Faculty Bibliography

BACKGROUND:Four-dimensional computed tomography is routinely used to localize parathyroid disease, with consistently excellent parathyroid gland localization rates reported. This study evaluated whether pairing 4-dimensional computed tomography results with preoperative clinical variables can accurately predict single-gland disease in primary hyperparathyroidism. METHODS:Patients with primary hyperparathyroidism who underwent both 4-dimensional computed tomography imaging and parathyroidectomy between January 2019 and September 2021 at a large academic health system were included. Patient demographics, preoperative characteristics, and peri- and postoperative data were collected. The accuracy of 4-dimensional computed tomography in correctly identifying patients with single-gland disease with and without preoperative calcium and parathyroid hormone levels was calculated. Single-gland disease was defined by intraoperative parathyroid hormone decrease >50% and a hypercellular gland on pathology. RESULTS:One hundred seventy-five patients had 4-dimensional computed tomography results suggestive of single gland disease. One hundred fifty-two patients (87%) were predicted correctly to have single-gland disease. The predictive accuracy increased when stratifying by preoperative calcium (≥10.5 mg/dL, ≥11 mg/dL, and ≥12 mg/dL) and parathyroid hormone levels (≥65 pg/mL, ≥100 pg/mL, and ≥200 pg/dL). The accuracy further increased when stratifying by age (≤50 years). Accuracy for single gland disease was 100% when combined with any of the following: (1) calcium ≥12 mg/dL, (2) parathyroid hormone ≥200 pg/dL, or (3) calcium ≥11 mg/dL in patients ≤50 years. CONCLUSION/CONCLUSIONS:Four-dimensional computed tomography alone accurately predicted single gland disease in 87% of patients with primary hyperparathyroidism. When combined with preoperative calcium, parathyroid hormone and age thresholds, predictive accuracy for single-gland disease approached 100%. Given the high likelihood of single-gland disease in these scenarios, clinicians may consider offering focused unilateral parathyroidectomy without intraoperative parathyroid hormone monitoring in selected patients.

BACKGROUND:Patient electronic messaging has increased clinician workload contributing to burnout. Large language models can respond to these patient queries, but no studies exist on large language model responses in thyroid disease. METHODS:This cross-sectional study randomly selected 33 of 52 patient questions found on Reddit/askdocs. Questions were found through a "thyroid + cancer" or "thyroid + disease" search and had verified-physician responses. Additional responses were generated using ChatGPT-3.5 and GPT-4. Questions and responses were anonymized and graded for accuracy, quality, and empathy using a 4-point Likert scale by blinded providers, including 4 surgeons, 1 endocrinologist, and 2 physician assistants (n = 7). Results were analyzed using a single-factor analysis of variance. RESULTS:For accuracy, the results averaged 2.71/4 (standard deviation 1.04), 3.49/4 (0.391), and 3.66/4 (0.286) for physicians, GPT-3.5, and GPT-4, respectively (P < .01), where 4 = completely true information, 3 = greater than 50% true information, and 2 = less than 50% true information. For quality, the results were 2.37/4 (standard deviation 0.661), 2.98/4 (0.352), and 3.81/4 (0.36) for physicians, GPT-3.5, and GPT-4, respectively (P < .01), where 4 = provided information beyond what was asked, 3 = completely answers the question, and 2 = partially answers the question. For empathy, the mean scores were 2.37/4 (standard deviation 0.661), 2.80/4 (0.582), and 3.14/4 (0.578) for physicians, GPT-3.5, and GPT-4, respectively (P < .01), where 4 = anticipates and infers patient feelings from the expressed question, 3 = mirrors the patient's feelings, and 2 = contains no dismissive comments. Responses by GPT were ranked first 95% of the time. CONCLUSIONS:Large language model responses to patient queries about thyroid disease have the potential to be more accurate, complete, empathetic, and consistent than physician responses.

BACKGROUND:Racial and ethnic disparities in thyroid cancer care may be mitigated by improving enrollment of more diverse patient populations in clinical trials. We studied trial eligibility criteria and enrollment to assess barriers to equitable representation. METHODS:ClinicalTrials.gov was searched for studies on thyroid cancer treatment conducted between 1993 and 2023. The inclusion and exclusion criteria of each study were examined. For published studies, reported demographic information was collected. Observed enrollment by race was compared with the expected distribution as determined using data from the US Census and the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) databases. Over- and under-representation was defined as the ratio of observed to expected (O/E) enrollment by the race and ethnicity group. RESULTS:Of 309 thyroid cancer-related trials, 23 (7.4%) used language as an exclusion criterion. Most were interventional (n = 239, 77.3%), university-initiated (194, 62.8%), and drug/device-focused (195, 63.1%). Of studies that excluded by language, 20 (87.0%) were university-initiated. Eighty-eight trials were subsequently published, with 16 (18.2%) reporting race and/or ethnicity distributions. When comparing O/E ratios, White American participants were over-represented (O/E ratio: 1.2, P < .0001). Under-represented groups included Asian/Native Hawaiian (O/E ratio: 0.6, P = .0085), Black (0.6, P = .014), Native American (0.2, P = .072), and Hispanic patients (0.2, P < .0001). CONCLUSION/CONCLUSIONS:Over the last 3 decades, 1 in 13 thyroid cancer-related clinical trials excluded patients based on language. In the fraction of published studies to report on racial and ethnic demographics, Asian/Native Hawaiian, Black, and Hispanic patients were under-represented. Improved reporting of demographics in published studies and elimination of exclusion criteria such as language that hinder enrollment of minority patients could improve equitable representation of patients in thyroid cancer clinical trials.

BACKGROUND:Radioactive iodine therapy (RAI) is a frequently chosen therapy for Graves' disease. The aim of this study was to determine whether RAI for Graves' disease increases the risk of thyroid malignancy. METHODS:A retrospective analysis was performed of all Graves' disease patients who underwent thyroidectomy at a single institution between 2013 and 2022. Comparative analyses were performed with cohorts based on RAI therapy as the primary grouping variable. RESULTS:413 patients were identified, of which 38 received RAI prior to surgery. RAI treated patients were more likely to undergo surgery for known malignancy or indeterminate nodules. RAI patients were also more likely to have malignancies larger than 1 ​cm. Among RAI treated patients, those who developed malignancy were older at the time of Graves' diagnosis and received early RAI therapy. CONCLUSIONS:Use of RAI for treatment of Graves' disease increases the progression of thyroid carcinoma, but not the prevalence. Older age and early RAI therapy may be risk factors for malignancy in RAI treated patients.

BACKGROUND:Fluorodeoxyglucose uptake on positron emission tomography imaging has been shown to be an independent risk factor for malignancy in thyroid nodules. More recently, a new positron emission tomography radiotracer-Gallium-68 DOTATATE-has gained popularity as a sensitive method to detect neuroendocrine tumors. With greater availability of this imaging, incidental Gallium-68 DOTATATE uptake in the thyroid gland has increased. It is unclear whether current guideline-directed management of thyroid nodules remains appropriate in those that are Gallium-68 DOTATATE avid. METHODS:We retrospectively reviewed Gallium-68 DOTATATE positron emission tomography scans performed at our institution from 2012 to 2022. Patients with incidental focal Gallium-68 DOTATATE uptake in the thyroid gland were included. Fine needle aspiration biopsies were characterized via the Bethesda System for Reporting Thyroid Cytopathology. Bethesda III/IV nodules underwent molecular testing (ThyroSeq v3), and malignancy risk ≥50% was considered positive. RESULTS:In total, 1,176 Gallium-68 DOTATATE PET scans were reviewed across 837 unique patients. Fifty-three (6.3%) patients demonstrated focal Gallium-68 DOTATATE thyroid uptake. Nine patients were imaged for known medullary thyroid cancer. Forty-four patients had incidental radiotracer uptake in the thyroid and were included in our study. Patients included in the study were predominantly female sex (75%), with an average age of 62.9 ± 13.9 years and a maximum standardized uptake value in the thyroid of 7.3 ± 5.3. Frequent indications for imaging included neuroendocrine tumors of the small bowel (n = 17), lung (n = 8), and pancreas (n = 7). Thirty-three patients underwent subsequent thyroid ultrasound. Sonographic findings warranted biopsy in 24 patients, of which 3 were lost to follow-up. Cytopathology and molecular testing results are as follows: 12 Bethesda II (57.1%), 6 Bethesda III/ThyroSeq-negative (28.6%), 1 Bethesda III/ThyroSeq-positive (4.8%), 2 Bethesda V/VI (9.5%). Four nodules were resected, revealing 2 papillary thyroid cancers, 1 neoplasm with papillary-like nuclear features, and 1 follicular adenoma. There was no difference in maximum standardized uptake value between benign and malignant nodules (7.0 ± 4.6 vs 13.1 ± 5.7, P = .106). Overall, the malignancy rate among patients with sonography and appropriate follow-up was 6.7% (2/30). Among patients with cyto- or histopathology, the malignancy rate was 9.5% (2/21). There were no incidental cases of medullary thyroid cancer. CONCLUSION/CONCLUSIONS:The malignancy rate among thyroid nodules with incidental Gallium-68 DOTATATE uptake is comparable to rates reported among thyroid nodules in the general population. Guideline-directed management of thyroid nodules remains appropriate in those with incidental Gallium-68 DOTATATE uptake.

BACKGROUND:Parathyroidectomy by a high-volume surgeon is associated with a reduced risk of perioperative complications and of failure to cure primary and secondary hyperparathyroidism. There are limited data on disparities in access to high-volume parathyroid surgeons in the United States. METHODS:We used publicly available 2019 Medicare Provider Utilization and Payment data to identify all surgeons who performed >10 parathyroidectomies for Medicare fee-for-service beneficiaries, anticipating that fee-for-service beneficiaries likely represent only a subset of their high-volume practices. High-volume parathyroid surgeon characteristics and geographic distribution were evaluated. Inequality in the distribution of surgeons was measured by the Gini coefficient. The association between neighborhood disadvantage, based on the Area Deprivation Index, and proximity to high-volume parathyroid surgeons was evaluated using a one-way analysis of variance with Bonferroni-corrected pairwise comparisons. A sensitivity analysis was performed restricting to high-volume parathyroid surgeons within each hospital referral region, evidence-based regional markets for tertiary medical care. RESULTS:We identified 445 high-volume parathyroid surgeons who met inclusion criteria with >10 parathyroidectomies for Medicare fee-for-service beneficiaries. High-volume parathyroid surgeons were 71% male sex, and 59.8% were general surgeons. High-volume parathyroid surgeons were more likely to practice in a Metropolitan Statistical Area with a population >1 million than in less populous metropolitan or rural areas. The number of high-volume parathyroid surgeons per 100,000 fee-for-service Medicare beneficiaries in the 53 most populous Metropolitan Statistical Areas ranged from 0 to 4.94, with the highest density identified in Salt Lake City, Utah. In 2019, 50% of parathyroidectomies performed by high-volume parathyroid surgeons were performed by 20% of surgeons in this group, suggesting unequal distribution of surgical care (Gini coefficient 0.41). Patients in disadvantaged neighborhoods were farther from high-volume parathyroid surgeons than those in advantaged neighborhoods (median distance: disadvantaged 27.8 miles, partially disadvantaged 20.7 miles, partially advantaged 12.1 miles, advantaged 8.4 miles; P < .001). This association was also shown in the analysis of distance to high-volume parathyroid surgeons within the hospital referral region (P < .001). CONCLUSION/CONCLUSIONS:Older adults living in disadvantaged neighborhoods have less access to high-volume parathyroid surgeons, which may adversely affect treatment and outcomes for patients with primary and secondary hyperparathyroidism. This disparity highlights the need for actionable strategies to provide equitable access to care, including improved regionalization of high-volume parathyroid surgeon services and easing travel-related burdens for underserved patients.

OBJECTIVE:Hungry bone syndrome (HBS) is a known complication of parathyroidectomy. Patients with renal hyperparathyroidism are particularly vulnerable to HBS because of their prolonged exposure to electrolyte abnormalities and elevated parathyroid hormone (PTH). However, in-depth characterization of predictive factors for HBS in these patients is lacking. METHODS:A retrospective analysis was performed of patients with renal hyperparathyroidism who underwent parathyroidectomy at a single institution from 2011-2021. Patient demographics, clinical characteristics, and biochemical data were collected and analyzed. Boruta and binary logistic regression analyses were used to develop a scoring system. RESULTS:Thirty-three patients were identified; 16 (48%) developed HBS. Patients with HBS had significantly higher preoperative levels of serum PTH (mean difference [MS] = 2167.2 pg/mL, P <.001), phosphorus (MD = 3.5 mg/dl, P <.001), and alkaline phosphatase (ALP) (MD = 344.2 U/L, P =.002) and significantly lower levels of preoperative serum calcium (MD = -0.96 mg/dL, P =.004). Stepwise regression analysis identified elevated ALP (>150 U/L) and markedly elevated PTH (>1000 pg/mL) as positive predictors of HBS. A two-point scoring system with these 2 variables had overall diagnostic accuracy of 96.8% (sensitivity 100% and specificity 94.1%) with 1 point conferring 93.8% positive predictive value and 2 points conferring 100% positive predictive value. CONCLUSION/CONCLUSIONS:Preoperative serum PTH and ALP are significantly associated with HBS in patients with renal hyperparathyroidism undergoing parathyroidectomy for renal hyperparathyroidism. A scoring system with these 2 variables may be of clinical utility in predicting patients at high risk of HBS.

OBJECTIVE:We sought to compare the incidence of adverse cardiovascular events in older adults with primary hyperparathyroidism (PHPT) treated with parathyroidectomy versus non-operative management. SUMMARY OF BACKGROUND DATA/BACKGROUND:PHPT is a common endocrine disorder that is associated with increased cardiovascular mortality, but it is not known whether parathyroidectomy reduces the incidence of adverse cardiovascular events. METHODS:We conducted a population-based, longitudinal cohort study of Medicare beneficiaries diagnosed with PHPT (2006-2017). Multivariable, inverse probability weighted Cox proportional hazards regression was used to determine the associations of parathyroidectomy with major adverse cardiovascular events (MACE), cardiovascular disease-related hospitalization, and cardiovascular hospitalization-associated mortality. RESULTS:We identified 210,206 beneficiaries diagnosed with PHPT from 2006-2017. Among 63,136 (30.0%) treated with parathyroidectomy and 147,070 (70.0%) managed non-operatively within one year of diagnosis, the unadjusted incidence of MACE was 10.0% (mean follow-up 59.1 [SD 35.6] months) and 11.5% (mean follow-up 54.1 [SD 34.0] months), respectively. In multivariable analysis, parathyroidectomy was associated with a lower incidence of MACE (HR 0.92 [95%CI 0.90-0.94]), cardiovascular disease-related hospitalization (HR 0.89 [95%CI 0.87-0.91]), and cardiovascular hospitalization-associated mortality (HR 0.76 [95%CI 0.71-0.81]) compared to non-operative management. At 10 years, parathyroidectomy was associated with adjusted absolute risk reduction for MACE of 1.7% (95%CI 1.3%-2.1%), for cardiovascular disease-related hospitalization of 2.5% (95%CI 2.1%-2.9%), and for cardiovascular hospitalization-associated mortality of 1.4% (95%CI 1.2%-1.6%). CONCLUSIONS:In this large, population-based cohort study, parathyroidectomy was associated with a lower long-term incidence of adverse cardiovascular outcomes when compared with non-operative management for older adults with PHPT, which is relevant to surgical decision-making for patients with a long life expectancy.