Estimated Effect of Parathyroidectomy on Long-Term Kidney Function in Adults With Primary Hyperparathyroidism.

BACKGROUND: Multidisciplinary guidelines recommend parathyroidectomy to slow the progression of chronic kidney disease in patients with primary hyperparathyroidism (PHPT) and an estimated glomerular filtration rate (eGFR) less than 60 mL/min/1.73 m2. Limited data address the effect of parathyroidectomy on long-term kidney function. OBJECTIVE: To compare the incidence of a sustained decline in eGFR of at least 50% among patients with PHPT treated with parathyroidectomy versus nonoperative management. DESIGN: Target trial emulation was done using observational data from adults with PHPT, using an extended Cox model with time-varying inverse probability weighting. SETTING: Veterans Health Administration. PATIENTS: Patients with a new biochemical diagnosis of PHPT in 2000 to 2019. MEASUREMENTS: Sustained decline of at least 50% from pretreatment eGFR. RESULTS: Among 43 697 patients with PHPT (mean age, 66.8 years), 2928 (6.7%) had a decline of at least 50% in eGFR over a median follow-up of 4.9 years. The weighted cumulative incidence of eGFR decline was 5.1% at 5 years and 10.8% at 10 years in patients managed with parathyroidectomy, compared with 5.1% and 12.0%, respectively, in those managed nonoperatively. The adjusted hazard of eGFR decline did not differ between parathyroidectomy and nonoperative management (hazard ratio [HR], 0.98 [95% CI, 0.82 to 1.16]). Subgroup analyses found no heterogeneity of treatment effect based on pretreatment kidney function. Parathyroidectomy was associated with a reduced hazard of the primary outcome among patients younger than 60 years (HR, 0.75 [CI, 0.59 to 0.93]) that was not evident among those aged 60 years or older (HR, 1.08 [CI, 0.87 to 1.34]). LIMITATION: Analyses were done in a predominantly male cohort using observational data. CONCLUSION: Parathyroidectomy had no effect on long-term kidney function in older adults with PHPT. Potential benefits related to kidney function should not be the primary consideration for PHPT treatment decisions. PRIMARY FUNDING SOURCE: National Institute on Aging.

Adverse Cardiovascular Outcomes Among Older Adults With Primary Hyperparathyroidism Treated With Parathyroidectomy Versus Nonoperative Management.

OBJECTIVE: The authors sought to compare the incidence of adverse cardiovascular (CV) events in older adults with primary hyperparathyroidism (PHPT) treated with parathyroidectomy versus nonoperative management. BACKGROUND: PHPT is a common endocrine disorder that is associated with increased CV mortality, but it is not known whether parathyroidectomy reduces the incidence of adverse CV events. METHODS: The authors 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 (MACEs), CV disease-related hospitalization, and CV hospitalization-associated mortality. RESULTS: The authors identified 210,206 beneficiaries diagnosed with PHPT from 2006 to 2017. Among 63,136 (30.0%) treated with parathyroidectomy and 147,070 (70.0%) managed nonoperatively within 1 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 [hazard ratio (HR): 0.92; 95% confidence interval (95% CI): 0.90-0.94], CV disease-related hospitalization (HR: 0.89; 95% CI: 0.87-0.91), and CV hospitalization-associated mortality (HR: 0.76; 95% CI: 0.71-0.81) compared to nonoperative management. At 10 years, parathyroidectomy was associated with adjusted absolute risk reduction for MACE of 1.7% (95% CI: 1.3%-2.1%), for CV disease-related hospitalization of 2.5% (95% CI: 2.1%-2.9%), and for CV 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 CV outcomes when compared with nonoperative management for older adults with PHPT, which is relevant to surgical decision making for patients with a long life expectancy.

A Tool to Estimate Risk of 30-day Mortality and Complications After Hip Fracture Surgery: Accurate Enough for Some but Not All Purposes? A Study From the ACS-NSQIP Database.

BACKGROUND: Surgical repair of hip fracture carries substantial short-term risks of mortality and complications. The risk-reward calculus for most patients with hip fractures favors surgical repair. However, some patients have low prefracture functioning, frailty, and/or very high risk of postoperative mortality, making the choice between surgical and nonsurgical management more difficult. The importance of high-quality informed consent and shared decision-making for frail patients with hip fracture has recently been demonstrated. A tool to accurately estimate patient-specific risks of surgery could improve these processes. QUESTIONS/PURPOSES: With this study, we sought (1) to develop, validate, and estimate the overall accuracy (C-index) of risk prediction models for 30-day mortality and complications after hip fracture surgery; (2) to evaluate the accuracy (sensitivity, specificity, and false discovery rates) of risk prediction thresholds for identifying very high-risk patients; and (3) to implement the models in an accessible web calculator. METHODS: In this comparative study, preoperative demographics, comorbidities, and preoperatively known operative variables were extracted for all 82,168 patients aged 18 years and older undergoing surgery for hip fracture in the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) between 2011 and 2017. Eighty-two percent (66,994 of 82,168 ) of patients were at least 70 years old, 21% (17,007 of 82,168 ) were at least 90 years old, 70% (57,260 of 82,168 ) were female, and 79% (65,301 of 82,168 ) were White. A total of 5% (4260 of 82,168) of patients died within 30 days of surgery, and 8% (6786 of 82,168) experienced a major complication. The ACS-NSQIP database was chosen for its clinically abstracted and reliable data from more than 600 hospitals on important surgical outcomes, as well as rich characterization of preoperative demographic and clinical predictors for demographically diverse patients. Using all the preoperative variables in the ACS-NSQIP dataset, least absolute shrinkage and selection operator (LASSO) logistic regression, a type of machine learning that selects variables to optimize accuracy and parsimony, was used to develop and validate models to predict two primary outcomes: 30-day postoperative mortality and any 30-day major complications. Major complications were defined by the occurrence of ACS-NSQIP complications including: on a ventilator longer than 48 hours, intraoperative or postoperative unplanned intubation, septic shock, deep incisional surgical site infection (SSI), organ/space SSI, wound disruption, sepsis, intraoperative or postoperative myocardial infarction, intraoperative or postoperative cardiac arrest requiring cardiopulmonary resuscitation, acute renal failure needing dialysis, pulmonary embolism, stroke/cerebral vascular accident, and return to the operating room. Secondary outcomes were six clusters of complications recently developed and increasingly used for the development of surgical risk models, namely: (1) pulmonary complications, (2) infectious complications, (3) cardiac events, (4) renal complications, (5) venous thromboembolic events, and (6) neurological events. Tenfold cross-validation was used to assess overall model accuracy with C-indexes, a measure of how well models discriminate patients who experience an outcome from those who do not. Using the models, the predicted risk of outcomes for each patient were used to estimate the accuracy (sensitivity, specificity, and false discovery rates) of a wide range of predicted risk thresholds. We then implemented the prediction models into a web-accessible risk calculator. RESULTS: The 30-day mortality and major complication models had good to fair discrimination (C-indexes of 0.76 and 0.64, respectively) and good calibration throughout the range of predicted risk. Thresholds of predicted risk to identify patients at very high risk of 30-day mortality had high specificity but also high false discovery rates. For example, a 30-day mortality predicted risk threshold of 15% resulted in 97% specificity, meaning 97% of patients who lived longer than 30 days were below that risk threshold. However, this threshold had a false discovery rate of 78%, meaning 78% of patients above that threshold survived longer than 30 days and might have benefitted from surgery. The tool is available here: https://s-spire-clintools.shinyapps.io/hip_deploy/ . CONCLUSION: The models of mortality and complications we developed may be accurate enough for some uses, especially personalizing informed consent and shared decision-making with patient-specific risk estimates. However, the high false discovery rate suggests the models should not be used to restrict access to surgery for high-risk patients. Deciding which measures of accuracy to prioritize and what is "accurate enough" depends on the clinical question and use of the predictions. Discrimination and calibration are commonly used measures of overall model accuracy but may be poorly suited to certain clinical questions and applications. Clinically, overall accuracy may not be as important as knowing how accurate and useful specific values of predicted risk are for specific purposes.Level of Evidence Level III, therapeutic study.

Anatomic Variations From 120 Mental Nerve Dissections: Lessons for Transoral Thyroidectomy.

BACKGROUND: Transoral endoscopic thyroidectomy vestibular approach (TOETVA) is a promising technique for eliminating a neck incision. A new risk of TOETVA is the potential for injury to the mental nerves during placement of three oral endoscopic ports. A better understanding of the variations in mental nerve anatomy is needed to inform safer TOETVA technique. MATERIALS AND METHODS: We performed 120 dissections of mental nerve branches exiting the mental foramen in 60 human cadavers. Anatomic distances and relationships of the foramen to the midline were evaluated. Mental nerve branching patterns were studied and compared with previously reported classification systems to determine surgical safe zones free of nerve branches. RESULTS: The mean midline-to-mental foramen distance was 29.2 ± 3.3 mm, with high variability across individuals (18.8-36.8 mm). There were differences in this distance between the left and right foramina (29.8 ± 3.2 versus 28.8 ± 3.3 mm, P = 0.03). All mental nerve branches exiting the mental foramen distributed medially. The branching patterns were classified into eight distinct categories, three of which are previously undescribed. One of these novel patterns, occurring in 9.2% of cases, had a dense and wide clustering of branches traveling toward the midline. CONCLUSIONS: The location of the mental foramen and mental nerve branching patterns demonstrate high variability. To avoid mental nerve injury in TOETVA, we identify a safe zone for lateral port placement lateral to the plane of the mental foramen. Placement and extension of the middle port incision should proceed with caution, as clustering of mental nerve branches in this area can frequently be present.

Reducing Opioid Use in Endocrine Surgery Through Patient Education and Provider Prescribing Patterns.

BACKGROUND: Postoperative opioid use can lead to dependence, contributing to the opioid epidemic in the United States. New persistent opioid use after minor surgeries occurs in 5.9% of patients. With increased documentation of persistent opioid use postoperatively, surgeons must pursue interventions to reduce opioid use perioperatively. METHODS: We performed a prospective cohort study to assess the feasibility of a preoperative intervention via patient education or counseling and changes in provider prescribing patterns to reduce postoperative opioid use. We included adult patients undergoing thyroidectomy and parathyroidectomy from January 22, 2019 to February 28, 2019 at a tertiary referral, academic endocrine surgery practice. Surveys were administered to assess pain and patient satisfaction postoperatively. Prescription, demographic, and comorbidity data were collected from the electronic health record. RESULTS: Sixty six patients (74.2% women, mean age 58.6 [SD 14.9] y) underwent thyroidectomy (n = 35), parathyroidectomy (n = 24), and other cervical endocrine operations (n = 7). All patients received a preoperative educational intervention in the form of a paper handout. 90.9% of patients were discharged with prescriptions for nonopioid pain medications, and 7.6% were given an opioid prescription on discharge. Among those who received an opioid prescription, the median quantity of opioids prescribed was 135 (IQR 120-150) oral morphine equivalents. On survey, four patients (6.1%) reported any postoperative opioid use, and 94.6% of patients expressed satisfaction with their preoperative education and postoperative pain management. CONCLUSIONS: Clear and standardized education regarding postoperative pain management is feasible and associated with high patient satisfaction. Initiation of such education may support efforts to minimize unnecessary opioid prescriptions in the population undergoing endocrine surgery.

Treatment of Primary Aldosteronism Reduces the Probability of Obstructive Sleep Apnea.

BACKGROUND: Aldosterone excess is hypothesized to worsen obstructive sleep apnea (OSA) symptoms by promoting peripharyngeal edema. However, the extent to which primary aldosteronism (PA), hypertension, and body mass index (BMI) influence OSA pathogenesis remains unclear. METHODS: We conducted a cross-sectional study of PA patients from our endocrine database to retrospectively evaluate OSA probability before and after adrenalectomy or medical management of PA. A control group of patients undergoing adrenalectomy for nonfunctioning benign adrenal masses was also evaluated. We categorized patients as high or low OSA probability after evaluation with the Berlin Questionnaire, a validated 10-question survey that explores sleep, fatigue, hypertension, and BMI. RESULTS: We interviewed 91 patients (83 PA patients and eight control patients). Median follow-up time was 2.6 y. The proportion of high OSA probability in all PA patients decreased from 64% to 35% after treatment for PA (mean Berlin score 1.64 versus 1.35, P < 0.001). This decline correlated with improvements in hypertension (P < 0.001) and fatigue symptoms (P = 0.03). Both surgical (n = 48; 1.69 versus 1.33, P < 0.001) and medical (n = 35; 1.57 versus 1.37, P = 0.03) treatment groups demonstrated reduced OSA probability. BMI remained unchanged after PA treatment (29.1 versus 28.6, P = nonsignificant), and the impact of treatment on OSA probability was independent of BMI. The control surgical group showed no change in OSA probability after adrenalectomy (1.25 versus 1.25, P = nonsignificant). CONCLUSIONS: Both surgical and medical treatments of PA reduce sleep apnea probability independent of BMI and are associated with improvements in hypertension and fatigue. Improved screening for PA could reduce OSA burden.

Technical Innovation in Transoral Endoscopic Endocrine Surgery: A Modified "Scarless" Technique.

BACKGROUND: The transoral endoscopic approach to thyroidectomy aims to eliminate a visible neck incision. Early experience has demonstrated promising safety and efficacy results but has uncovered unique drawbacks from the middle oral incision. We present a case series of our institutional experience with a technical innovation called the TransOral and Submental Technique (TOaST) designed to address these limitations. MATERIALS AND METHODS: We reviewed all patients who successfully underwent TOaST thyroidectomy at our institution from November 2017 to November 2018. Demographics, surgical indications, technical details, and perioperative outcomes were recorded in a prospective database and analyzed retrospectively. RESULTS: Fourteen patients underwent TOaST thyroidectomy, with mean follow-up of 17 wk. Mean age was 38 y, and all but one was female. Most cases were cytologically benign or indeterminate nodules. There were no injuries to the recurrent laryngeal or mental nerves. TOaST had no instances of chin pain or specimen disruption, two complications that have been associated with the standard transoral approach. The cosmetic outcomes remained excellent. CONCLUSIONS: This pilot study of TOaST indicates that it is a technically feasible and safe approach to thyroidectomy for selected patients.

Patient Frailty Should Be Used to Individualize Treatment Decisions in Primary Hyperparathyroidism.

BACKGROUND: Primary hyperparathyroidism (PHPT) is a common endocrine disorder that predominantly affects patients >60 and is increasing in prevalence. Identifying risk factors for poor outcomes after parathyroidectomy in older adults will help tailor operative decision making. The impact of frailty on surgical outcomes in parathyroidectomy has not been established. METHODS: We performed a retrospective review of patients ≥40 years who underwent parathyroidectomy in the 2005-2010 ACS NSQIP. Frailty was assessed using the modified frailty index (mFI). Multivariable regression was used to determine the association of frailty with 30-day complications, length of stay (LOS), and reoperation. RESULTS: We identified 13,123 patients ≥40 who underwent parathyroidectomy for PHPT. The majority of patients were not frail, with 80% with a low NSQIP mFI score (0-1 frailty traits), 19% with an intermediate mFI score (2-3), and 0.9% with a high mFI score (≥4). Overall 30-day complications were rare, occurring in 141 (1.1%) patients. Increasing frailty was associated with an increased risk of complications with adjusted odds ratios (ORs) of 1.76 (95% CI 1.20-2.59; p = 0.004) for intermediate and 8.43 (95% CI 4.33-16.41; p < 0.001) for high mFI score. Patient age was independently associated with an increased risk of complications only when ≥75, as was African-American race. Anesthesia with local, monitored anesthesia care, or regional block was the only factor associated with decreased odds of complications. A high NSQIP mFI was also associated with a significant 4.77-day adjusted increase in LOS (95% CI 4.28-5.25; p < 0.001) and increased odds of reoperation (OR 4.20, 95% CI 1.64-10.74; p = 0.003). CONCLUSION: Patient frailty is associated with increased complications, reoperation and prolonged LOS in patients undergoing parathyroidectomy for PHPT. The risks of surgical management should be weighed against potential benefits in frail patients with PHPT to individualize treatment decisions in this vulnerable population.

Recombinant Parathyroid Hormone Versus Usual Care: Do the Outcomes Justify the Cost?

BACKGROUND: Hypoparathyroidism is a potential outcome of anterior neck surgery. Commonly it is managed by calcium and vitamin D supplementation in large doses, with attendant side effects. A recombinant human parathyroid hormone (rhPTH) is now available in the USA, offering a potentially more effective treatment. No cost-effectiveness model investigating this new medication versus standard care has yet been published. METHODS: We constructed a decision analytic model comparing usual care versus rhPTH treatment for postsurgical hypoparathyroidism. Threshold and sensitivity analyses on key parameters were conducted to assess robustness of the model. Costs and health outcomes were represented in US dollars and quality-adjusted life-years (QALYs). RESULTS: The rhPTH strategy was both more costly and more effective than the usual care (UC) strategy. In the base case, UC cost $37,196 and provided 7.54 QALYs. The rhPTH strategy cost $777,224 and provided 8.46 QALYs for an incremental cost-effectiveness ratio of $804,378/QALY. As this was above our willingness-to-pay of $100,000, treatment with rhPTH was not considered cost-effective. The model was robust to all other parameters. CONCLUSIONS: To our knowledge, this is the first formal cost-effectiveness analysis of rhPTH in comparison with UC. Our model suggests that although the new treatment is slightly more effective than UC, the modest gain in quality of life for patients who are reasonably well-managed by UC does not justify the cost. However, consideration must be given to rhPTH for patients who have failed UC, as the expenditure may be justified in that context.

Unanticipated thyroid cancer in patients with substernal goiters: are we underestimating the risk?

BACKGROUND: The rate of unexpected thyroid cancers found at the time of thyroidectomy is thought to be similar in patients with cervical and substernal multinodular goiters (MNGs). METHODS: The objective of this study was to compare the prevalence of undiagnosed cancer found in patients undergoing a thyroidectomy for a cervical or substernal MNG. We conducted a review of patients with a preoperative diagnosis of an MNG (both cervical and substernal) at a tertiary referral center between 2005 and 2012. RESULTS: We identified 538 patients who underwent thyroidectomy for an MNG (144 with substernal MNGs and 394 with cervical MNGs). Patients with substernal MNGs were older (59.6 vs. 52.3; p < 0.001), more likely to be men (34 vs. 11.1 %; p < 0.001), and less likely to have a history of radiation exposure to the neck (2.1 vs. 12.4 %; p < 0.001). Thyroid cancer (>1 cm) was found in 13.7 % of substernal MNG specimens and in 6.3 % of cervical MNG specimens (p = 0.003). On multivariate analysis, substernal location [odds ratio (OR) = 2.360; confidence interval (CI), 1.201-4.638] was the only variable independently associated with an unexpected thyroid cancer on surgical pathology. CONCLUSION: The rate of postoperatively discovered thyroid cancer is significant in patients with substernal MNGs and is increased when compared to patients with cervical MNGs. Surgeons should counsel their patients regarding the possibility of this unexpected result.

The underestimated risk of cancer in patients with multinodular goiters after a benign fine needle aspiration.

IMPORTANCE: Ultrasound-guided fine needle aspiration (FNA) is an excellent tool for evaluating patients with solitary thyroid nodules, with a false-negative malignancy rate of <3%. The utility of FNA in patients with a cervical multinodular goiter (MNG) is unknown, because biopsy and surveillance of thyroids with numerous nodules may be impractical. OBJECTIVE: To evaluate the incidence and risk factors for unsuspected thyroid cancer on final pathology in patients with a non-functional, cervical MNG who had a benign preoperative FNA and underwent thyroidectomy. DESIGN, SETTING AND PARTICIPANTS: Retrospective review of patients with non-functional, cervical MNG at a high-volume tertiary referral center between 2005 and 2012. MAIN OUTCOME MEASURE(S): Incidence of thyroid cancer on surgical pathology. RESULTS: Of the 134 patients included in the study, 31 (23.1%) were found to have thyroid cancer on final pathology. Twenty-one (15.7%) patients had a microscopic papillary cancer (<1 cm) and 10 (7.5%) patients had other forms of thyroid cancer [five follicular, four papillary (>1 cm), and one patient with a papillary and follicular cancer]. On univariate analysis, male gender had a near-significant association with non-micropapillary thyroid cancer (p = 0.06). On multivariate analysis, male gender (OR = 10.2, 95% CI 1.35-76.8) and FNA cytology not reviewed at our institution (OR = 6.0, 95% CI 1.2-30) were independently associated with non-micropapillary thyroid cancer. CONCLUSIONS AND RELEVANCE: The incidence of thyroid cancer in patients with MNG and benign FNA is significant. Men and patients in whom the FNA cytology is not reviewed by an experienced cytopathologist may be at an increased risk for an undetected thyroid cancer.

Disparities in access to high-volume parathyroid surgeons in the United States: A call to action.

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: 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.

Vandetanib and the management of advanced medullary thyroid cancer.

PURPOSE OF REVIEW: Vandetanib is a small molecule tyrosine kinase inhibitor that has been recently approved as an 'orphan drug' for the treatment of patients with unresectable, locally advanced, or metastatic medullary thyroid cancer (MTC). RECENT FINDINGS: MTC is a neuroendocrine malignancy frequently associated with mutations to the RET proto-oncogene. Vandetanib selectively targets RET, vascular endothelial growth factor receptor-2, and epidermal growth factor receptor dependent signaling. Vandetanib has been shown to improve progression-free survival in patients with advanced MTC. In general, vandetanib is well tolerated, but QTc prolongation remains a potential concern demanding careful patient selection and monitoring. SUMMARY: Vandetanib has emerged as one of the more promising small molecule tyrosinse kinase inhibitors, providing durable rates of disease stabilization, with an acceptable adverse event profile in patients with advanced MTC.

Operative Management of Thyroid Disease in Older Adults.

As the population ages, both domestically and globally, clinicians will increasingly find themselves navigating treatment decisions for thyroid disease in older adults. When considering surgical treatment, individualizing risk assessment is particularly important, as older patients can present with very different health profiles. While fit, independent individuals may benefit from thyroidectomy with minimal risk, those with multiple comorbidities and poor functional status are at higher risk of perioperative complications, which can have adverse health effects and detract from long-term quality of life. In order to optimize surgical outcomes for older adults, strategies for accurate risk assessment and mitigation are being explored. Surgical decision-making also should consider the characteristics of the thyroid disease being treated, given many benign thyroid disorders and some well-differentiated thyroid cancers can be appropriately managed nonoperatively without compromising longevity. Shared decision-making becomes increasingly important to respect the health priorities and optimize outcomes for older adults with thyroid disease. This review summarizes the current knowledge of thyroid surgery in older adults to help inform decision-making among patients and their physicians.

A Contemporary Review of the Treatment of Medullary Thyroid Carcinoma in the Era of New Drug Therapies.

Medullary thyroid cancer (MTC) is a rare neuroendocrine tumor that can be sporadic or inherited and is often associated with mutations in the RET (Rearranged during Transfection) oncogene. The primary treatment for MTC is surgical resection of all suspected disease, but recent advances in targeted therapies for MTC, including the selective RET inhibitors selpercatinib and pralsetinib, have led to changes in the management of patients with locally advanced, metastatic, or recurrent MTC. In this article, we review updates on the evaluation and management of patients with MTC, focusing on new and emerging therapies that are likely to improve patient outcomes.

Kidney Stone Events Following Parathyroidectomy vs Nonoperative Management for Primary Hyperparathyroidism.

CONTEXT: Primary hyperparathyroidism (PHPT) is associated with an increased risk of kidney stones. Few studies account for PHPT severity or stone risk when comparing stone events after parathyroidectomy vs nonoperative management. OBJECTIVE: Compare the incidence of kidney stone events in PHPT patients treated with parathyroidectomy vs nonoperative management. DESIGN: Longitudinal cohort study with propensity score inverse probability weighting and multivariable Cox proportional hazards regression. SETTING: Veterans Health Administration integrated health care system. PATIENTS: A total of 44 978 patients with > 2 years follow-up after PHPT diagnosis (2000-2018); 5244 patients (11.7%) were treated with parathyroidectomy. MAIN OUTCOMES MEASURE: Clinically significant kidney stone event. RESULTS: The cohort had a mean age of 66.0 years, was 87.8% male, and 66.4% White. Patients treated with parathyroidectomy had higher mean serum calcium (11.2 vs 10.8mg/dL) and were more likely to have a history of kidney stone events. Among patients with baseline history of kidney stones, the unadjusted incidence of ≥ 1 kidney stone event was 30.5% in patients managed with parathyroidectomy (mean follow-up, 5.6 years) compared with 18.0% in those managed nonoperatively (mean follow-up, 5.0 years). Patients treated with parathyroidectomy had a higher adjusted hazard of recurrent kidney stone events (hazard ratio [HR], 1.98; 95% CI, 1.56-2.51); however, this association declined over time (parathyroidectomy × time: HR, 0.80; 95% CI, 0.73-0.87). CONCLUSION: In this predominantly male cohort with PHPT, patients treated with parathyroidectomy continued to be at higher risk of kidney stone events in the immediate years after treatment than patients managed nonoperatively, although the adjusted risk of stone events declined with time, suggesting a benefit to surgical treatment.

Preventive Health Screening in Veterans Undergoing Bariatric Surgery.

INTRODUCTION: Individuals with obesity are vulnerable to low rates of preventive health screening. Veterans with obesity seeking bariatric surgery are also hypothesized to have gaps in preventive health screening. Evaluation in a multidisciplinary bariatric surgery clinic is a point of interaction with the healthcare system that could facilitate improvements in screening. METHODS: This is a retrospective cohort study of 381 consecutive patients undergoing bariatric surgery at a Veterans Affairs Hospital from January 2010 to October 2021. Age- and sex-appropriate health screening rates were determined at initial referral to a multidisciplinary bariatric surgery clinic and at the time of surgery. Rates of guideline concordance at both time points were compared using McNemar's test. Univariate and multivariate analyses were performed to identify the risk factors for nonconcordance. RESULTS: Concordance with all recommended screening was low at initial referral and significantly improved by time of surgery (39.1%‒63.8%; p<0.001). Screening rates significantly improved for HIV (p<0.001), cervical cancer (p=0.03), and colon cancer (p<0.001). Increases in BMI (p=0.005) and the number of indicated screening tests (p=0.029) were associated with reduced odds of concordance at initial referral. Smoking history (p=0.012) and increasing distance to the nearest Veterans Affairs Medical Center (p=0.039) were associated with reduced odds of change from nonconcordance at initial referral to concordance at the time of surgery. CONCLUSIONS: Rates of preventive health screening in Veterans with obesity are low. A multidisciplinary bariatric surgery clinic is an opportunity to improve preventive health screening in Veterans referred for bariatric surgery.

Risk of Fracture Among Older Adults With Primary Hyperparathyroidism Receiving Parathyroidectomy vs Nonoperative Management.

Importance: 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: To compare the incidence of clinical fracture among older adults with PHPT treated with parathyroidectomy vs nonoperative management. Design, Setting, and Participants: 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: The primary outcome was clinical fracture at any anatomic site not associated with major trauma during the follow-up period. Results: 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: 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.

Racial disparities in the utilization of parathyroidectomy among patients with primary hyperparathyroidism: Evidence from a nationwide analysis of Medicare claims.

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: 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.