The Current Status of Preclinical Endocrine Education in U.S. Medical Schools.

OBJECTIVE: To characterize the current landscape of preclinical medical endocrine education in U.S. allopathic medical schools. METHODS: U.S. endocrine curriculum directors were asked to voluntarily complete a 16-question email survey surveying the status of endocrine preclinical education at their medical school. RESULTS: Sixty-nine of 155 (45%) endocrine block director respondents completed the online survey between July 2021 and September 2021. A larger incoming class, a longer duration of the endocrine curriculum, and the offering of a separate endocrine curriculum (ie apart from the teaching of other organ systems) were each independently associated with an increased number of faculty teaching the course. Schools that used a gland-/organ-based curriculum only and those that used a combination of gland-/organ-based curriculum with topic-based curriculum differed significantly in their use of large lectures, small groups, and several curriculum components, including point of care glucose testing, continuous glucose monitoring, and insulin pumps. CONCLUSION: This survey study reports the current landscape of preclinical endocrine education in the United States and describes opportunities to improve interest in pursuing endocrinology as a career.

Driving Factors to Pursue Endocrinology Training Fellowship: Empirical Survey Data and Future Strategies.

OBJECTIVE: There is a current and anticipated labor shortage of endocrinologists in the United States. Over the past decade, the number of applications to endocrinology fellowship programs has plateaued despite increased available positions, and interest in endocrinology has declined relative to other internal medicine subspecialty fields. The examination of driving factors for pursuit of endocrinology as a subspecialty career is needed. METHODS: A 12-question online survey was developed to identify the primary reasons for current endocrinology fellows/trainees to pursue the field. This survey was sent to 152 U.S. endocrinology fellowship program directors for completion by their fellows between July and August 2021. RESULTS: A total of 176 of 629 fellows (28.0%) completed the survey. The majority (57.4%) had decided to pursue endocrinology as a career during residency, while 27.3% had decided during medical school. The endocrinology rotation during residency was ranked by 79 fellows (44.9%) as the most influential factor, followed by having positive experiences with a clinical mentor (27.3%). Endocrinology exposure during medical school was sparse, with only 2.8% noting the availability of an endocrinology student interest group, while 59.7% reported inadequate endocrinology exposure during their medical school curriculum. CONCLUSION: The majority of current endocrinology fellows/trainees report that exposure to the field during medical school was limited, and that their endocrinology elective and mentorship experiences during residency were the most influential factors for pursuing endocrinology as a subspecialty. Improved integration of endocrinology experiences between medical school and residency may enhance career interest in endocrinology.

Efficacy of an Integrated Hands-On Thyroid Ultrasound Session for Medical Student Education.

As ultrasound has gained popularity with improving technology and ease-of-use, a push has been made to integrate ultrasound into the medical school curriculum. Many institutions are reporting one- to four-year integrated ultrasound curricula to augment anatomy and pathophysiology teaching. Our goal was to integrate a thyroid ultrasound scanning session into the endocrinology block of our institution's medical school curriculum to enhance medical student understanding of thyroid anatomy and pathophysiology. We conducted a prospective, single-center cohort (pre-experimental) study to evaluate student performance and knowledge acquisition using a pretest-posttest design. These multimodal sessions, consisting of a didactic, hands-on scanning sessions, and knowledge integration tests, covered ultrasound technique and thyroid evaluation and advanced to diagnosing an abnormal thyroid and working up a thyroid nodule. There were 26 to 27 second-year medical students per session who rotated between three stations proctored by credentialled physicians. Students participated in hands-on scanning of patients with or without thyroid pathology at each station. Out of the 209 students who participated in the ultrasound sessions, 114 (54.5%) consented to participate in the research project and completed both the pretest and posttest. Test data from the 114 students showed a mean pretest score of 57.5% ± 14.6% and the mean posttest score of 73.9% ± 17.4%. They had a 16.5% ± 19.6% (p < 0.001) increase in score between the two tests. Our study demonstrates that a multimodal thyroid ultrasound scanning session is an effective tool to augment the medical school endocrinology curriculum and to improve students' knowledge of thyroid anatomy, pathophysiology, and diagnostic workup of thyroid nodules.

Co-occurrence of multiple endocrine neoplasia type 4 and spinal neurofibromatosis: a case report.

Multiple Endocrine Neoplasia (MEN) type 4 is a rare genetic condition that results from variants of the CDKN1B gene and predisposes individuals to develop endocrine tumors. Spinal neurofibromatosis (SNF) is an uncommon subtype of neurofibromatosis type 1 (NF1) characterized by bilateral neurofibromas of all spinal roots. Here we report a case of the co-occurrence of these syndromes, which has not yet been described in the literature. A male in his 60s presented with Gleason 5 + 4 localized prostate adenocarcinoma treated with radical prostatectomy. Two years later, he developed liver and bone metastasis consistent with trans-differentiation into small cell carcinoma. He developed hypercalcemia due to primary hyperparathyroidism from a parathyroid adenoma treated surgically. His family history was significant for a first-degree relative with a clinical diagnosis of NF1 and several second-degree relatives with multiple café-au-lait macules. Spine MRI showed multiple bilateral neurofibromas. Germline genetic testing showed a pathogenic variant in the CDKN1B gene, a variant in the NF1 gene, and a normal MEN1 gene. In this rare case of MEN4 and SNF, the patient was asymptomatic for much of his life. In addition to parathyroid adenoma and spinal neurofibromas, he had prostate adenocarcinoma with trans-differentiation into metastatic small cell cancer. Whether this diagnosis was coincidental or related to an emerging phenotype remains to be elucidated.

Afirma Gene Sequencing Classifier Compared with Gene Expression Classifier in Indeterminate Thyroid Nodules.

Background: The Afirma Gene Expression Classifier (GEC) has been used to further characterize cytologically indeterminate (cyto-I) thyroid nodules into either benign or suspicious categories. However, its relatively low positive predictive value (PPV) limited its use as a classifier for patients with suspicious results. The Afirma Gene Sequencing Classifier (GSC) was developed to improve PPV while maintaining a high negative predictive value (NPV), yet real-world assessment of its performance is lacking. Methods: We analyzed all patients who had cyto-I nodules and molecular testing with either GEC or GSC between 2011 and 2018 at a single academic medical center. Clinical information was obtained for 343 GEC-tested nodules and 164 GSC-tested nodules. Results: The GSC had a statistically significant higher benign call rate (76.2% vs. 48.1%, p < 0.001), PPV (60.0% vs. 33.3%, p = 0.01), and specificity (94.3% vs. 61.4%, p < 0.001) than the GEC. Improvement was statistically significant in both Bethesda III and Bethesda IV nodules. In particular, the benign call rate of GSC was significantly higher in nodules with Hürthle cell changes (88.8% vs. 25.7%, p < 0.01). The rate of surgical intervention in the indeterminate nodule cohort has decreased by 66.4% since switching to the GSC; 52.5% of indeterminate nodules went to surgery while using the GEC compared with 17.6% with the GSC (p < 0.001). This reduction was statistically significant in nodules with Bethesda III diagnoses, demonstrating a 70.9% decrease (GEC 51.3% vs. GSC 14.9%, p < 0.001), and in nodules with Bethesda IV cytology, a 39.2% decrease was noted (GEC 54.8% vs. GSC 33.3%, p = 0.003). Conclusions: Data from a single academic tertiary center show an improved specificity and PPV while maintaining high sensitivity and NPV for GSC compared with GEC. A statistically significant increase in benign call rates was observed in GSC compared with GEC, likely indicating fewer false positive results. After implementation of GSC, surgical interventions have been reduced by 68%.

Performance of a Multigene Genomic Classifier in Thyroid Nodules With Indeterminate Cytology: A Prospective Blinded Multicenter Study.

Importance: Approximately 20% of fine-needle aspirations (FNA) of thyroid nodules have indeterminate cytology, most frequently Bethesda category III or IV. Diagnostic surgeries can be avoided for these patients if the nodules are reliably diagnosed as benign without surgery. Objective: To determine the diagnostic accuracy of a multigene classifier (GC) test (ThyroSeq v3) for cytologically indeterminate thyroid nodules. Design, Setting, and Participants: Prospective, blinded cohort study conducted at 10 medical centers, with 782 patients with 1013 nodules enrolled. Eligibility criteria were met in 256 patients with 286 nodules; central pathology review was performed on 274 nodules. Interventions: A total of 286 FNA samples from thyroid nodules underwent molecular analysis using the multigene GC (ThyroSeq v3). Main Outcomes and Measures: The primary outcome was diagnostic accuracy of the test for thyroid nodules with Bethesda III and IV cytology. The secondary outcome was prediction of cancer by specific genetic alterations in Bethesda III to V nodules. Results: Of the 286 cytologically indeterminate nodules, 206 (72%) were benign, 69 (24%) malignant, and 11 (4%) noninvasive follicular thyroid neoplasms with papillary-like nuclei (NIFTP). A total of 257 (90%) nodules (154 Bethesda III, 93 Bethesda IV, and 10 Bethesda V) had informative GC analysis, with 61% classified as negative and 39% as positive. In Bethesda III and IV nodules combined, the test demonstrated a 94% (95% CI, 86%-98%) sensitivity and 82% (95% CI, 75%-87%) specificity. With a cancer/NIFTP prevalence of 28%, the negative predictive value (NPV) was 97% (95% CI, 93%-99%) and the positive predictive value (PPV) was 66% (95% CI, 56%-75%). The observed 3% false-negative rate was similar to that of benign cytology, and the missed cancers were all low-risk tumors. Among nodules testing positive, specific groups of genetic alterations had cancer probabilities varying from 59% to 100%. Conclusions and Relevance: In this prospective, blinded, multicenter study, the multigene GC test demonstrated a high sensitivity/NPV and reasonably high specificity/PPV, which may obviate diagnostic surgery in up to 61% of patients with Bethesda III to IV indeterminate nodules, and up to 82% of all benign nodules with indeterminate cytology. Information on specific genetic alterations obtained from FNA may help inform individualized treatment of patients with a positive test result.

In thyroidectomized patients with thyroid cancer, a serum thyrotropin of 30 µU/mL after thyroxine withdrawal is not always adequate for detecting an elevated stimulated serum thyroglobulin.

BACKGROUND: The thyrotropin (TSH) level or duration of thyroid hormone withdrawal (THW) required to detect stimulated thyroglobulin (Tg) in differentiated thyroid cancer (DTC) monitoring is unknown. The objective of this study was to evaluate the TSH cutoff of >30 µU/mL as a means to detect stimulated Tg ≥2 ng/mL after THW (THW-Tg≥2), and sensitivity of the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) questionnaire for detecting hypothyroid symptoms. METHODS: This was a prospective longitudinal cohort study done at a tertiary academic medical center. Forty-seven patients with DTC undergoing their first Tg stimulation or after previously abnormal Tg stimulation had weekly measurements of TSH and Tg during the 4 weeks THW, and repeated questionnaire assessments. RESULTS: TSH did not reach a plateau in any patient, and in those whose Tg did not remain undetectable, Tg continued to rise. Seventy-five percent of patients had an undetectable Tg <0.2 ng/mL at baseline (95% were <0.5 mg/mL) with 16% remaining undetectable throughout THW. The majority of patients (72.7% and 97.8%) achieved TSH >30 µU/mL by 3 and 4 weeks THW, respectively. Of the 15 patients with maximum stimulated THW-Tg≥2, 38% were detected before the minimal TSH >30 µU/mL cutoff. At 2 weeks THW, 3 had a TSH>30 µU/mL, and none of them had Tg ≥2 ng/mL. At 3 weeks THW, 11 had a TSH >30 µU/mL, and 64% of them had Tg ≥2 ng/mL. Only 60% were detected at 3-week THW regardless of their TSH level. Eighty-six percent were detected by TSH 60-<80 µU/mL. Conversely, all patients whose serum Tg was <0.2 ng/mL when their serum TSH was >20 µU/mL did not achieve a THW-Tg≥2. CONCLUSION: The minimal TSH cutoff of >30 µU/mL was inadequate to detect many patients with final stimulated THW-Tg≥2 during complete THW. TSH >80-100 µU/mL was a better cutoff, achieved in only 53% after 4-week THW. Conversely, we propose a preliminary THW-stopping rule for ending THW early in selected patients. In patients with a Tg <0.2 ng/mL when TSH >20 µU/mL, all had a final stimulated Tg ≤2 ng/mL, potentially saving qualifying patients 40% of THW duration compared to 4-week THW. FACIT-F correlated with TSH, but was not sensitive to detect mild hypothyroidism.