Management of Thyrotoxicosis Among General Practitioners in Trinidad Compared with 2016 American Thyroid Association Guidelines for Hyperthyroidism

Objective: A previous Trinidadian survey highlighted the investigative and therapeutic approaches selected by general practitioners (GPs) in managing thyrotoxicosis. The main objective of this study was to compare practice with existing guidelines.Methods: In this cross-sectional study a pretested de novo questionnaire was self-administered to GPs throughout Trinidad. The survey evaluated GPs' choices in management of thyrotoxicosis cases and compared their responses to the 2016 American Thyroid Association guidelines as well as with those previously reported locally.Results: A total of 159 completed questionnaires were analyzed (59% response rate). Thyroid stimulating hormone was the preferred (94%) biochemical test to confirm thyrotoxicosis etiology. A combination of ultra-sound and thyroid scintigraphy, thyroid ultrasound alone, and scintigraphy only were the testing options selected by 41%, 38%, and 12%, respectively. Generally medical therapy with antithyroid drugs was the preferred treatment option with 86% of respondents selecting this option for the index case of newly diagnosed female Graves disease. The greatest proportion of respondents that selected radioactive iodine (RAI) was 35% for both the index case as well as the male equivalent. Surgery was the most popular option at 25% for patients with a toxic multinodular goiter. Having access to RAI and scintigraphy was reported by 32% and 28%, respectively.Conclusion: GPs appear to be constrained to making rational choices based upon availability rather than what the guidelines recommend. In the absence of formal continuing medical education for GPs on thyrotoxicosis, dissemination of guidelines at the primary care level may reduce this gap.Abbreviations: ATA = American Thyroid Association; ATD = antithyroid drugs; CME = continued medical education; GP = general practitioner; RAI = radioactive iodine; SURG = surgery; T4 = thyroxine; TSH = thyroid-stimulating hormone     

Management of Hyperparathyroidism in Kidney Transplantation Candidates: A Need for Consensus

Objective: To assess the evolving standards of care for hyperparathyroidism in kidney transplant candidates.Methods: An 11-question, Institutional Review Board–approved survey was designed and reviewed by multiple institutions. The questionnaire was made available to the American Society of Transplantation's Kidney Pancreas Community of Practice membership via their online hub from April through July 2019.Results: Twenty percent (n = 41) of kidney transplant centers responded out of 202 programs in the United States. Forty-one percent (n = 17) of respondents believed medical literature supports the concept that a serum parathyroid hormone level greater than 800 pg/mL could endanger the survival of a transplanted kidney and therefore makes transplantation in an affected patient relatively or absolutely contraindicated. Sixty-six percent (n = 27) said they occasionally recommend parathyroidectomy for secondary hyperparathyroidism prior to transplantation, and 66% (n = 27) recommend parathyroidectomy after transplantation based on persistent, unsatisfactory posttransplantation parathyroid hormone levels. Forty-six percent (n = 19) prefer subtotal parathyroidectomy as their choice; 44% (n = 18) had no standard preference. Endocrine surgery and otolaryngology were the most common surgical specialties consulted to perform parathyroidectomy in kidney transplant candidates. The majority of respondents (71%, n = 29) do not involve endocrinologists in the management of kidney transplantation candidates.Conclusion: Our survey shows wide divergence of clinical practice in the area of surgical management of kidney transplantation candidates with hyperparathyroidism. We suggest that medical/surgical societies involved in the transplantation care spectrum convene a multidisciplinary group of experts to create a new section in the kidney transplantation guidelines addressing the collaborative management of parathyroid disease in transplantation candidates.Abbreviations: AACE = American Association of Clinical Endocrinologists; AAES = American Association of Endocrine Surgeons; AHNS = American Head and Neck Society; CKD = chronic kidney disease; CKD-MBD = chronic kidney disease–mineral and bone disorder; ESRD = end-stage renal disease; HPT = hyperparathyroidism; KDIGO = Kidney Disease Improving Global Outcomes; KT = kidney transplantation; KTC = kidney transplant candidate; PTH = parathyroid hormone; PTX = parathyroidectomy; US = ultrasonography     

Implementing Key Changes in The American Thyroid Association 2015 Thyroid Nodules/Differentiated Thyroid Cancer Guidelines Across Practice Types

Objective: This article provides suggestions to help clinicians implement important changes in the 2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Carcinoma (“ATA 2015”) across diverse settings.Methods: Key ATA 2015 changes are summarized regarding: (1) thyroid nodule management; (2) lobectomy versus thyroidectomy for differentiated thyroid carcinoma (DTC); and (3) surveillance following primary treatment of DTC. Advice to facilitate implementation is based on clinical experience and selected literature.Results: Strategies are described to enhance acquisition of high-quality information that helps identify patients who may possibly avoid fine-needle aspiration (FNA) of thyroid nodules or total thyroidectomy for DTC, or undergo less intense postoperative surveillance. Sonographic imaging of nodules may improve if sonograms are obtained by clinicians ordering or performing FNA or trusted high-volume sonographers. Cytopathologic assessment and reporting can be improved by working with regional or national experts. Pre-operative evaluation by endocrinologists is important so that patients are referred to experienced, proficient surgeons and assisted with well-informed decision-making regarding surgical radicality. Endocrinologists and surgeons should ensure performance of pre-operative neck ultrasonography, voice/laryngeal evaluation, and contrast-enhanced cross-sectional imaging when appropriate. Findings should be disseminated to all healthcare team members, ideally through a comprehensive medical record accessible to the entire team.Conclusion: Optimization of the sequence of specialist visits and assembly of interactive multidisciplinary teams coupled with intensified interdisciplinary and patient communication may enable clinicians to more effectively implement ATA 2015, which calls for more individualized, and often, less “invasive” management of thyroid nodules and DTC.Abbreviations: ATA 2009 = 2009 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Carcinoma; ATA 2015 = 2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Carcinoma; DTC = differentiated thyroid carcinoma; FNA = fine-needle aspiration; PET/CT = positron emission tomography/computed tomography     

Historical and Current Perspective in the Use of Thyroid Extracts for the Treatment of Hypothyroidism

Objective: To describe the history, refinements, implementation, physiology, and clinical outcomes achieved over the past several centuries of thyroid hormone replacement strategies.Methods: A Medline search was initiated using the following search terms: bioidentical thyroid hormone, thyroid hormone extract, combination thyroxine (T4) and tri-iodothyronine (T3) therapy, homeopathic thyroid hormone therapy, and thyroid hormone replacement. Pertinent articles of interest were identified by title (and where available abstract) for further review. Additional references were identified during a review of the identified literature.Results: A rich history of physician intervention in thyroid dysfunction was identified dating back more than 2 millennia. Although not precisely documented, thyroid ingestion from animal sources had been used for centuries but was finally scientifically described and documented in Europe over 130 years ago. Since the reports by Bettencourt and Murray, there has been a continuous documentation of outcomes, refinement of hormone preparation production, and updating of recommendations for the most effective and safe use of these hormones for relieving the symptoms of hypothyroidism. As the thyroid extract preparations contain both levothyroxine (LT4) and liothyronine (LT3), current guidelines do not endorse their use as controlled studies do not clearly document enhanced objective outcomes compared with LT4 monotherapy. Among current issues cited, the optimum ratio of LT4 to LT3 has yet to be determined, and the U.S. Food and Drug Administration (FDA) does not appear to be monitoring the thyroid hormone ratios or content in extract preparations on the market. Taken together, these limitations are important detriments to the use of thyroid extract products.Conclusion: The evolution of thyroid hormone therapies has been significant over the extended period of time they have been in use to treat hypothyroidism. Although numerous websites continue to advocate the use of thyroid hormone extracts as a superior therapy for hypothyroidism, none of the most recent guidelines of major endocrine societies recommend thyroid extract use for hypothyroidism.Abbreviations: AACE = American Association of Clinical Endocrinologists ATA = American Thyroid Association BMR = basal metabolic rate FDA = Food and Drug Administration FT4 = free thyroxine 131-I = radioactive iodine 131 LT3 = liothyronine LT4= levothyroxine NDA = new drug application PBI = proteinbound iodine T3 = triiodothyronine T4 = thyroxine TSH = thyroid-stimulating hormone TT3 = total triiodothyronine USP = U.S. Pharmacopeia     

No Benefit of Dedicated Thyroid Nodule Screening in Patients with Acromegaly

Objective: Acromegaly results from the excessive production of growth hormone and insulin-like growth factor-1. While there is up to a 2-fold increased prevalence of thyroid nodules in patients with acromegaly, the incidence of thyroid cancer in this population varies from 1.6 to 10.6% in several European studies. The goal of our study was to determine the prevalence of thyroid nodules and thyroid cancer among patients with acromegaly at a large urban academic medical center in the United States (U.S.).Methods: A retrospective chart review was performed of all patients with acromegaly between 2006–2015 within the University of California, Los Angeles health system. Data were collected regarding patient demographics, thyroid ultrasounds, thyroid nodule fine needle aspiration (FNA) biopsy cytology, and thyroid surgical pathology.Results: In this cohort (n = 221, 49.3% women, mean age 53.8 ± 15.2 [SD] years, 55.2% Caucasian), 102 patients (46.2%) underwent a thyroid ultrasound, from which 71 patients (52.1% women, mean age 52.9 ± 15.2 [SD] years, 56.3% Caucasian) were found to have a thyroid nodule. Seventeen patients underwent a thyroid nodule FNA biopsy and the results revealed 12 benign biopsies, 1 follicular neoplasm, 3 suspicious for malignancy, and 1 papillary thyroid cancer (PTC), from which 6 underwent thyroidectomy; PTC was confirmed by surgical pathology for all cases (8.5% of all nodules observed).Conclusion: In this sample, the prevalence of thyroid cancer in patients with acromegaly and coexisting thyroid nodules is similar to that reported in the general U.S. population with thyroid nodules (7 to 15%). These findings suggest that there is no benefit of dedicated thyroid nodule screening in patients newly diagnosed with acromegaly.Abbreviations: AACE = American Association of Clinical Endocrinologists; ATA = American Thyroid Association; DTC = differentiated thyroid cancer; FNA = fine needle aspiration; GH = growth hormone; IGF-1 = insulin-like growth factor-1; PTC = papillary thyroid cancer; U.S. = United States     

Additional Surgery for Occult Risk Factors After Lobectomy in Solitary Thyroid Nodules is Predicted by Cytopathology Classification and Tumor Size

Objective: Clinical practice for differentiated thyroid cancer is moving towards lobectomy rather than total thyroidectomy in patients at low risk of recurrence. However, recurrence risk assessment depends on post-operative findings, while the surgical decision is based on preoperative factors. We determined the preoperative predictors of occult higher-risk pathology and rates of completion thyroidectomy among surgical candidates with nonbenign thyroid nodules 10 to 40 mm and no evidence of extrathyroidal extension or metastasis on preoperative evaluation.Methods: Thyroid surgery cases at a single institution from 2005–2015 were reviewed to identify those meeting American Thyroid Association (ATA) criteria for lobectomy. ATA-based risk stratification from postoperative surgical pathology was compared to preoperative cytopathology, ultrasound, and clinical findings.Results: Of 1,995 thyroid surgeries performed for nonbenign thyroid nodules 10 to 40 mm, 349 met ATA criteria for lobectomy. Occult high-risk features such as tall cell variant, gross extrathyroidal invasion, or vascular invasion were found in 36 cases (10.7%), while intraoperative lymphadenopathy led to surgical upstaging in 13 (3.7%). Intermediate risk features such as moderate lymphadenopathy or minimal extrathyroidal extension were present in an additional 44 cases. Occult risk features were present twice as often in Bethesda class 6 cases (35%) as in lower categories (12 to 17%). In multivariable analysis, Bethesda class and nodule size, but not age, race, sex, or ultrasound features, were significant predictors of occult higher-risk pathology.Conclusion: Most solitary thyroid nodules less than 4 cm and with cytology findings including atypia of undetermined significance through suspicious for papillary thyroid cancer would be sufficiently treated by lobectomy.Abbreviations: ATA = American Thyroid Association; CND = central neck dissection; DTC = differentiated thyroid cancer; ETE = extrathyroidal extension; FNA = fine needle aspiration; FTC/HCC = follicular thyroid carcinoma/Hurthle cell carcinoma; NIFTP = noninvasive follicular thyroid neoplasm with papillary-like nuclear features; OR = odds ratio; PTC = papillary thyroid cancer; US = ultrasound     

Is it Worth Suppressing Tsh in low- and Intermediate-Risk Papillary Thyroid Cancer Patients Before the First Disease Assessment?

Objective: Guidelines recommend thyroid-stimulating hormone (TSH) suppression before the first response to treatment assessment in papillary thyroid cancer (PTC) patients. The aim of this study was to assess the rate of structural disease (SD) in low- and intermediate-risk PTC patients according to TSH levels measured 1 year after primary treatment.Methods: A consecutive, prospective series of low- and intermediate-risk PTC patients with 3-years follow-up was collected. TSH, thyroglobulin (Tg), antithyroglobulin antibodies (TgAb), and neck ultrasonography (US) 1 and 3 years after primary treatment were analyzed. Recurrence risk and disease status at 1 year were defined according to the American Thyroid Association (ATA) guidelines and as the presence or absence of SD after 3 years. Patients were grouped according to TSH level at 1 year: group 1, TSH <0.1 μUI/mL; group 2, TSH 0.1 to 0.5 μUI/mL; group 3, 0.5 to 2 μUI/mL; and group 4 >2 μUI/mL.Results: This study included 263 patients (70.9% female, median age 47.2 years) of whom the risk of recurrence was low in 170 (65%), intermediate-low in 63 (24%), and intermediate-high in 30 (11%). The response to initial treatment at 1 year was excellent in 149 (57%), biochemical incomplete in 18 (7%), indeterminate in 84 (32%), and structural incomplete in 12 (4%). Group 1 consisted of 53 (20%) patients, group 2 of 85 (32%), group 3 of 61 (23%), and group 4 of 64 (24%). The rate of SD at 1 and 3 years from primary treatment was not significantly different between TSH groups.Conclusion: TSH suppression before the first response to treatment assessment does not appear to influence the rate of SD evaluated 1 and 3 years after primary treatment.Abbreviations: ATA = American Thyroid Association; DTC = differentiated thyroid cancer; FTC = follicular thyroid cancer; LT4 = levothyroxine; PTC = papillary thyroid cancer; SD = structural disease; Tg = thyroglobulin; TgAb = antithyroglobulin antibodies; TSH = thyroid-stimulating hormone; US = ultrasonography     

Drivers of the Decision to Biopsy and Follow-Up of Small Suspicious Thyroid Nodules

Objective: In 2015, the updated American Thyroid Association (ATA) guidelines recommended observation for suspicious subcentimeter thyroid nodules, based on their indolent course. We aimed to evaluate the frequency of biopsy in suspicious thyroid nodules since the introduction of these guidelines, including factors contributing to clinical decision-making in a tertiary care center.Methods: We conducted a retrospective study of patients in the Mayo Clinic, Rochester, Minnesota, with new, subcentimeter suspicious thyroid nodules (by report or by sonographic features) between March, 2015, and November, 2017, not previously biopsied.Results: We identified 141 nodules in 129 patients: mean age 58.1 ± 14.1 years, 74% female, 87% Caucasian. The frequency of biopsy in suspicious thyroid nodules was 39%. Ultrasound features that were the strongest predictors for biopsy on multivariate analysis included: nodule volume (odds ratio [OR] 37.3 [7.5–188.7]), radiology recommendation for biopsy (OR 2.6 [1.8–3.9]) and radiology report of the nodule as “suspicious” (OR 2.1 [1.4–3.2]). Patient’s age and degree of comorbidities did not change the likelihood for biopsy, nor did it vary by clinician type or how the nodule was initially found (incidentally or not incidentally). Among 86 nodules that were not biopsied, 41% had no specific follow-up recommendations.Conclusion: One third of suspicious thyroid nodules underwent biopsy since the release of updated ATA guidelines. Factors driving thyroid biopsy seem to be associated with nodule characteristics but not with patient factors including age and comorbidities. Further studies and development of decision aides may be helpful in providing individualized approaches for suspicious thyroid nodules.Abbreviations: ATA = American Thyroid Association; OR = odds ratio     

A 2017 Survey of the Clinical Practice Patterns in the Management of Relapsing Graves Disease

Objective: Previous surveys from different world regions have demonstrated variations in the clinical management of Graves disease (GD). We aimed to investigate the clinical approach to GD relapse among endocrinologists.Methods: Electronic questionnaires were e-mailed to all members of the Israeli Endocrine Society. Questionnaires included demographic data and different scenarios regarding treatment and follow-up of patients with GD relapse.Results: The response rate was 49.4% (98/198). For a young male with GD relapse, 68% would restart antithyroid drug (ATD) (98% methimazole), while 32% would refer to radioactive iodine (RAI) treatment. Endocrinologists who treat >10 thyroid patients a week tended to choose ATDs over RAI (P = .04). In the case of GD relapse with ophthalmopathy, 50% would continue ATDs, whereas 22.4% would recommend RAI treatment and 27.6% surgery. Most endocrinologists (56%) would continue ATDs for 12 to 24 months. Seventy-five percent would monitor complete blood count and liver function (39% for the first month and 36% for 6 months), and 44% would recommend a routine neck ultrasound. In a case of thyrotoxicosis due to a 3-cm hot nodule, most endocrinologists (70%) would refer to RAI ablation, 46.4% without and 23.7% with a previous fine-needle aspiration. No significant differences were found regarding gender, year of board certification, or work environment.Conclusion: Our survey demonstrates diverging patterns in the diagnosis and management of GD relapse that correlate well with previous surveys from other countries on GD-naïve patients and a less than optimal adherence to recently published clinical guidelines.Abbreviations: ATA = American Thyroid Association; ATD = antithyroid drug; CBC = complete blood count; GD = Graves disease; GO = Graves ophthalmopathy; LFT = liver function test; MMI = methimazole; PTU = propylthiouracil; RAI = radioactive iodine; TSI = thyroid-stimulating immunoglobulin     

Comparison of Diagnostic Performance between the American College of Radiology Thyroid Imaging Reporting and Data System and American Thyroid Association Guidelines: A Systematic Review

Objective: We aimed to compare the diagnostic accuracy of the American College of Radiology Thyroid Imaging Reporting and Data System (ACR TI-RADS) with the American Thyroid Association (ATA) guidelines in risk stratification of thyroid nodules.Methods: We performed a computerized search of Medline, EMBASE, Web of Science, Cochrane Library, and Google Scholar to identify eligible articles published before July 31, 2019. We included studies providing head-to-head comparison between ACR TI-RADS and ATA guidelines, with fine-needle aspiration biopsy cytology results or pathology results as the reference standard. Quality assessment of included studies was conducted using the Quality Assessment of Diagnostic Accuracy Studies–2 tool. Summary estimates of sensitivity and specificity were calculated by bivariate modeling and hierarchical summary receiver operating characteristic modeling. We also performed multiple subgroup analyses and meta-regression.Results: Twelve original articles with 13,000 patients were included, involving a total of 14,867 thyroid nodules. The pooled sensitivity of ACR TI-RADS and ATA guidelines was 0.84 (95% confidence interval [CI], 0.76–0.89) and 0.89 (95% CI, 0.80–0.95), with specificity of 0.67 (95% CI, 0.56–0.76) and 0.46 (95% CI, 0.29–0.63), respectively. There were no significant differences between the two classification criteria in terms of both sensitivity (P = .26) and specificity (P = .05). For five studies providing direct comparison of ACR TI-RADS, ATA guidelines, and Korean TI-RADS, our analyses showed that the Korean TI-RADS yielded the highest sensitivity (0.89; 95% CI, 0.82–0.94), but at the cost of a significant decline in specificity (0.23; 95% CI, 0.17–0.30).Conclusion: Both classification criteria demonstrated favorable sensitivity and moderate specificity in the stratification of thyroid nodules. However, use of ACR TI-RADS could avoid a large number of biopsies at the cost of only a slight decrease in sensitivity.Abbreviations: ACR = American College of Radiology; ATA = American Thyroid Association; FNAB = fine-needle aspiration biopsy; HSROC = hierarchical summary receiver operating characteristic; SROC = summary receiver operating characteristic; TI-RADS = Thyroid Imaging Reporting and Data System; US = ultrasonography     

Programmed Cell Death–Ligand 1 Overexpression in Thyroid Cancer

Objective: Programmed cell death–ligand 1 (PD-L1) expression on tumor tissue has been associated with favorable response to anti–programmed cell death–receptor 1/PD-L1 therapy in many human cancers. Studies have reported that PD-L1 is also expressed in thyroid cancer. The objective of this paper is to introduce the potential predictive and therapeutic values of PD-L1 in thyroid cancer.Methods: A literature search was conducted in the PubMed database using the terms “PD-L1,” “B7-H1,” and “thyroid cancer.” PD-L1 positivity was determined by immunohistochemical assay.Results: The frequency of PD-L1 positivity in different studies ranged from 6.1 to 82.5% in papillary thyroid cancer (PTC) patients and 22.2 to 81.2% in anaplastic thyroid cancer (ATC) patients. PD-L1 positivity rate was higher in ATC than in PTC within the same studies, and its expression intensity was significantly higher in tumor tissue than in the corresponding nontumor thyroid tissues. Moreover, PD-L1 expression was positively associated with the aggressiveness and recurrence of thyroid cancers and negatively associated with the differentiation status and outcomes. PD-L1 checkpoint pathway blockade may emerge as a promising therapeutic target in the treatment of thyroid cancers.Conclusion: PD-L1 is a potential biomarker to predict the recurrence and prognosis of thyroid cancers. It is also a novel immunotherapy target for optimizing the management landscape of radioiodine-refractory and ATCs.Abbreviations: ATC = anaplastic thyroid cancer; DTC = differentiated thyroid cancer; IHC = immunohistochemical; OS = overall survival; PD-1 = programmed cell death–receptor 1; PD-L1 = programmed cell death–ligand 1; PD-L2 = programmed cell death–ligand 2; PTC = papillary thyroid cancer; TNM = tumor-node-metastasis; Treg = regulatory T cell     

An Italian Survey of Compliance With Major Guidelines for L-Thyroxine of Primary Hypothyroidism

Objective: The adherence by endocrinologists to guideline regarding levothyroxine (LT4) therapy and the compliance of patients may impact the management of hypothyroidism. The aim of this study was to compare the adherence of Italian endocrinologists to the ATA/AACE and ETA guidelines on the management of newly diagnosed primary hypothyroidism and to validate the Italian version of the Morisky-Green Medical Adherence Scale-8 (MMAS-8) questionnaire as applied to the evaluation of the adherence of patients with hypothyroidism to LT4 treatment.Methods: This was an observational, longitudinal, multicenter, cohort study, involving 12 Italian Units of Endocrinology.Results: The study enrolled 1,039 consecutive outpatients (mean age 48 years; 855 women, 184 men). The concordance of Italian endocrinologists with American Association of Clinical Endocrinologists/American Thyroid Association (AACE/ATA) and European Thyroid Association (ETA) recommendations was comparable (77.1% and 71.7%) and increased (86.7 and 88.6%) after the recommendations on LT4 dose were excluded, considering only the remaining recommendations on diagnosis, therapy, and follow-up. The MMAS-8 was filled out by 293 patients. The mean score was 6.71 with 23.9% low (score <6), 38.6% medium (6 to <8), 37.5% highly (= 8) adherers; the internal validation coefficient was 0.613. Highly adherent patients were not more likely to have good control of hypothyroidism compared with either medium (69% versus 72%, P = .878) or low (69% versus 43%, P = .861) adherers.Conclusion: Clinical management of hypothyroidism in Italy demonstrated an observance of international guidelines by Italian endocrinologists. Validation of the Italian version of the MMAS-8 questionnaire provides clinicians with a reliable and simple tool for assessing the adherence of patients to LT4 treatment.Abbreviations: AACE = American Association of Clinical Endocrinologists; ATA = American Thyroid Association; EDIPO = Endotrial SIE: DIagnosis and clinical management of Primitive hypothyrOidism in Italy; eCRF = electronic case report form; ETA = European Thyroid Association; fT3 = free triiodothyronine; fT4 = free thyroxine; LT4 = levothyroxine; MMAS-8 = Morisky-Green Medical Adherence Scale-8; PH = primary hypothyroidism; T3 = triiodothyronine; T4 = thyroxine; TSH = thyroid-stimulating hormone; US = ultrasonography     

Thyroid Nodule Location on Ultrasonography as a Predictor of Malignancy

Objective: The diagnostic capacity of ultrasonography (US) for differentiating between malignant and benign thyroid nodules is crucial in preventing unnecessary invasive procedures. This is the first study to evaluate whether thyroid nodule location on US has predictive value for malignancy.Methods: We retrospectively reviewed data from 219 patients with thyroid nodules who underwent fine-needle aspiration biopsy in 1 year. Patients' demographics as well as nodule's laterality, polarity, morphology, and multinodularity were analyzed. All malignant lesions were confirmed by surgical pathology.Results: The majority of the patients were female (86.2%). Nodules were evenly distributed between the right lobe (46.3%) and left lobe (49.5%). Eight nodules (4.2%) were located in the isthmus. Most nodules (79.3%) were located in the lower pole, while 9.6% were located in the upper pole and 6.9% in the middle pole. Seventy-five patients (39.9%) had multiple nodules. Fourteen nodules were malignant, representing a prevalence of 7.4%. A significantly higher frequency of malignancy was observed in upper pole (22.2%) compared to lower pole (4.7%) and middle pole (15.4%). A multiple logistic regression model confirmed such association after adjusting for age, body mass index, multinodularity, and laterality. The odds of malignancy in the upper pole were 4 times higher than other locations (odds ratio, 4.6; P = .03).Conclusion: Our study is the first showing that thyroid nodules located in the upper pole can be considered as having higher risk for malignancy. It may enhance the predictive value of malignancy if it is included in thyroid nodule ultrasound classification guidelines.Abbreviations: AACE = American Association of Clinical Endocrinologists; ATA = American Thyroid Association; BMI = body mass index; FNA = fine-needle aspiration; TMS = total malignancy score; TTW = taller than wide; US = ultrasonography     

A Novel Double Mutation Val648ile and Val804leu of Ret Proto-Oncogene in Multiple Endocrine Neoplasia Type 2

Objective: We report the case of a female patient with multiple endocrine neoplasia type 2A (MEN2A) who was found to have a double mutation in the RET (rearranged during transfection) proto-oncogene.Methods:RET mutational analysis was performed by Sanger DNA sequencing.Results: The proband was a compound heterozygote for the RET germline mutations Val648Ile and Val804Leu on exons 11 and 14, respectively. Genetic analysis of family members showed the presence of the Val648Ile mutation in all except 1 daughter who carried the Val804Leu mutation. However, none of them showed any clinical, biochemical, or histologic signs of neoplastic disease either in the thyroid or adrenal gland. Furthermore, a daughter and the proband's sister who underwent a prophylactic thyroidectomy did not show pathologic evidence of C-cell disease.Conclusions: We hypothesize that the combined effect of the 2 mutations may have induced the development of pheochromocytoma (PHEO) in our patient. Thus, in the presence of single RET-induced mild medullary thyroid cancer (MTC) phenotype, the search for additional genetic anomalies may lead to the discovery of rare but potentially more aggressive double mutation genotypes.Abbreviations: ACTH = adrenocorticotropic hormone ATA = American Thyroid Association CT = calcitonin FMTC = familial medullary thyroid cancer HSCR = Hirschsprung disease MEN2A/B = multiple endocrine neoplasia type 2A/2B MTC = medullary thyroid cancer PHEO = pheochromocytoma RET = rearranged during transfection SDHB/D = succinate dehydrogenase subunits B/D VHL = Von Hippel-Lindau     

Utility of Afirma Gene Expression Classifier for Evaluation of Indeterminate Thyroid Nodules and Correlation with Ultrasound Risk Assessment: Single Institutional Experience

Objective: We assessed our experience with Afirma gene expression classifier (GEC) combined with sono-graphic risk assessment, using both the American Thyroid Association (ATA) and the Thyroid Imaging Reporting and Data System (TI-RADS) in evaluating indeterminate thyroid nodules.Methods: We identified 98 patients with 101 nodules who had a second fine needle aspiration biopsy (FNA) between January 1, 2014, and September 30, 2017, and sent to Veracyte for cytopathology and subsequent Afirma GEC testing. A second FNA biopsy was performed if the initial cytopathology was either Bethesda III or IV (n = 94) or nondiagnostic (n = 7). We correlated cytopathology, histopathology, and Afirma GEC results with sonographic risk assessment using both the ATA system and TI-RADS.Results: The mean age of the cohort was 57.4 ± 12.3 years; 84% women and 60% white. Repeat FNA was benign in 51 of 101 nodules, and of the remaining 50 nodules, 18 (36%) were GEC-benign and 32 (64%) GEC-suspicious. Eighteen of the 32 GEC-suspicious nodules underwent surgery with the following results: 7 benign (39%), 1 follicular thyroid carcinoma (6%), 6 follicular variant of papillary thyroid cancer (33%), and 4 noninvasive follicular tumor with papillary-like nuclear features (22%). The malignancy rate among the surgical cohort was 39% (without noninvasive follicular tumor with papillary-like nuclear features [NIFTP]) and 61% (with NIFTP) and about 50% and 20% of this group scored in the high suspicion category by ATA and TR5 by TI-RADS, respectively.Conclusion: Afirma GEC was useful in avoiding surgery in one-third of indeterminate nodules and performed similarly to ATA and TI-RADS. However, the use of echogenicity in scoring may underestimate the risk of malignancy in patients with indeterminate nodules.Abbreviations:ATA = American Thyroid Association; AUS = Atypia of Undetermined Significance; FLUS = Follicular Lesion of Undetermined Significance; FN = follicular neoplasm; FNA = fine needle aspiration; FTC = follicular thyroid cancer; FVPTC = follicular variant of papillary thyroid cancer; GEC = Gene Expression Classifier; ND = nondiagnostic; NIFTP = noninvasive follicular tumor with papillary-like nuclear features; TI-RADS = Thyroid Imaging Reporting and Data System; TR = TI-RADS     

Clinical Practice Patterns for Postoperative Water Balance After Pituitary Surgery

Objective: Abnormalities of water and sodium balance, including diabetes insipidus and the syndrome of inappropriate antidiuretic hormone (SIADH), are common complications of transsphenoidal surgery. Postoperative practice patterns vary among clinicians, and no consensus guidelines exist to direct their monitoring and management. We aimed to identify and compare practice patterns regarding the evaluation and management to these postoperative complications.Methods: A questionnaire was utilized to capture demographic data and practice habits in the postoperative setting. Respondents were members of the Pituitary Society, an international organization comprised of clinicians and researchers dedicated to the study of pituitary disease.Results: Eighty-six respondents completed at least part of the survey. The geographic distribution of respondents was roughly even between American and non-American practitioners. The majority of respondents practiced at academic institutions (67.4%), worked in multidisciplinary teams (88.4%), and possessed significantly greater than 10 years of clinical experience (71%). Compared to non-American practitioners, American practitioners described a shorter length of stay postoperatively (P<.001) and prescribed more restrictive volume recommendations for postoperative SIADH (P = .0035). Early career clinicians (less than 10 years in practice) checked first postoperative sodium level earlier than later career clinicians (P = .010).Conclusion: Water and sodium dysregulation are common following transsphenoidal surgery, but their management is not well-standardized in clinical practice. We created a questionnaire to define and compare practice patterns. Most respondents practice in academic settings in multidisciplinary teams. The length of clinical experience did not significantly impact practice habits. Practice location influenced length of stay postoperatively and fluid restriction in SIADH.Abbreviations: AVP = arginine vasopressin; DI = diabetes insipidus; LOS = length of stay; SIADH = syndrome of inappropriate antidiuretic hormone     

Transculturalization Recommendations For Developing Latin American Clinical Practice Algorithms In Endocrinology Proceedings Of The 2015 Pan-American Workshop By The American Association Of Clinical Endocrinologists And American College Of Endocrinology

The American Association of Clinical Endocrinologists (AACE) and American College of Endocrinology (ACE) convened their first Workshop for recommendations to optimize Clinical Practice Algorithm (CPA) development for Latin America (LA) in diabetes (focusing on glycemic control), obesity (focusing on weight loss), thyroid (focusing on thyroid nodule diagnostics), and bone (focusing on postmenopausal osteoporosis) on February 28, 2015, in San Jose, Costa Rica. A standardized methodology is presented incorporating various transculturalization factors: resource availability (including imaging equipment and approved pharmaceuticals), health care professional and patient preferences, lifestyle variables, socio-economic parameters, web-based global accessibility, electronic implementation, and need for validation protocols. A standardized CPA template with node-specific recommendations to assist the local transculturalization process is provided. Participants unanimously agreed on the following five overarching principles for LA: (1) there is only one level of optimal endocrine care, (2) hemoglobin A1C should be utilized at every level of diabetes care, (3) nutrition education and increased pharmaceutical options are necessary to optimize the obesity care model, (4) quality neck ultrasound must be part of an optimal thyroid nodule care model, and (5) more scientific evidence is needed on osteoporosis prevalence and cost to justify intervention by governmental health care authorities. This 2015 AACE/ACE Workshop marks the beginning of a structured activity that assists local experts in creating culturally sensitive, evidence-based, and easy-to-implement tools for optimizing endocrine care on a global scale.Abbreviations:A1C = glycated hemoglobinAACE = American Association of Clinical EndocrinologistsACE = American College of EndocrinologyBG = blood glucoseBMI = body mass indexCPA = Clinical Practice AlgorithmCPG = Clinical Practice GuidelineCVD = cardiovascular diseaseDXA = dual-energy X-ray absorptiometryEDC = endocrine-disrupting compoundFBG = fasting blood glucoseFNA = fine-needle aspirationHCP = health care professionalLA = Latin AmericaPAACE = Pan-American AACESU = sulfonylureaT2D = type 2 diabetestDNA = transcultural Diabetes Nutrition AlgorithmTSH = thyroid-stimulating hormoneWC = waist circumferenceWHO = World Health Organization     

Study Of The Prevalence Of Autoimmune Thyroid Disease In Women With Breast Cancer

Objective: The aim of this study was to analyze the prevalence of thyroid disorders in patients with a positive biopsy for breast cancer prior to specific antitumor treatment.Methods: The frequency and pattern of thyroid disorders were evaluated in 112 patients with breast cancer (G1) and 125 control patients (G2) by analyzing serum thyroid-stimulating hormone (TSH), anti–thyroid peroxidase antibodies, and anti-thyroglobulin antibodies. In addition, the expression of estrogen receptors, progesterone receptors, and human epidermal growth factor receptor 2 (HER2) was assessed in the breast biopsies by immunohistochemistry.Results: The frequency of thyroid disorders, such as changes in TSH levels and/or the presence of thyroid antibodies, was not different between the 2 groups examined (30.4% in G1 versus 28.0% in G2) (P = .69). However, a family history of thyroid disease was more frequent in patients with breast cancer (50.5% in G1 versus 28.2% in G2) (P = .001). Regarding the clinical stage of breast cancer, there was no difference between women with autoimmune thyroiditis and those without thyroid dysfunction (P = .316). Similarly, there were no differences in hormone receptor (estrogen or progesterone) and HER2 expression between patients who tested positive and those who tested negative for anti-thyroid antibodies (P = .052 and P = .549, respectively).Conclusion: The data obtained in this study did not reveal a higher frequency of autoimmune thyroid disease in patients with breast cancer compared to controls. A family history of thyroid disease was more common in those with breast cancer.Abbreviations:anti-Tg = anti-thyroglobulinanti-TPO = anti–thyroid peroxidaseBIRADS = Breast Imaging-Reporting and Data SystemER = estrogen receptorFT₄ = free thyroxineG1 = study groupG2 = final control groupHER2 = human epidermal growth factor receptor 2PR = progesterone receptorTSH = thyroid-stimulating hormone     

Referral Patterns for Patients With High-Risk Thyroid Cancer

ObjectiveKnowledge of referral patterns for specialty cancer care is sparse. Information on both the need and reasons for referral of high-risk, well-differentiated thyroid cancer patients should provide a foundation for eliminating obstacles to appropriate patient referrals and improving patient care.MethodsWe surveyed 370 endocrinologists involved in thyroid cancer management. From information in a clinical vignette, respondents were asked to identify the reasons they would need to refer a high-risk patient to a more specialized facility for care. We performed multivariable analysis controlling for hospital and physician characteristics.ResultsThirty-two percent of respondents reported never referring thyroid cancer patients to another facility. Of those that would refer a high-risk patient to another facility, the opportunity for a patient to enter a clinical trial was the most common reason reported (44%), followed by high-dose radioactive iodine (RAI) with or without dosimetry (33%), lateral neck dissection (24%), and external beam radiation (15%). In multivariable analysis, endocrinologists with a higher percentage of their practice devoted to thyroid cancer care were significantly less likely to refer patients to another facility (P = .003).ConclusionsThe majority of endocrinologists treating thyroid cancer patients report referring a high-risk patient to another facility for some or all of their care. Knowledge of the patterns of physician referrals and the likelihood of need for referral are key to understanding discrepancies in referral rates and obstacles in the referral process. (Endocr Pract. 2013;19:638-643)     

National Survey of Endocrinologists and Surgeons Regarding Active Surveillance for Low-Risk Papillary Thyroid Cancer

ObjectiveActive surveillance for low-risk papillary thyroid cancer (PTC) was endorsed by the American Thyroid Association guidelines in 2015. The attitudes and beliefs of physicians treating thyroid cancer regarding the active surveillance approach are not known.MethodsA national survey of endocrinologists and surgeons treating thyroid cancer was conducted from August to September 2017 via professional society emails. This mixed-methods analysis reported attitudes toward potential factors impacting decision-making regarding active surveillance, beliefs about barriers and facilitators of its use, and reasons why physicians would pick a given management strategy for themselves if they were diagnosed with a low-risk PTC. Survey items about attitudes and beliefs were derived from the Cabana model of barriers to guideline adherence and theoretical domains framework of behavior change.ResultsAmong 345 respondents, 324 (94%) agreed that active surveillance was appropriate for at least some patients, 81% agreed that active surveillance was at least somewhat underused, and 76% said that they would choose surgery for themselves if diagnosed with a PTC of ≤1 cm. Majority of the respondents believed that the guidelines supporting active surveillance were too vague and that the current supporting evidence was too weak. Malpractice and financial concerns were identified as additional barriers to offering active surveillance. The respondents endorsed improved information resources and evidence as possible facilitators to offering active surveillance.ConclusionAlthough there is general support among physicians who treat low-risk PTC for the active surveillance approach, there is reluctance to offer it because of the lack of robust evidence, guidelines, and protocols.