAI to patients with a high Tg level but a negative body scan, “you're very likely to find real disease,” Dr. Tuttle said, “and I think it's that finding of the lung metastasis that made us all do this.”

Rationale for RAI Changes Over Time

One rationale for using a therapeutic level of RAI when stimulated Tg levels remain high despite a negative diagnostic whole body scan was to localize the disease, not necessarily to treat it, Dr. Tuttle pointed out. Today's imaging modalities of helical CT and PET scans and neck ultrasounds can give the same information that RAI scanning would, without the possibility of side effects.

There is no evidence that repeat RAI treatment for patients who have a high stimulated Tg level after an initially negative whole body scan increases disease-specific or overall survival, Dr. Tuttle said.

Most clinicians would give another course of therapeutic RAI if the stimulated Tg level rose above 10 ng/mL, and most would not use repeat RAI if the stimulated level was below 2 ng/mL. RAI treatment for Tg levels of less than 2 ng/mL offers little potential benefit, while potentially causing complications, including damage to salivary glands, taste buds, and tear ducts. “We don't know what to do between 2 and 10,” Dr. Tuttle said.

Multiple RAI treatments appear to clear small-volume papillary thyroid cancer from pediatric to 30-year-old patients with positive lymph nodes by consistently decreasing stimulated Tg levels and clearing evidence of the tumor on CT scans and x-rays. These patients, who do not have distant metastases, are either cured or go into long-term remissions.

But older patients with thyroid cancer extending beyond the thyroid are more commonly seen than are younger patients with less aggressive, localized disease. Older patients may have a negative whole body scan and the same level of Tg as a younger patient, but the tumor is likely to be visible in the lungs on x-ray, CT, and PET scans. RAI will not help these patients if the lung lesions are poorly differentiated.

In a soon-to-be published study, Dr. Tuttle found that of about 400 thyroid cancer patients who received

Observe or Treat?

Another study involved 70 patients with thyroid cancer who had detectable Tg levels despite having a total thyroidectomy, RAI ablation, a negative whole body scan, and no structural evidence of disease. Of the 28 patients with a median stimulated Tg level of 9.5 ng/mL who were observed instead of being treated with RAI, 19 (68%) had an undetectable stimulated Tg level after 12 years of follow-up. Among the 42 patients with a median Tg level of 55 ng/mL who received RAI, only 12 (29%) had an undetectable stimulated Tg level after 7 years of follow-up (J. Clin. Endocrinol. Metab. 2001;86:4092–7).

Most patients who have undergone thyroidectomy and RAI ablation and have a negative whole body scan and a stimulated Tg level in the range of 2–10 ng/mL will see their Tg level decline to an undetectable level, so they probably should not be treated subsequently with RAI, Dr. Tuttle advised. It is likely that “if you do nothing, you are going to take credit for this thyroglobulin number going down over time all by itself.”

It is not necessary to treat patients with high Tg levels with two to three doses of RAI, he added. In a study of 17 patients with a negative initial whole body scan and an elevated Tg level, 16 patients had a positive scan after RAI therapy. During the course of three subsequent RAI doses, the percentage of patients with a decreasing Tg level increased from 81% to 90% to 100%, but the mean stimulated Tg level only decreased from 74 to 62 to 32 ng/mL, respectively (J. Clin. Endocrinol. Metab. 1995;80:1488–92).

Low Tg: RAI Probably Not Helpful

To determine if follow-up RAI therapy contributes to any changes in the stimulated Tg level of patients with an initial stimulated Tg level below 10 ng/mL, Dr. Tuttle conducted a study of 110 thyroid cancer patients who had Tg levels between 0.6 and 10 ng/mL and a negative whole body scan 1 year after receiving a total thyroidectomy and RAI ablation. At that point, 18 patients received repeat RAI therapy and 92 were observed.

After 1–2 years, stimulated Tg levels subsequently decreased in 71% and became undetectable in 29% of patients who had an initial stimulated Tg level between 0.6 and 2 ng/mL. In patients with an initial stimulated Tg level between 2 and 10 ng/mL, a significantly lower percentage of patients (3%) had an undetectable stimulated Tg level than those who had a decreased level (42%).

But among observed and RAI-treated patients with an initial stimulated Tg level between 2 and 10 ng/mL, there was no significant difference in the percentage of patients who had a reduction (40% vs. 45%, respectively), no change (12% vs. 18%), or an increase (48% vs. 37%) in their stimulated Tg level at follow-up.

There is no evidence that repeat RAI after negative whole body scan increases survival. DR. TUTTLE

CHANTILLY, VA. — Thyroid cancer patients who have received radioactive iodine ablation after thyroidectomy and who later have a negative whole body scan for thyroid cancer probably do not need to receive radioactive iodine therapy if their stimulated thyroglobulin levels stay below 10 ng/mL, Dr. R. Michael Tuttle said at the annual meeting of the Mid-Atlantic Chapter of the American Association of Clinical Endocrinologists.

Whether a patient with a very low stimulated thyroglobulin level should be treated again with radioactive iodine (RAI) “is probably one of the most common phone calls I get from around the country,” said Dr. Tuttle of Memorial Sloan-Kettering Cancer Center, New York.

The way thyroid cancer is treated today is “so remarkably different now than it was 10 or 15 years ago,” he said, adding that the detection of persistent thyroid cancer has improved to the point where thyroglobulin (Tg) levels of 1, 0.5, or 0.2 ng/mL can be detected and 3-mm lymph nodes in the tracheal-esophageal groove can be seen with ultrasound in patients who were thought to be cured 20 years ago.

“I can't tell you the number of patients who leave my office mad at me because I've explained to them that I cannot cure their thyroid cancer. Their thyroglobulin level of 0.3 ng/mL is probably going to be there for awhile and taking out that 2-mm lymph node beside their recurrent laryngeal nerve is probably only going to help the surgeon and pathologist because they can bill and code for it, and it is unlikely to help our patient.”

About 80% of full body scans after repeat administration of therapeutic RAI appear to show some uptake by thyroid cells in the neck, but about 40% of these may be lung metastases, based on experience with all forms of thyroid cancer. If physicians give 100–150 mCi of RAI to patients with a high Tg level but a negative body scan, “you're very likely to find real disease,” Dr. Tuttle said, “and I think it's that finding of the lung metastasis that made us all do this.”

Rationale for RAI Changes Over Time

One rationale for using a therapeutic level of RAI when stimulated Tg levels remain high despite a negative diagnostic whole body scan was to localize the disease, not necessarily to treat it, Dr. Tuttle pointed out. Today's imaging modalities of helical CT and PET scans and neck ultrasounds can give the same information that RAI scanning would, without the possibility of side effects.

There is no evidence that repeat RAI treatment for patients who have a high stimulated Tg level after an initially negative whole body scan increases disease-specific or overall survival, Dr. Tuttle said.

Most clinicians would give another course of therapeutic RAI if the stimulated Tg level rose above 10 ng/mL, and most would not use repeat RAI if the stimulated level was below 2 ng/mL. RAI treatment for Tg levels of less than 2 ng/mL offers little potential benefit, while potentially causing complications, including damage to salivary glands, taste buds, and tear ducts. “We don't know what to do between 2 and 10,” Dr. Tuttle said.

Multiple RAI treatments appear to clear small-volume papillary thyroid cancer from pediatric to 30-year-old patients with positive lymph nodes by consistently decreasing stimulated Tg levels and clearing evidence of the tumor on CT scans and x-rays. These patients, who do not have distant metastases, are either cured or go into long-term remissions.

But older patients with thyroid cancer extending beyond the thyroid are more commonly seen than are younger patients with less aggressive, localized disease. Older patients may have a negative whole body scan and the same level of Tg as a younger patient, but the tumor is likely to be visible in the lungs on x-ray, CT, and PET scans. RAI will not help these patients if the lung lesions are poorly differentiated.

In a soon-to-be published study, Dr. Tuttle found that of about 400 thyroid cancer patients who received

Observe or Treat?

Another study involved 70 patients with thyroid cancer who had detectable Tg levels despite having a total thyroidectomy, RAI ablation, a negative whole body scan, and no structural evidence of disease. Of the 28 patients with a median stimulated Tg level of 9.5 ng/mL who were observed instead of being treated with RAI, 19 (68%) had an undetectable stimulated Tg level after 12 years of follow-up. Among the 42 patients with a median Tg level of 55 ng/mL who received RAI, only 12 (29%) had an undetectable stimulated Tg level after 7 years of follow-up (J. Clin. Endocrinol. Metab. 2001;86:4092–7).

Most patients who have undergone thyroidectomy and RAI ablation and have a negative whole body scan and a stimulated Tg level in the range of 2–10 ng/mL will see their Tg level decline to an undetectable level, so they probably should not be treated subsequently with RAI, Dr. Tuttle advised. It is likely that “if you do nothing, you are going to take credit for this thyroglobulin number going down over time all by itself.”

It is not necessary to treat patients with high Tg levels with two to three doses of RAI, he added. In a study of 17 patients with a negative initial whole body scan and an elevated Tg level, 16 patients had a positive scan after RAI therapy. During the course of three subsequent RAI doses, the percentage of patients with a decreasing Tg level increased from 81% to 90% to 100%, but the mean stimulated Tg level only decreased from 74 to 62 to 32 ng/mL, respectively (J. Clin. Endocrinol. Metab. 1995;80:1488–92).

Low Tg: RAI Probably Not Helpful

To determine if follow-up RAI therapy contributes to any changes in the stimulated Tg level of patients with an initial stimulated Tg level below 10 ng/mL, Dr. Tuttle conducted a study of 110 thyroid cancer patients who had Tg levels between 0.6 and 10 ng/mL and a negative whole body scan 1 year after receiving a total thyroidectomy and RAI ablation. At that point, 18 patients received repeat RAI therapy and 92 were observed.

After 1–2 years, stimulated Tg levels subsequently decreased in 71% and became undetectable in 29% of patients who had an initial stimulated Tg level between 0.6 and 2 ng/mL. In patients with an initial stimulated Tg level between 2 and 10 ng/mL, a significantly lower percentage of patients (3%) had an undetectable stimulated Tg level than those who had a decreased level (42%).

But among observed and RAI-treated patients with an initial stimulated Tg level between 2 and 10 ng/mL, there was no significant difference in the percentage of patients who had a reduction (40% vs. 45%, respectively), no change (12% vs. 18%), or an increase (48% vs. 37%) in their stimulated Tg level at follow-up.

There is no evidence that repeat RAI after negative whole body scan increases survival. DR. TUTTLE

CHANTILLY, VA. — Thyroid cancer patients who have received radioactive iodine ablation after thyroidectomy and who later have a negative whole body scan for thyroid cancer probably do not need to receive radioactive iodine therapy if their stimulated thyroglobulin levels stay below 10 ng/mL, Dr. R. Michael Tuttle said at the annual meeting of the Mid-Atlantic Chapter of the American Association of Clinical Endocrinologists.

Whether a patient with a very low stimulated thyroglobulin level should be treated again with radioactive iodine (RAI) “is probably one of the most common phone calls I get from around the country,” said Dr. Tuttle of Memorial Sloan-Kettering Cancer Center, New York.

The way thyroid cancer is treated today is “so remarkably different now than it was 10 or 15 years ago,” he said, adding that the detection of persistent thyroid cancer has improved to the point where thyroglobulin (Tg) levels of 1, 0.5, or 0.2 ng/mL can be detected and 3-mm lymph nodes in the tracheal-esophageal groove can be seen with ultrasound in patients who were thought to be cured 20 years ago.

“I can't tell you the number of patients who leave my office mad at me because I've explained to them that I cannot cure their thyroid cancer. Their thyroglobulin level of 0.3 ng/mL is probably going to be there for awhile and taking out that 2-mm lymph node beside their recurrent laryngeal nerve is probably only going to help the surgeon and pathologist because they can bill and code for it, and it is unlikely to help our patient.”

About 80% of full body scans after repeat administration of therapeutic RAI appear to show some uptake by thyroid cells in the neck, but about 40% of these may be lung metastases, based on experience with all forms of thyroid cancer. If physicians give 100–150 mCi of RAI to patients with a high Tg level but a negative body scan, “you're very likely to find real disease,” Dr. Tuttle said, “and I think it's that finding of the lung metastasis that made us all do this.”

Rationale for RAI Changes Over Time

One rationale for using a therapeutic level of RAI when stimulated Tg levels remain high despite a negative diagnostic whole body scan was to localize the disease, not necessarily to treat it, Dr. Tuttle pointed out. Today's imaging modalities of helical CT and PET scans and neck ultrasounds can give the same information that RAI scanning would, without the possibility of side effects.

There is no evidence that repeat RAI treatment for patients who have a high stimulated Tg level after an initially negative whole body scan increases disease-specific or overall survival, Dr. Tuttle said.

Most clinicians would give another course of therapeutic RAI if the stimulated Tg level rose above 10 ng/mL, and most would not use repeat RAI if the stimulated level was below 2 ng/mL. RAI treatment for Tg levels of less than 2 ng/mL offers little potential benefit, while potentially causing complications, including damage to salivary glands, taste buds, and tear ducts. “We don't know what to do between 2 and 10,” Dr. Tuttle said.

Multiple RAI treatments appear to clear small-volume papillary thyroid cancer from pediatric to 30-year-old patients with positive lymph nodes by consistently decreasing stimulated Tg levels and clearing evidence of the tumor on CT scans and x-rays. These patients, who do not have distant metastases, are either cured or go into long-term remissions.

But older patients with thyroid cancer extending beyond the thyroid are more commonly seen than are younger patients with less aggressive, localized disease. Older patients may have a negative whole body scan and the same level of Tg as a younger patient, but the tumor is likely to be visible in the lungs on x-ray, CT, and PET scans. RAI will not help these patients if the lung lesions are poorly differentiated.

In a soon-to-be published study, Dr. Tuttle found that of about 400 thyroid cancer patients who received

Observe or Treat?

Another study involved 70 patients with thyroid cancer who had detectable Tg levels despite having a total thyroidectomy, RAI ablation, a negative whole body scan, and no structural evidence of disease. Of the 28 patients with a median stimulated Tg level of 9.5 ng/mL who were observed instead of being treated with RAI, 19 (68%) had an undetectable stimulated Tg level after 12 years of follow-up. Among the 42 patients with a median Tg level of 55 ng/mL who received RAI, only 12 (29%) had an undetectable stimulated Tg level after 7 years of follow-up (J. Clin. Endocrinol. Metab. 2001;86:4092–7).

Most patients who have undergone thyroidectomy and RAI ablation and have a negative whole body scan and a stimulated Tg level in the range of 2–10 ng/mL will see their Tg level decline to an undetectable level, so they probably should not be treated subsequently with RAI, Dr. Tuttle advised. It is likely that “if you do nothing, you are going to take credit for this thyroglobulin number going down over time all by itself.”

It is not necessary to treat patients with high Tg levels with two to three doses of RAI, he added. In a study of 17 patients with a negative initial whole body scan and an elevated Tg level, 16 patients had a positive scan after RAI therapy. During the course of three subsequent RAI doses, the percentage of patients with a decreasing Tg level increased from 81% to 90% to 100%, but the mean stimulated Tg level only decreased from 74 to 62 to 32 ng/mL, respectively (J. Clin. Endocrinol. Metab. 1995;80:1488–92).

Low Tg: RAI Probably Not Helpful

To determine if follow-up RAI therapy contributes to any changes in the stimulated Tg level of patients with an initial stimulated Tg level below 10 ng/mL, Dr. Tuttle conducted a study of 110 thyroid cancer patients who had Tg levels between 0.6 and 10 ng/mL and a negative whole body scan 1 year after receiving a total thyroidectomy and RAI ablation. At that point, 18 patients received repeat RAI therapy and 92 were observed.

After 1–2 years, stimulated Tg levels subsequently decreased in 71% and became undetectable in 29% of patients who had an initial stimulated Tg level between 0.6 and 2 ng/mL. In patients with an initial stimulated Tg level between 2 and 10 ng/mL, a significantly lower percentage of patients (3%) had an undetectable stimulated Tg level than those who had a decreased level (42%).

But among observed and RAI-treated patients with an initial stimulated Tg level between 2 and 10 ng/mL, there was no significant difference in the percentage of patients who had a reduction (40% vs. 45%, respectively), no change (12% vs. 18%), or an increase (48% vs. 37%) in their stimulated Tg level at follow-up.

There is no evidence that repeat RAI after negative whole body scan increases survival. DR. TUTTLE

BETHESDA, MD. — With timely diagnosis and treatment, the prognosis can be good for women with pheochromocytoma during pregnancy, Dr. Henri Timmers said at an international symposium on pheochromocytoma sponsored by the National Institutes of Health.

His conclusion, based on a literature review of more than 100 cases, also found that maternal morbidity is high when diagnosis is delayed, said Dr. Timmers, of the department of endocrinology, Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands.

Pheochromocytoma affects an estimated 1/50,000 full-term pregnancies and is associated with high maternal and fetal morbidity and mortality. Pheochromocytoma during pregnancy is often missed because it can mimic preeclampsia, delaying diagnosis and appropriate treatment.

Dr. Timmers and associates found a total of 174 reports of histology-confirmed cases of pheochromocytoma during pregnancy, in a PubMed database search for case reports in English. The mean age of the women was 28 years, 7% had previously been diagnosed with pheochromocytoma and 17% had been previously diagnosed with hypertension; 61% had been pregnant before and 14% had been previously diagnosed with pregnancy-induced hypertension.

In 73% of cases, the diagnosis of pheochromocytoma was made before delivery, with the remainder diagnosed postpartum (17%) or postmortem (10%).

Nearly 90% of the patients were hypertensive, but in only 42% of the cases was presentation typical for pheochromocytoma, where hypertension is usually accompanied by headache, palpitations, or sweating. In 25% of the cases, presentation was a hypertensive emergency, which included cases of severe pulmonary edema, Dr. Timmers said.

In 31% of the cases (54 patients), the initial diagnosis was incorrect, with almost half of the incorrectly diagnosed patients presenting with a severe cardiovascular complication, such as heart failure; of these 24 patients, 10 patients died. Fetal and neonatal mortality was 22%. Overall maternal mortality was about 14%, but it was markedly higher in different subgroups: It was 38% among the women who were incorrectly diagnosed and 49% among those with a cardiovascular emergency.

The biochemical test with the greatest diagnostic sensitivity was urinary metanephrines, with a sensitivity of 98%; the lowest sensitivity was for plasma catecholamines (91%). The sensitivity of MRI was 95%.

Surgery was performed either before 24 weeks' gestation or during a cesarean section in 69 patients. Surgery was performed post partum in 68.

During the discussion, moderator Dr. William Manger, chairman of the National Hypertension Association, New York, said pheochromocytoma, though rare, is devastating and should be routinely considered in pregnant women with hypertension.

BETHESDA, MD. — With timely diagnosis and treatment, the prognosis can be good for women with pheochromocytoma during pregnancy, Dr. Henri Timmers said at an international symposium on pheochromocytoma sponsored by the National Institutes of Health.

His conclusion, based on a literature review of more than 100 cases, also found that maternal morbidity is high when diagnosis is delayed, said Dr. Timmers, of the department of endocrinology, Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands.

Pheochromocytoma affects an estimated 1/50,000 full-term pregnancies and is associated with high maternal and fetal morbidity and mortality. Pheochromocytoma during pregnancy is often missed because it can mimic preeclampsia, delaying diagnosis and appropriate treatment.

Dr. Timmers and associates found a total of 174 reports of histology-confirmed cases of pheochromocytoma during pregnancy, in a PubMed database search for case reports in English. The mean age of the women was 28 years, 7% had previously been diagnosed with pheochromocytoma and 17% had been previously diagnosed with hypertension; 61% had been pregnant before and 14% had been previously diagnosed with pregnancy-induced hypertension.

In 73% of cases, the diagnosis of pheochromocytoma was made before delivery, with the remainder diagnosed postpartum (17%) or postmortem (10%).

Nearly 90% of the patients were hypertensive, but in only 42% of the cases was presentation typical for pheochromocytoma, where hypertension is usually accompanied by headache, palpitations, or sweating. In 25% of the cases, presentation was a hypertensive emergency, which included cases of severe pulmonary edema, Dr. Timmers said.

In 31% of the cases (54 patients), the initial diagnosis was incorrect, with almost half of the incorrectly diagnosed patients presenting with a severe cardiovascular complication, such as heart failure; of these 24 patients, 10 patients died. Fetal and neonatal mortality was 22%. Overall maternal mortality was about 14%, but it was markedly higher in different subgroups: It was 38% among the women who were incorrectly diagnosed and 49% among those with a cardiovascular emergency.

The biochemical test with the greatest diagnostic sensitivity was urinary metanephrines, with a sensitivity of 98%; the lowest sensitivity was for plasma catecholamines (91%). The sensitivity of MRI was 95%.

Surgery was performed either before 24 weeks' gestation or during a cesarean section in 69 patients. Surgery was performed post partum in 68.

During the discussion, moderator Dr. William Manger, chairman of the National Hypertension Association, New York, said pheochromocytoma, though rare, is devastating and should be routinely considered in pregnant women with hypertension.

BETHESDA, MD. — With timely diagnosis and treatment, the prognosis can be good for women with pheochromocytoma during pregnancy, Dr. Henri Timmers said at an international symposium on pheochromocytoma sponsored by the National Institutes of Health.

His conclusion, based on a literature review of more than 100 cases, also found that maternal morbidity is high when diagnosis is delayed, said Dr. Timmers, of the department of endocrinology, Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands.

Pheochromocytoma affects an estimated 1/50,000 full-term pregnancies and is associated with high maternal and fetal morbidity and mortality. Pheochromocytoma during pregnancy is often missed because it can mimic preeclampsia, delaying diagnosis and appropriate treatment.

Dr. Timmers and associates found a total of 174 reports of histology-confirmed cases of pheochromocytoma during pregnancy, in a PubMed database search for case reports in English. The mean age of the women was 28 years, 7% had previously been diagnosed with pheochromocytoma and 17% had been previously diagnosed with hypertension; 61% had been pregnant before and 14% had been previously diagnosed with pregnancy-induced hypertension.

In 73% of cases, the diagnosis of pheochromocytoma was made before delivery, with the remainder diagnosed postpartum (17%) or postmortem (10%).

Nearly 90% of the patients were hypertensive, but in only 42% of the cases was presentation typical for pheochromocytoma, where hypertension is usually accompanied by headache, palpitations, or sweating. In 25% of the cases, presentation was a hypertensive emergency, which included cases of severe pulmonary edema, Dr. Timmers said.

In 31% of the cases (54 patients), the initial diagnosis was incorrect, with almost half of the incorrectly diagnosed patients presenting with a severe cardiovascular complication, such as heart failure; of these 24 patients, 10 patients died. Fetal and neonatal mortality was 22%. Overall maternal mortality was about 14%, but it was markedly higher in different subgroups: It was 38% among the women who were incorrectly diagnosed and 49% among those with a cardiovascular emergency.

The biochemical test with the greatest diagnostic sensitivity was urinary metanephrines, with a sensitivity of 98%; the lowest sensitivity was for plasma catecholamines (91%). The sensitivity of MRI was 95%.

Surgery was performed either before 24 weeks' gestation or during a cesarean section in 69 patients. Surgery was performed post partum in 68.

During the discussion, moderator Dr. William Manger, chairman of the National Hypertension Association, New York, said pheochromocytoma, though rare, is devastating and should be routinely considered in pregnant women with hypertension.

MONTREAL — The addition of simvastatin to an oral contraceptive regimen significantly reduces hirsutism and elevated levels of total testosterone in women with polycystic ovary syndrome, according to a study conducted by Dr. Antoni J. Duleba of Yale University, New Haven, Conn., and associates.

“This is the first report that simvastatin improves a clinical end point of polycystic ovary syndrome/hirsutism,” Dr. Duleba, the lead investigator, said in an interview.

The data were presented by another investigator in the study, Dr. Beata Banaszewska, at the conjoint annual meeting of the American Society for Reproductive Medicine and the Canadian Fertility and Andrology Society.

Oral contraceptives “do reduce testosterone levels, but in this crossover study, we can appreciate that statins have a greater power to this effect,” said Dr. Banaszewska, of Poznan University of Medical Sciences in Poland.

PCOS affects 5%–10% of women of childbearing age, according to Dr. Duleba. Estimates of the annual cost of evaluation and care in the United States are about $4 billion. “Symptomatic treatments partly improve the situation, and long term, these patients are at increased risk of cardiovascular problems.”

The study randomized 48 PCOS patients (mean age 24 years) into two groups. One received oral contraceptives (OC) (20-mcg ethinyl estradiol and 150-mcg desogestrel) for 12 weeks. Then 20-mg simvastatin was added to their regimen daily for 12 more weeks.

The other group received the combined regimen for 12 weeks then was given OCs alone for 12 weeks. Clinical, endocrine, and metabolic evaluations were performed at baseline, at crossover (12 weeks), and at 24 weeks.

“Simvastatin decreased total testosterone by 18% below the effect of OCs,” Dr. Duleba said. “This effect was paralleled by a 16% decrease of free testosterone below the effect of OCs. We also found that the hirsutism declined, and there was a strong trend toward an improvement in acne, which did not reach statistical significance.”

A simvastatin-attributable decline of hirsutism was modestly but significantly greater than with OC alone; this 4% difference was statistically significant. “Patients were happy. … They did not want to stop therapy,” Dr. Duleba said.

“In PCOS, there is an abnormal hypothalamic-pituitary function characterized by elevated LH. It's usually measured by the ratio of LH to FSH, and we observed that statins also improved this ratio,” he added. Simvastatin, in comparison with OCs, decreased LH by 24% and the LH-FSH ratio by 22%.

Furthermore, simvastatin (as compared with OCs) decreased total cholesterol by 12%, LDL cholesterol by 21%, and triglycerides by 18%—preventing the OC-induced rise in triglycerides.

“So the statin not only normalized androgens, it also normalized hypothalamic-pituitary function. And of course, the statin improved lipid profiles,” Dr. Duleba said.

BMI was not significantly affected.

Kate Johnson contributed to this report.

'The statin not only normalized androgens, it also normalized hypothalamic-pituitary function.' DR. DULEBA

MONTREAL — The addition of simvastatin to an oral contraceptive regimen significantly reduces hirsutism and elevated levels of total testosterone in women with polycystic ovary syndrome, according to a study conducted by Dr. Antoni J. Duleba of Yale University, New Haven, Conn., and associates.

“This is the first report that simvastatin improves a clinical end point of polycystic ovary syndrome/hirsutism,” Dr. Duleba, the lead investigator, said in an interview.

The data were presented by another investigator in the study, Dr. Beata Banaszewska, at the conjoint annual meeting of the American Society for Reproductive Medicine and the Canadian Fertility and Andrology Society.

Oral contraceptives “do reduce testosterone levels, but in this crossover study, we can appreciate that statins have a greater power to this effect,” said Dr. Banaszewska, of Poznan University of Medical Sciences in Poland.

PCOS affects 5%–10% of women of childbearing age, according to Dr. Duleba. Estimates of the annual cost of evaluation and care in the United States are about $4 billion. “Symptomatic treatments partly improve the situation, and long term, these patients are at increased risk of cardiovascular problems.”

The study randomized 48 PCOS patients (mean age 24 years) into two groups. One received oral contraceptives (OC) (20-mcg ethinyl estradiol and 150-mcg desogestrel) for 12 weeks. Then 20-mg simvastatin was added to their regimen daily for 12 more weeks.

The other group received the combined regimen for 12 weeks then was given OCs alone for 12 weeks. Clinical, endocrine, and metabolic evaluations were performed at baseline, at crossover (12 weeks), and at 24 weeks.

“Simvastatin decreased total testosterone by 18% below the effect of OCs,” Dr. Duleba said. “This effect was paralleled by a 16% decrease of free testosterone below the effect of OCs. We also found that the hirsutism declined, and there was a strong trend toward an improvement in acne, which did not reach statistical significance.”

A simvastatin-attributable decline of hirsutism was modestly but significantly greater than with OC alone; this 4% difference was statistically significant. “Patients were happy. … They did not want to stop therapy,” Dr. Duleba said.

“In PCOS, there is an abnormal hypothalamic-pituitary function characterized by elevated LH. It's usually measured by the ratio of LH to FSH, and we observed that statins also improved this ratio,” he added. Simvastatin, in comparison with OCs, decreased LH by 24% and the LH-FSH ratio by 22%.

Furthermore, simvastatin (as compared with OCs) decreased total cholesterol by 12%, LDL cholesterol by 21%, and triglycerides by 18%—preventing the OC-induced rise in triglycerides.

“So the statin not only normalized androgens, it also normalized hypothalamic-pituitary function. And of course, the statin improved lipid profiles,” Dr. Duleba said.

BMI was not significantly affected.

Kate Johnson contributed to this report.

'The statin not only normalized androgens, it also normalized hypothalamic-pituitary function.' DR. DULEBA

MONTREAL — The addition of simvastatin to an oral contraceptive regimen significantly reduces hirsutism and elevated levels of total testosterone in women with polycystic ovary syndrome, according to a study conducted by Dr. Antoni J. Duleba of Yale University, New Haven, Conn., and associates.

“This is the first report that simvastatin improves a clinical end point of polycystic ovary syndrome/hirsutism,” Dr. Duleba, the lead investigator, said in an interview.

The data were presented by another investigator in the study, Dr. Beata Banaszewska, at the conjoint annual meeting of the American Society for Reproductive Medicine and the Canadian Fertility and Andrology Society.

Oral contraceptives “do reduce testosterone levels, but in this crossover study, we can appreciate that statins have a greater power to this effect,” said Dr. Banaszewska, of Poznan University of Medical Sciences in Poland.

PCOS affects 5%–10% of women of childbearing age, according to Dr. Duleba. Estimates of the annual cost of evaluation and care in the United States are about $4 billion. “Symptomatic treatments partly improve the situation, and long term, these patients are at increased risk of cardiovascular problems.”

The study randomized 48 PCOS patients (mean age 24 years) into two groups. One received oral contraceptives (OC) (20-mcg ethinyl estradiol and 150-mcg desogestrel) for 12 weeks. Then 20-mg simvastatin was added to their regimen daily for 12 more weeks.

The other group received the combined regimen for 12 weeks then was given OCs alone for 12 weeks. Clinical, endocrine, and metabolic evaluations were performed at baseline, at crossover (12 weeks), and at 24 weeks.

“Simvastatin decreased total testosterone by 18% below the effect of OCs,” Dr. Duleba said. “This effect was paralleled by a 16% decrease of free testosterone below the effect of OCs. We also found that the hirsutism declined, and there was a strong trend toward an improvement in acne, which did not reach statistical significance.”

A simvastatin-attributable decline of hirsutism was modestly but significantly greater than with OC alone; this 4% difference was statistically significant. “Patients were happy. … They did not want to stop therapy,” Dr. Duleba said.

“In PCOS, there is an abnormal hypothalamic-pituitary function characterized by elevated LH. It's usually measured by the ratio of LH to FSH, and we observed that statins also improved this ratio,” he added. Simvastatin, in comparison with OCs, decreased LH by 24% and the LH-FSH ratio by 22%.

Furthermore, simvastatin (as compared with OCs) decreased total cholesterol by 12%, LDL cholesterol by 21%, and triglycerides by 18%—preventing the OC-induced rise in triglycerides.

“So the statin not only normalized androgens, it also normalized hypothalamic-pituitary function. And of course, the statin improved lipid profiles,” Dr. Duleba said.

BMI was not significantly affected.

Kate Johnson contributed to this report.

'The statin not only normalized androgens, it also normalized hypothalamic-pituitary function.' DR. DULEBA

BETHESDA, MD. — Sustained, severe hypertension was among the clinical features of pheochromocytoma seen more frequently in patients under age 20, compared with adults, Dr. Marta Barontini said at an international symposium on pheochromocytoma sponsored by the National Institutes of Health.

Familial pheochromocytoma, mainly von Hippel-Lindau (VHL) disease, was also more common in the younger patients, “which may account for the noradrenergic profile” of their presenting symptoms, said Dr. Barontini of the center for endocrine research at the R. Gutiérrez Hospital for Children, Buenos Aires.

These findings were based on a review of 58 patients aged 4–20 (12 boys and 1 girl were younger than age 10; the rest were older), who represented 23% of the 255 pheochromocytoma patients studied at the endocrinology research center during a 40-year period. The purpose of the study was to establish clinical features of pheochromocytoma. Laboratory tests used to make the diagnosis, which was confirmed at the time of surgery, included urinary and plasma catecholamines (epinephrine, norepinephrine, and dopamine), as well as urinary levels of vanillylmandelic acid.

The differences between the clinical signs in the older patients at the center and those in the younger patients were “remarkable,” Dr. Barontini said. Sustained hypertension, headaches, and sweating were among the predominant characteristics seen in the younger patients: 93% had severe sustained hypertension, 7% had paroxysmal hypertension, and none was normotensive. Of the older patients, 69% had severe sustained hypertension, 26% had paroxysmal hypertension, and 5% were normotensive.

Other clinical signs often found in the younger patients were headaches in 95%, sweating in 90%, blurred vision in 80%, and encephalopathy in 65%. Palpitations, present in 35% of the younger patients, and weight loss, in 15%, were less common than they were in adults, she said.

Among the younger patients, 2% had normal norepinephrine levels, 55% had normal epinephrine levels, and 7% had normal urinary vanillylmandelic acid levels.

Of the patients under age 20, 34% had bilateral adrenal pheochromocytoma and 22% had extraadrenal pheochromocytoma. The incidence of both conditions was lower in the older patients.

Among the 58 younger patients, 7 (12%) had a malignant tumor, which was fatal in 4 patients: 1 patient died a few months after surgery and 3 died 8–18 years after surgery. The three patients still alive 5–21 years after surgery include one patient who has hypertension that is treated with four drugs. This patient also has high catecholamine levels and widespread bone metastases, but maintains a good quality of life, Dr. Barontini said.

Familial pheochromocytoma was identified in 36% of those younger than age 20, compared with 22% of the older patients. Genetic testing, which was performed in familial cases, found surprising differences.

VHL disease—an autosomal-dominant neoplasia disorder—had a higher prevalence in the younger population (28%), compared with that in the older patients. Multiple endocrine neoplasia (MEN) type 2a was identified in 2% of the younger patients, MEN type 2b in 2%, neurofibromatosis in 3%, and succinate dehydrogenase subunit B mutations in 2%.

In contrast, the most common mutation among the older patients with familial pheochromocytoma was MEN type 2a, in 15%. Dr. Barontini speculated that the higher incidence of VHL in the younger patients may account for the biochemical and clinical features—the noradrenergic profile—seen in this age group.

BETHESDA, MD. — Sustained, severe hypertension was among the clinical features of pheochromocytoma seen more frequently in patients under age 20, compared with adults, Dr. Marta Barontini said at an international symposium on pheochromocytoma sponsored by the National Institutes of Health.

Familial pheochromocytoma, mainly von Hippel-Lindau (VHL) disease, was also more common in the younger patients, “which may account for the noradrenergic profile” of their presenting symptoms, said Dr. Barontini of the center for endocrine research at the R. Gutiérrez Hospital for Children, Buenos Aires.

These findings were based on a review of 58 patients aged 4–20 (12 boys and 1 girl were younger than age 10; the rest were older), who represented 23% of the 255 pheochromocytoma patients studied at the endocrinology research center during a 40-year period. The purpose of the study was to establish clinical features of pheochromocytoma. Laboratory tests used to make the diagnosis, which was confirmed at the time of surgery, included urinary and plasma catecholamines (epinephrine, norepinephrine, and dopamine), as well as urinary levels of vanillylmandelic acid.

The differences between the clinical signs in the older patients at the center and those in the younger patients were “remarkable,” Dr. Barontini said. Sustained hypertension, headaches, and sweating were among the predominant characteristics seen in the younger patients: 93% had severe sustained hypertension, 7% had paroxysmal hypertension, and none was normotensive. Of the older patients, 69% had severe sustained hypertension, 26% had paroxysmal hypertension, and 5% were normotensive.

Other clinical signs often found in the younger patients were headaches in 95%, sweating in 90%, blurred vision in 80%, and encephalopathy in 65%. Palpitations, present in 35% of the younger patients, and weight loss, in 15%, were less common than they were in adults, she said.

Among the younger patients, 2% had normal norepinephrine levels, 55% had normal epinephrine levels, and 7% had normal urinary vanillylmandelic acid levels.

Of the patients under age 20, 34% had bilateral adrenal pheochromocytoma and 22% had extraadrenal pheochromocytoma. The incidence of both conditions was lower in the older patients.

Among the 58 younger patients, 7 (12%) had a malignant tumor, which was fatal in 4 patients: 1 patient died a few months after surgery and 3 died 8–18 years after surgery. The three patients still alive 5–21 years after surgery include one patient who has hypertension that is treated with four drugs. This patient also has high catecholamine levels and widespread bone metastases, but maintains a good quality of life, Dr. Barontini said.

Familial pheochromocytoma was identified in 36% of those younger than age 20, compared with 22% of the older patients. Genetic testing, which was performed in familial cases, found surprising differences.

VHL disease—an autosomal-dominant neoplasia disorder—had a higher prevalence in the younger population (28%), compared with that in the older patients. Multiple endocrine neoplasia (MEN) type 2a was identified in 2% of the younger patients, MEN type 2b in 2%, neurofibromatosis in 3%, and succinate dehydrogenase subunit B mutations in 2%.

In contrast, the most common mutation among the older patients with familial pheochromocytoma was MEN type 2a, in 15%. Dr. Barontini speculated that the higher incidence of VHL in the younger patients may account for the biochemical and clinical features—the noradrenergic profile—seen in this age group.

BETHESDA, MD. — Sustained, severe hypertension was among the clinical features of pheochromocytoma seen more frequently in patients under age 20, compared with adults, Dr. Marta Barontini said at an international symposium on pheochromocytoma sponsored by the National Institutes of Health.

Familial pheochromocytoma, mainly von Hippel-Lindau (VHL) disease, was also more common in the younger patients, “which may account for the noradrenergic profile” of their presenting symptoms, said Dr. Barontini of the center for endocrine research at the R. Gutiérrez Hospital for Children, Buenos Aires.

These findings were based on a review of 58 patients aged 4–20 (12 boys and 1 girl were younger than age 10; the rest were older), who represented 23% of the 255 pheochromocytoma patients studied at the endocrinology research center during a 40-year period. The purpose of the study was to establish clinical features of pheochromocytoma. Laboratory tests used to make the diagnosis, which was confirmed at the time of surgery, included urinary and plasma catecholamines (epinephrine, norepinephrine, and dopamine), as well as urinary levels of vanillylmandelic acid.

The differences between the clinical signs in the older patients at the center and those in the younger patients were “remarkable,” Dr. Barontini said. Sustained hypertension, headaches, and sweating were among the predominant characteristics seen in the younger patients: 93% had severe sustained hypertension, 7% had paroxysmal hypertension, and none was normotensive. Of the older patients, 69% had severe sustained hypertension, 26% had paroxysmal hypertension, and 5% were normotensive.

Other clinical signs often found in the younger patients were headaches in 95%, sweating in 90%, blurred vision in 80%, and encephalopathy in 65%. Palpitations, present in 35% of the younger patients, and weight loss, in 15%, were less common than they were in adults, she said.

Among the younger patients, 2% had normal norepinephrine levels, 55% had normal epinephrine levels, and 7% had normal urinary vanillylmandelic acid levels.

Of the patients under age 20, 34% had bilateral adrenal pheochromocytoma and 22% had extraadrenal pheochromocytoma. The incidence of both conditions was lower in the older patients.

Among the 58 younger patients, 7 (12%) had a malignant tumor, which was fatal in 4 patients: 1 patient died a few months after surgery and 3 died 8–18 years after surgery. The three patients still alive 5–21 years after surgery include one patient who has hypertension that is treated with four drugs. This patient also has high catecholamine levels and widespread bone metastases, but maintains a good quality of life, Dr. Barontini said.

Familial pheochromocytoma was identified in 36% of those younger than age 20, compared with 22% of the older patients. Genetic testing, which was performed in familial cases, found surprising differences.

VHL disease—an autosomal-dominant neoplasia disorder—had a higher prevalence in the younger population (28%), compared with that in the older patients. Multiple endocrine neoplasia (MEN) type 2a was identified in 2% of the younger patients, MEN type 2b in 2%, neurofibromatosis in 3%, and succinate dehydrogenase subunit B mutations in 2%.

In contrast, the most common mutation among the older patients with familial pheochromocytoma was MEN type 2a, in 15%. Dr. Barontini speculated that the higher incidence of VHL in the younger patients may account for the biochemical and clinical features—the noradrenergic profile—seen in this age group.