Faculty Bibliography

BACKGROUND:Guidelines recommend screening for primary aldosteronism in patients diagnosed with hypertension and obstructive sleep apnea. Recent studies have shown that adherence to these recommendations is extremely low. It has been suggested that cost is a barrier to implementation. No analysis has been done to rigorously evaluate the cost-effectiveness of widespread implementation of these guidelines. METHODS:We constructed a decision-analytic model to evaluate screening of the hypertensive obstructive sleep apnea population for primary aldosteronism as per guideline recommendations in comparison with current rates of screening. Probabilities, utility values, and costs were identified in the literature. Threshold and sensitivity analyses assessed robustness of the model. Costs were represented in 2020 US dollars and health outcomes in quality-adjusted life-years. The model assumed a societal perspective with a lifetime time horizon. RESULTS:Screening per guideline recommendations had an expected cost of $47,016 and 35.27 quality-adjusted life-years. Continuing at current rates of screening had an expected cost of $48,350 and 34.86 quality-adjusted life-years. Screening was dominant, as it was both less costly and more effective. These results were robust to sensitivity analysis of disease prevalence, test sensitivity, patient age, and expected outcome of medical or surgical treatment of primary aldosteronism. The screening strategy remained cost-effective even if screening were conservatively presumed to identify only 3% of new primary aldosteronism cases. CONCLUSIONS:For patients with hypertension and obstructive sleep apnea, rigorous screening for primary aldosteronism is cost-saving due to cardiovascular risk averted. Cost should not be a barrier to improving primary aldosteronism screening adherence.

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: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:F-fluorocholine positron emission tomography for preoperative parathyroid localization on patients with primary hyperparathyroidism. METHODS:F-fluorocholine positron emission tomography imaging was assessed using 3 anatomic locations (left neck, right neck, and mediastinum), with surgery as the gold standard. RESULTS:F-fluorocholine positron emission tomography (88.9%) outperformed both ultrasound (37.1%) and sestamibi (27.5%), as well as ultrasound and sestamibi combined (47.8%). CONCLUSION/CONCLUSIONS:F-fluorocholine positron emission tomography for parathyroid localization confirm its utility in a challenging cohort, with better sensitivity than ultrasound or sestamibi.

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: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.

The purpose of this prospective study was to determine the correct localization rate (CLR) of ¹⁸F-fluorocholine PET for the detection of parathyroid adenomas in comparison to ^99mTc-sestamibi imaging. Methods: This was a single-arm prospective trial. Ninety-eight patients with biochemical evidence of primary hyperparathyroidism were imaged before parathyroidectomy using ¹⁸F-fluorocholine PET/MRI. ^99mTc-sestamibi imaging performed separately from the study was evaluated for comparison. The primary endpoint of the study was the CLR on a patient level. Each imaging study was interpreted by 3 masked readers on a per-region basis. Lesions were validated by histopathologic analysis of surgical specimens. Results: Of the 98 patients who underwent ¹⁸F-fluorocholine PET, 77 subsequently underwent parathyroidectomy and 60 of those had ^99mTc-sestamibi imaging. For ¹⁸F-fluorocholine PET in patients who underwent parathyroidectomy, the CLR based on the masked reader consensus was 75% (95% CI, 0.63-0.82). In patients who underwent surgery and had an available ^99mTc-sestamibi study, the CLR increased from 17% (95% CI, 0.10-0.27) for ^99mTc-sestamibi imaging to 70% (95% CI, 0.59-0.79) for ¹⁸F-fluorocholine PET. Conclusion: In this prospective study using masked readers, the CLR for ¹⁸F-fluorocholine PET was 75%. In patients with a paired ^99mTc-sestamibi study, the use of ¹⁸F-fluorocholine PET increased the CLR from 17% to 70%. ¹⁸F-fluorocholine PET is a superior imaging modality for the localization of parathyroid adenomas.

Background: Preoperative parathyroid imaging guides surgeons during parathyroidectomy. This study evaluates the clinical impact of ¹⁸F-fluorocholine positron emission tomography for preoperative parathyroid localization on patients with primary hyperparathyroidism.
Method(s): Patients with primary hyperparathyroidism and indications for parathyroidectomy had simultaneous ¹⁸F-fluorocholine positron emission tomography imaging/magnetic resonance imaging. In patients who underwent subsequent parathyroidectomy, cure was based on lab values at least 6 months after surgery. Location-based sensitivity and specificity of ¹⁸F-fluorocholine positron emission tomography imaging was assessed using 3 anatomic locations (left neck, right neck, and mediastinum), with surgery as the gold standard.
Result(s): In 101 patients, ¹⁸F-fluorocholine positron emission tomography localized at least 1 candidate lesion in 93% of patients overall and in 91% of patients with previously negative imaging, leading to a change in preoperative strategy in 60% of patients. Of 76 patients who underwent parathyroidectomy, 58 (77%) had laboratory data at least 6 months postoperatively, with 55/58 patients (95%) demonstrating cure. ¹⁸F-fluorocholine positron emission tomography successfully guided curative surgery in 48/58 (83%) patients, compared with 20/57 (35%) based on ultrasound and 13/55 (24%) based on sestamibi. In a location-based analysis, sensitivity of ¹⁸F-fluorocholine positron emission tomography (88.9%) outperformed both ultrasound (37.1%) and sestamibi (27.5%), as well as ultrasound and sestamibi combined (47.8%).
Conclusion(s): Long-term results in the first cohort in the United States to use ¹⁸F-fluorocholine positron emission tomography for parathyroid localization confirm its utility in a challenging cohort, with better sensitivity than ultrasound or sestamibi.
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OBJECTIVE:Patients with primary hyperparathyroidism (PHPT) are at increased risk of kidney stones. Guidelines recommend parathyroidectomy in patients with PHPT with a history of stone disease. This study aimed to compare the 5-year incidence of clinically significant kidney stone events in patients with PHPT treated with parathyroidectomy versus nonoperative management. METHODS:We performed a longitudinal cohort study of patients with PHPT in a national commercial insurance claims database (2006-2019). Propensity score inverse probability weighting-adjusted multivariable regression models were calculated. RESULTS:We identified 7623 patients aged ≥35 years old with continuous enrollment >1 year before and >5 years after PHPT diagnosis. A total of 2933 patients (38.5%) were treated with parathyroidectomy. The cohort had a mean age of 66.5 years, 5953 (78.1%) were female, and 5520 (72.4%) were White. Over 5 years, the unadjusted incidence of ≥1 kidney stone event was higher in patients who were managed with parathyroidectomy compared with those who were managed nonoperatively overall (5.4% vs 4.1%, respectively) and among those with a history of kidney stones at PHPT diagnosis (17.9% vs 16.4%, respectively). On multivariable analysis, parathyroidectomy was associated with no statistically significant difference in the odds of a 5-year kidney stone event among patients with a history of kidney stones (odds ratio, 1.03; 95% CI, 0.71-1.50) or those without a history of kidney stones (odds ratio, 1.16; 95% CI, 0.84-1.60). CONCLUSION/CONCLUSIONS:Based on this claim analysis, there was no difference in the odds of 5-year kidney stone events in patients with PHPT who were treated with parathyroidectomy versus nonoperative management. Time horizon for benefit should be considered when making treatment decisions for PHPT based on the risk of kidney stone events.