Thyroid Carcinoma, Version 2.2022, NCCN Clinical Practice Guidelines in Oncology.

Differentiated thyroid carcinomas is associated with an excellent prognosis. The treatment of choice for differentiated thyroid carcinoma is surgery, followed by radioactive iodine ablation (iodine-131) in select patients and thyroxine therapy in most patients. Surgery is also the main treatment for medullary thyroid carcinoma, and kinase inhibitors may be appropriate for select patients with recurrent or persistent disease that is not resectable. Anaplastic thyroid carcinoma is almost uniformly lethal, and iodine-131 imaging and radioactive iodine cannot be used. When systemic therapy is indicated, targeted therapy options are preferred. This article describes NCCN recommendations regarding management of medullary thyroid carcinoma and anaplastic thyroid carcinoma, and surgical management of differentiated thyroid carcinoma (papillary, follicular, Hürthle cell carcinoma).

Rapid Relief: Thyroidectomy is a Quicker Cure than Radioactive Iodine Ablation (RAI) in Patients with Hyperthyroidism.

BACKGROUND: Time to hormonal control after definitive management of hyperthyroidism is unknown but may influence patient and physician decision making when choosing between treatment options. The hypothesis is that the euthyroid state is achieved faster after thyroidectomy than RAI ablation. METHODS: A retrospective review of all patients undergoing definitive therapy for hyperthyroidism was performed. Outcomes after thyroidectomy were compared to RAI. RESULTS: Over 3 years, 217 patients underwent definitive therapy for hyperthyroidism at a county hospital: 121 patients received RAI, and 96 patients underwent thyroidectomy. Age was equivalent (p = 0.72). More males underwent RAI (25% vs 15%, p = 0.05). Endocrinologists referred for both treatments equally (p = 0.82). Both treatments were offered after a minimum 1-year trial of medical management (p = 0.15). RAI patients mostly had Graves (93%), versus 73% of thyroidectomy patients (p < 0.001). Thyroidectomy patients more frequently had eye symptoms (35% vs 13%, p < 0.001), compressive symptoms (74% vs 15%, p < 0.001), or were pregnant/nursing (14% vs 0, p < 0.001). While the thyroidectomy patients had a documented discussion of all treatment modalities, 79% of RAI patients did not have a documented discussion regarding the option of surgical management (p < 0.001). Both treatment groups achieved an euthyroid state (71% vs 65%, p = 0.39). Thyroidectomy patients became euthyroid faster [3 months (2-7 months) versus 9 months (4-14 months); p < 0.001]. CONCLUSIONS: Thyroidectomy for hyperthyroidism renders a patient to an euthyroid state faster than RAI. This finding may be important for patients and clinicians considering definitive options for hyperthyroidism.

Contralateral adrenal abnormalities in Conn's syndrome.

BACKGROUND: During the course of evaluation for primary hyperaldosteronism, cross-sectional imaging is obtained in efforts to identify patients with an aldosterone producing adenoma (APA). A subset of these patients will have a synchronous, contralateral adrenal abnormality. Adrenal vein sampling (AVS) further guides clinical decision making by identifying unilateral (APA) versus bilateral hypersecretion. In the subset of patients with contralateral adrenal abnormalities, it is unclear how this affects the durability of an adrenalectomy for APA. This study characterizes this group of patients to assess the efficacy of surgical intervention. METHODS: A retrospective review of patients undergoing adrenalectomy for APA based on AVS at a university practice. Preoperative and postoperative patient characteristics, laboratory evaluations, imaging results, and final pathology were noted. RESULTS: From 2000 to 2011, 103 patients with APA underwent unilateral adrenalectomy. Eighteen patients (17%) had discordant results between AVS and imaging. Most of these patients were male (78%), and the mean age was 57 ± 13 y. Median duration of follow-up was 3.5 y [1 y, 6 y]. All patients with initial hypokalemia were rendered normokalemic after the operation. Four patients increased their antihypertensive regimen during the follow-up period. These patients all had nodular hyperplasia on final pathology. CONCLUSIONS: In patients with bilateral adrenal abnormalities who have undergone unilateral adrenalectomy for primary hyperaldosteronism, patients with clear APAs on final pathology appear to have durable outcomes after resection. Conversely, nodular hyperplasia on final pathology may be a risk factor for ongoing aldosterone hypersecretion. An algorithm for biochemical surveillance in this subset of patients should be considered.

Early endocrine attending surgeon presence increases operating room efficiency.

BACKGROUND: Preincision operating room (OR) preparation varies greatly. Cases requiring exacting preoperative setup may be more sensitive to inconsistent team members and trainees. Leadership and oversight by the surgeon may facilitate a timely start. The study hypothesized that early attending presence in the OR expedites surgery start time, improving efficiency, and decreasing cost. METHODS: Prospective data collection of endocrine surgery cases at an urban teaching hospital was performed. Time points recorded in minutes. Cost/min of OR time was $54. Patients classified as in the OR ≤10 min before attending arrival or >10 min before attending arrival. RESULTS: A total of 227 cases (166 thyroid, 54 parathyroid, 10 adrenal) were performed over 14 mo. Of the patients, 128 were in the OR ≤10 min before attending arrival, and 99 patients were >10 min (3 ± 3 min versus 35 ± 14 min, P < 0.01). The ≤10 min procedures started sooner after patient arrival in OR (40 ± 11 versus 63 ± 19, P < 0.01) which equated to $1202 of savings before incision. Although attending time in the OR before incision was equivalent between groups for adrenal and parathyroid, time to incision was shorter in the ≤10 min groups, saving $2416 ± 477 and $1458 ± 244, respectively (P < 0.01). Attending time in OR before thyroidectomy was 13 min longer in ≤10 min than >10 min (P < 0.01), but incisions were made 20 min sooner (P < 0.01) equating to $1076 ± 120 in savings. CONCLUSIONS: Early attending presence in the OR shortens time to incision. For parathyroid and adrenal cases, this does not require additional surgeon time. In ORs without consistent teams, early attending presence in the OR improves efficiency and yields significant cost savings.

Avoidable biopsies? Validating artificial intelligence-based decision support software in indeterminate thyroid nodules.

BACKGROUND: Multiple artificial intelligence (AI) systems have been approved to risk-stratify thyroid nodules through sonographic characterization. We sought to validate the ability of one such AI system, Koios DS (Koios Medical, Chicago, IL), to aid in improving risk stratification of indeterminate thyroid nodules. METHODS: A retrospective single-institution dataset was compiled of 28 cytologically indeterminate thyroid nodules having undergone molecular testing and surgical resection, with surgical pathology categorized as malignant or benign. Nodules were retrospectively evaluated with Koios DS. After nodule selection, automated and AI-adapter-derived Thyroid Imaging Reporting and Data System (TI-RADS) levels were recorded, and agreement with radiologist-derived levels was assessed using Cohen's κ statistic. The performance of malignancy classification was compared between the radiologist and AI-adapter. Biopsy thresholds were re-evaluated using the AI-adapter. RESULTS: In this cohort, 7 (25%) nodules were malignant on surgical pathology. The median nodule size was 2.4 cm (interquartile range: 1.8-2.9 cm). Median radiologist and automated TI-RADS levels were both 4, with κ 0.25 ("fair agreement"). Malignancy classification by the radiologist provided sensitivity 100%, specificity 33.3%, positive predictive value (PPV) 33.3%, and negative predictive value (NPV) 100%, compared with the AI-adapter's performance with sensitivity 85.7%, specificity 76.2%, PPV 54.5%, and NPV 94.1%. Using the AI-adapter, 14 of 28 biopsies would have been deferred, 13 of which were surgically benign. CONCLUSION: Koios automated and radiologist-derived TI-RADS levels were in consistent agreement for indeterminate thyroid nodules. Malignancy reclassification with the AI-adapter improved PPV at minimal cost to NPV. Risk stratification with the addition of the AI-adapter may allow for more accurate patient counseling and the avoidance of biopsies in select cases that would otherwise be cytologically indeterminate.

Risk of malignancy in cytologically indeterminate thyroid nodules harboring thyroid stimulating hormone receptor mutations.

Objectives: To evaluate the frequency and risk of malignancy of TSHRpI568T mutations discovered in indeterminate thyroid nodules (ITN) within the Veracyte CLIA laboratory undergoing Afirma® Genomic Sequencing Classifier (GSC) testing, and to evaluate a broader cohort of TSHR variants and their categorization as Afirma GSC benign (GSC-B) or suspicious (GSC-S). Finally, we seek to assess the risk of malignancy (ROM) of this group of TSHR mutated ITN in the GSC-S category. Methods: ITN submitted to Veracyte for Afirma GSC testing between October 2017 and February 2022 were analyzed for TSHR variants and rates of GSC-B and GSC-S were calculated based upon BIII or IV cytology, by TSHR variant codon amino acid (AA) substitution, age, and gender. For GSC-S samples, surgical pathology reports were requested, and the rate of malignancy was calculated. Results: Five percent of the ITN samples harbored an isolated TSHR variant and 5% of those were classified as GSC-S. Among TSHRpI568T samples, 96% were GSC-B and of the GSC-S samples, 21% were malignant. Among an unselected group of TSHR, absent TSHRpI568T mutations, 16.3% of GSC-S samples were malignant, all but one with codon mutations in the transmembrane subdomains of the TSHR. This prompted a dedicated evaluation of transmembrane codons which revealed a malignancy rate of 10.7% among GSC-S nodules. In total, 13/85 (15.3%) TSHR mutated ITN with Afirma GSC-S results were found to be malignant. Conclusions: TSHR variants are rare in ITN, and most are categorized as benign under Afirma GSC testing which carries a < 4% risk of malignancy. For GSC-S ITN with TSHR mutations, the risk of malignancy is ≥= 15%, which is clinically meaningful and may alter treatment or monitoring recommendations for patients.

Papillary thyroid carcinoma shows elevated levels of 2-hydroxyglutarate.

Elevated levels of D: -2-hydroxyglutarate (D: -2-HG) occur in gliomas and myeloid leukemias associated with mutations of IDH1 and IDH2. L: -2-Hydroxyglutaric aciduria, an inherited metabolic disorder, predisposes to brain tumors. Therefore, we asked whether sporadic cancers, without IDH1 or IDH2 hot-spot mutations, show elevated 2-hydroxyglutarate levels. We retrieved 15 pairs of frozen papillary thyroid carcinoma (PTC) and adjacent non-neoplastic thyroid, and 14 pairs of hyperplastic nodule (HN) and adjacent non-hyperplastic thyroid. In all lesions, exon 4 sequencing confirmed the absence of known mutations of IDH1 and IDH2. We measured 2-hydroxyglutarate by liquid chromatography-tandem mass spectrometry. Compared to normal thyroid, PTCs had significantly higher D: -2-HG and L: -2-hydroxyglutarate (L: -2-HG) levels, and compared to HNs, PTCs had significantly higher D: -2-HG levels. D: -2-HG/L: -2-HG levels were not significantly different between HNs and normal thyroid. Further studies should clarify if elevated 2-hydroxyglutarate in PTC may be useful as cancer biomarker and evaluate the role of 2-hydroxyglutarate in cancer biology.

Long-Term Outcomes of Thyroid Nodule AFIRMA GEC Testing and Literature Review: An Institutional Experience.

OBJECTIVE: To assess outcomes of thyroid nodules analyzed with the AFIRMA gene expression classifier (GEC) and to perform a comprehensive literature review. STUDY DESIGN: Retrospective analysis of patients with thyroid nodules who underwent AFIRMA GEC testing at our institution. SETTINGS: A tertiary care academic institution. SUBJECTS AND METHODS: We collected clinical outcomes for 416 thyroid nodules that were analyzed with AFIRMA GEC between 2011 and 2015, including long-term follow-up through 2019. We performed a comprehensive literature review. RESULTS: The resection rate for nodules with "suspicious" GEC results was 85% with a positive predictive value of 37%. The resection rate for nodules with "benign" GEC results was 24% with a negative predictive value of 90%. The prevalence of thyroid malignancy in patients with thyroid nodules with indeterminate cytology at our institution during this timeframe was 41%, thus lowering our negative predictive value. Mean follow-up duration for unresected nodules was 27.8 months. Our resection rates for nodules with "benign" GEC were among the highest reported in the literature. CONCLUSIONS: Molecular marker testing of thyroid nodules with indeterminate cytology can aid in the surgical decision making by obviating the need for diagnostic surgery and/or guiding extent of resection. Patients with other indications for surgery may not benefit from such costly testing.

What Predicts Recurrent Kidney Stone after Parathyroidectomy in Patients with Primary Hyperparathyroidism?

BACKGROUND: Some, but not all, patients with primary hyperparathyroidism (PHPT) and kidney stone disease (KSD) are cured of their nephrolithiasis after parathyroidectomy. The goal of this study was to identify risk factors for recurrent KSD despite successful parathyroidectomy in known stone formers with PHPT. STUDY DESIGN: We conducted a single-center retrospective review of patients presenting to urology clinic with KSD between January 2008 and July 2018, who were diagnosed with concurrent PHPT, and underwent definitive parathyroidectomy. Laboratory testing for serum calcium, PTH (parathyroid hormone), phosphorus and 25-OH-vitamin D, and 24-hour urine studies for volume, pH, calcium, citrate, oxalate, uric acid, sodium, and creatinine was performed pre- and post-parathyroidectomy. Stone recurrence was determined on routine diagnostic imaging or by symptomatic KSD. RESULTS: Mean age at parathyroidectomy was 57 ± 14 years. Pre-parathyroidectomy, mean serum calcium, 24-hour urine calcium, and PTH were 10.6 ± 0.5 mg/dL, 378 ± 209 mg/day, and 114 ± 97 pg/mL, respectively. Twenty-six of 69 patients (38%) had multigland parathyroid disease. After parathyroidectomy, serum calcium and PTH levels normalized in 69 of 69 and 62 of 69 patients, respectively. However, 37 of 69 patients (54%) had persistent hypercalciuria postoperatively, and 16 of 69 (23%) had recurrent KSD, on average, 2.0 ± 1.6 years after parathyroidectomy. Patients with recurrent KSD post-parathyroidectomy were significantly younger compared with patients without recurrent KSD (51 ± 15 vs 60 ± 13 years, p = 0.02). In a logistic regression model, younger age remains a strong predictive factor for recurrent KSD. CONCLUSIONS: Nearly one-quarter of PHPT patients with KSD who undergo successful parathyroidectomy present with recurrent KSD despite normalization of serum calcium, and more than half exhibit persistent calciuria. These patients were younger and may require closer monitoring for stone recurrence after successful parathyroidectomy. Further studies are needed to better identify the etiology of KSD post-parathyroidectomy.

Surgical approach and perioperative complications determine short-term outcomes in patients with insulinoma: results of a bi-institutional study.

BACKGROUND: Despite advancements in radiologic imaging and minimally invasive surgery, the evaluation and management of insulinomas is institution and surgeon dependent. Therefore, the reported surgical outcomes are highly variable. We compared the surgical management and outcomes of insulinomas between two international tertiary-care surgical units to better identify the best management as determined by short-term outcomes. METHODS: We performed a retrospective review of patients who underwent surgery for insulinomas over a 117-month period at UT Southwestern Medical Center in Dallas (UTSW) and Queen Mary Hospital in Hong Kong (QMHK). Data collected included imaging studies, operative procedure, complications, and outcomes. RESULTS: Thirty-seven patients were identified. Preoperative localization by computed tomography (CT) scan was successful in 21 patients (63.9%). In Hong Kong, 16 patients underwent selective arterial cannulation and calcium stimulation (SACST) with a success rate of 87.5%. Surgical management consisted of enucleation in 24 patients and distal pancreatectomy in 13 patients. Thirty patients underwent a concurrent intraoperative ultrasound, with localization in 96.7%. Laparoscopic procedures were accomplished in 20 patients. Nine postoperative complications were identified, four occurring in the laparoscopic group. Patients undergoing laparoscopic procedures had a decreased length-of-stay (LOS) compared with patients undergoing an open procedure and patients who had uncomplicated surgery had a trend toward decreased LOS. CONCLUSION: Though the accuracy of CT scans for localizing insulinomas is only 64%, the addition of SACST or intraoperative ultrasound and pancreatic palpation increases accuracy to 97.1%. Compared with open procedures, laparoscopic resection is associated with comparable complication rates and shorter hospital length of stay.

Measurement of 18-hydroxycorticosterone during adrenal vein sampling for primary aldosteronism.

CONTEXT: In primary aldosteronism, elevated serum 18-hydroxycorticosterone (18OHB) suggests aldosterone-producing adenoma (APA) rather than bilateral, idiopathic hyperaldosteronism (IHA), but little is known about the relative production of 18OHB and aldosterone (A) in APAs compared with IHA. OBJECTIVES: We measured 18OHB, A, and cortisol (F) in blood from adrenal vein sampling (AVS) studies. We compared the discriminatory power of gradients in 18OHB/A and 18OHB/F ratios with A/F ratio gradients for distinguishing APA from IHA. DESIGN, SETTING, AND SUBJECTS: We measured 18OHB and A in excess serum from 23 AVS studies performed at our university hospitals. MAIN OUTCOME MEASURES: We calculated the ratios 18OHB/A, 18OHB/F, and A/F for all specimens, and determined the adrenal vein gradients for these ratios. RESULTS: The 18OHB/A ratios were much lower in blood draining APAs (2.17 +/- 0.62) than in blood draining the contralateral adrenals (12.96 +/- 12.76; P < 0.001) but similar to blood draining IHA adrenals (4.69 +/- 4.32; P = 0.02). In contrast, the 18OHB/F ratios were elevated in specimens from APAs (26.03 +/- 11.51) compared with IHA adrenals (9.22 +/- 5.18; P < 0.001) or the contralateral adrenals (6.23 +/- 2.97; P < 0.001). Using 18OHB/F gradient greater than two or 18OHB/A gradient less than 0.5 as criteria for lateralization, interpretations agreed with lateralizations based on A/F gradients in 21 of 23 cases. CONCLUSIONS: High serum 18OHB in APA reflects augmented production of both 18OHB and A, not disproportionate 18OHB secretion relative to A. The 18OHB/A and 18OHB/F gradients are useful adjuncts but not as reliable as A/F gradients for A lateralization during AVS.

Glucocorticoid-responsive lymphocytic parathyroiditis and hypocalciuric hypercalcemia due to autoantibodies against the calcium-sensing receptor: a case report and literature review.

OBJECTIVE: Autoimmune lymphocytic parathyroiditis and acquired hypocalciuric hypercalcemia associated with autoantibodies against the calcium-sensing receptor (anti-CaSR) are rare and poorly understood conditions. Here, we describe a patient with acquired parathyroid hormone (PTH)-dependent hypercalcemia with associated hypocalciuria, found to have true lymphocytic parathyroiditis on histopathology, and circulating anti-CaSR antibodies in serum. DESIGN AND METHODS: A 64-year-old woman was referred to our clinic for persistent hypercalcemia after a subtotal parathyroidectomy. She was normocalcemic until the age of 63 years when she was diagnosed with primary hyperparathyroidism. She underwent subtotal parathyroidectomy with appropriate intraoperative PTH decline. Two weeks post-parathyroidectomy, she presented with persistent hypercalcemia and hyperparathyroidism. Urine studies revealed an inappropriately low 24-h urine calcium (Ca)/creatinine clearance ratio. Surgical pathology was consistent with true lymphocytic parathyroiditis with lymphoid follicles. The presence of circulating anti-CaSR antibodies was detected by immunoprecipitation of CaSR by the patient's serum. After a 4-week course of prednisone, serum Ca and PTH normalized, and her anti-CaSR titers declined. She remains normocalcemic 10 months after the discontinuation of glucocorticoid therapy. We present this patient in the context of the relevant published literature on lymphocytic parathyroiditis and acquired hypocalciuric hypercalcemia related to anti-CaSR antibodies. CONCLUSIONS: Autoimmune lymphocytic parathyroiditis and acquired hypocalciuric hypercalcemia associated with anti-CaSR antibodies is a very rare yet important condition to be considered in a patient with acquired PTH-dependent hypercalcemia with inappropriate hypocalciuria. Although subtotal parathyroidectomy is unlikely to correct the hypercalcemia, this entity may respond to a short course of prednisone therapy.

Primary hyperaldosteronism: effect of adrenal vein sampling on surgical outcome.

HYPOTHESIS: Adrenal vein sampling is superior to computed tomography for subtype differentiation of primary hyperaldosteronism. DESIGN: Retrospective review. SETTING: University medical center. PATIENTS: Forty-eight patients (32 men and 16 women) with biochemically confirmed primary hyperaldosteronism. MAIN OUTCOME MEASURES: We compared demographic factors, results of biochemical and imaging studies (computed tomography and adrenal vein sampling), therapy, and patient outcomes. RESULTS: Mean +/- SEM adrenal nodule size was 1.54 +/- 0.2 cm. Adrenal vein sampling was performed in 41 (85%) of 48 patients, and it was successful in 39 (95%) of those 41 patients. Concordance between computed tomography and adrenal vein sampling was observed in 22 (54%) of the 41 patients. Thirty-two patients underwent successful laparoscopic adrenalectomy. There was 1 complication and no deaths. All 32 patients were cured of hypokalemia. CONCLUSION: Adrenal vein sampling is superior to image-based techniques for subtype differentiation of primary hyperaldosteronism.

The impact of obesity on the presentation of primary hyperparathyroidism.

CONTEXT: Obesity has been associated with elevated serum PTH (sPTH) in the general population. Obesity may also alter the clinical presentation in patients with primary hyperparathyroidism (PHPT). OBJECTIVES: The objectives of the study were to compare the clinical presentation of obese (OB) vs nonobese (NO) PHPT patients and to assess the impact of obesity on the presentation of PHPT independent of serum calcium and PTH. PATIENTS: Consecutive PHPT patients who underwent parathyroidectomy between 2003 and 2012 by a single surgical group participated in the study. SETTING: The study was conducted at an academic medical center. DESIGN: Cross-sectional review of records of preoperative demographic, historical, laboratory, and densitometry findings and intraoperative pathological findings were compared in OB vs NO patients. MAIN OUTCOME MEASURES: The prevalence of nephrolithiasis and osteoporosis was measured. RESULTS: Two hundred forty-seven PHPT patients were included in this analysis. Fifty percent were OB and 79% were women. Mean body mass index was 25.3 ± 3.3 and 36.0 ± 5.2 kg/m(2) in the NO and OB groups, respectively. Age, gender, and race distribution was similar between the two groups. Serum calcium was similar between the groups (11.0 ± 0.7 mg/dL in NO vs 11.1 ± 0.9 mg/dL in OB, P = .13), whereas sPTH was higher in OB (151 ± 70 vs 136 ± 69 pg/mL, P = .03). The OB group exhibited higher prevalence of hypercalciuria (urine calcium > 400 mg per 24 h) (41% vs 23% in NO, P = .01) and nephrolithiasis (36% vs 21% in NO, P = .03). Despite higher sPTH, OB patients showed higher bone mineral density and a lower rate of osteoporosis (21% vs 35%, P = .05). Differences in the prevalence of hypercalciuria and osteoporosis between the groups persisted after adjustment for age, race, estimated glomerular filtration rate, gender, sPTH, and calcium. CONCLUSIONS: In PHPT patients, obesity is a risk factor for hypercalciuria and nephrolithiasis and is protective against osteoporosis. The impact of parathyroidectomy on the clinical features of obese PHPT patients merits further evaluation.

Significance of elevated parathyroid hormone after parathyroidectomy for primary hyperparathyroidism.

OBJECTIVE: To provide a clinical update on persistent parathyroid hormone (PTH) elevation after surgical resection for primary hyperparathyroidism (PHPT) and to suggest a schedule for follow-up monitoring and strategies for future study. METHODS: We reviewed the literature targeting studies with detailed analysis of biochemical parameters before and after parathyroidectomy for PHPT. We focused on potential etiologies and currently available outcome data. RESULTS: PTH elevation with eucalcemia after parathyroidectomy for PHPT occurs in 12% to 43% of patients. Underlying etiology is probably multifactorial, and possible causes include bone hunger, vitamin D deficiency, inadequate calcium intake or absorption, reduced peripheral sensitivity to PTH, underlying chronic kidney disease, and/or a renal leak of calcium. No consensus exists on how to follow-up and treat these patients. CONCLUSIONS: Although most patients with PTH elevation after parathyroidectomy will have normalization of PTH levels with time and/or calcium and vitamin D supplementation, this finding may be an early indicator of autonomous parathyroid secretion in a small number of patients. Patients with persistent PTH elevation should be monitored over time for recurrence of PHPT and other possible complications. A standardized follow-up protocol is needed to better study and elucidate the clinical significance of elevated PTH after parathyroidectomy.

Effect of the Bethesda system for reporting thyroid cytopathology on thyroidectomy rates and malignancy risk in cytologically indeterminate lesions.

BACKGROUND: Cytologically indeterminate thyroid nodules represent a diagnostic and therapeutic challenge. In 2007, the National Cancer Institute recommended The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) as a means of improving the accuracy of thyroid cytopathology. Our objective was to determine the effect of TBSRTC on thyroidectomy rates and malignancy risk in cytologically indeterminate lesions. METHODS: We compared thyroidectomy rates and malignancy risk in patients with indeterminate thyroid cytopathology across 2 time periods, spanning January 2000 and November 2009; pre-TBSRTC (January 2000 to September 2003) and post-TBSRTC (June 2008 to November 2009). Statistical comparisons were performed using the Fisher's exact test and chi-square analysis (P = .05 significant). RESULTS: We performed 938 fine-needle aspirations in the first period, 765 in the second. We identified 78 (8.3%) cytologically indeterminate lesions in the pre-TBSRTC group and 91 (11.9%) lesions in the post-TBSRTC group. We found no difference in thyroidectomy rates between the groups (37/78 [47%] pre-Bethesda versus 32/91 [35%] post-Bethesda; P = .12). However, the malignancy rate was significantly lower in the post-TBSRTC group (13/37 [35%] pre-Bethesda versus 4/32 [13%] post-Bethesda; P = .02). CONCLUSION: Application of TBSRTC is associated with lower malignancy risk in indeterminate thyroid nodules, despite similar thyroidectomy rates. These findings imply that standardization of cytologic classification improves diagnostic accuracy.

Trends in thyroid cancer demographics and surgical therapy in the United States.

BACKGROUND: The incidence of thyroid cancer is increasing. Our objective was to characterize the demographic pattern of this increase and to examine trends in surgical therapy for thyroid cancer. METHODS: Analysis of the SEER and NHDS databases was performed from 1974 to 2000 and from 1979 to 2004, respectively. Thyroid-related diagnoses were extracted, and thyroid cancer (ICD 193.X) were analyzed using the SAS statistical package. We compared the population-adjusted incidence of thyroid cancer and examined regional variations in the operative therapy for thyroid cancer. RESULTS: The incidence of thyroid cancer has increased during the past 26 years. This increase occurred predominantly in women and in the Northeastern and Southern United States, whereas there has been a decrease in thyroid cancers in the Midwest. Papillary cancer accounts for most of this increase. Total thyroidectomy (TT) is now the most common operation for thyroid cancer. No differences in the use of TT were observed based on hospital size or insurance status. CONCLUSION: The increasing incidence of thyroid cancer in the United States is predominantly in women. These results suggest that women are a high-risk group for developing thyroid cancer although men have higher stage disease.

"Subclinical Cushing's syndrome" is not subclinical: improvement after adrenalectomy in 9 patients.

BACKGROUND: A subgroup of patients with adrenal cortisol hypersecretion fails to meet the biochemical criteria for Cushing's syndrome. Appropriate therapy for this entity, subclinical Cushing's syndrome (subclinical CS), is unclear. We examined outcomes for patients who underwent unilateral adrenalectomy for subclinical CS. METHODS: Between 2003 and 2006, all patients who underwent adrenalectomy for cortisol hypersecretion caused by an adrenal mass were examined. We analyzed biochemical, metabolic, and clinical outcomes. RESULTS: Overall, 24 patients underwent adrenalectomy for adrenal cortisol hypersecretion, of which 9 were found to have subclinical CS. Median serum cortisol was 2.0 microg/dL (range, 1.1-6.1) after 1-mg overnight dexamethasone suppression testing. Suspicious clinical findings on preoperative examination included skin bruising, unexplained weight gain, proximal muscle weakness, abnormal fat pads, skin thinning, fatigue, and facial plethora. During a median follow-up period of 5 months (range, 1-30 months), all 8 patients with easy bruising noted resolution postoperatively. Fatigue improved in 4 of 5 patients, muscle weakness in 6 of 8 patients, and weight in 7 of 9 patients, with a median body mass index change of -2.0 kg/m(2) (range, -7.1 to +0.5 kg/m(2)). CONCLUSION: Adrenalectomy improves clinical and metabolic parameters for many patients with subclinical CS.