Ultrasound Follow-Up of Benign Thyroid Nodules: A Scoping Review.

Background: For cytologically benign thyroid nodules with very low to intermediate suspicion ultrasound patterns, optimal ultrasound follow-up intervals and outcomes of discontinuing follow-up are unclear. Methods: Ovid MEDLINE, Embase, and Cochrane Central were searched through August 2022 for studies comparing different ultrasound follow-up intervals and discontinuation versus continuation of ultrasound follow-up. The population was patients with cytologically benign thyroid nodules and very low to intermediate suspicion ultrasound patterns, and the primary outcome was missed thyroid cancers. Utilizing a scoping approach, we also included studies that were not restricted to very low to intermediate suspicion ultrasound patterns or evaluated additional outcomes such as thyroid cancer-related mortality rate, nodule growth, and subsequent procedures. Quality assessment was performed, and evidence was synthesized qualitatively. Results: One retrospective cohort study (n = 1254; 1819 nodules) compared different first follow-up ultrasound intervals for cytologically benign thyroid nodules. There was no difference between >4- versus 1- to 2-year intervals to first follow-up ultrasound in the likelihood of malignancy (0.4% [1/223] vs. 0.3% [2/715]), and no cancer-related deaths occurred. Follow-up ultrasound at >4 years was associated with increased likelihood of ≥50% nodule growth (35.0% [78/223] vs. 15.1% [108/715]), repeat fine needle aspiration (19.3% [43/223] vs. 5.6% [40/715]), and thyroidectomy (4.0% [9/223] vs. 0.8% [6/715]). The study did not describe ultrasound patterns or control for confounders, and analyses were based on interval to first follow-up ultrasound only. Other methodological limitations were not controlling for variability in follow-up duration and unclear attrition. The certainty of evidence was very low. No study compared discontinuation of ultrasound follow-up versus continuation. Conclusions: This scoping review found that evidence comparing different ultrasound follow-up intervals in patients with benign thyroid nodules is limited to one observational study, but suggests that the subsequent development of thyroid malignancies is very uncommon regardless of follow-up interval. Longer follow-up may be associated with more repeat biopsies and thyroidectomies, which could be related to more interval nodule growth that meets thresholds for further evaluation. Research is needed to clarify optimal ultrasound follow-up intervals for low to intermediate suspicion cytologically benign thyroid nodules and outcomes of discontinuing ultrasound follow-up for very low suspicion nodules.

An Assessment of Diversity, Inclusion, and Health Equity Training in Endocrinology Fellowship Programs in the United States.

CONTEXT: The Accreditation Council for Graduate Medical Education has instituted common program requirements related to diversity, equity, and inclusion (DEI) for postgraduate trainees in the United States; however, the extent to which DEI training is being incorporated across endocrinology fellowship programs is unknown. OBJECTIVES: To describe the sociodemographic representation and DEI training experiences within endocrinology fellowship programs. DESIGN, SETTING, AND PARTICIPANTS: National cross-sectional survey study of fellows and fellowship program leaders in the United States whose fellowships were members of the Association of Program Directors in Endocrinology and Metabolism. MAIN OUTCOME MEASURES: (1) Demographics of fellows and program leaders and (2) programs' experience, confidence, and interest in formal DEI training. RESULTS: A total of 108 and 106 fellow and faculty responded to the survey, respectively. The majority of fellows and faculty are female. Less than 3% of fellows and 3.7% of faculty identify as Black. More than 90% of fellows/faculty are heterosexual and no respondents identified as transgender/nonbinary; however, 5% and 2% of all respondents preferred not to disclose their sexual orientation and gender identity, respectively. While 85% of faculty received institutional diversity and inclusion training, 67.6% of fellows did. Fellows are more likely to have received training in health equity than program leaders. Both fellows and program leaders express a high interest in health equity curriculum. CONCLUSIONS: Within the diversity of endocrinology training programs, Black physicians are underrepresented in medicine, which persists in endocrinology fellowships. Fellowship programs express enthusiasm for national diversity and health equity curricula, with the majority of programs reporting institutional DEI training.

Do Ultrasound Patterns and Clinical Parameters Inform the Probability of Thyroid Cancer Predicted by Molecular Testing in Nodules with Indeterminate Cytology?

Background: Molecular testing (MT) is commonly used to refine cancer probability in thyroid nodules with indeterminate cytology. Whether or not ultrasound (US) patterns and clinical parameters can further inform the risk of thyroid cancer in nodules predicted to be positive or negative by MT remains unknown. The aim of this study was to test if clinical parameters, including patient age, sex, nodule size (by US), Bethesda category (III, IV, V), US pattern (American Thyroid Association [ATA] vs. American College of Radiology Thyroid Image Reporting and Data System [TI-RADS] systems), radiation exposure, or family history of thyroid cancer can modify the probability of thyroid cancer or noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) predicted by MT. Methods: We studied 257 thyroid nodules in 232 patients from 10 study centers with indeterminate fine needle aspiration cytology and informative MT results using the ThyroSeq v3 genomic classifier (TSv3). Univariate and multivariate logistic regression was used for data analysis. Results: The presence of cancer/NIFTP was associated with positive TSv3 results (odds ratio 61.39, p < 0.0001). On univariate regression, patient sex, age, and Bethesda category were associated with cancer/NIFTP probability (p < 0.05 for each). Although ATA (p = 0.1211) and TI-RADS (p = 0.1359) US categories demonstrated positive trends, neither was significantly associated with cancer/NIFTP probability. A multivariate regression model incorporating the four most informative non-MT covariates (sex, age, Bethesda category, and ATA US pattern; Model No. 1) yielded a C index of 0.653; R2 = 0.108. When TSv3 was added to Model number 1, the C index increased to 0.888; R2 = 0.572. However, age (p = 0.341), Bethesda category (p = 0.272), and ATA US pattern (p = 0.264) were nonsignificant, and other than TSv3 (p < 0.0001), male sex was the only non-MT parameter that potentially contributed to cancer/NIFTP risk (p = 0.095). The simplest and most efficient clinical model (No. 3) incorporated TSv3 and sex (C index = 0.889; R2 = 0.588). Conclusions: In this multicenter study of thyroid nodules with indeterminate cytology and MT, neither the ATA nor TI-RADS US scoring systems further informed the risk of cancer/NIFTP beyond that predicted by TSv3. Although age and Bethesda category were associated with cancer/NIFTP probability on univariate analysis, in sequential nomograms they provided limited incremental value above the high predictive ability of TSv3. Patient sex may contribute to cancer/NIFTP risk in thyroid nodules with indeterminate cytology.

Tailoring the approach to radioactive iodine treatment in thyroid cancer.

The treatment of differentiated thyroid cancer continues to move away from a 'one size fits all' approach to a process of tailored therapeutic decision-making that incorporates disease-specific factors and individual patient preferences. Management options range from active surveillance to thyroid lobectomy to total thyroidectomy with or without the use of postoperative radioactive iodine (RAI). RAI may be administered for one or more reasons: Thyroid remnant ablation, adjuvant therapy, or therapy for persistent structural disease. It is important to be cognizant of the therapeutic intent of RAI and weigh the risks and benefits of treatment for each individual patient. Risk stratification should be used to identify those patients who are most likely to benefit from RAI and guide therapeutic choices. Available data suggest that RAI can be safely deferred for most patients considered at low risk for structural recurrence, while adjuvant RAI is associated with improved disease-free survival in patients with higher-risk disease. Although progress has been made, many areas of uncertainty related to the use of RAI remain. These include: (1) The appropriate selection of intermediate-risk patients to receive adjuvant RAI, (2) the superiority or inferiority of different RAI dosing activities, (3) the optimal approach to the use of RAI in special populations, including patients with end-stage renal disease and children, and (4) the management of patients with RAI-refractory disease.

Molecular Diagnostic Evaluation of Thyroid Nodules.

The historical management approach for many patients with indeterminate thyroid nodule fine needle aspiration cytology is a diagnostic lobectomy or thyroidectomy. However, the majority of patients undergo surgery unnecessarily, because most are proven to have benign disease on histology. Molecular testing is a diagnostic tool that can be used to help guide the clinical management of thyroid nodules with indeterminate cytology results. Testing has evolved substantially over the last decade with significant advances in testing methodology and improvements in our understanding of the genetic basis of thyroid cancer.

Prevalence of clinically silent corticotroph macroadenomas.

OBJECTIVE: The prevalence of clinically silent corticotroph macroadenomas is unknown. Our aim was to determine the prevalence of clinically silent corticotroph macroadenomas among all pituitary macroadenomas. DESIGN: Patients scheduled to have transsphenoidal surgery for any sellar mass were prospectively evaluated clinically and biochemically. PATIENTS: Adults who were scheduled for transsphenoidal surgery for a sellar mass at a single academic medical centre. MEASUREMENTS: Patients were assessed clinically prior to surgery and graded as having typical, mild or no Cushingoid features. They were assessed biochemically by plasma ACTH and 24-h urine free cortisol (UFC). Excised tissue was examined histologically, and pituitary macroadenomas, examined by immunohistochemistry. Patients with corticotroph macroadenomas were classified as clinically silent if they exhibited no Cushingoid features but had elevated plasma ACTH and/or 24-h UFC. They were classified as totally silent if they exhibited neither Cushingoid features nor elevated plasma ACTH or 24-h UFC. RESULTS: Of 124 patients who had pathologically confirmed pituitary macroadenomas, 20 (16%) had corticotroph macroadenomas. Eight (40%) of these were clinically silent, in that they had no Cushingoid features but could be identified biochemically by elevated plasma ACTH (seven) and/or 24-h UFC (three). Five (25%) were totally silent. CONCLUSIONS: A substantial minority (16%) of pituitary macroadenomas treated surgically are corticotroph adenomas. Of these, 40% are clinically silent but can be recognized by elevated plasma ACTH and/or 24-h UFC. Recognizing these adenomas may influence the surgical approach and provide a marker by which to follow the response to treatment.

Silent pituitary adenomas.

Pituitary adenomas are frequently silent. Among silent adenomas, some are clinically silent but can be detected on the basis of the excessive secretion of hormonal products, whereas others are totally silent and cannot be detected by hormonal measurements. Treatment of a silent pituitary adenoma depends on its size and extent. Silent adenomas that are associated with neurologic compromise should be treated by surgery. Postoperative radiation therapy may be used to prevent or treat recurrences. Only occasional silent pituitary adenomas respond to treatment with dopamine agonists or somatostatin analogs.

The evolving use of radioiodine therapy in differentiated thyroid cancer.

The incidence of differentiated thyroid cancer has increased worldwide over the last three decades, but thyroid cancer-related mortality remains stable. Until recently, the standard treatment for most thyroid cancers has been near-total thyroidectomy followed by radioiodine remnant ablation. Observational data support lower recurrence rates and improved survival after radioiodine ablation in patients with high-risk cancers; however, a similar benefit has not been established for all patients with thyroid cancer. Risk stratification should be used to identify patients who are likely to benefit from radioiodine ablation and guide therapeutic decisions. For most patients who need radioiodine remnant ablation, preparation for therapy with recombinant human thyroid-stimulating hormone stimulation is as effective as thyroid hormone withdrawal. Lower therapeutic doses of radioiodine are recommended for the majority of thyroid remnant ablations. Higher doses are reserved for advanced disease at initial diagnosis, local recurrences that cannot be treated with surgery alone, and distant metastatic disease.

Silent (clinically nonfunctioning) pituitary adenomas.

Silent, or clinically nonfunctioning, pituitary adenomas can arise from any anterior pituitary cell type. Some are "clinically silent" in that they result in a supranormal serum concentration of the hormonal product of the cell type from which the adenoma arose but do not cause the clinical manifestations typical of excessive levels of that hormone. Others are "totally silent" in that they result in neither hormonal excess nor clinical manifestations. Gonadotroph and null cell adenomas are the most prevalent types and are typically silent. Somatotroph and corticotroph adenomas typically cause clinical syndromes but occasionally are clinically or totally silent. Those that are silent are usually larger and grow more aggressively than those that cause clinical syndromes. Silent adenomas are usually not discovered until they become very large and cause neurologic defects, such as visual impairment, but are also often discovered incidentally when neuroimaging is performed for another reason. Silent adenomas may become, rarely, clinically apparent over time. The diagnosis of a silent pituitary adenoma begins with the detection of a sellar mass by MRI. Biochemical testing can identify the adenoma cell type in those that are clinically silent. Silent adenomas that cause neurologic deficits require transsphenoidal surgery, but those that do not can be followed by MRI. Residual or recurrent disease is treated by radiation therapy, which is usually effective in preventing further growth but results in hormonal deficiencies in about half of patients. Dopamine agonists and somatostatin analogs are usually ineffective, but occasionally have been associated with reduced adenoma size.

Severe insulin resistance and hypertriglyceridemia after childhood total body irradiation.

OBJECTIVE: To characterize the metabolic phenotype of 2 cases of normal weight young women who developed type 2 diabetes (T2D), severe insulin resistance (insulin requirement >200 units/day), marked hypertriglyceridemia (>2000 mg/dL), and hepatic steatosis beginning 9 years after undergoing total body irradiation (TBI) and bone marrow transplantation for childhood cancer. METHODS: Fasting plasma glucose, insulin, free fatty acids (FFAs), leptin, adiponectin, resistin, TNFα, and IL-6 were measured in each case and in 8 healthy women; Case 1 was also assessed after initiating pioglitazone. Coding regions and splice junctions of PPARG, LMNA, and AKT2 were sequenced in Case 1 and of PPARG in Case 2 to evaluate for familial partial lipodystrophies. Genotyping of APOE was performed in Case 1 to rule out type III hyperlipoproteinemia. RESULTS: Both cases had elevated plasma levels of insulin, leptin, resistin, and IL-6, high-normal to elevated TNFα, and low to low-normal adiponectin in keeping with post-receptor insulin resistance and adipose tissue inflammation. Case 1 experienced a biochemical response to pioglitazone. No causative mutations for partial lipodystrophies or type III hyperlipoproteinemia were identified. CONCLUSION: Though metabolic derangements have previously been reported in association with TBI, few cases have described insulin resistance and hypertriglyceridemia as severe as that seen in our patients. We speculate that early childhood TBI may impede adipose tissue development leading to metabolic complications from an attenuated ability of adipose tissue to accommodate caloric excess, and propose that this extreme metabolic syndrome be evaluated for as a late complication of TBI.

The changing face of postoperative atrial fibrillation prevention: a review of current medical therapy.

Atrial fibrillation is the most common postoperative arrhythmia with significant consequences on patient health. Postoperative atrial fibrillation (POAF) complicates up to 8% of all noncardiac surgeries, between 3% and 30% of noncardiac thoracic surgeries, and between 16% and 46% of cardiac surgeries. POAF has been associated with increased morbidity, mortality, and longer, more costly hospital stays. The risk of POAF after cardiac and noncardiac surgery may be affected by several epidemiologic and intraoperative factors, as well as by the presence of preexisting cardiovascular and pulmonary disorders. POAF is typically a transient, reversible phenomenon that may develop in patients who possess an electrophysiologic substrate for the arrhythmia that is present before or as a result of surgery. Numerous studies support the efficacy of beta-blockers in POAF prevention; they are currently the most common medication used in POAF prophylaxis. Perioperative amiodarone, sotalol, nondihydropyridine calcium channel blockers, and magnesium sulfate have been associated with a reduction in the occurrence of POAF. Biatrial pacing is a nonpharmacologic method that has been associated with a reduced risk of POAF. Additionally, recent studies have demonstrated that hydroxymethylglutaryl-CoA reductase inhibitors may decrease the risk of POAF. Finally, based on recent evidence that angiotensin converting enzyme inhibitors and angiotensin receptor blockers reduce the risk of permanent atrial fibrillation, these medications may also hold promise in POAF prophylaxis. However, there is a need for further large-scale investigations that incorporate standard methodologies and diagnostic criteria, which have been lacking in past trials.