Prevalence and Outcomes of Primary Hyperparathyroidism in Sarcoidosis Patients: A Large-Scale Retrospective Cohort Study.

Abstract

Among 117,395 U.S. adults with sarcoidosis, primary hyperparathyroidism was markedly underdiagnosed: 75.4% of biochemically defined cases carried no corresponding ICD-10 code, and parathyroidectomy was associated with a 4.2-fold reduction in 3-year mortality. Hypercalcemia in sarcoidosis is classically attributed to granuloma-mediated calcitriol excess, but primary hyperparathyroidism (PHPT)-the most common cause of ambulatory hypercalcemia-frequently coexists. These two etiologies are mechanistically distinct: sarcoid hypercalcemia is suppressed-PTH and 1,25(OH)2D-driven, while PHPT is autonomous-PTH-driven and surgically curable. Because both can independently sustain hypercalcemia, attribution to sarcoidosis alone risks anchoring bias and delayed identification of PHPT. To determine PHPT prevalence in sarcoidosis, characterize hypercalcemia-evaluation adequacy, and assess parathyroidectomy (PTX) impact on all-cause mortality. Retrospective cohort study. TriNetX U.S. Collaborative Network, federated EHR data from >120 million patients. 117,395 adults with ICD-10 sarcoidosis (D86) and ≥1 serum calcium measurement. None (observational). iPTH assessment rate; biochemical and coded PHPT prevalence; PTX utilization and outcomes; all-cause mortality. Hypercalcemia: 31.3% (n=36,790); only 30.5% received iPTH. Biochemical PHPT: 3.0% (n=3,493)-of whom 75.4% (n=2,633) had no ICD-10 code. PTX in coded PHPT: 36.6% (n=315), with 74.6% biochemical cure. Hypercalcemia HR 1.33 (1.29-1.38), coded PHPT HR 1.50 (1.40-1.60), no-PTX HR 4.2 (2.7-6.4); all p<0.001. PHPT is prevalent, profoundly under-evaluated, and undertreated in sarcoidosis. Routine iPTH measurement and timely surgical referral are essential.