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Moderate THST linked to improved survival in thyroid cancer
CORONADO, CALIF.– In an analysis of primary treatments for all stages of differentiated thyroid carcinoma, only thyroid hormone suppressive therapy was associated with both improved overall survival and disease-free survival.
Further, when examining the degree of thyroid hormone suppressive therapy (THST), aggressive THST conferred no additional survival benefit when compared with moderate THST, even when limiting the analysis to patients with distant metastatic disease, results from a long-term analysis of registry showed.
Those are key findings from an updated analysis of data from the National Thyroid Cancer Treatment Cooperative Study Group Registry, which were presented by lead study author Dr. Aubrey Carhill during the annual meeting of the American Thyroid Association.
“To date there are no prospective studies evaluating the longitudinal outcomes of initial long-term therapies in differentiated thyroid carcinoma,” said Dr. Carhill of MD Anderson Cancer Center, Houston. “In the absence of prospective trials, there has been significant reliance on retrospective studies with limited numbers of patients and low event rates as well as significant reliance on expert opinion to guide clinical practice.”
For example, current ATA guidelines for TSH suppression suggest that in long-term follow-up of patients with differentiated thyroid cancer, “those with persistent disease should have TSH levels suppressed to undetectable levels and maintained indefinitely,” Dr. Carhill said, while disease-free, higher-risk patients “should be suppressed to low-moderate levels continued between 5 and 10 years and low-risk patients should be maintained in the low-normal range. Similar levels of evidence exist to support the use of radioactive iodine and the degree of surgical extent.”
The challenge for clinicians, she continued, becomes balancing the potential risks of more aggressive therapies, such as aggressive thyroid hormone suppression, and the risks associated with long-term thyrotoxicosis with the potential benefits of treatment. “This is not always clear, especially in patients who are at very low risk for cancer-specific mortality,” she said. “There remains a need for accurate prognostication in order to identify which patients will benefit from different treatment modalities because current staging systems have limited ability to predict response to treatment.”
Formed in 1987, the National Thyroid Treatment Cooperative Study Group is a multi-institutional effort to assess long-term management of outcomes on patients with differentiated thyroid cancer. The purpose of the present study was to provide a more current analysis of the prospectively collected data, which was last analyzed in 2001. All staging is tracked according to the registry’s staging system, which is very similar to that of the American Joint Committee on Cancer’s TNM Staging System. Therapies analyzed included total/near total thyroidectomy (T/NTT) vs. a lesser extent of surgery; radioactive iodine (RAI) vs. no RAI; and increasing degrees of THST over time.
Dr. Carhill presented findings from an analysis of the effects of initial therapies in 4,941 patients treated at 11 centers in North America between 1987 and 2012. The median length of follow-up was 6 years, which translated to 34,631 person-years of documented follow-up time. The researchers used univariate and multivariate analyses to assess overall and disease-free survival. Moderate THST was defined as TSH maintained in subnormal or normal levels, while aggressive THST was defined as that maintained in undetectable or subnormal levels.
Improved overall survival was observed in stage III patients who received RAI (risk ratio, 0.66; P = .04) and in stage IV patients who received T/NTT and RAI (RR, 0.66 and 0.70, respectively; combined P = .049). Moderate but not aggressive THST was associated with significantly improved overall survival in all stages (RR, 0.13 in stage I, 0.09 in stage II, 0.13 in stage III, and 0.33 in stage IV), as well as with improved disease-free survival (RR, 0.52 in stage I, 0.40 in stage II, 0.18 in stage III, and no RR in stage IV).
In stage I patients, RAI conferred worse disease-free survival (RR, 1.79; P = .0005). “However, further propensity analysis demonstrated that there was no difference in disease-free survival when patients were stratified according to their propensity to receive radioactive iodine,” Dr. Carhill said.
To evaluate the optimal duration of THST, the researchers examined the effect of continuing degrees of suppression beyond 1, 3, and 5 years of follow-up. After 1 and 3 years of follow-up, both initial stage and moderate TSH suppression were independently predictive of improved overall survival (RR, 0.31 and 0.29, respectively). However, after 5 years of follow-up, “although initial stage remained independently predictive, there was no further benefit with any subsequent degree of TSH suppression,” Dr. Carhill said.
The study “confirms prior registry findings of a survival benefit in high-risk groups treated with T/NTT and RAI, and there is no disease-free survival benefit in low-risk groups receiving postoperative RAI,” she concluded. “We also report for the first time that in multivariate analysis of primary treatments for DTC [differentiated thyroid cancer], in all stages, only THST was associated with both improved overall survival and disease-free survival. When examining the degree of THST, aggressive THST confers no additional survival advantage as compared with moderate THST, even in patients with distant metastatic disease, which remains particularly relevant given the risks associated with long-term thyrotoxicosis.” She acknowledged certain limitations of the study, including the potential for institutional bias. “However, we feel that this is somewhat offset due to the size of the registry cohort and the number of sites involved” Dr. Carhill said.
The registry has received support from Genzyme and Pfizer. Dr. Carhill reported having no financial disclosures.
On Twitter @dougbrunk
CORONADO, CALIF.– In an analysis of primary treatments for all stages of differentiated thyroid carcinoma, only thyroid hormone suppressive therapy was associated with both improved overall survival and disease-free survival.
Further, when examining the degree of thyroid hormone suppressive therapy (THST), aggressive THST conferred no additional survival benefit when compared with moderate THST, even when limiting the analysis to patients with distant metastatic disease, results from a long-term analysis of registry showed.
Those are key findings from an updated analysis of data from the National Thyroid Cancer Treatment Cooperative Study Group Registry, which were presented by lead study author Dr. Aubrey Carhill during the annual meeting of the American Thyroid Association.
“To date there are no prospective studies evaluating the longitudinal outcomes of initial long-term therapies in differentiated thyroid carcinoma,” said Dr. Carhill of MD Anderson Cancer Center, Houston. “In the absence of prospective trials, there has been significant reliance on retrospective studies with limited numbers of patients and low event rates as well as significant reliance on expert opinion to guide clinical practice.”
For example, current ATA guidelines for TSH suppression suggest that in long-term follow-up of patients with differentiated thyroid cancer, “those with persistent disease should have TSH levels suppressed to undetectable levels and maintained indefinitely,” Dr. Carhill said, while disease-free, higher-risk patients “should be suppressed to low-moderate levels continued between 5 and 10 years and low-risk patients should be maintained in the low-normal range. Similar levels of evidence exist to support the use of radioactive iodine and the degree of surgical extent.”
The challenge for clinicians, she continued, becomes balancing the potential risks of more aggressive therapies, such as aggressive thyroid hormone suppression, and the risks associated with long-term thyrotoxicosis with the potential benefits of treatment. “This is not always clear, especially in patients who are at very low risk for cancer-specific mortality,” she said. “There remains a need for accurate prognostication in order to identify which patients will benefit from different treatment modalities because current staging systems have limited ability to predict response to treatment.”
Formed in 1987, the National Thyroid Treatment Cooperative Study Group is a multi-institutional effort to assess long-term management of outcomes on patients with differentiated thyroid cancer. The purpose of the present study was to provide a more current analysis of the prospectively collected data, which was last analyzed in 2001. All staging is tracked according to the registry’s staging system, which is very similar to that of the American Joint Committee on Cancer’s TNM Staging System. Therapies analyzed included total/near total thyroidectomy (T/NTT) vs. a lesser extent of surgery; radioactive iodine (RAI) vs. no RAI; and increasing degrees of THST over time.
Dr. Carhill presented findings from an analysis of the effects of initial therapies in 4,941 patients treated at 11 centers in North America between 1987 and 2012. The median length of follow-up was 6 years, which translated to 34,631 person-years of documented follow-up time. The researchers used univariate and multivariate analyses to assess overall and disease-free survival. Moderate THST was defined as TSH maintained in subnormal or normal levels, while aggressive THST was defined as that maintained in undetectable or subnormal levels.
Improved overall survival was observed in stage III patients who received RAI (risk ratio, 0.66; P = .04) and in stage IV patients who received T/NTT and RAI (RR, 0.66 and 0.70, respectively; combined P = .049). Moderate but not aggressive THST was associated with significantly improved overall survival in all stages (RR, 0.13 in stage I, 0.09 in stage II, 0.13 in stage III, and 0.33 in stage IV), as well as with improved disease-free survival (RR, 0.52 in stage I, 0.40 in stage II, 0.18 in stage III, and no RR in stage IV).
In stage I patients, RAI conferred worse disease-free survival (RR, 1.79; P = .0005). “However, further propensity analysis demonstrated that there was no difference in disease-free survival when patients were stratified according to their propensity to receive radioactive iodine,” Dr. Carhill said.
To evaluate the optimal duration of THST, the researchers examined the effect of continuing degrees of suppression beyond 1, 3, and 5 years of follow-up. After 1 and 3 years of follow-up, both initial stage and moderate TSH suppression were independently predictive of improved overall survival (RR, 0.31 and 0.29, respectively). However, after 5 years of follow-up, “although initial stage remained independently predictive, there was no further benefit with any subsequent degree of TSH suppression,” Dr. Carhill said.
The study “confirms prior registry findings of a survival benefit in high-risk groups treated with T/NTT and RAI, and there is no disease-free survival benefit in low-risk groups receiving postoperative RAI,” she concluded. “We also report for the first time that in multivariate analysis of primary treatments for DTC [differentiated thyroid cancer], in all stages, only THST was associated with both improved overall survival and disease-free survival. When examining the degree of THST, aggressive THST confers no additional survival advantage as compared with moderate THST, even in patients with distant metastatic disease, which remains particularly relevant given the risks associated with long-term thyrotoxicosis.” She acknowledged certain limitations of the study, including the potential for institutional bias. “However, we feel that this is somewhat offset due to the size of the registry cohort and the number of sites involved” Dr. Carhill said.
The registry has received support from Genzyme and Pfizer. Dr. Carhill reported having no financial disclosures.
On Twitter @dougbrunk
CORONADO, CALIF.– In an analysis of primary treatments for all stages of differentiated thyroid carcinoma, only thyroid hormone suppressive therapy was associated with both improved overall survival and disease-free survival.
Further, when examining the degree of thyroid hormone suppressive therapy (THST), aggressive THST conferred no additional survival benefit when compared with moderate THST, even when limiting the analysis to patients with distant metastatic disease, results from a long-term analysis of registry showed.
Those are key findings from an updated analysis of data from the National Thyroid Cancer Treatment Cooperative Study Group Registry, which were presented by lead study author Dr. Aubrey Carhill during the annual meeting of the American Thyroid Association.
“To date there are no prospective studies evaluating the longitudinal outcomes of initial long-term therapies in differentiated thyroid carcinoma,” said Dr. Carhill of MD Anderson Cancer Center, Houston. “In the absence of prospective trials, there has been significant reliance on retrospective studies with limited numbers of patients and low event rates as well as significant reliance on expert opinion to guide clinical practice.”
For example, current ATA guidelines for TSH suppression suggest that in long-term follow-up of patients with differentiated thyroid cancer, “those with persistent disease should have TSH levels suppressed to undetectable levels and maintained indefinitely,” Dr. Carhill said, while disease-free, higher-risk patients “should be suppressed to low-moderate levels continued between 5 and 10 years and low-risk patients should be maintained in the low-normal range. Similar levels of evidence exist to support the use of radioactive iodine and the degree of surgical extent.”
The challenge for clinicians, she continued, becomes balancing the potential risks of more aggressive therapies, such as aggressive thyroid hormone suppression, and the risks associated with long-term thyrotoxicosis with the potential benefits of treatment. “This is not always clear, especially in patients who are at very low risk for cancer-specific mortality,” she said. “There remains a need for accurate prognostication in order to identify which patients will benefit from different treatment modalities because current staging systems have limited ability to predict response to treatment.”
Formed in 1987, the National Thyroid Treatment Cooperative Study Group is a multi-institutional effort to assess long-term management of outcomes on patients with differentiated thyroid cancer. The purpose of the present study was to provide a more current analysis of the prospectively collected data, which was last analyzed in 2001. All staging is tracked according to the registry’s staging system, which is very similar to that of the American Joint Committee on Cancer’s TNM Staging System. Therapies analyzed included total/near total thyroidectomy (T/NTT) vs. a lesser extent of surgery; radioactive iodine (RAI) vs. no RAI; and increasing degrees of THST over time.
Dr. Carhill presented findings from an analysis of the effects of initial therapies in 4,941 patients treated at 11 centers in North America between 1987 and 2012. The median length of follow-up was 6 years, which translated to 34,631 person-years of documented follow-up time. The researchers used univariate and multivariate analyses to assess overall and disease-free survival. Moderate THST was defined as TSH maintained in subnormal or normal levels, while aggressive THST was defined as that maintained in undetectable or subnormal levels.
Improved overall survival was observed in stage III patients who received RAI (risk ratio, 0.66; P = .04) and in stage IV patients who received T/NTT and RAI (RR, 0.66 and 0.70, respectively; combined P = .049). Moderate but not aggressive THST was associated with significantly improved overall survival in all stages (RR, 0.13 in stage I, 0.09 in stage II, 0.13 in stage III, and 0.33 in stage IV), as well as with improved disease-free survival (RR, 0.52 in stage I, 0.40 in stage II, 0.18 in stage III, and no RR in stage IV).
In stage I patients, RAI conferred worse disease-free survival (RR, 1.79; P = .0005). “However, further propensity analysis demonstrated that there was no difference in disease-free survival when patients were stratified according to their propensity to receive radioactive iodine,” Dr. Carhill said.
To evaluate the optimal duration of THST, the researchers examined the effect of continuing degrees of suppression beyond 1, 3, and 5 years of follow-up. After 1 and 3 years of follow-up, both initial stage and moderate TSH suppression were independently predictive of improved overall survival (RR, 0.31 and 0.29, respectively). However, after 5 years of follow-up, “although initial stage remained independently predictive, there was no further benefit with any subsequent degree of TSH suppression,” Dr. Carhill said.
The study “confirms prior registry findings of a survival benefit in high-risk groups treated with T/NTT and RAI, and there is no disease-free survival benefit in low-risk groups receiving postoperative RAI,” she concluded. “We also report for the first time that in multivariate analysis of primary treatments for DTC [differentiated thyroid cancer], in all stages, only THST was associated with both improved overall survival and disease-free survival. When examining the degree of THST, aggressive THST confers no additional survival advantage as compared with moderate THST, even in patients with distant metastatic disease, which remains particularly relevant given the risks associated with long-term thyrotoxicosis.” She acknowledged certain limitations of the study, including the potential for institutional bias. “However, we feel that this is somewhat offset due to the size of the registry cohort and the number of sites involved” Dr. Carhill said.
The registry has received support from Genzyme and Pfizer. Dr. Carhill reported having no financial disclosures.
On Twitter @dougbrunk
AT THE ATA ANNUAL MEETING
Key clinical point: Only moderate thyroid hormone suppressive therapy is associated with better outcomes in all stages of differentiated thyroid cancer.
Major finding: Moderate, but not aggressive, THST was linked with significantly improved overall survival in all stages of differentiated thyroid cancer (RR, .13 in stage I, .09 in stage II, .13 in stage III, and .33 in stage IV).
Data source: An analysis of the effects of initial therapies in 4,941 patients from the National Thyroid Cancer Treatment Cooperative Study Group Registry who were treated at 11 centers in North America between 1987 and 2012.
Disclosures:The registry has received support from Genzyme and Pfizer. Dr. Carhill reported having no financial disclosures.
No survival benefit of RAI seen in early-stage thyroid cancer
CORONADO, CALIF. – In a large cohort of patients with differentiated thyroid cancer, the use of radioactive iodine was associated with improved disease-specific survival in those with advanced disease but not in those with papillary thyroid microcarcinoma.
“Everything in medicine is a risk-benefit balance,” lead author Dr. Ryan K. Orosco said in an interview in advance of the annual meeting of the American Thyroid Association, where the work was presented. “Any two patients that receive radioactive iodine (RAI) for differentiated thyroid cancer are likely to have different survival benefit from that therapy. This study provides a quantitative comparison of the impact of RAI in various patient subgroups.”
In one of the largest studies of its kind, Dr. Orosco of the division of head and neck surgery at the University of California, San Diego, and his associates identified 85,740 patients with differentiated thyroid carcinoma from the Surveillance, Epidemiology, and End Results database from 1973 through 2009. They used multivariate analyses to explore the association between RAI and cancer-specific survival in 149 population subgroups, controlling for age, decade of diagnosis, race, gender, tumor type, nodal involvement, metastasis stage, and RAI therapy.
More than three-quarters of the patients (78%) were female, 68% were white, their mean age at diagnosis was 46 years, and the median follow-up time was 85 months. The researchers found that nearly half of patients (43%) received RAI. By American Joint Committee on Cancer stage, RAI was used in 55% of stage I patients, 41% of stage II patients, 94% of stage III patients, and 85% of stage IV patients. In addition, 42% of patients with T1a disease and 88% of those with T4 disease received RAI.
Use of RAI was positively associated with survival in the overall cohort (hazard ratio 1.3; P = .002), while statistically significant HRs for RAI were observed in 49 population subgroups. In patients with metastatic disease, use of RAI was associated with a decreased risk for disease-specific mortality (HR range of 2.28-3.82). Protective effects of RAI were also observed in patients with regional metastases (HR 1.4-1.9), those with T3-positive tumors (HR 1.36-1.39), those with T4 tumors (HR 1.85), and in those with stage IV disease (HR 1.47-1.73).
Dr. Orosco and his associates observed a negative effect of RAI in patients with macropapillary carcinoma. Specifically, those with T1a disease had an increased likelihood of thyroid cancer–specific mortality (HR .13; P less than .001), while similar associations were seen in multiple subgroups of patients with T1a disease (HR 0.04-0.25). No statistically significant effects of RAI were observed in patients with T1b or T2 tumors.
“RAI appears to offer the best survival impact in patients with advanced differentiated thyroid carcinoma,” Dr. Orosco said. “Its use in early-stage patients should be carefully considered.”
In their abstract, the researchers noted that the findings “might help clinicians personalize RAI therapy to specific differentiated thyroid cancer populations – offering treatment in patients most likely to benefit, and sparing others unnecessary costs and potential side effects.”
Dr. Orosco acknowledged certain limitations of the study, including the fact that the SEER database does not contain details about each patient’s surgery, the dose of RAI used, other comorbidities, or data on cancer recurrence. “This study does not attempt to explore the reasons behind the apparent survival disadvantage seen in patients with T1a disease,” he said. “We don’t know exactly why early-stage patients have an increased risk of disease-specific mortality when RAI is used. Additional work is needed to explore this further.”
Dr. Orosco reported having no financial disclosures.
On Twitter @dougbrunk
CORONADO, CALIF. – In a large cohort of patients with differentiated thyroid cancer, the use of radioactive iodine was associated with improved disease-specific survival in those with advanced disease but not in those with papillary thyroid microcarcinoma.
“Everything in medicine is a risk-benefit balance,” lead author Dr. Ryan K. Orosco said in an interview in advance of the annual meeting of the American Thyroid Association, where the work was presented. “Any two patients that receive radioactive iodine (RAI) for differentiated thyroid cancer are likely to have different survival benefit from that therapy. This study provides a quantitative comparison of the impact of RAI in various patient subgroups.”
In one of the largest studies of its kind, Dr. Orosco of the division of head and neck surgery at the University of California, San Diego, and his associates identified 85,740 patients with differentiated thyroid carcinoma from the Surveillance, Epidemiology, and End Results database from 1973 through 2009. They used multivariate analyses to explore the association between RAI and cancer-specific survival in 149 population subgroups, controlling for age, decade of diagnosis, race, gender, tumor type, nodal involvement, metastasis stage, and RAI therapy.
More than three-quarters of the patients (78%) were female, 68% were white, their mean age at diagnosis was 46 years, and the median follow-up time was 85 months. The researchers found that nearly half of patients (43%) received RAI. By American Joint Committee on Cancer stage, RAI was used in 55% of stage I patients, 41% of stage II patients, 94% of stage III patients, and 85% of stage IV patients. In addition, 42% of patients with T1a disease and 88% of those with T4 disease received RAI.
Use of RAI was positively associated with survival in the overall cohort (hazard ratio 1.3; P = .002), while statistically significant HRs for RAI were observed in 49 population subgroups. In patients with metastatic disease, use of RAI was associated with a decreased risk for disease-specific mortality (HR range of 2.28-3.82). Protective effects of RAI were also observed in patients with regional metastases (HR 1.4-1.9), those with T3-positive tumors (HR 1.36-1.39), those with T4 tumors (HR 1.85), and in those with stage IV disease (HR 1.47-1.73).
Dr. Orosco and his associates observed a negative effect of RAI in patients with macropapillary carcinoma. Specifically, those with T1a disease had an increased likelihood of thyroid cancer–specific mortality (HR .13; P less than .001), while similar associations were seen in multiple subgroups of patients with T1a disease (HR 0.04-0.25). No statistically significant effects of RAI were observed in patients with T1b or T2 tumors.
“RAI appears to offer the best survival impact in patients with advanced differentiated thyroid carcinoma,” Dr. Orosco said. “Its use in early-stage patients should be carefully considered.”
In their abstract, the researchers noted that the findings “might help clinicians personalize RAI therapy to specific differentiated thyroid cancer populations – offering treatment in patients most likely to benefit, and sparing others unnecessary costs and potential side effects.”
Dr. Orosco acknowledged certain limitations of the study, including the fact that the SEER database does not contain details about each patient’s surgery, the dose of RAI used, other comorbidities, or data on cancer recurrence. “This study does not attempt to explore the reasons behind the apparent survival disadvantage seen in patients with T1a disease,” he said. “We don’t know exactly why early-stage patients have an increased risk of disease-specific mortality when RAI is used. Additional work is needed to explore this further.”
Dr. Orosco reported having no financial disclosures.
On Twitter @dougbrunk
CORONADO, CALIF. – In a large cohort of patients with differentiated thyroid cancer, the use of radioactive iodine was associated with improved disease-specific survival in those with advanced disease but not in those with papillary thyroid microcarcinoma.
“Everything in medicine is a risk-benefit balance,” lead author Dr. Ryan K. Orosco said in an interview in advance of the annual meeting of the American Thyroid Association, where the work was presented. “Any two patients that receive radioactive iodine (RAI) for differentiated thyroid cancer are likely to have different survival benefit from that therapy. This study provides a quantitative comparison of the impact of RAI in various patient subgroups.”
In one of the largest studies of its kind, Dr. Orosco of the division of head and neck surgery at the University of California, San Diego, and his associates identified 85,740 patients with differentiated thyroid carcinoma from the Surveillance, Epidemiology, and End Results database from 1973 through 2009. They used multivariate analyses to explore the association between RAI and cancer-specific survival in 149 population subgroups, controlling for age, decade of diagnosis, race, gender, tumor type, nodal involvement, metastasis stage, and RAI therapy.
More than three-quarters of the patients (78%) were female, 68% were white, their mean age at diagnosis was 46 years, and the median follow-up time was 85 months. The researchers found that nearly half of patients (43%) received RAI. By American Joint Committee on Cancer stage, RAI was used in 55% of stage I patients, 41% of stage II patients, 94% of stage III patients, and 85% of stage IV patients. In addition, 42% of patients with T1a disease and 88% of those with T4 disease received RAI.
Use of RAI was positively associated with survival in the overall cohort (hazard ratio 1.3; P = .002), while statistically significant HRs for RAI were observed in 49 population subgroups. In patients with metastatic disease, use of RAI was associated with a decreased risk for disease-specific mortality (HR range of 2.28-3.82). Protective effects of RAI were also observed in patients with regional metastases (HR 1.4-1.9), those with T3-positive tumors (HR 1.36-1.39), those with T4 tumors (HR 1.85), and in those with stage IV disease (HR 1.47-1.73).
Dr. Orosco and his associates observed a negative effect of RAI in patients with macropapillary carcinoma. Specifically, those with T1a disease had an increased likelihood of thyroid cancer–specific mortality (HR .13; P less than .001), while similar associations were seen in multiple subgroups of patients with T1a disease (HR 0.04-0.25). No statistically significant effects of RAI were observed in patients with T1b or T2 tumors.
“RAI appears to offer the best survival impact in patients with advanced differentiated thyroid carcinoma,” Dr. Orosco said. “Its use in early-stage patients should be carefully considered.”
In their abstract, the researchers noted that the findings “might help clinicians personalize RAI therapy to specific differentiated thyroid cancer populations – offering treatment in patients most likely to benefit, and sparing others unnecessary costs and potential side effects.”
Dr. Orosco acknowledged certain limitations of the study, including the fact that the SEER database does not contain details about each patient’s surgery, the dose of RAI used, other comorbidities, or data on cancer recurrence. “This study does not attempt to explore the reasons behind the apparent survival disadvantage seen in patients with T1a disease,” he said. “We don’t know exactly why early-stage patients have an increased risk of disease-specific mortality when RAI is used. Additional work is needed to explore this further.”
Dr. Orosco reported having no financial disclosures.
On Twitter @dougbrunk
AT THE ATA ANNUAL MEETING
Key clinical point: Radioactive iodine appears to offer the best survival impact in patients with advanced differentiated thyroid carcinoma.
Major finding: In patients with metastatic disease, use of RAI was associated with a decreased risk for disease-specific mortality (HR range of 2.28-3.82). However, those with T1a disease had an increased likelihood of thyroid cancer-specific mortality (HR .13; P less than .001), while similar associations were seen in multiple subgroups of patients with T1a disease (HR .04-.25).
Data source: An analysis of 85,740 patients with differentiated thyroid carcinoma from the Surveillance, Epidemiology, and End Results database from 1973 through 2009.
Disclosures: Dr. Orosco reported having no financial disclosures.
Anticoagulants sharply increase hematoma risk after thyroid, parathyroid surgery
SAN FRANCISCO – Patients undergoing thyroid or parathyroid surgery have a sharply higher risk of postoperative hematoma if they are on clopidogrel or anticoagulants – even if these agents are stopped in advance – researchers reported at the annual clinical congress of the American College of Surgeons.
“Patients with multiple factors considered high risk for postoperative hematoma formation after parathyroid or thyroid surgery should probably undergo a period of observation,” recommended lead investigator Dr. Sarah C. Oltmann, who at the time of the study was the director of endocrine surgery at Parkland Memorial Hospital, University of Texas Southwestern Medical Center, Dallas.
“The need specifically for anticoagulation in the perioperative period should really be carefully assessed, and decisions regarding their use in the perioperative period need to be made very cautiously,” she added. “This is particularly important when considering the need for an injectable bridge [anticoagulant], and discussions with the patient’s primary care provider or cardiologist should be prompted because obviously a hematoma risk of 11% [seen with injectable anticoagulants] is not insignificant.”
The researchers retrospectively studied 4,514 patients who underwent thyroid or parathyroid surgery at the center between 1994 and 2013. Most of the operations were performed by high-volume surgeons.
Overall, 25% of patients were using an antiplatelet agent and 3% were using an anticoagulant agent, defined in the study as current use or use up to 5-7 days before surgery. “We felt that there may be some alteration of hemostasis both at the time of surgery and in the days following surgery if they were resumed on their home meds,” explained Dr. Oltmann, who is now a clinical instructor of surgery at the University of Wisconsin–Madison.
Overall, 0.5% of patients developed a postoperative hematoma, with the majority of these events occurring in the first 24 hours. Three-fourths of the affected patients had to undergo repeat surgery.
In multivariate analyses, clopidogrel (Plavix) users had 5.6 times the odds of developing a hematoma. But neither lower-dose aspirin (less than 325 mg daily) alone nor higher-dose aspirin alone was associated with this complication.
Hematoma odds were elevated by an even greater extent, 7.5 and 29.5 times, for patients using oral and injectable anticoagulants, respectively. (Subcutaneous heparin was not included among injectable anticoagulants because surgeons at the center seldom use it in this setting, according to Dr. Oltmann.)
Patients also had increased odds of hematoma if they underwent thyroid surgery as compared with parathyroid surgery (odds ratio, 7.9), and had a bilateral procedure as compared with a unilateral one (OR, 4.9).
“Additional studies are needed to better clarify both the risk-benefit ratio of injectable anticoagulation in this patient population and potentially being able to better risk-stratify which patients would be better served with a period of overnight observation,” Dr. Oltmann concluded.
Invited discussant Dr. Raymon H. Grogan, director of the endocrine surgery research program at University of Chicago Medicine, commented, “I think this work represents a level of detail and granularity in regard to anticoagulants that we haven’t seen before in this literature, so it’s really important for us to see these data.
“We tend to get lulled into a false sense of security when we talk about complications related to thyroidectomy because they are so rare. But the truth of the matter is that this is a complication that causes deaths. A recent Nationwide Inpatient Sample study showed that about 1.3% of people who developed a hematoma will actually die in the United States, which is not an insignificant number of people who will die from a complication that’s directly caused by something we’ve done as surgeons,” he said.
Patients often have other risk factors for hematoma, Dr. Grogan noted. Therefore, he wondered, “Who can actually be sent home as a same-day patient after thyroidectomy? … When you combine your … people on these medications, along with all these other risk factors, as well as the risk of significant hypocalcemia postop, it starts to get to the point where, is it really safe to send anyone home the same day after thyroidectomy, given this overwhelming number of different factors that could cause problems?”
“That’s something we all struggle with to a certain degree, trying to be able to best determine who is safe to go home at night and who is not,” Dr. Oltmann replied, noting that risk in the study was greatest for the small proportion of patients on anticoagulants. “So I think a patient who is on some form of anticoagulant, I would definitely have significant reservations about sending home on the same day. They would be somebody I would at least want to keep overnight.”
“As far as the other variables – Graves disease, the size of the tumor, some people would also argue smoking and poorly controlled hypertension – it really becomes a conversation between the surgeon and the patient to know how reliable is the patient, how do you feel the operation went. … Hopefully, the next step is being able to find a way to weigh these different factors to be able to figure out, well, if my patient has A, B, and C, I must observe versus if they don’t, this might be somebody I can send home.”
Another attendee asked, “How do you [handle] aspirin use, given that it’s low risk as seen in your data set? How do you preop the patients, [do you] ask them to stop any low-risk agents, such as aspirin, or if they take the combination of aspirin and Plavix, which one do you hold and which do you continue in your practice?”
“After kind of combing through this data and becoming very familiar with it, I feel very comfortable with continuing aspirin use through the perioperative period,” Dr. Oltmann commented.
“For Plavix, obviously, you just have to juggle the risk-benefit ratio of why they are on that medication,” she said. “I think the most compelling situation is for our patients with atrial fibrillation, with the primary care provider wanting to … have them done on a Lovenox [enoxaparin] bridge, and now having some sort of objective data to get back with them and say, ‘Listen, they have an 11% risk of this really bad complication. Do you really think their risk of stroke trumps that?’ In most patients, that’s not the case, and I think [these data are] finally going to be able to give us some ammunition in that particular battle.”
Dr. Oltmann disclosed that she had no relevant conflicts of interest.
SAN FRANCISCO – Patients undergoing thyroid or parathyroid surgery have a sharply higher risk of postoperative hematoma if they are on clopidogrel or anticoagulants – even if these agents are stopped in advance – researchers reported at the annual clinical congress of the American College of Surgeons.
“Patients with multiple factors considered high risk for postoperative hematoma formation after parathyroid or thyroid surgery should probably undergo a period of observation,” recommended lead investigator Dr. Sarah C. Oltmann, who at the time of the study was the director of endocrine surgery at Parkland Memorial Hospital, University of Texas Southwestern Medical Center, Dallas.
“The need specifically for anticoagulation in the perioperative period should really be carefully assessed, and decisions regarding their use in the perioperative period need to be made very cautiously,” she added. “This is particularly important when considering the need for an injectable bridge [anticoagulant], and discussions with the patient’s primary care provider or cardiologist should be prompted because obviously a hematoma risk of 11% [seen with injectable anticoagulants] is not insignificant.”
The researchers retrospectively studied 4,514 patients who underwent thyroid or parathyroid surgery at the center between 1994 and 2013. Most of the operations were performed by high-volume surgeons.
Overall, 25% of patients were using an antiplatelet agent and 3% were using an anticoagulant agent, defined in the study as current use or use up to 5-7 days before surgery. “We felt that there may be some alteration of hemostasis both at the time of surgery and in the days following surgery if they were resumed on their home meds,” explained Dr. Oltmann, who is now a clinical instructor of surgery at the University of Wisconsin–Madison.
Overall, 0.5% of patients developed a postoperative hematoma, with the majority of these events occurring in the first 24 hours. Three-fourths of the affected patients had to undergo repeat surgery.
In multivariate analyses, clopidogrel (Plavix) users had 5.6 times the odds of developing a hematoma. But neither lower-dose aspirin (less than 325 mg daily) alone nor higher-dose aspirin alone was associated with this complication.
Hematoma odds were elevated by an even greater extent, 7.5 and 29.5 times, for patients using oral and injectable anticoagulants, respectively. (Subcutaneous heparin was not included among injectable anticoagulants because surgeons at the center seldom use it in this setting, according to Dr. Oltmann.)
Patients also had increased odds of hematoma if they underwent thyroid surgery as compared with parathyroid surgery (odds ratio, 7.9), and had a bilateral procedure as compared with a unilateral one (OR, 4.9).
“Additional studies are needed to better clarify both the risk-benefit ratio of injectable anticoagulation in this patient population and potentially being able to better risk-stratify which patients would be better served with a period of overnight observation,” Dr. Oltmann concluded.
Invited discussant Dr. Raymon H. Grogan, director of the endocrine surgery research program at University of Chicago Medicine, commented, “I think this work represents a level of detail and granularity in regard to anticoagulants that we haven’t seen before in this literature, so it’s really important for us to see these data.
“We tend to get lulled into a false sense of security when we talk about complications related to thyroidectomy because they are so rare. But the truth of the matter is that this is a complication that causes deaths. A recent Nationwide Inpatient Sample study showed that about 1.3% of people who developed a hematoma will actually die in the United States, which is not an insignificant number of people who will die from a complication that’s directly caused by something we’ve done as surgeons,” he said.
Patients often have other risk factors for hematoma, Dr. Grogan noted. Therefore, he wondered, “Who can actually be sent home as a same-day patient after thyroidectomy? … When you combine your … people on these medications, along with all these other risk factors, as well as the risk of significant hypocalcemia postop, it starts to get to the point where, is it really safe to send anyone home the same day after thyroidectomy, given this overwhelming number of different factors that could cause problems?”
“That’s something we all struggle with to a certain degree, trying to be able to best determine who is safe to go home at night and who is not,” Dr. Oltmann replied, noting that risk in the study was greatest for the small proportion of patients on anticoagulants. “So I think a patient who is on some form of anticoagulant, I would definitely have significant reservations about sending home on the same day. They would be somebody I would at least want to keep overnight.”
“As far as the other variables – Graves disease, the size of the tumor, some people would also argue smoking and poorly controlled hypertension – it really becomes a conversation between the surgeon and the patient to know how reliable is the patient, how do you feel the operation went. … Hopefully, the next step is being able to find a way to weigh these different factors to be able to figure out, well, if my patient has A, B, and C, I must observe versus if they don’t, this might be somebody I can send home.”
Another attendee asked, “How do you [handle] aspirin use, given that it’s low risk as seen in your data set? How do you preop the patients, [do you] ask them to stop any low-risk agents, such as aspirin, or if they take the combination of aspirin and Plavix, which one do you hold and which do you continue in your practice?”
“After kind of combing through this data and becoming very familiar with it, I feel very comfortable with continuing aspirin use through the perioperative period,” Dr. Oltmann commented.
“For Plavix, obviously, you just have to juggle the risk-benefit ratio of why they are on that medication,” she said. “I think the most compelling situation is for our patients with atrial fibrillation, with the primary care provider wanting to … have them done on a Lovenox [enoxaparin] bridge, and now having some sort of objective data to get back with them and say, ‘Listen, they have an 11% risk of this really bad complication. Do you really think their risk of stroke trumps that?’ In most patients, that’s not the case, and I think [these data are] finally going to be able to give us some ammunition in that particular battle.”
Dr. Oltmann disclosed that she had no relevant conflicts of interest.
SAN FRANCISCO – Patients undergoing thyroid or parathyroid surgery have a sharply higher risk of postoperative hematoma if they are on clopidogrel or anticoagulants – even if these agents are stopped in advance – researchers reported at the annual clinical congress of the American College of Surgeons.
“Patients with multiple factors considered high risk for postoperative hematoma formation after parathyroid or thyroid surgery should probably undergo a period of observation,” recommended lead investigator Dr. Sarah C. Oltmann, who at the time of the study was the director of endocrine surgery at Parkland Memorial Hospital, University of Texas Southwestern Medical Center, Dallas.
“The need specifically for anticoagulation in the perioperative period should really be carefully assessed, and decisions regarding their use in the perioperative period need to be made very cautiously,” she added. “This is particularly important when considering the need for an injectable bridge [anticoagulant], and discussions with the patient’s primary care provider or cardiologist should be prompted because obviously a hematoma risk of 11% [seen with injectable anticoagulants] is not insignificant.”
The researchers retrospectively studied 4,514 patients who underwent thyroid or parathyroid surgery at the center between 1994 and 2013. Most of the operations were performed by high-volume surgeons.
Overall, 25% of patients were using an antiplatelet agent and 3% were using an anticoagulant agent, defined in the study as current use or use up to 5-7 days before surgery. “We felt that there may be some alteration of hemostasis both at the time of surgery and in the days following surgery if they were resumed on their home meds,” explained Dr. Oltmann, who is now a clinical instructor of surgery at the University of Wisconsin–Madison.
Overall, 0.5% of patients developed a postoperative hematoma, with the majority of these events occurring in the first 24 hours. Three-fourths of the affected patients had to undergo repeat surgery.
In multivariate analyses, clopidogrel (Plavix) users had 5.6 times the odds of developing a hematoma. But neither lower-dose aspirin (less than 325 mg daily) alone nor higher-dose aspirin alone was associated with this complication.
Hematoma odds were elevated by an even greater extent, 7.5 and 29.5 times, for patients using oral and injectable anticoagulants, respectively. (Subcutaneous heparin was not included among injectable anticoagulants because surgeons at the center seldom use it in this setting, according to Dr. Oltmann.)
Patients also had increased odds of hematoma if they underwent thyroid surgery as compared with parathyroid surgery (odds ratio, 7.9), and had a bilateral procedure as compared with a unilateral one (OR, 4.9).
“Additional studies are needed to better clarify both the risk-benefit ratio of injectable anticoagulation in this patient population and potentially being able to better risk-stratify which patients would be better served with a period of overnight observation,” Dr. Oltmann concluded.
Invited discussant Dr. Raymon H. Grogan, director of the endocrine surgery research program at University of Chicago Medicine, commented, “I think this work represents a level of detail and granularity in regard to anticoagulants that we haven’t seen before in this literature, so it’s really important for us to see these data.
“We tend to get lulled into a false sense of security when we talk about complications related to thyroidectomy because they are so rare. But the truth of the matter is that this is a complication that causes deaths. A recent Nationwide Inpatient Sample study showed that about 1.3% of people who developed a hematoma will actually die in the United States, which is not an insignificant number of people who will die from a complication that’s directly caused by something we’ve done as surgeons,” he said.
Patients often have other risk factors for hematoma, Dr. Grogan noted. Therefore, he wondered, “Who can actually be sent home as a same-day patient after thyroidectomy? … When you combine your … people on these medications, along with all these other risk factors, as well as the risk of significant hypocalcemia postop, it starts to get to the point where, is it really safe to send anyone home the same day after thyroidectomy, given this overwhelming number of different factors that could cause problems?”
“That’s something we all struggle with to a certain degree, trying to be able to best determine who is safe to go home at night and who is not,” Dr. Oltmann replied, noting that risk in the study was greatest for the small proportion of patients on anticoagulants. “So I think a patient who is on some form of anticoagulant, I would definitely have significant reservations about sending home on the same day. They would be somebody I would at least want to keep overnight.”
“As far as the other variables – Graves disease, the size of the tumor, some people would also argue smoking and poorly controlled hypertension – it really becomes a conversation between the surgeon and the patient to know how reliable is the patient, how do you feel the operation went. … Hopefully, the next step is being able to find a way to weigh these different factors to be able to figure out, well, if my patient has A, B, and C, I must observe versus if they don’t, this might be somebody I can send home.”
Another attendee asked, “How do you [handle] aspirin use, given that it’s low risk as seen in your data set? How do you preop the patients, [do you] ask them to stop any low-risk agents, such as aspirin, or if they take the combination of aspirin and Plavix, which one do you hold and which do you continue in your practice?”
“After kind of combing through this data and becoming very familiar with it, I feel very comfortable with continuing aspirin use through the perioperative period,” Dr. Oltmann commented.
“For Plavix, obviously, you just have to juggle the risk-benefit ratio of why they are on that medication,” she said. “I think the most compelling situation is for our patients with atrial fibrillation, with the primary care provider wanting to … have them done on a Lovenox [enoxaparin] bridge, and now having some sort of objective data to get back with them and say, ‘Listen, they have an 11% risk of this really bad complication. Do you really think their risk of stroke trumps that?’ In most patients, that’s not the case, and I think [these data are] finally going to be able to give us some ammunition in that particular battle.”
Dr. Oltmann disclosed that she had no relevant conflicts of interest.
AT THE ACS CLINICAL CONGRESS
Key clinical point: Clopidogrel and anticoagulants are risk factors for hematoma after thyroid or parathyroid surgery.
Major finding: The odds of hematoma were 5.6 times higher with clopidogrel use and 7.5 and 29.5 times higher with oral and injectable anticoagulant use, respectively.
Data source: A retrospective study of 4,514 patients undergoing thyroid or parathyroid surgery.
Disclosures: Dr. Oltmann disclosed that she had no relevant conflicts of interest.
Postdiagnosis imaging common in thyroid cancer
CORONADO, CALIF.– Today’s clinicians are ordering more postdiagnosis imaging tests in patients with thyroid cancer than they did in the early 1990s, results from the largest study of its kind showed.
“There is very little data on surveillance imaging for cancers in general, and especially for thyroid cancer,” lead author Dr. Jaime L. Wiebel said in an interview in advance of at the annual meeting of the American Thyroid Association, where the work was presented. “This study revealed that, over time, there has been an increase in all postdiagnosis imaging studies: ultrasound, I-131 [radioactive iodine] scans, and PET scans.”
Dr. Wiebel of the University of Michigan’s metabolism, endocrinology, and diabetes clinic, Ann Arbor, and her associates used records from the linked database to identify patients diagnosed with localized, regional, or distant well-differentiated thyroid cancer between 1991 and 2009. Next, they reviewed medical claims and determined the use of thyroid ultrasound, I-131 scan, or PET scan within 3 years post diagnosis. The researchers used linear regression analysis to evaluate imaging trends during the study period and multivariate logistic regression to estimate the likelihood of imaging use based on patient characteristics.
In all, 23,669 patients with well-differentiated thyroid cancer were included in the analysis. Most (79%) were younger than age 75 years, and 70% were female. Dr. Wiebel and her associates observed an increased use of both thyroid ultrasound and I-131 among patients with localized disease (P < .001 and P = .003, respectively). Use of the two modalities also increased among patients with regional disease (both P < .001) as well as among patients with distant disease (P = .001 and P = .015).
After controlling for patient characteristics, the researchers found that patients diagnosed during 2001-2009 were 2.15 times more likely to undergo a thyroid ultrasound, compared with those diagnosed during 1991-2000. In addition, PET scan use during 2005-2009, compared with 1996-2004, increased 32.4-fold among those with localized disease, 13.1-fold among those with regional disease, and 33.4-fold among those with distant disease (all significant at P < .001). Patients diagnosed with thyroid cancer after the year 2000 were more likely to have smaller, localized cancer.
“A few of our findings were unexpected,” Dr. Wiebel said. “We had anticipated that since more low-risk thyroid cancer is being diagnosed in the United States, that postdiagnosis surveillance imaging would decrease over time. We found the exact opposite. Despite the rise in low-risk thyroid cancer, there has been an increase in postdiagnosis imaging in the United States. Especially surprising was the very large increase in PET scan use.”
She acknowledged certain limitations of the analysis, including lack of data regarding indications for the imaging studies, “including iodine avidity of the tumor, disease recurrence, or patient preferences,” and the fact that most of the patients were over age 65 years. “However, we suspect that imaging practices in younger patients are similar,” she said.
Dr. Wiebel reported having no financial disclosures.
On Twitter @dougbrunk
CORONADO, CALIF.– Today’s clinicians are ordering more postdiagnosis imaging tests in patients with thyroid cancer than they did in the early 1990s, results from the largest study of its kind showed.
“There is very little data on surveillance imaging for cancers in general, and especially for thyroid cancer,” lead author Dr. Jaime L. Wiebel said in an interview in advance of at the annual meeting of the American Thyroid Association, where the work was presented. “This study revealed that, over time, there has been an increase in all postdiagnosis imaging studies: ultrasound, I-131 [radioactive iodine] scans, and PET scans.”
Dr. Wiebel of the University of Michigan’s metabolism, endocrinology, and diabetes clinic, Ann Arbor, and her associates used records from the linked database to identify patients diagnosed with localized, regional, or distant well-differentiated thyroid cancer between 1991 and 2009. Next, they reviewed medical claims and determined the use of thyroid ultrasound, I-131 scan, or PET scan within 3 years post diagnosis. The researchers used linear regression analysis to evaluate imaging trends during the study period and multivariate logistic regression to estimate the likelihood of imaging use based on patient characteristics.
In all, 23,669 patients with well-differentiated thyroid cancer were included in the analysis. Most (79%) were younger than age 75 years, and 70% were female. Dr. Wiebel and her associates observed an increased use of both thyroid ultrasound and I-131 among patients with localized disease (P < .001 and P = .003, respectively). Use of the two modalities also increased among patients with regional disease (both P < .001) as well as among patients with distant disease (P = .001 and P = .015).
After controlling for patient characteristics, the researchers found that patients diagnosed during 2001-2009 were 2.15 times more likely to undergo a thyroid ultrasound, compared with those diagnosed during 1991-2000. In addition, PET scan use during 2005-2009, compared with 1996-2004, increased 32.4-fold among those with localized disease, 13.1-fold among those with regional disease, and 33.4-fold among those with distant disease (all significant at P < .001). Patients diagnosed with thyroid cancer after the year 2000 were more likely to have smaller, localized cancer.
“A few of our findings were unexpected,” Dr. Wiebel said. “We had anticipated that since more low-risk thyroid cancer is being diagnosed in the United States, that postdiagnosis surveillance imaging would decrease over time. We found the exact opposite. Despite the rise in low-risk thyroid cancer, there has been an increase in postdiagnosis imaging in the United States. Especially surprising was the very large increase in PET scan use.”
She acknowledged certain limitations of the analysis, including lack of data regarding indications for the imaging studies, “including iodine avidity of the tumor, disease recurrence, or patient preferences,” and the fact that most of the patients were over age 65 years. “However, we suspect that imaging practices in younger patients are similar,” she said.
Dr. Wiebel reported having no financial disclosures.
On Twitter @dougbrunk
CORONADO, CALIF.– Today’s clinicians are ordering more postdiagnosis imaging tests in patients with thyroid cancer than they did in the early 1990s, results from the largest study of its kind showed.
“There is very little data on surveillance imaging for cancers in general, and especially for thyroid cancer,” lead author Dr. Jaime L. Wiebel said in an interview in advance of at the annual meeting of the American Thyroid Association, where the work was presented. “This study revealed that, over time, there has been an increase in all postdiagnosis imaging studies: ultrasound, I-131 [radioactive iodine] scans, and PET scans.”
Dr. Wiebel of the University of Michigan’s metabolism, endocrinology, and diabetes clinic, Ann Arbor, and her associates used records from the linked database to identify patients diagnosed with localized, regional, or distant well-differentiated thyroid cancer between 1991 and 2009. Next, they reviewed medical claims and determined the use of thyroid ultrasound, I-131 scan, or PET scan within 3 years post diagnosis. The researchers used linear regression analysis to evaluate imaging trends during the study period and multivariate logistic regression to estimate the likelihood of imaging use based on patient characteristics.
In all, 23,669 patients with well-differentiated thyroid cancer were included in the analysis. Most (79%) were younger than age 75 years, and 70% were female. Dr. Wiebel and her associates observed an increased use of both thyroid ultrasound and I-131 among patients with localized disease (P < .001 and P = .003, respectively). Use of the two modalities also increased among patients with regional disease (both P < .001) as well as among patients with distant disease (P = .001 and P = .015).
After controlling for patient characteristics, the researchers found that patients diagnosed during 2001-2009 were 2.15 times more likely to undergo a thyroid ultrasound, compared with those diagnosed during 1991-2000. In addition, PET scan use during 2005-2009, compared with 1996-2004, increased 32.4-fold among those with localized disease, 13.1-fold among those with regional disease, and 33.4-fold among those with distant disease (all significant at P < .001). Patients diagnosed with thyroid cancer after the year 2000 were more likely to have smaller, localized cancer.
“A few of our findings were unexpected,” Dr. Wiebel said. “We had anticipated that since more low-risk thyroid cancer is being diagnosed in the United States, that postdiagnosis surveillance imaging would decrease over time. We found the exact opposite. Despite the rise in low-risk thyroid cancer, there has been an increase in postdiagnosis imaging in the United States. Especially surprising was the very large increase in PET scan use.”
She acknowledged certain limitations of the analysis, including lack of data regarding indications for the imaging studies, “including iodine avidity of the tumor, disease recurrence, or patient preferences,” and the fact that most of the patients were over age 65 years. “However, we suspect that imaging practices in younger patients are similar,” she said.
Dr. Wiebel reported having no financial disclosures.
On Twitter @dougbrunk
AT THE ATA ANNUAL MEETING
Key clinical point: Regardless of stage, clinicians are doing more postdiagnosis imaging of thyroid cancer patients than they were in the 1990s.
Major finding: Between 1991 and 2009, the use of both thyroid ultrasound and I-131 scans increased significantly among patients with localized thyroid disease. Imaging also increased among those with regional and distant disease.
Data source: An analysis of 23,669 patients diagnosed with localized, regional, or distant well-differentiated thyroid cancer between 1991 and 2009 who were identified from the linked SEER-Medicare database.
Disclosures: Dr. Wiebel reported having no financial disclosures.
Growth hormone replacement may prevent fractures
CHICAGO – Growth hormone therapy appears to protect against fractures in adults with growth hormone deficiency and no history of osteoporosis, according to an analysis from the HypoCCS study.
In contrast, growth hormone (GH)-deficient patients with preexisting osteoporosis are another story. GH replacement didn’t affect fracture risk in that subgroup of participants in HypoCCS (the Hypopituitary Control and Complications Study), Christopher J. Child, Ph.D., reported at the joint meeting of the International Congress of Endocrinology and the Endocrine Society. It’s well established that GH-deficient adults have lower bone mass and a two- to fivefold increased risk of fractures, compared with controls. Moreover, GH replacement therapy has been shown to increase bone-mineral density and bone-mass density and produce salutary effects on bone turnover markers.
But HypoCCS is the first prospective controlled study to suggest long-term GH therapy actually prevents fractures in adults with GH deficiency, noted Dr. Child of Lilly Research Laboratories in Windlesham, England.
He presented a retrospective analysis of prospectively collected data from the observational study, which included 8,374 GH-treated adults and 1,267 untreated controls, all with GH deficiency alone or in combination with other pituitary hormone deficiencies.
During a mean follow-up of 4.6 years in the GH-treated group, the combined incidence of vertebral and nonvertebral fractures was 11.9/1,000 person-years, compared with 19.1/1,000 person-years in controls, for a 37% relative risk reduction. The risk of vertebral fractures was 45% lower in the GH-treated patients; nonvertebral fractures were decreased by 32%.
In a multivariate Cox proportionate regression analysis, the protective effect of GH replacement therapy remained significant after adjustment for the common fracture risk factors, including age greater than 60 years, female gender, depression, the use of corticosteroids, and increased body weight. Dr. Child stressed in an interview that physicians shouldn’t take these HypoCCS findings as the final word on the issue of whether growth hormone replacement prevents fractures in GH-deficient adults. While this is the first-ever analysis of fracture risk from a long-term adult GH replacement study, as in any nonrandomized observational study selection bias is a possibility. And data were lacking on several potentially important confounding factors, including participants’ alcohol and calcium intake, as well as their level of physical activity.
Still, he said, the notion that GH replacement therapy may have a reduction in fracture risk as a side benefit is attractive.
He is an employee of Eli Lilly, which funds HypoCCS.
CHICAGO – Growth hormone therapy appears to protect against fractures in adults with growth hormone deficiency and no history of osteoporosis, according to an analysis from the HypoCCS study.
In contrast, growth hormone (GH)-deficient patients with preexisting osteoporosis are another story. GH replacement didn’t affect fracture risk in that subgroup of participants in HypoCCS (the Hypopituitary Control and Complications Study), Christopher J. Child, Ph.D., reported at the joint meeting of the International Congress of Endocrinology and the Endocrine Society. It’s well established that GH-deficient adults have lower bone mass and a two- to fivefold increased risk of fractures, compared with controls. Moreover, GH replacement therapy has been shown to increase bone-mineral density and bone-mass density and produce salutary effects on bone turnover markers.
But HypoCCS is the first prospective controlled study to suggest long-term GH therapy actually prevents fractures in adults with GH deficiency, noted Dr. Child of Lilly Research Laboratories in Windlesham, England.
He presented a retrospective analysis of prospectively collected data from the observational study, which included 8,374 GH-treated adults and 1,267 untreated controls, all with GH deficiency alone or in combination with other pituitary hormone deficiencies.
During a mean follow-up of 4.6 years in the GH-treated group, the combined incidence of vertebral and nonvertebral fractures was 11.9/1,000 person-years, compared with 19.1/1,000 person-years in controls, for a 37% relative risk reduction. The risk of vertebral fractures was 45% lower in the GH-treated patients; nonvertebral fractures were decreased by 32%.
In a multivariate Cox proportionate regression analysis, the protective effect of GH replacement therapy remained significant after adjustment for the common fracture risk factors, including age greater than 60 years, female gender, depression, the use of corticosteroids, and increased body weight. Dr. Child stressed in an interview that physicians shouldn’t take these HypoCCS findings as the final word on the issue of whether growth hormone replacement prevents fractures in GH-deficient adults. While this is the first-ever analysis of fracture risk from a long-term adult GH replacement study, as in any nonrandomized observational study selection bias is a possibility. And data were lacking on several potentially important confounding factors, including participants’ alcohol and calcium intake, as well as their level of physical activity.
Still, he said, the notion that GH replacement therapy may have a reduction in fracture risk as a side benefit is attractive.
He is an employee of Eli Lilly, which funds HypoCCS.
CHICAGO – Growth hormone therapy appears to protect against fractures in adults with growth hormone deficiency and no history of osteoporosis, according to an analysis from the HypoCCS study.
In contrast, growth hormone (GH)-deficient patients with preexisting osteoporosis are another story. GH replacement didn’t affect fracture risk in that subgroup of participants in HypoCCS (the Hypopituitary Control and Complications Study), Christopher J. Child, Ph.D., reported at the joint meeting of the International Congress of Endocrinology and the Endocrine Society. It’s well established that GH-deficient adults have lower bone mass and a two- to fivefold increased risk of fractures, compared with controls. Moreover, GH replacement therapy has been shown to increase bone-mineral density and bone-mass density and produce salutary effects on bone turnover markers.
But HypoCCS is the first prospective controlled study to suggest long-term GH therapy actually prevents fractures in adults with GH deficiency, noted Dr. Child of Lilly Research Laboratories in Windlesham, England.
He presented a retrospective analysis of prospectively collected data from the observational study, which included 8,374 GH-treated adults and 1,267 untreated controls, all with GH deficiency alone or in combination with other pituitary hormone deficiencies.
During a mean follow-up of 4.6 years in the GH-treated group, the combined incidence of vertebral and nonvertebral fractures was 11.9/1,000 person-years, compared with 19.1/1,000 person-years in controls, for a 37% relative risk reduction. The risk of vertebral fractures was 45% lower in the GH-treated patients; nonvertebral fractures were decreased by 32%.
In a multivariate Cox proportionate regression analysis, the protective effect of GH replacement therapy remained significant after adjustment for the common fracture risk factors, including age greater than 60 years, female gender, depression, the use of corticosteroids, and increased body weight. Dr. Child stressed in an interview that physicians shouldn’t take these HypoCCS findings as the final word on the issue of whether growth hormone replacement prevents fractures in GH-deficient adults. While this is the first-ever analysis of fracture risk from a long-term adult GH replacement study, as in any nonrandomized observational study selection bias is a possibility. And data were lacking on several potentially important confounding factors, including participants’ alcohol and calcium intake, as well as their level of physical activity.
Still, he said, the notion that GH replacement therapy may have a reduction in fracture risk as a side benefit is attractive.
He is an employee of Eli Lilly, which funds HypoCCS.
AT ICE/ENDO 2014
Key clinical point: Growth hormone replacement therapy in adults with GH deficiency may have an appealing side benefit: reduced fracture risk.
Major finding: In a multivariate analysis, adults on GH replacement therapy for GH deficiency had an adjusted 31% reduction in fracture risk compared to untreated controls.
Data source: A retrospective analysis of the prospective, observational HypoCCS study involving 8,374 GH-treated adults and 1,267 untreated controls, all with GH deficiency.
Disclosures: The HypoCCS study is funded by Eli Lilly. The presenter is a company employee.
Depression, withdrawal worse when short children treated with GH
CHICAGO – In very short children, the slight increase in adult height from growth hormone treatment comes at the cost of psychological well-being, at least at first, according to a prospective cohort study.
So far in the ongoing investigation, the parents of 12 children with growth hormone (GH) deficiency, defined as peak stimulated GH of less than 5 ng/mL, and 7 children with idiopathic short stature (ISS) filled out the Behavior Assessment System for Children, Second Edition (BASC-2) at baseline and after 9-12 months of GH treatment. The results were compared to what the parents of nine ISS children who were not treated reported on the assessment.
GH-deficient children grew a bit, moving from –2.3 to –1.9 standard deviations below growth chart means, and ISS children grew from –2.6 to –2.2 standard deviations. Untreated children remained about 2.5 standard deviations behind their peers.
There were no statistically significant differences in baseline BASC-2 scores. However, while untreated children improved from a mean baseline depression score of 63 to 55 points, depression scores in treated children rose from 59 to 63 points. Similarly, social withdrawal in untreated children improved from 52 to 47 points, but rose from 54 to 60 points in treated children, lead investigator Dr. Emily Walvoord reported at the joint meeting of the International Congress of Endocrinology and the Endocrine Society.
Scores below 60 are considered nonclinical, scores of 60-65 indicate risk, and scores above 65 indicate pathology, explained Dr. Walvoord, a pediatric endocrinologist at Indiana University in Indianapolis.
"For short, otherwise healthy children, ... daily injections, visits to the endocrinologist every 4-6 months, and repeated discussion [of] their height might exacerbate instead of improve psychosocial concerns about being different. This [study] raises concerns that psychosocial benefits may not be achieved despite improvements in height," she and her colleagues concluded.
"I worry that we are medicalizing these kids. The message we send them is, ‘You’re not okay; there’s something wrong with you because you are too short. So you have to get a shot every day, you have to go see the doctor, and we have to talk about your height all the time.’ That’s the message I worry they internalize," Dr. Walvoord said.
"Are we really helping them? We have to be very careful about what we think is the most important outcome. Is it making the kid an inch or two taller as an adult, or is it that they have better self-esteem and psychological functioning?" she said.
If nothing else, the findings highlight the need to remind children that they are more than a number on a growth curve, and that other things matter in life.
There were no between-group differences in parent-reported cognitive functioning at baseline or follow-up. Anxiety scores improved in both cohorts, falling from 58 to 54 points in treated children, and 52 to 47 in untreated children; the meaning of that finding is uncertain. In addition, "it is possible that there was a bias toward treatment of ISS children who had underlying emotional issues," the investigators noted.
The children in the study were about 11 years old on average, with no significant differences in age, sex, or initial height standard deviations between the two groups.
Dr. Walvoord is gathering results for 13 additional children; of the total 41 subjects, 25 are boys. She hopes to follow the children for more than a year, and split out results for GH-deficient and ISS patients.
Dr. Walvoord and her colleagues had no disclosures. She initiated the work, and Eli Lilly funded it at her request.
CHICAGO – In very short children, the slight increase in adult height from growth hormone treatment comes at the cost of psychological well-being, at least at first, according to a prospective cohort study.
So far in the ongoing investigation, the parents of 12 children with growth hormone (GH) deficiency, defined as peak stimulated GH of less than 5 ng/mL, and 7 children with idiopathic short stature (ISS) filled out the Behavior Assessment System for Children, Second Edition (BASC-2) at baseline and after 9-12 months of GH treatment. The results were compared to what the parents of nine ISS children who were not treated reported on the assessment.
GH-deficient children grew a bit, moving from –2.3 to –1.9 standard deviations below growth chart means, and ISS children grew from –2.6 to –2.2 standard deviations. Untreated children remained about 2.5 standard deviations behind their peers.
There were no statistically significant differences in baseline BASC-2 scores. However, while untreated children improved from a mean baseline depression score of 63 to 55 points, depression scores in treated children rose from 59 to 63 points. Similarly, social withdrawal in untreated children improved from 52 to 47 points, but rose from 54 to 60 points in treated children, lead investigator Dr. Emily Walvoord reported at the joint meeting of the International Congress of Endocrinology and the Endocrine Society.
Scores below 60 are considered nonclinical, scores of 60-65 indicate risk, and scores above 65 indicate pathology, explained Dr. Walvoord, a pediatric endocrinologist at Indiana University in Indianapolis.
"For short, otherwise healthy children, ... daily injections, visits to the endocrinologist every 4-6 months, and repeated discussion [of] their height might exacerbate instead of improve psychosocial concerns about being different. This [study] raises concerns that psychosocial benefits may not be achieved despite improvements in height," she and her colleagues concluded.
"I worry that we are medicalizing these kids. The message we send them is, ‘You’re not okay; there’s something wrong with you because you are too short. So you have to get a shot every day, you have to go see the doctor, and we have to talk about your height all the time.’ That’s the message I worry they internalize," Dr. Walvoord said.
"Are we really helping them? We have to be very careful about what we think is the most important outcome. Is it making the kid an inch or two taller as an adult, or is it that they have better self-esteem and psychological functioning?" she said.
If nothing else, the findings highlight the need to remind children that they are more than a number on a growth curve, and that other things matter in life.
There were no between-group differences in parent-reported cognitive functioning at baseline or follow-up. Anxiety scores improved in both cohorts, falling from 58 to 54 points in treated children, and 52 to 47 in untreated children; the meaning of that finding is uncertain. In addition, "it is possible that there was a bias toward treatment of ISS children who had underlying emotional issues," the investigators noted.
The children in the study were about 11 years old on average, with no significant differences in age, sex, or initial height standard deviations between the two groups.
Dr. Walvoord is gathering results for 13 additional children; of the total 41 subjects, 25 are boys. She hopes to follow the children for more than a year, and split out results for GH-deficient and ISS patients.
Dr. Walvoord and her colleagues had no disclosures. She initiated the work, and Eli Lilly funded it at her request.
CHICAGO – In very short children, the slight increase in adult height from growth hormone treatment comes at the cost of psychological well-being, at least at first, according to a prospective cohort study.
So far in the ongoing investigation, the parents of 12 children with growth hormone (GH) deficiency, defined as peak stimulated GH of less than 5 ng/mL, and 7 children with idiopathic short stature (ISS) filled out the Behavior Assessment System for Children, Second Edition (BASC-2) at baseline and after 9-12 months of GH treatment. The results were compared to what the parents of nine ISS children who were not treated reported on the assessment.
GH-deficient children grew a bit, moving from –2.3 to –1.9 standard deviations below growth chart means, and ISS children grew from –2.6 to –2.2 standard deviations. Untreated children remained about 2.5 standard deviations behind their peers.
There were no statistically significant differences in baseline BASC-2 scores. However, while untreated children improved from a mean baseline depression score of 63 to 55 points, depression scores in treated children rose from 59 to 63 points. Similarly, social withdrawal in untreated children improved from 52 to 47 points, but rose from 54 to 60 points in treated children, lead investigator Dr. Emily Walvoord reported at the joint meeting of the International Congress of Endocrinology and the Endocrine Society.
Scores below 60 are considered nonclinical, scores of 60-65 indicate risk, and scores above 65 indicate pathology, explained Dr. Walvoord, a pediatric endocrinologist at Indiana University in Indianapolis.
"For short, otherwise healthy children, ... daily injections, visits to the endocrinologist every 4-6 months, and repeated discussion [of] their height might exacerbate instead of improve psychosocial concerns about being different. This [study] raises concerns that psychosocial benefits may not be achieved despite improvements in height," she and her colleagues concluded.
"I worry that we are medicalizing these kids. The message we send them is, ‘You’re not okay; there’s something wrong with you because you are too short. So you have to get a shot every day, you have to go see the doctor, and we have to talk about your height all the time.’ That’s the message I worry they internalize," Dr. Walvoord said.
"Are we really helping them? We have to be very careful about what we think is the most important outcome. Is it making the kid an inch or two taller as an adult, or is it that they have better self-esteem and psychological functioning?" she said.
If nothing else, the findings highlight the need to remind children that they are more than a number on a growth curve, and that other things matter in life.
There were no between-group differences in parent-reported cognitive functioning at baseline or follow-up. Anxiety scores improved in both cohorts, falling from 58 to 54 points in treated children, and 52 to 47 in untreated children; the meaning of that finding is uncertain. In addition, "it is possible that there was a bias toward treatment of ISS children who had underlying emotional issues," the investigators noted.
The children in the study were about 11 years old on average, with no significant differences in age, sex, or initial height standard deviations between the two groups.
Dr. Walvoord is gathering results for 13 additional children; of the total 41 subjects, 25 are boys. She hopes to follow the children for more than a year, and split out results for GH-deficient and ISS patients.
Dr. Walvoord and her colleagues had no disclosures. She initiated the work, and Eli Lilly funded it at her request.
AT ICE/ENDO 2014
Key clinical point: The slight increase in adult height might not be worth the psychological risks of GH treatment in children.
Major finding: After 9-12 months, the mean depression score for children treated with GH rose from 59 to 63 points on the Behavior Assessment System for Children, Second Edition, but improved from 63 to 55 points in their untreated peers.
Data source: Prospective cohort study.
Disclosures: Dr. Walvoord and her colleagues had no disclosures. She initiated the work, and Eli Lilly funded it at her request.
Mifepristone for Cushing’s brings sustained weight loss
CHICAGO – Mifepristone therapy for Cushing’s syndrome provides an important side benefit: clinically meaningful weight loss that persists over time.
That’s a key finding from the long-term extension phase of the SEISMIC study, a 24-week, multicenter study that led to Food and Drug Administration approval of mifepristone (Korlym) in 2012 as the first and only medication indicated for the treatment of endogenous Cushing’s syndrome.
In the long-term extension phase of the SEISMIC study, mifepristone therapy for up to 3.5 years was associated with a mean 9.3% weight loss from baseline, Dr. Henry G. Fein reported at the joint meeting of the International Congress of Endocrinology and the Endocrine Society.
Of patients who lost at least 5% of their body weight during the initial 24-week treatment period in the SEISMIC study, 83% maintained that amount of weight loss through the long-term extension phase. A sustained weight loss of that scope is likely to translate into a reduced risk of cardiovascular disease and metabolic dysfunction, said Dr. Fein of Johns Hopkins University, Baltimore.
Endogenous Cushing’s syndrome is a rare disease, and the phase III SEISMIC study (J. Clin. Endocrinol. Metab. 2012;97:2039-49), while pivotal, was small, involving 50 patients treated with the glucocorticoid receptor antagonist at 300-1,200 mg once daily for 24 weeks. Afterward, 29 patients underwent a 6-week period off drug for safety assessment and then went back on mifepristone for a median of 29.2 months and a maximum of 3.5 years in the extension study.
At baseline, the mean body weight in these 29 patients was 105.4 kg. It dropped to 97.2 kg by week 24. Six weeks later, when patients went back on mifepristone, their mean weight was 98.6 kg. At last follow-up – with patients still on the drug – their mean weight was 95.1 kg, a 9.3% decrease from baseline.
Eighteen of 29 patients achieved a 5% or better weight loss by week 24; at the most recent follow-up, 15 of the 18 (83%) maintained or improved upon that degree of weight loss. Moreover, of the 10 patients who lost at least 10% of their body weight during the first 24 weeks of treatment, 8 maintained that amount of weight loss by study’s end.
Surgery is accepted as the treatment of choice for most patients with Cushing’s syndrome. However, various studies have shown that 10%-45% of surgically treated patients have persistent or recurrent hypercortisolism postoperatively, with accompanying weight gain. That’s where mifepristone plays a key role. In addition, the drug is valuable in patients who aren’t surgical candidates, the endocrinologist noted.
Mifepristone was formerly known as RU-486, "the abortion pill."
The SEISMIC study and its long-term extension were funded by Corcept Therapeutics. Dr. Fein is on the company’s speakers bureau.
CHICAGO – Mifepristone therapy for Cushing’s syndrome provides an important side benefit: clinically meaningful weight loss that persists over time.
That’s a key finding from the long-term extension phase of the SEISMIC study, a 24-week, multicenter study that led to Food and Drug Administration approval of mifepristone (Korlym) in 2012 as the first and only medication indicated for the treatment of endogenous Cushing’s syndrome.
In the long-term extension phase of the SEISMIC study, mifepristone therapy for up to 3.5 years was associated with a mean 9.3% weight loss from baseline, Dr. Henry G. Fein reported at the joint meeting of the International Congress of Endocrinology and the Endocrine Society.
Of patients who lost at least 5% of their body weight during the initial 24-week treatment period in the SEISMIC study, 83% maintained that amount of weight loss through the long-term extension phase. A sustained weight loss of that scope is likely to translate into a reduced risk of cardiovascular disease and metabolic dysfunction, said Dr. Fein of Johns Hopkins University, Baltimore.
Endogenous Cushing’s syndrome is a rare disease, and the phase III SEISMIC study (J. Clin. Endocrinol. Metab. 2012;97:2039-49), while pivotal, was small, involving 50 patients treated with the glucocorticoid receptor antagonist at 300-1,200 mg once daily for 24 weeks. Afterward, 29 patients underwent a 6-week period off drug for safety assessment and then went back on mifepristone for a median of 29.2 months and a maximum of 3.5 years in the extension study.
At baseline, the mean body weight in these 29 patients was 105.4 kg. It dropped to 97.2 kg by week 24. Six weeks later, when patients went back on mifepristone, their mean weight was 98.6 kg. At last follow-up – with patients still on the drug – their mean weight was 95.1 kg, a 9.3% decrease from baseline.
Eighteen of 29 patients achieved a 5% or better weight loss by week 24; at the most recent follow-up, 15 of the 18 (83%) maintained or improved upon that degree of weight loss. Moreover, of the 10 patients who lost at least 10% of their body weight during the first 24 weeks of treatment, 8 maintained that amount of weight loss by study’s end.
Surgery is accepted as the treatment of choice for most patients with Cushing’s syndrome. However, various studies have shown that 10%-45% of surgically treated patients have persistent or recurrent hypercortisolism postoperatively, with accompanying weight gain. That’s where mifepristone plays a key role. In addition, the drug is valuable in patients who aren’t surgical candidates, the endocrinologist noted.
Mifepristone was formerly known as RU-486, "the abortion pill."
The SEISMIC study and its long-term extension were funded by Corcept Therapeutics. Dr. Fein is on the company’s speakers bureau.
CHICAGO – Mifepristone therapy for Cushing’s syndrome provides an important side benefit: clinically meaningful weight loss that persists over time.
That’s a key finding from the long-term extension phase of the SEISMIC study, a 24-week, multicenter study that led to Food and Drug Administration approval of mifepristone (Korlym) in 2012 as the first and only medication indicated for the treatment of endogenous Cushing’s syndrome.
In the long-term extension phase of the SEISMIC study, mifepristone therapy for up to 3.5 years was associated with a mean 9.3% weight loss from baseline, Dr. Henry G. Fein reported at the joint meeting of the International Congress of Endocrinology and the Endocrine Society.
Of patients who lost at least 5% of their body weight during the initial 24-week treatment period in the SEISMIC study, 83% maintained that amount of weight loss through the long-term extension phase. A sustained weight loss of that scope is likely to translate into a reduced risk of cardiovascular disease and metabolic dysfunction, said Dr. Fein of Johns Hopkins University, Baltimore.
Endogenous Cushing’s syndrome is a rare disease, and the phase III SEISMIC study (J. Clin. Endocrinol. Metab. 2012;97:2039-49), while pivotal, was small, involving 50 patients treated with the glucocorticoid receptor antagonist at 300-1,200 mg once daily for 24 weeks. Afterward, 29 patients underwent a 6-week period off drug for safety assessment and then went back on mifepristone for a median of 29.2 months and a maximum of 3.5 years in the extension study.
At baseline, the mean body weight in these 29 patients was 105.4 kg. It dropped to 97.2 kg by week 24. Six weeks later, when patients went back on mifepristone, their mean weight was 98.6 kg. At last follow-up – with patients still on the drug – their mean weight was 95.1 kg, a 9.3% decrease from baseline.
Eighteen of 29 patients achieved a 5% or better weight loss by week 24; at the most recent follow-up, 15 of the 18 (83%) maintained or improved upon that degree of weight loss. Moreover, of the 10 patients who lost at least 10% of their body weight during the first 24 weeks of treatment, 8 maintained that amount of weight loss by study’s end.
Surgery is accepted as the treatment of choice for most patients with Cushing’s syndrome. However, various studies have shown that 10%-45% of surgically treated patients have persistent or recurrent hypercortisolism postoperatively, with accompanying weight gain. That’s where mifepristone plays a key role. In addition, the drug is valuable in patients who aren’t surgical candidates, the endocrinologist noted.
Mifepristone was formerly known as RU-486, "the abortion pill."
The SEISMIC study and its long-term extension were funded by Corcept Therapeutics. Dr. Fein is on the company’s speakers bureau.
AT ICE/ENDO 2014
Key clinical point: Treatment of Cushing’s syndrome with the glucocorticoid receptor antagonist mifepristone results in sustained significant weight loss, with its attendant cardiometabolic benefits.
Major finding: More than 80% of patients with Cushing’s syndrome who lost at least 5% of their initial body weight during 24 weeks of mifepristone therapy maintained that degree of weight loss for up to 3.5 years.
Data source: The long-term extension study of SEISMIC, an open-label, multicenter study involving 50 mifepristone-treated patients with Cushing’s syndrome.
Disclosures: The study was funded by Corcept Therapeutics, and its presenter is a member of the company’s speakers bureau.
Hold the central lymph node dissection for small parathyroid tumors?
BOSTON – Central lymph node dissection may not be necessary in patients with small parathyroid carcinomas, results of a data review suggest.
Among 405 U.S. patients treated in the last two decades for parathyroid carcinomas, disease-specific mortality and degree of local tumor invasion did not differ depending on nodal involvement, reported Dr. Kun-Tai Hsu, an associate research specialist in the surgery department at the University of Wisconsin, Madison.
Patients with tumors greater than 3 cm in diameter and distal metastasis had worse disease-specific mortality, and larger tumors were significantly more likely to be associated with positive lymph nodes, Dr. Hsu reported at the annual meeting of the American Association of Endocrine Surgeons.
The findings raise the question of whether central lymph node dissection is necessary for all patients with parathyroid carcinomas, but "our conclusions may not translate directly into definitive recommendations," said Dr. Hsu, who advised further study of whether patients with tumors larger than 3 cm may benefit from lymph node dissection.
Parathyroid carcinomas are rare cancers, accounting for 0.005% of all malignancies and less than 1% of primary hyperparathyroidism. The current standard of therapy is en bloc removal of the parathyroid tumor and ipsilateral lobectomy, isthmusectomy, and central lymph node dissection.
Over at least 5 years of follow-up, neither tumor size nor lymph node status was significantly predictive of outcomes in an earlier retrospective study of 286 patients treated in the 1980s and 1990s.
In addition, a 2006 study using data from the Surveillance, Epidemiology and End Results (SEER) database showed a significant increase in the incidence of this malignancy from 1988 through 2003. The authors identified younger age, female sex, more recent diagnosis, and absence of distant metastases as favorable prognostic factors (Cancer 2007;109:1736-41).
What the previous studies could not answer, however, was whether lymph node metastases were associated with worse disease-specific mortality and whether central lymph node dissection might improve survival in patients with parathyroid carcinomas, Dr. Hsu noted.
He and his colleagues queried SEER for disease-specific survival outcomes and lymph-node status of all patients treated in the United States for parathyroid carcinomas from 1988 through 2010.
They identified 212 female and 193 male patients. Among all patients, 112 (27.7%) had tumors 3 cm or greater, and 12 (3%) had positive lymph nodes. Median follow-up was 68 months.
In a multivariate analysis of disease-specific mortality predictors adjusted for sex and age only, tumors 3 cm or greater and the presence of metastasis were predictive of worse survival, with respective hazard ratios of 5.35 (P = .01) and 45.1 (P less than .01).
Similarly, an analysis adjusted for sex, age, and year of diagnosis showed that tumor size but not age or sex significantly predicted lymph node metastasis (HR, 19.48; P = .02)
A comparison of outcomes between patients with and without lymph node examinations found no differences in disease-specific mortality by sex, age, year of diagnosis, tumor size, local invasion, or metastasis. Significant predictors of disease-specific mortality in this analysis included surgery type (parathyroidectomy, en bloc excision, or debulking), the use of radiation, and white race.
Dr. Hsu noted that the study was limited by its retrospective design, lack of information on other significant clinical variables, lack of detailed follow-up data, and the possibility of misclassification or miscoding of cases.
He acknowledged that uncertainty about the diagnosis is a drawback to SEER-based studies, but that given the rarity of the disease, SEER data are the most reliable source of information.
The study was supported by the Wisconsin Surgical Outcomes Research Program. Dr. Hsu reported having no relevant disclosures. Study coauthor Dr. Rebecca Sippel is a member of this publication’s editorial advisory board.
The accuracy of diagnoses is questionable among patients in this study. A diagnosis of parathyroid carcinoma is based on several factors, including the presence of local invasion, lymph node metastases, or systemic metastases, but only a relatively small percentage of patients in the study had local invasion, suggesting that the diagnosis was based on examination of microscopic tumor features in the absence of local invasion.
An alternative explanation for the lack of a disease-specific mortality difference by lymph node status is that you may have included patients who really don’t have parathyroid cancer.
Dr. Christopher McHenry is vice-chair of surgery at MetroHealth in Cleveland. He had no relevant disclosures.
The accuracy of diagnoses is questionable among patients in this study. A diagnosis of parathyroid carcinoma is based on several factors, including the presence of local invasion, lymph node metastases, or systemic metastases, but only a relatively small percentage of patients in the study had local invasion, suggesting that the diagnosis was based on examination of microscopic tumor features in the absence of local invasion.
An alternative explanation for the lack of a disease-specific mortality difference by lymph node status is that you may have included patients who really don’t have parathyroid cancer.
Dr. Christopher McHenry is vice-chair of surgery at MetroHealth in Cleveland. He had no relevant disclosures.
The accuracy of diagnoses is questionable among patients in this study. A diagnosis of parathyroid carcinoma is based on several factors, including the presence of local invasion, lymph node metastases, or systemic metastases, but only a relatively small percentage of patients in the study had local invasion, suggesting that the diagnosis was based on examination of microscopic tumor features in the absence of local invasion.
An alternative explanation for the lack of a disease-specific mortality difference by lymph node status is that you may have included patients who really don’t have parathyroid cancer.
Dr. Christopher McHenry is vice-chair of surgery at MetroHealth in Cleveland. He had no relevant disclosures.
BOSTON – Central lymph node dissection may not be necessary in patients with small parathyroid carcinomas, results of a data review suggest.
Among 405 U.S. patients treated in the last two decades for parathyroid carcinomas, disease-specific mortality and degree of local tumor invasion did not differ depending on nodal involvement, reported Dr. Kun-Tai Hsu, an associate research specialist in the surgery department at the University of Wisconsin, Madison.
Patients with tumors greater than 3 cm in diameter and distal metastasis had worse disease-specific mortality, and larger tumors were significantly more likely to be associated with positive lymph nodes, Dr. Hsu reported at the annual meeting of the American Association of Endocrine Surgeons.
The findings raise the question of whether central lymph node dissection is necessary for all patients with parathyroid carcinomas, but "our conclusions may not translate directly into definitive recommendations," said Dr. Hsu, who advised further study of whether patients with tumors larger than 3 cm may benefit from lymph node dissection.
Parathyroid carcinomas are rare cancers, accounting for 0.005% of all malignancies and less than 1% of primary hyperparathyroidism. The current standard of therapy is en bloc removal of the parathyroid tumor and ipsilateral lobectomy, isthmusectomy, and central lymph node dissection.
Over at least 5 years of follow-up, neither tumor size nor lymph node status was significantly predictive of outcomes in an earlier retrospective study of 286 patients treated in the 1980s and 1990s.
In addition, a 2006 study using data from the Surveillance, Epidemiology and End Results (SEER) database showed a significant increase in the incidence of this malignancy from 1988 through 2003. The authors identified younger age, female sex, more recent diagnosis, and absence of distant metastases as favorable prognostic factors (Cancer 2007;109:1736-41).
What the previous studies could not answer, however, was whether lymph node metastases were associated with worse disease-specific mortality and whether central lymph node dissection might improve survival in patients with parathyroid carcinomas, Dr. Hsu noted.
He and his colleagues queried SEER for disease-specific survival outcomes and lymph-node status of all patients treated in the United States for parathyroid carcinomas from 1988 through 2010.
They identified 212 female and 193 male patients. Among all patients, 112 (27.7%) had tumors 3 cm or greater, and 12 (3%) had positive lymph nodes. Median follow-up was 68 months.
In a multivariate analysis of disease-specific mortality predictors adjusted for sex and age only, tumors 3 cm or greater and the presence of metastasis were predictive of worse survival, with respective hazard ratios of 5.35 (P = .01) and 45.1 (P less than .01).
Similarly, an analysis adjusted for sex, age, and year of diagnosis showed that tumor size but not age or sex significantly predicted lymph node metastasis (HR, 19.48; P = .02)
A comparison of outcomes between patients with and without lymph node examinations found no differences in disease-specific mortality by sex, age, year of diagnosis, tumor size, local invasion, or metastasis. Significant predictors of disease-specific mortality in this analysis included surgery type (parathyroidectomy, en bloc excision, or debulking), the use of radiation, and white race.
Dr. Hsu noted that the study was limited by its retrospective design, lack of information on other significant clinical variables, lack of detailed follow-up data, and the possibility of misclassification or miscoding of cases.
He acknowledged that uncertainty about the diagnosis is a drawback to SEER-based studies, but that given the rarity of the disease, SEER data are the most reliable source of information.
The study was supported by the Wisconsin Surgical Outcomes Research Program. Dr. Hsu reported having no relevant disclosures. Study coauthor Dr. Rebecca Sippel is a member of this publication’s editorial advisory board.
BOSTON – Central lymph node dissection may not be necessary in patients with small parathyroid carcinomas, results of a data review suggest.
Among 405 U.S. patients treated in the last two decades for parathyroid carcinomas, disease-specific mortality and degree of local tumor invasion did not differ depending on nodal involvement, reported Dr. Kun-Tai Hsu, an associate research specialist in the surgery department at the University of Wisconsin, Madison.
Patients with tumors greater than 3 cm in diameter and distal metastasis had worse disease-specific mortality, and larger tumors were significantly more likely to be associated with positive lymph nodes, Dr. Hsu reported at the annual meeting of the American Association of Endocrine Surgeons.
The findings raise the question of whether central lymph node dissection is necessary for all patients with parathyroid carcinomas, but "our conclusions may not translate directly into definitive recommendations," said Dr. Hsu, who advised further study of whether patients with tumors larger than 3 cm may benefit from lymph node dissection.
Parathyroid carcinomas are rare cancers, accounting for 0.005% of all malignancies and less than 1% of primary hyperparathyroidism. The current standard of therapy is en bloc removal of the parathyroid tumor and ipsilateral lobectomy, isthmusectomy, and central lymph node dissection.
Over at least 5 years of follow-up, neither tumor size nor lymph node status was significantly predictive of outcomes in an earlier retrospective study of 286 patients treated in the 1980s and 1990s.
In addition, a 2006 study using data from the Surveillance, Epidemiology and End Results (SEER) database showed a significant increase in the incidence of this malignancy from 1988 through 2003. The authors identified younger age, female sex, more recent diagnosis, and absence of distant metastases as favorable prognostic factors (Cancer 2007;109:1736-41).
What the previous studies could not answer, however, was whether lymph node metastases were associated with worse disease-specific mortality and whether central lymph node dissection might improve survival in patients with parathyroid carcinomas, Dr. Hsu noted.
He and his colleagues queried SEER for disease-specific survival outcomes and lymph-node status of all patients treated in the United States for parathyroid carcinomas from 1988 through 2010.
They identified 212 female and 193 male patients. Among all patients, 112 (27.7%) had tumors 3 cm or greater, and 12 (3%) had positive lymph nodes. Median follow-up was 68 months.
In a multivariate analysis of disease-specific mortality predictors adjusted for sex and age only, tumors 3 cm or greater and the presence of metastasis were predictive of worse survival, with respective hazard ratios of 5.35 (P = .01) and 45.1 (P less than .01).
Similarly, an analysis adjusted for sex, age, and year of diagnosis showed that tumor size but not age or sex significantly predicted lymph node metastasis (HR, 19.48; P = .02)
A comparison of outcomes between patients with and without lymph node examinations found no differences in disease-specific mortality by sex, age, year of diagnosis, tumor size, local invasion, or metastasis. Significant predictors of disease-specific mortality in this analysis included surgery type (parathyroidectomy, en bloc excision, or debulking), the use of radiation, and white race.
Dr. Hsu noted that the study was limited by its retrospective design, lack of information on other significant clinical variables, lack of detailed follow-up data, and the possibility of misclassification or miscoding of cases.
He acknowledged that uncertainty about the diagnosis is a drawback to SEER-based studies, but that given the rarity of the disease, SEER data are the most reliable source of information.
The study was supported by the Wisconsin Surgical Outcomes Research Program. Dr. Hsu reported having no relevant disclosures. Study coauthor Dr. Rebecca Sippel is a member of this publication’s editorial advisory board.
AT AAES 2014
Key clinical point: Central lymph node dissection may not be needed for patients with small parathyroid tumors.
Major finding: In a multivariate analysis, tumors 3 cm or greater and the presence of metastasis were predictive of worse survival, with respective hazard ratios of 5.35 (P = .01) and 45.1 (P less than .01).
Data source: Retrospective study of SEER data on 405 patients.
Disclosures: The study was supported by the Wisconsin Surgical Outcomes Research Program. Dr. Hsu reported having no relevant disclosures.
Check thyroid function in children with vitiligo
COEUR D’ALENE, IDAHO – Every child and adolescent with vitiligo should undergo a laboratory evaluation that includes thyroid function tests and antibody levels, Dr. Pearl E. Grimes advised at the annual meeting of the Society for Pediatric Dermatology.
"At some point, we used to debate whether thyroid disease really is more common in the pediatric population with vitiligo. But now we have multiple studies in the literature to suggest that it is. And that certainly has also been my own clinical experience in looking at thyroid function tests as well as thyroid antibodies for the past 25 years in the pediatric population," said Dr. Grimes, director of the Vitiligo and Pigmentation Institute of Southern California and a dermatologist at the University of California, Los Angeles.
Vitiligo is an autoimmune disease. As such, it is well known to be associated with other autoimmune diseases in adults, with Hashimoto’s thyroiditis and other forms of thyroid disease being the most common comorbid autoimmune conditions.
Dr. Grimes cited two recent studies showing a sharply increased prevalence of thyroid abnormalities as well in the pediatric population with vitiligo.
Investigators at the Netherlands Institute for Pigment Disorders in Amsterdam reported on 260 children and adolescents with vitiligo who underwent measurement of thyroid-stimulating hormone, free thyroxine, and antithyroid peroxidase antibody levels. The results indicated 6.2% had autoimmune thyroiditis with thyroid hormone disturbances, a prevalence far greater than that seen in the general pediatric population. Moreover, 10.5% of patients had elevated levels of antithyroid peroxidase antibodies without disturbance of thyroid hormone, a condition known to be associated with an increased risk of developing overt thyroid disease down the road (Horm. Res. Paediatr. 2013;79:137-44).
In another study, investigators at Children’s Hospital in Izmir, Turkey, retrospectively reviewed laboratory findings in 79 vitiligo patients, aged 2-15 years. Fully one-quarter had abnormal results on thyroid function tests and/or elevated thyroid autoantibodies (Indian J. Endocrinol. Metab. 2013;1096-9).
Dr. Grimes recommended that a routine laboratory screening panel for children and adolescents with vitiligo should "at a bare minimum" consist of a CBC with differential, a thyroid panel, thyroid antibodies, and an anti-nuclear antibody level.
"I’ve been looking at ANAs [antinuclear antibody test results] in children and adults with vitiligo for a very long time. I find that about 30% of patients, including kids, will have a positive ANA. What’s the significance? A small cohort of vitiligo patients will go on to develop lupus. Although lupus is not one of our more common autoimmune diseases, it happens. If the ANA titer is less than 1:160, I typically don’t get a lupus panel; but if it is greater than 1:160, I will follow up with a lupus panel – and that determines whether I will send that patient for a rheumatologic consultation. The ANA is also very important in determining whether a vitiligo patient is a candidate for phototherapy. If there’s a high-titer ANA, I will not place a patient on narrow band UVB (therapy)," according to Dr. Grimes.
She reported having performed clinical research for and serving as a consultant to several pharmaceutical and cosmetics companies.
COEUR D’ALENE, IDAHO – Every child and adolescent with vitiligo should undergo a laboratory evaluation that includes thyroid function tests and antibody levels, Dr. Pearl E. Grimes advised at the annual meeting of the Society for Pediatric Dermatology.
"At some point, we used to debate whether thyroid disease really is more common in the pediatric population with vitiligo. But now we have multiple studies in the literature to suggest that it is. And that certainly has also been my own clinical experience in looking at thyroid function tests as well as thyroid antibodies for the past 25 years in the pediatric population," said Dr. Grimes, director of the Vitiligo and Pigmentation Institute of Southern California and a dermatologist at the University of California, Los Angeles.
Vitiligo is an autoimmune disease. As such, it is well known to be associated with other autoimmune diseases in adults, with Hashimoto’s thyroiditis and other forms of thyroid disease being the most common comorbid autoimmune conditions.
Dr. Grimes cited two recent studies showing a sharply increased prevalence of thyroid abnormalities as well in the pediatric population with vitiligo.
Investigators at the Netherlands Institute for Pigment Disorders in Amsterdam reported on 260 children and adolescents with vitiligo who underwent measurement of thyroid-stimulating hormone, free thyroxine, and antithyroid peroxidase antibody levels. The results indicated 6.2% had autoimmune thyroiditis with thyroid hormone disturbances, a prevalence far greater than that seen in the general pediatric population. Moreover, 10.5% of patients had elevated levels of antithyroid peroxidase antibodies without disturbance of thyroid hormone, a condition known to be associated with an increased risk of developing overt thyroid disease down the road (Horm. Res. Paediatr. 2013;79:137-44).
In another study, investigators at Children’s Hospital in Izmir, Turkey, retrospectively reviewed laboratory findings in 79 vitiligo patients, aged 2-15 years. Fully one-quarter had abnormal results on thyroid function tests and/or elevated thyroid autoantibodies (Indian J. Endocrinol. Metab. 2013;1096-9).
Dr. Grimes recommended that a routine laboratory screening panel for children and adolescents with vitiligo should "at a bare minimum" consist of a CBC with differential, a thyroid panel, thyroid antibodies, and an anti-nuclear antibody level.
"I’ve been looking at ANAs [antinuclear antibody test results] in children and adults with vitiligo for a very long time. I find that about 30% of patients, including kids, will have a positive ANA. What’s the significance? A small cohort of vitiligo patients will go on to develop lupus. Although lupus is not one of our more common autoimmune diseases, it happens. If the ANA titer is less than 1:160, I typically don’t get a lupus panel; but if it is greater than 1:160, I will follow up with a lupus panel – and that determines whether I will send that patient for a rheumatologic consultation. The ANA is also very important in determining whether a vitiligo patient is a candidate for phototherapy. If there’s a high-titer ANA, I will not place a patient on narrow band UVB (therapy)," according to Dr. Grimes.
She reported having performed clinical research for and serving as a consultant to several pharmaceutical and cosmetics companies.
COEUR D’ALENE, IDAHO – Every child and adolescent with vitiligo should undergo a laboratory evaluation that includes thyroid function tests and antibody levels, Dr. Pearl E. Grimes advised at the annual meeting of the Society for Pediatric Dermatology.
"At some point, we used to debate whether thyroid disease really is more common in the pediatric population with vitiligo. But now we have multiple studies in the literature to suggest that it is. And that certainly has also been my own clinical experience in looking at thyroid function tests as well as thyroid antibodies for the past 25 years in the pediatric population," said Dr. Grimes, director of the Vitiligo and Pigmentation Institute of Southern California and a dermatologist at the University of California, Los Angeles.
Vitiligo is an autoimmune disease. As such, it is well known to be associated with other autoimmune diseases in adults, with Hashimoto’s thyroiditis and other forms of thyroid disease being the most common comorbid autoimmune conditions.
Dr. Grimes cited two recent studies showing a sharply increased prevalence of thyroid abnormalities as well in the pediatric population with vitiligo.
Investigators at the Netherlands Institute for Pigment Disorders in Amsterdam reported on 260 children and adolescents with vitiligo who underwent measurement of thyroid-stimulating hormone, free thyroxine, and antithyroid peroxidase antibody levels. The results indicated 6.2% had autoimmune thyroiditis with thyroid hormone disturbances, a prevalence far greater than that seen in the general pediatric population. Moreover, 10.5% of patients had elevated levels of antithyroid peroxidase antibodies without disturbance of thyroid hormone, a condition known to be associated with an increased risk of developing overt thyroid disease down the road (Horm. Res. Paediatr. 2013;79:137-44).
In another study, investigators at Children’s Hospital in Izmir, Turkey, retrospectively reviewed laboratory findings in 79 vitiligo patients, aged 2-15 years. Fully one-quarter had abnormal results on thyroid function tests and/or elevated thyroid autoantibodies (Indian J. Endocrinol. Metab. 2013;1096-9).
Dr. Grimes recommended that a routine laboratory screening panel for children and adolescents with vitiligo should "at a bare minimum" consist of a CBC with differential, a thyroid panel, thyroid antibodies, and an anti-nuclear antibody level.
"I’ve been looking at ANAs [antinuclear antibody test results] in children and adults with vitiligo for a very long time. I find that about 30% of patients, including kids, will have a positive ANA. What’s the significance? A small cohort of vitiligo patients will go on to develop lupus. Although lupus is not one of our more common autoimmune diseases, it happens. If the ANA titer is less than 1:160, I typically don’t get a lupus panel; but if it is greater than 1:160, I will follow up with a lupus panel – and that determines whether I will send that patient for a rheumatologic consultation. The ANA is also very important in determining whether a vitiligo patient is a candidate for phototherapy. If there’s a high-titer ANA, I will not place a patient on narrow band UVB (therapy)," according to Dr. Grimes.
She reported having performed clinical research for and serving as a consultant to several pharmaceutical and cosmetics companies.
EXPERT ANALYSIS FROM THE SPD ANNUAL MEETING
A third of follicular thyroid lesions of undetermined significance were malignant
CHICAGO – At least in some institutions, about a third of follicular thyroid lesions of undetermined significance are malignant, reported researchers from the University of Wisconsin, Madison.
That rate is a higher proportion than the 5%-15% rate estimated by the Bethesda System, a national standard for reporting thyroid cytopathology, said Dr. Juan Carlos Jaume at the joint meeting of the International Congress of Endocrinology and the Endocrine Society.
"The message here is to be aware of your local institutional rates for cancer in FLUS, because following [the Bethesda System] may mislead you and your patient" when deciding on a course of action, be it surgery, repeat biopsy, or observation, he said. "Other institutions [should be encouraged to] do similar analyses to generate more accurate local guidelines for management of FLUS," noted Dr. Jaume, senior author of the study.
Of 1,420 nodules assessed over 2 years at the thyroid clinic at the University of Wisconsin, Madison, 134 (9.4%) were reported as follicular lesions of undetermined significance (FLUS) on fine-needle aspiration. Eighty patients opted for surgery; pathology revealed that 27 (34%) actually had differentiated thyroid cancer. Cancer also was found in four more patients, but at sites different from the original fine-needle aspiration. Most of the cancers (27) were papillary, 3 were follicular, and 1 was a Hurthle cell tumor, the investigators reported.
It’s unlikely the findings were due to selection bias, with patients who were more likely to have cancer opting for surgery. More than half of the patients chose surgery after discussing risks and benefits with their providers, not because of tumor progression. Almost all the others opted for surgery because of compression symptoms or because they had a nodule larger than 4 cm.
Even if there was a bias, "the highest expectation [with Bethesda] is 15%; our rate was 34%," a large difference, Dr. Jaume said. "As soon as we had the rate available, we conveyed the information" to providers so they could more accurately counsel patients. "I think eventually we will see an increase in the number of patients deciding on surgery."
The team performed the study because providers at the university had been relying on the Bethesda estimate to guide patients, but had a hunch that their local FLUS cancer rates were higher.
The majority of the 134 FLUS patients who opted against surgery chose ultrasound monitoring. Among the 22 who chose repeat fine-needle aspiration, half were rediagnosed with benign cytology, 5 were again diagnosed with FLUS, and most of the rest were lost to follow-up.
Among the 80 surgical patients, pathology was benign in 47 and parathyroid tissue was present in 1 biopsy. Records were unavailable for the final patient.
Some cytopathologists tend to call thyroid lesions FLUS more frequently than others; possibly, that predilection has something to do with the discordance in reported cancer rates, Dr. Jaume said.
Ultimately, the solution will be genetic analysis of fine-needle aspiration samples. There is a commercial product on the market, but "we are not using [it] in our institution because the negative predictive value is high, but the positive predictive value is low," he said.
The investigators had no relevant disclosures and had no outside funding for their work.
*Correction, 8/25/2014: An earlier version of this article misspelled Dr. Jaume's name.
CHICAGO – At least in some institutions, about a third of follicular thyroid lesions of undetermined significance are malignant, reported researchers from the University of Wisconsin, Madison.
That rate is a higher proportion than the 5%-15% rate estimated by the Bethesda System, a national standard for reporting thyroid cytopathology, said Dr. Juan Carlos Jaume at the joint meeting of the International Congress of Endocrinology and the Endocrine Society.
"The message here is to be aware of your local institutional rates for cancer in FLUS, because following [the Bethesda System] may mislead you and your patient" when deciding on a course of action, be it surgery, repeat biopsy, or observation, he said. "Other institutions [should be encouraged to] do similar analyses to generate more accurate local guidelines for management of FLUS," noted Dr. Jaume, senior author of the study.
Of 1,420 nodules assessed over 2 years at the thyroid clinic at the University of Wisconsin, Madison, 134 (9.4%) were reported as follicular lesions of undetermined significance (FLUS) on fine-needle aspiration. Eighty patients opted for surgery; pathology revealed that 27 (34%) actually had differentiated thyroid cancer. Cancer also was found in four more patients, but at sites different from the original fine-needle aspiration. Most of the cancers (27) were papillary, 3 were follicular, and 1 was a Hurthle cell tumor, the investigators reported.
It’s unlikely the findings were due to selection bias, with patients who were more likely to have cancer opting for surgery. More than half of the patients chose surgery after discussing risks and benefits with their providers, not because of tumor progression. Almost all the others opted for surgery because of compression symptoms or because they had a nodule larger than 4 cm.
Even if there was a bias, "the highest expectation [with Bethesda] is 15%; our rate was 34%," a large difference, Dr. Jaume said. "As soon as we had the rate available, we conveyed the information" to providers so they could more accurately counsel patients. "I think eventually we will see an increase in the number of patients deciding on surgery."
The team performed the study because providers at the university had been relying on the Bethesda estimate to guide patients, but had a hunch that their local FLUS cancer rates were higher.
The majority of the 134 FLUS patients who opted against surgery chose ultrasound monitoring. Among the 22 who chose repeat fine-needle aspiration, half were rediagnosed with benign cytology, 5 were again diagnosed with FLUS, and most of the rest were lost to follow-up.
Among the 80 surgical patients, pathology was benign in 47 and parathyroid tissue was present in 1 biopsy. Records were unavailable for the final patient.
Some cytopathologists tend to call thyroid lesions FLUS more frequently than others; possibly, that predilection has something to do with the discordance in reported cancer rates, Dr. Jaume said.
Ultimately, the solution will be genetic analysis of fine-needle aspiration samples. There is a commercial product on the market, but "we are not using [it] in our institution because the negative predictive value is high, but the positive predictive value is low," he said.
The investigators had no relevant disclosures and had no outside funding for their work.
*Correction, 8/25/2014: An earlier version of this article misspelled Dr. Jaume's name.
CHICAGO – At least in some institutions, about a third of follicular thyroid lesions of undetermined significance are malignant, reported researchers from the University of Wisconsin, Madison.
That rate is a higher proportion than the 5%-15% rate estimated by the Bethesda System, a national standard for reporting thyroid cytopathology, said Dr. Juan Carlos Jaume at the joint meeting of the International Congress of Endocrinology and the Endocrine Society.
"The message here is to be aware of your local institutional rates for cancer in FLUS, because following [the Bethesda System] may mislead you and your patient" when deciding on a course of action, be it surgery, repeat biopsy, or observation, he said. "Other institutions [should be encouraged to] do similar analyses to generate more accurate local guidelines for management of FLUS," noted Dr. Jaume, senior author of the study.
Of 1,420 nodules assessed over 2 years at the thyroid clinic at the University of Wisconsin, Madison, 134 (9.4%) were reported as follicular lesions of undetermined significance (FLUS) on fine-needle aspiration. Eighty patients opted for surgery; pathology revealed that 27 (34%) actually had differentiated thyroid cancer. Cancer also was found in four more patients, but at sites different from the original fine-needle aspiration. Most of the cancers (27) were papillary, 3 were follicular, and 1 was a Hurthle cell tumor, the investigators reported.
It’s unlikely the findings were due to selection bias, with patients who were more likely to have cancer opting for surgery. More than half of the patients chose surgery after discussing risks and benefits with their providers, not because of tumor progression. Almost all the others opted for surgery because of compression symptoms or because they had a nodule larger than 4 cm.
Even if there was a bias, "the highest expectation [with Bethesda] is 15%; our rate was 34%," a large difference, Dr. Jaume said. "As soon as we had the rate available, we conveyed the information" to providers so they could more accurately counsel patients. "I think eventually we will see an increase in the number of patients deciding on surgery."
The team performed the study because providers at the university had been relying on the Bethesda estimate to guide patients, but had a hunch that their local FLUS cancer rates were higher.
The majority of the 134 FLUS patients who opted against surgery chose ultrasound monitoring. Among the 22 who chose repeat fine-needle aspiration, half were rediagnosed with benign cytology, 5 were again diagnosed with FLUS, and most of the rest were lost to follow-up.
Among the 80 surgical patients, pathology was benign in 47 and parathyroid tissue was present in 1 biopsy. Records were unavailable for the final patient.
Some cytopathologists tend to call thyroid lesions FLUS more frequently than others; possibly, that predilection has something to do with the discordance in reported cancer rates, Dr. Jaume said.
Ultimately, the solution will be genetic analysis of fine-needle aspiration samples. There is a commercial product on the market, but "we are not using [it] in our institution because the negative predictive value is high, but the positive predictive value is low," he said.
The investigators had no relevant disclosures and had no outside funding for their work.
*Correction, 8/25/2014: An earlier version of this article misspelled Dr. Jaume's name.
AT ICE/ENDO 2014
Key clinical point: National estimates of FLUS malignancy may not apply to your institution.
Major finding: Among 80 patients diagnosed with FLUS who opted for surgery, the lesion turned out to be differentiated thyroid cancer in 27 (34%).
Data source: Retrospective study of outcomes for 134 FLUS nodules.
Disclosures: The investigators had no disclosures and had no outside funding for their study.
