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Question听 Among patients with primary hyperparathyroidism, can parathyroidectomy reduce the risk of a subsequent diagnosis of depression?

Findings听 In this trial emulation of 40鈥�231 adults with primary hyperparathyroidism, the study team was unable to find a difference in the 10-year cumulative incidence of new depression between patients who underwent early parathyroidectomy compared with nonoperative management. Patients treated with parathyroidectomy experienced no significant difference in the adjusted rate of new depression compared with nonoperative management.

Meaning听 In this study, early parathyroidectomy for patients with primary hyperparathyroidism did not affect the incidence of new depression compared with nonoperative management.

Importance听 Primary hyperparathyroidism (PHPT) is a common endocrine disorder associated with neuropsychiatric symptoms. Although parathyroidectomy has been associated with improvement of preexisting depression among adults with PHPT, the effect of parathyroidectomy on the development of new depression is unknown.

Objective听 To determine the effect of early parathyroidectomy on the incidence of new depression among adults with PHPT compared with nonoperative management.

Design, Setting, and Participants听 Analyzed data included observational national Veterans Affairs data from adults with a new diagnosis of PHPT from 2000 through 2019 using target trial emulation with cloning, a biostatistical method that uses observational data to emulate a randomized clinical trial. New depression rates were compared between those treated with early parathyroidectomy vs nonoperative management using an extended Cox model with time-varying inverse probability censoring weighting, adjusted for patient demographics, comorbidities, and depression risk factors. Eligible adults with a new biochemical diagnosis of PHPT, excluding those with past depression diagnoses, residing in an assisted living/nursing facility, or with Charlson Comorbidity Index score higher than 4 were included. These data were analyzed January 4, 2023, through June 15, 2023.

Exposure听 Early parathyroidectomy (within 1 year of PHPT diagnosis) vs nonoperative management.

Main Outcome听 New depression, including among subgroups according to patient age (65 years or older; younger than 65 years) and baseline serum calcium (11.3 mg/dL or higher; less than 11.3 mg/dL).

Results听 The study team identified 40鈥�231 adults with PHPT and no history of depression of whom 35896 were male (89%) and the mean (SD) age was 67 (11.3) years. A total of 3294 patients underwent early parathyroidectomy (8.2%). The weighted cumulative incidence of depression was 11% at 5 years and 18% at 10 years among patients who underwent parathyroidectomy, compared with 9% and 18%, respectively, among nonoperative patients. Those treated with early parathyroidectomy experienced no difference in the adjusted rate of new depression compared with nonoperative management (hazard ratio, 1.05; 95% CI, 0.94-1.17). There was also no estimated effect of early parathyroidectomy on new depression in subgroup analyses based on patient age or serum calcium.

Conclusions听 In this study, there was no difference in the incidence of new depression among adults with PHPT treated with early parathyroidectomy vs nonoperative management, which is relevant to preoperative discussions about the benefits and risks of operative treatment.