Analysis of Comorbidities, Clinical Outcomes, and Parathyroidectomy in Adults with Primary Hyperparathyroidism

Kristian F. Axelsson, Märit Wallander, Helena Johansson, Nicholas C. Harvey, Liesbeth Vandenput, Eugene McCloskey, Enwu Liu, John A. Kanis, Henrik Litsne, Mattias Lorentzon

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Importance: Patients with primary hyperparathyroidism (pHPT) appear to have an increased risk of fractures and other comorbidities, such as cardiovascular disease, although results from previous studies have been inconsistent. Evidence of the association of parathyroidectomy (PTX) with these outcomes is also limited because of the lack of large well-controlled trials. Objective: To investigate whether untreated pHPT was associated with an increased risk of incident fractures and cardiovascular events (CVEs) and whether PTX was associated with a reduced risk of these outcomes. Design, Setting, and Participants: This cohort study included all patients who were diagnosed with pHPT at hospitals in Sweden between July 1, 2006, and December 31, 2017. Each patient was matched with 10 control individuals from the general population by sex, birth year, and county of residence. The patients were followed up until December 31, 2017. Data analyses were performed from October 2021 to April 2022. Main Outcomes and Measures: The primary outcomes were fractures, CVEs, and death. Cumulative incidence of events was estimated using the 1-minus Kaplan-Meier estimator of corresponding survival function. Cox proportional hazards regression models were used to calculate hazard ratios (HRs). Results: A total of 16374 patients with pHPT were identified (mean [SD] age, 67.5 [12.9] years; 12806 women [78.2%]), with 163740 control individuals. The follow-up time was 42310 person-years for the pHPT group and 803522 person-years for the control group. Compared with the control group, the pHPT group had a higher risk of any fracture (unadjusted HR, 1.39; 95% CI, 1.31-1.48), hip fracture (unadjusted HR, 1.51; 95% CI, 1.35-1.70), CVEs (unadjusted HR, 1.45; 95% CI, 1.34-1.57), and death (unadjusted HR, 1.72; 95% CI, 1.65-1.80). In a time-dependent Poisson regression model, PTX was associated with a reduced risk of any fracture (HR, 0.83; 95% CI, 0.75-0.93), hip fracture (HR, 0.78; 95% CI, 0.61-0.98), CVEs (HR, 0.84; 95% CI, 0.73-0.97), and death (HR, 0.59; 95% CI, 0.53-0.65). Conclusions and Relevance: Results of this study suggest that pHPT is associated with increased risk of fractures, CVEs, and death, highlighting the importance of identifying patients with this condition to prevent serious unfavorable outcomes. The reduced risk of these outcomes associated with PTX suggests a clinical benefit of surgery.

Original languageEnglish
Article numbere2215396
Number of pages14
JournalJAMA network open
Issue number6
Publication statusPublished - 3 Jun 2022
Externally publishedYes


  • Primary hyperparathyroidism
  • comorbidities
  • parathyroidectomy
  • Fractures
  • cardiovascular disease
  • Cardiovascular events and deaths


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