Mortality and Morbidity in Mild Primary Hyperparathyroidism: Results From a 10-Year Prospective Randomized Controlled Trial of Parathyroidectomy Versus Observation

Ann Intern Med. 2022 Jun;175(6):812-819. doi: 10.7326/M21-4416. Epub 2022 Apr 19.


Background: Primary hyperparathyroidism (PHPT) is a common endocrine disorder associated with increased risk for fractures, cardiovascular disease, kidney disease, and cancer and increased mortality. In mild PHPT with modest hypercalcemia and without known morbidities, parathyroidectomy (PTX) is debated because no long-term randomized trials have been performed.

Objective: To examine the effect of PTX on mild PHPT with regard to mortality (primary end point) and key morbidities (secondary end point).

Design: Prospective randomized controlled trial. ( NCT00522028).

Setting: Eight Scandinavian referral centers.

Patients: From 1998 to 2005, 191 patients with mild PHPT were included.

Intervention: Ninety-five patients were randomly assigned to PTX, and 96 were assigned to observation without intervention (OBS).

Measurements: Date and causes of death were obtained from the Swedish and Norwegian Cause of Death Registries 10 years after randomization and after an extended observation period lasting until 2018. Morbidity events were prospectively registered annually.

Results: After 10 years, 15 patients had died (8 in the PTX group and 7 in the OBS group). Within the extended observation period, 44 deaths occurred, which were evenly distributed between groups (24 in the PTX group and 20 in the OBS group). A total of 101 morbidity events (cardiovascular events, cerebrovascular events, cancer, peripheral fractures, and renal stones) were also similarly distributed between groups (52 in the PTX group and 49 in the OBS group). During the study, a total of 16 vertebral fractures occurred in 14 patients (7 in each group).

Limitation: During the study period, 23 patients in the PTX group and 27 in the OBS group withdrew.

Conclusion: Parathyroidectomy does not appear to reduce morbidity or mortality in mild PHPT. Thus, no evidence of adverse effects of observation was seen for at least a decade with respect to mortality, fractures, cancer, cardiovascular and cerebrovascular events, or renal morbidities.

Primary funding source: Swedish government, Norwegian Research Council, and South-Eastern Norway Regional Health Authority.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Humans
  • Hypercalcemia*
  • Hyperparathyroidism, Primary* / complications
  • Hyperparathyroidism, Primary* / surgery
  • Morbidity
  • Parathyroidectomy / adverse effects
  • Prospective Studies

Associated data