Faculty Bibliography

Introduction: Thyroid fine-needle aspiration (FNA) cytology combined with molecular testing guides individualized patient management by providing information regarding tumor biology and the risk of recurrence associated with specific mutations in the indeterminate groups (Bethesda group III-V). Thyroid adenomaassociated (THADA)-IGF2BP3 fusions have been identified as an oncogenic event in thyroid neoplasms, but the clinical-pathologic features and subsequent management are not well-established. Here we report the findings associated with thyroid nodules with THADA-IGFBP3 fusions in our institution.
Material(s) and Method(s): FNA cytology samples of thyroid nodules during 01/2015-12/2016 with the diagnosis of atypia of undetermined significance or follicular lesion of undetermined significance (AUS/FLUS; Bethesda III), follicular neoplasm/ suspicious for follicular neoplasm (FN/SFN; Bethesda IV) and suspicious for malignancy (Bethesda V) with corresponding ThyroSeqV2 data were assessed. Molecular test results yielding a THADA gene fusion were identified. In addition, follow-up surgical pathology and available radiology results were reviewed.
Result(s): 186 out of 558 (33.3%) thyroid nodules displayed molecular alterations; 7 out of 186 (3.8%) Bethesda category III-V nodules with ThyroSeq molecular alterations displayed isolated THADA-IGFBP2 fusions (Table 1). The median age was 45 years. The female to male ratio was 5:2. The nodule sizes ranged from 1.8 to 5.0 cm. Four (57%) patients had surgery; three cases displayed noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) on histology; one case was a follicular adenoma. No patients had recurrence or metastasis on follow-up.
Conclusion(s): Our pilot study shows that thyroid nodules with THADA-IGF2BP3 fusions display low-risk/indolent features. These findings may aid in clinical management decisions in patients presenting with thyroid nodules with isolated THADAIGF2BP3 fusions on molecular testing

During cervical surgery, localization and identification of parathyroid glands is key to both the removal of abnormal hyperfunctioning glands and the preservation of normal glands. The challenging nature of parathyroid localization has fostered innovation in imaging techniques to localize glands both before and during cervical operations. Advances in preoperative imaging include PET-based imaging modalities paired with computed tomography or MRI for anatomic correlation. During surgery, both parathyroid autofluorescence and contrast-enhanced fluorescence techniques are useful adjuncts for intraoperative identification.

OBJECTIVE:Cancer patients and survivors may be disproportionately affected by COVID-19. We sought to determine the effects of the pandemic on thyroid cancer survivors' healthcare interactions and quality of life. METHODS:An anonymous survey including questions about COVID-19 and the Patient-Reported Outcomes Measurement Information System profile (PROMIS-29, version 2.0) was hosted on the ThyCa:Thyroid Cancer Survivors' Association, Inc. website. PROMIS scores were compared to previously published data. Factors associated with greater anxiety were evaluated with univariable and multivariable logistic regression. RESULTS:From 5/6/2020 - 10/8/2020, 413 participants consented to take the survey; 378 (92%) met inclusion criteria: diagnosed with thyroid cancer or NIFTP, within the United States, and completing all sections of the survey. Mean age was 53 years; 89% were female, and 74% had papillary thyroid cancer. Most respondents agreed/strongly agreed (83%) that their lives were very different during COVID-19, as was their interaction with doctors (79%). A minority (43%) were satisfied with information from their doctor regarding COVID-19 changes. Compared to pre-COVID-19, PROMIS scores were higher for anxiety (57.8 vs. 56.5, p<0.05) and lower for ability to participate in social activities (46.2 vs. 48.1, p<0.01), fatigue (55.8 vs. 57.9, p<0.01), and sleep disturbance (54.7 vs. 56.1, p<0.01). After adjusting for confounders, greater anxiety was associated with younger age (p<0.01) and change in treatment plan (p=0.04). CONCLUSIONS:During the COVID-19 pandemic, thyroid cancer survivors reported increased anxiety compared to a pre-COVID cohort. To deliver comprehensive care, providers must better understand patient concerns and improve communication about potential changes to their treatment plans.

Importance/UNASSIGNED:Primary hyperparathyroidism (PHPT) contributes to the development and progression of osteoporosis in older adults. The effectiveness of parathyroidectomy for reducing fracture risk in older adults is unknown. Objective/UNASSIGNED:To compare the incidence of clinical fracture among older adults with PHPT treated with parathyroidectomy vs nonoperative management. Design, Setting, and Participants/UNASSIGNED:This was a population-based, longitudinal cohort study of all Medicare beneficiaries with PHPT from 2006 to 2017. Multivariable, inverse probability weighted Cox proportional hazards and Fine-Gray competing risk regression models were constructed to determine the association of parathyroidectomy vs nonoperative management with incident fracture. Data analysis was conducted from February 17, 2021, to September 14, 2021. Main Outcomes and Measures/UNASSIGNED:The primary outcome was clinical fracture at any anatomic site not associated with major trauma during the follow-up period. Results/UNASSIGNED:Among the 210 206 Medicare beneficiaries with PHPT (mean [SD] age, 75 [6.8] years; 165 637 [78.8%] women; 183 433 [87.3%] White individuals), 63 136 (30.0%) underwent parathyroidectomy within 1 year of diagnosis, and 147 070 (70.0%) were managed nonoperatively. During a mean (SD) follow-up period of 58.5 (35.5) months, the unadjusted incidence of fracture was 10.2% in patients treated with parathyroidectomy. During a mean (SD) follow-up of 52.5 (33.8) months, the unadjusted incidence of fracture was 13.7% in patients observed nonoperatively. On multivariable analysis, parathyroidectomy was associated with lower adjusted rates of any fracture (hazard ratio [HR], 0.78; 95% CI, 0.76-0.80]) and hip fracture (HR, 0.76; 95% CI, 0.72-0.79). At 2, 5, and 10 years, parathyroidectomy was associated with adjusted absolute fracture risk reduction of 1.2% (95% CI, 1.0-1.4), 2.8% (95% CI, 2.5-3.1), and 5.1% (95% CI, 4.6-5.5), respectively, compared with nonoperative management. On subgroup analysis, there were no significant differences in the association of parathyroidectomy with fracture risk by age group, sex, frailty, history of osteoporosis, or meeting operative guidelines. Fine-Gray competing risk regression confirmed parathyroidectomy was associated with a lower probability of any fracture and hip fracture when accounting for the competing risk of death (HR, 0.84; 95% CI, 0.82-0.85; and HR, 0.83; 95% CI, 0.80-0.85, respectively). Conclusions and Relevance/UNASSIGNED:This longitudinal cohort study found that parathyroidectomy was associated with a lower risk of any fracture and hip fracture among older adults with PHPT, suggesting a clinically meaningful benefit of operative management in this population.

BACKGROUND:Among patients with primary hyperparathyroidism, parathyroidectomy offers a chance of cure and mitigation of disease-related complications. The impact of race/ethnicity on referral and utilization of parathyroidectomy has not been fully explored. METHODS:Population-based, retrospective cohort study using 100% Medicare claims from beneficiaries with primary hyperparathyroidism from 2006 to 2016. Associations of race/ethnicity with disease severity, surgeon evaluation, and subsequent parathyroidectomy were analyzed using adjusted multivariable logistic regression models. RESULTS:Among 210,206 beneficiaries with primary hyperparathyroidism, 63,136 (30.0%) underwent parathyroidectomy within 1 year of diagnosis. Black patients were more likely than other races/ethnicities to have stage 3 chronic kidney disease (10.8%) but had lower prevalence of osteoporosis and nephrolithiasis compared to White patients, Black and Hispanic patients were more likely to have been hospitalized for primary hyperparathyroidism-associated conditions (White 4.8%, Black 8.1%, Hispanic 5.8%; P < .001). Patients who were White and met operative criteria were more likely to undergo parathyroidectomy than Black, Hispanic, or Asian patients (White 30.5%, Black 23.0%, Hispanic 21.4%, Asian 18.7%; P < .001). Black and Hispanic patients had lower adjusted odds of being evaluated by a surgeon (odds ratios 0.71 [95% confidence interval 0.69-0.74], 0.68 [95% confidence interval 0.61-0.74], respectively) and undergoing parathyroidectomy if evaluated by a surgeon (odds ratios 0.72 [95% confidence interval 0.68-0.77], 0.82 [95% confidence interval 0.67-0.99]). Asian race was associated with lower adjusted odds of being evaluated by a surgeon (odds ratio 0.64 [95% confidence interval 0.57-0.71]), but no difference in odds of parathyroidectomy. CONCLUSION/CONCLUSIONS:Racial/ethnic disparities exist in the management of primary hyperparathyroidism among older adults. Determining the factors that account for this disparity require urgent attention to achieve parity in the management of primary hyperparathyroidism.

BACKGROUND:Radiofrequency ablation is an alternative strategy for the management of benign thyroid conditions. We analyzed the proportion of patients who underwent thyroid surgery for benign conditions who would be potentially eligible for radiofrequency ablation. METHODS:We identified patients who underwent thyroid surgery from 2015 to 2019 at the study institution for Bethesda II cytopathology or toxic adenoma. Patients were considered potentially eligible for radiofrequency ablation if they had a dominant nodule >2 cm with or without compression symptoms, a dominant nodule <2 cm with compression symptoms, or a toxic adenoma. RESULTS:Of 411 patients in total, 284 (69.1%) would be eligible to consider thyroid radiofrequency ablation. In the radiofrequency ablation-eligible group, 20 (7.0%) experienced voice change after surgery, and 2 (0.7%) were dissatisfied or concerned about their scar. In the radiofrequency ablation-eligible group, 70 patients (24.6%) had malignancy diagnosed by final pathology, and 23 patients (8.1%) had cancers that were equal to or larger than 1 cm in size. CONCLUSION/CONCLUSIONS:Many patients who undergo surgery for benign thyroid disease could be considered for radiofrequency ablation as an alternative treatment modality. Given the rate of occult malignancy, optimal evaluation of nondominant nodules before radiofrequency ablation and long-term thyroid surveillance for patients who undergo radiofrequency ablation should be further studied.

BACKGROUND:Primary hyperparathyroidism historically necessitated bilateral neck exploration to remove abnormal parathyroid tissue. Improved localization allows for focused parathyroidectomy with lower complication risks. Recently, positron emission tomography using radiolabeled 18F-fluorocholine demonstrated high accuracy in detecting these lesions, but its cost-effectiveness has not been studied in the United States. METHODS:A decision tree modeled patients who underwent parathyroidectomy for primary hyperparathyroidism using single preoperative localization modalities: (1) positron emission tomography using radiolabeled 18F-fluorocholine, (2) 4-dimensional computed tomography, (3) ultrasound, and (4) sestamibi single photon emission computed tomography (SPECT). All patients underwent either focused parathyroidectomy versus bilateral neck exploration, with associated cost ($) and clinical outcomes measured in quality-adjusted life-years gained. Model parameters were informed by literature review and Medicare costs. Incremental cost-utility ratios were calculated in US dollars/quality-adjusted life-years gained, with a willingness-to-pay threshold set at $100,000/quality-adjusted life-year. One-way, 2-way, and threshold sensitivity analyses were performed. RESULTS:Positron emission tomography using radiolabeled 18F-fluorocholine gained the most quality-adjusted life-years (23.9) and was the costliest ($2,096), with a total treatment cost of $11,245 or $470/quality-adjusted life-year gained. Sestamibi single photon emission computed tomography and ultrasound were dominated strategies. Compared with 4-dimentional computed tomography, the incremental cost-utility ratio for positron emission tomography using radiolabeled 18F-fluorocholine was $91,066/quality-adjusted life-year gained in our base case analysis, which was below the willingness-to-pay threshold. In 1-way sensitivity analysis, the incremental cost-utility ratio was sensitive to test accuracy, positron emission tomography using radiolabeled 18F-fluorocholine price, postoperative complication probabilities, proportion of bilateral neck exploration patients needing overnight hospitalization, and life expectancy. CONCLUSION/CONCLUSIONS:Our model elucidates scenarios in which positron emission tomography using radiolabeled 18F-fluorocholine can potentially be a cost-effective imaging option for primary hyperparathyroidism in the United States. Further investigation is needed to determine the maximal cost-effectiveness for positron emission tomography using radiolabeled 18F-fluorocholine in selected populations.

BACKGROUND:Resistant hypertension is common in patients with primary aldosteronism and in those with obstructive sleep apnea. Primary aldosteronism treatment improves sleep apnea. Despite Endocrine Society guidelines' inclusion of sleep apnea and hypertension co-diagnosis as a primary aldosteronism screening indication, the state of screening implementation is unknown. METHODS:All hypertensive adult patients with obstructive sleep apnea (n = 4751) at one institution between 2012 and 2020 were compared with a control cohort without sleep apnea (n = 117,815). We compared the association of primary aldosteronism diagnoses, risk factors, and screening between both groups. Patients were considered to have screening if they had a primary aldosteronism diagnosis or serum aldosterone or plasma renin activity evaluation. RESULTS:Obstructive sleep apnea patients were predominantly men and had higher body mass index. On multivariable analysis, hypertensive sleep apnea patients had higher odds of drug-resistant hypertension (odds ratio [OR] 2.70; P < .001) and hypokalemia (OR 1.26; P < .001) independent of body mass index, sex, and number of antihypertensive medications. Overall, sleep apnea patients were more likely to be screened for primary aldosteronism (OR 1.45; P < .001); however, few patients underwent screening whether they had sleep apnea or not (pre-guideline publication 7.8% vs 4.6%; post-guidelines 3.6% vs 4.6%; P < .01). Screening among eligible sleep apnea patients remained low prior to and after guideline publication (4.4% vs 3.4%). CONCLUSIONS:Obstructive sleep apnea is associated with primary aldosteronism risk factors without formal diagnosis, suggesting screening underutilization and underdiagnosis. Strategies are needed to increase screening adherence, as patients may benefit from treatment of concomitant primary aldosteronism to reduce sleep apnea severity and its associated cardiopulmonary morbidity.