Parathyroidectomy Can Reduce Adverse Outcomes Risk in Primary Hyperparathyroidism

Kristian Axelsson, MSc, MD, PHD

A new study from an international team representing institutions from Sweden, Australia, and the UK is providing clinicians with an overview of management of primary hyperparathyroidism, including prevalence of comorbidities and trends clinical outcomes, as well as the rate and impact of undergoing parathyroidectomy on risk of adverse outcomes.

Led by investigators at the University of Gothenburg, results of the study provide insight into the increased risk of adverse events associated with primary hyperparathyroidism, including a 51% increase in risk of hip fracture, 45% increase in risk of cardiovascular events, and a 72% increase in risk of mortality, compared to their counterparts without hyperparathyroidism, but also details the apparent reductions in risk associated with undergoing parathyroidectomy in this patient population.

“We show that untreated primary hyperparathyroidism means a 51% higher risk of hip fracture and a 45% increase in heart attack or stroke risk. The kidney stone risk is almost quadrupled and, additionally, the risk of death is raised by 72%. The increased likelihood of these complications highlights the importance of identifying patients with this hormonal disease,” said lead investigator Kristian Axelsson, MSc, MD, PhD, researcher at the University of Gothenburg, resident in general medicine within the public primary care in Region Västra Götaland, in a statement.

Citing a lack of well-controlled, large-scale trials, Axelsson and fellow investigators designed the current study with the intent of estimating associations of primary hyperparathyroidism with risk of fractures and other comorbidities as well as assigning whether parathyroidectomy might influence associations between primary hyperthyroidism and adverse outcomes. Using Swedish national registers, investigators identified all patients who were diagnosed with primary hyperparathyroidism at hospitals in Sweden from July 1, 2006 through December 31, 2017. Using the same registers, investigators identified 10 control individuals for each patient with primary hyperparathyroidism based on sex, birth year, and county of residence.

Overall, the study population included 16,374 patients with primary hyperparathyroidism and 163,740 matched controls. The study cohort had a mean age of 67.5 (SD, 12.9) years and 78.2% were women. Of the 16,374 patients with primary hyperparathyroidism, 42.3% (n=6934) underwent parathyroidectomy a median of 0.50 (IQR, 0.25-0.94) years after diagnosis. The total follow-up time was 42,310 person-years for the primary hyperparathyroidism group and 803,522 person-years for the control group.

Primary outcomes of interest for the investigators’ analyses were the incidence of fractures, cardiovascular events and death. Investigators used 1-minus Kaplan-Meier estimator of corresponding survival function to evaluate cumulative incidence of events and Cox proportional hazards regression models were used to calculate hazard ratios. Of note, cardiovascular events were defined as myocardial infarction, hemorrhagic stroke, or ischemic stroke and fractures were further assessed based on location.

Initial analysis revealed the incidence rates per 1000 person-years for any fracture (35.52 [95% CI, 33.50-37.64] vs 25.36 [95% CI, 24.98-25.74]), major osteoporotic fracture (23.46 [95% CI, 21.85-25.17] vs 16.35 [95% CI, 16.05-16.65]), hip fracture (9.30 [95% CI, 8.31-10.38] vs 6.26 [95% CI, 6.08-6.45]), injurious fall (28.59 [95% CI, 26.95-30.31] vs 18.97 [95% CI, 18.66-19.28]), any CVE (17.22 [95% CI, 15.97-18.54] vs 11.98 [95% CI, 11.74-12.22]), kidney stone (9.27 [95% CI, 8.37-10.25] vs 2.47 [95% CI, 2.36-2.58]), and death (51.83 [95% CI, 49.68-54.05] vs 30.95 [95% CI, 30.57-31.34]) were significantly higher for patients with primary hyperparathyroidism than among matched controls.

Compared to their matched controls, patients with primary hyperparathyroidism had a significantly greater risk of any fracture (HR, 1.39 [95% CI, 1.31-1.48]), major osteoporotic fracture (HR, 1.43 [95% CI, 1.33-1.54]), hip fracture (HR, 1.51 [95% CI, 1.35-1.70]), and injurious fall (HR, 1.51 [95% CI, 1.42-1.60]). A statistically significant increase in risk was also observed for cardiovascular events (HR, 1.45 [95% CI, 1.34-1.57]). Further analysis demonstrated this increase in risk was present for acute myocardial infarction (HR, 1.39 [95% CI, 1.24-1.56]) and ischemic stroke (HR, 1.51; [95% CI, 1.36-1.68]), but no significant increase in risk was observed for hemorrhagic stroke (HR, 1.09 [95% CI, 0.82-1.45]) in unadjusted models. Investigators pointed out the risk of developing kidney stones (HR, 3.65 [95% CI, 3.27-4.08]) and mortality was also significantly greater in those with primary hyperparathyroidism (HR, 1.72 [95% CI, 1.65-1.80]).

When assessing the effects of parathyroidectomy in a time-dependent Poisson regression models, results indicated undergoing parathyroidectomy was associated with a reduction in risk of any fracture (HR, 0.83 [95% CI, 0.75-0.93]), hip fracture (HR, 0.78 [95% CI, 0.61-0.98]), cardiovascular events (HR, 0.84 [95% CI, 0.73-0.97]), and mortality (HR, 0.59 [95% CI, 0.53-0.65]). In a Vox proportional hazards regression model adjusted for age and ex, investigators found undergoing parathyroidectomy was associated with a reduction in risk of any fracture (HR, 0.77; 95% CI, 0.63-0.95) and kidney stones (HR, 0.61; 95% CI, 0.48-0.78) after parathyroidectomy as compared to before, but there was no difference in risk observed for injurious falls (HR, 1.02 [95% CI, 0.80-1.31]).

“The study indicates that surgery clearly reduces the risk of osteoporosis fractures, fall injuries, and death in cardiovascular events, and these are vital findings that may lead to more patients being selected for surgery. Our results support the view that patients’ cardiovascular risk, as well as the high fracture risk, should be considered in surgery decisions,” added senior investigator Mattias Lorentzon, MD, PhD, professor of Geriatric Medicine at the University of Gothenburg and chief physician at Sahlgrenska University Hospital, in the aforementioned statement.

This study, “Analysis of Comorbidities, Clinical Outcomes, and Parathyroidectomy in Adults With Primary Hyperparathyroidism,” was published in JAMA Network Open.