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.

Effectiveness of Molecular Testing Techniques for Diagnosis of Indeterminate Thyroid Nodules: A Randomized Clinical Trial.

IMPORTANCE: Approximately 20% of thyroid nodules display indeterminate cytology. Molecular testing can refine the risk of malignancy and reduce the need for diagnostic hemithyroidectomy. OBJECTIVE: To compare the diagnostic performance between an RNA test (Afirma genomic sequencing classifier) and DNA-RNA test (ThyroSeq v3 multigene genomic classifier). DESIGN, SETTING, AND PARTICIPANTS: This parallel randomized clinical trial of monthly block randomization included patients in the UCLA Health system who underwent thyroid biopsy from August 2017 to January 2020 with indeterminate cytology (Bethesda System for Reporting Thyroid Cytopathology category III or IV). INTERVENTIONS: Molecular testing with the RNA test or DNA-RNA test. MAIN OUTCOMES AND MEASURES: Diagnostic test performance of the RNA test compared with the DNA-RNA test. The secondary outcome was comparison of test performance with prior versions of the molecular tests. RESULTS: Of 2368 patients, 397 were eligible for inclusion based on indeterminate cytology, and 346 (median [interquartile range] age, 55 [44-67] years; 266 [76.9%] women) were randomized to 1 of the 2 tests. In the total cohort assessed for eligibility, 3140 thyroid nodules were assessed, and 427 (13.6%) nodules were cytologically indeterminate. The prevalence of malignancy was 20% among indeterminate nodules. The benign call rate was 53% (95% CI, 47%-61%) for the RNA test and 61% (95% CI, 53%-68%) for the DNA-RNA test. The specificities of the RNA test and DNA-RNA test were 80% (95% CI, 72%-86%) and 85% (95% CI, 77%-91%), respectively (P = .33); the positive predictive values (PPV) of the RNA test and DNA-RNA test were 53% (95% CI, 40%-67%) and 63% (95% CI, 48%-77%), respectively (P = .33). The RNA test exhibited a higher PPV compared with the prior test version (Afirma gene expression classifier) (54% [95% CI, 40%-67%] vs 38% [95% CI, 27%-48%]; P = .01). The DNA-RNA test had no statistically significant difference in PPV compared with its prior version (ThyroSeq v2 next-generation sequencing) (63% [95% CI, 48%-77%] vs 58% [95% CI, 43%-73%]; P = .75). Diagnostic thyroidectomy was avoided in 87 (51%) patients tested with the RNA test and 83 (49%) patients tested with the DNA-RNA test. Surveillance ultrasonography was available for 90 nodules, of which 85 (94%) remained stable over a median of 12 months follow-up. CONCLUSIONS AND RELEVANCE: Both the RNA test and DNA-RNA test displayed high specificity and allowed 49% of patients with indeterminate nodules to avoid diagnostic surgery. Although previous trials demonstrated that the prior version of the DNA-RNA test was more specific than the prior version of the RNA test, the current molecular test techniques have no statistically significant difference in performance. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02681328.

Gene Expression Classifier vs Targeted Next-Generation Sequencing in the Management of Indeterminate Thyroid Nodules.

Context: Molecular testing has reduced the need for diagnostic hemithyroidectomy for indeterminate thyroid nodules. No studies have directly compared molecular testing techniques. Objective: Compare the diagnostic performance of Afirma Gene Expression Classifier (GEC) with that of ThyroSeq v2 next-generation sequencing assay. Design: Parallel randomized trial, monthly block randomization of patients with Bethesda III/IV cytology to GEC or ThyroSeq v2. Setting: University of California, Los Angeles. Participants: Patients who underwent thyroid biopsy (April 2016 to June 2017). Intervention: Testing with GEC or ThyroSeq v2. Main Outcome Measure: Molecular test performance. Results: Of 1372 thyroid nodules, 176 (13%) had indeterminate cytology and 149 of 157 eligible indeterminate nodules (95%) were included in the study. Of nodules tested with GEC, 49% were suspicious, 43% were benign, and 9% were insufficient. Of nodules tested with ThyroSeq v2, 19% were mutation positive, 77% were mutation negative, and 4% were insufficient. The specificities of GEC and ThyroSeq v2 were 66% and 91%, respectively (P = 0.002); the positive predictive values of GEC and ThyroSeq v2 were 39% and 57%, respectively. Diagnostic hemithyroidectomy was avoided in 28 patients tested with GEC (39%) and 49 patients tested with ThyroSeq v2 (62%). Surveillance ultrasonography was available for 46 nodules (45 remained stable). Conclusions: ThyroSeq v2 had higher specificity than Afirma GEC and allowed more patients to avoid surgery. Long-term surveillance is necessary to assess the false-negative rate of these particular molecular tests. Further studies are required for comparison with other available molecular diagnostics and for newer tests as they are developed.

Endocrinopathies with use of cancer immunotherapies.

BACKGROUND: Immunomodulatory therapies, including CTLA-4 and PD-1 inhibitors, provide a directed attack against cancer cells by preventing T cell deactivation. However, these drugs also prevent the downregulation of auto-reactive T cells, resulting in immune-related adverse events (IRAEs). Reports show a varied incidence of endocrine IRAEs, ranging from 0% to 63%. OBJECTIVE: To describe the frequency and clinical characteristics of endocrine IRAEs in patients taking cancer immunomodulatory therapies. DESIGN: Retrospective cohort study. PATIENTS: A total of 388 patients aged ≥18 years who were prescribed ipilimumab, nivolumab and/or pembrolizumab between 2009 and 2016 at our institution. MEASUREMENTS: Biochemical criteria were used to define endocrine IRAEs, including thyroid, pituitary, pancreas and adrenal dysfunction, following use of immunomodulatory therapies. RESULTS: Fifty endocrine IRAEs occurred in our cohort, corresponding to a rate of 12.9%. The most common endocrine IRAEs were thyroid dysfunction (11.1%), with a lower incidence of pituitary dysfunction (1.8% of patients). CONCLUSIONS: Over 12% of patients receiving ipilimumab, nivolumab and/or pembrolizumab in our study sample developed an endocrine IRAE. Patients who undergo treatment with immunomodulatory therapies should be monitored for the development of endocrine IRAEs.

Thyroglobulin antibody levels do not predict disease status in papillary thyroid cancer.

BACKGROUND: Thyroglobulin antibodies (TgAb) are present in approximately 20% of patients with papillary thyroid cancer (PTC) and invalidate the serum thyroglobulin (Tg) level as a tumour marker. We examined whether trends in the TgAb level could serve as a surrogate marker of disease status in the surveillance of patients with PTC. METHODS: All patients found to have a least one positive postoperative TgAb level (determined by the Beckman-Coulter Access Assay) after undergoing initial surgery for PTC from 2000 to 2010 at a single institution were included. Log-log transformation and linear regression were applied to longitudinal TgAb levels, yielding patient-specific regression coefficients that categorized as follows: highly negative, moderately negative and positive/no trend. The recurrence rate in each category was then assessed. RESULTS: Ninety-three of 967 patients with PTC were included. Recurrent disease was detected in 19 patients (20%) after a mean follow-up time of 51 months. Regression coefficients in the highly negative and moderately negative groups were not different, and hence these groups were pooled. The proportion of recurrent cases in the negative trend group was similar to that in the positive/no trend group (19.7% vs 21.9%, NS). The mean regression coefficients were similar for recurrent and nonrecurrent cases within both the negative trend group (-0.89 vs -0.80, NS) and the positive/no trend group (0.08 vs 0.33, NS). CONCLUSION: Trends in the TgAb level do not predict disease status in PTC in our experience. In the context of most commercially available TgAb assays, surveillance of TgAb-positive patients will hinge on high-quality imaging until a valid alternative serum marker to Tg is identified.

Effect of reoperation on outcomes in papillary thyroid cancer.

BACKGROUND: The influence of lymph node recurrences of papillary thyroid carcinoma (PTC) on overall prognosis is uncertain. We performed a population-based, longitudinal analysis to evaluate the impact of reoperation on mortality. METHODS: Patients who underwent initial operation for PTC >1 cm were abstracted from the California Cancer Registry database (1999-2008). Reoperation was defined as any lymph node dissection after total or near-total thyroidectomy. RESULTS: Of the 11,986 patients included in the study, 222 (1.9%) underwent one or more reoperations. The median time to reoperation was 8.7 months, with 58.6% and 83.8% of reoperations being performed within 1 and 2 years of initial thyroidectomy, respectively. The mortality rate from PTC was 2.3% (271 patients). After we adjusted for age, sex, tumor size, stage, and radioactive iodine treatment, we found that reoperation was associated with an increased risk of all-cause mortality in patients ≥45 years of age (hazard ratio [HR] 1.51, P < .05). Reoperation was associated with an increased risk of disease-specific mortality in both patients <45 (HR 6.22, P < .01) and ≥45 (HR 2.49, P < .001). CONCLUSION: Reoperation is independently associated with mortality in PTC. Most reoperations are performed soon after initial thyroidectomy and likely reflect persistent rather than recurrent disease.

A multicenter cohort study of total thyroidectomy and routine central lymph node dissection for cN0 papillary thyroid cancer.

BACKGROUND: The role of routine central lymph node dissection (CLND) for papillary thyroid cancer (PTC) remains controversial. The aim of this study was to evaluate the impact of routine CLND after total thyroidectomy (TTx) in the management of patients with PTC who were clinically node negative at presentation with emphasis on stimulated thyroglobulin (Tg) levels and reoperation rates. METHODS: This retrospective, multicenter, cohort study used pooled data from 3 international Endocrine Surgery units in Australia, the United States, and England. All study participants had PTC >1 cm without preoperative evidence of lymph node disease (cN0). Group A patients had TTx alone and group B had TTx with the addition of CLND. RESULTS: There were 606 patients included in the study. Group A had 347 patients and group B 259 patients. Stimulated Tg values were lower in group B before initial radioiodine ablation (15.0 vs 6.6 ng/mL; P = .025). There was a trend toward a lower Tg at final follow-up in group B (1.9 vs 7.2 ng/mL; P = .11). The rate of reoperation in the central compartment was lower in group B (1.5 vs 6.1%; P = .004). The number of CLND procedures required to prevent 1 central compartment reoperation was calculated at 20. CONCLUSION: The addition of routine CLND in cN0 papillary thyroid carcinoma is associated with lower postoperative Tg levels and reduces the need for reoperation in the central compartment.