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

PRÉCIS: 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.

CONTEXT: 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.

OBJECTIVE

To determine PHPT prevalence in sarcoidosis, characterize hypercalcemia-evaluation adequacy, and assess parathyroidectomy (PTX) impact on all-cause mortality.

DESIGN

Retrospective cohort study.

SETTING

TriNetX U.S. Collaborative Network, federated EHR data from >120 million patients.

PATIENTS: 117,395 adults with ICD-10 sarcoidosis (D86) and ≥1 serum calcium measurement.

INTERVENTIONS: None (observational).

MAIN OUTCOME MEASURES: iPTH assessment rate; biochemical and coded PHPT prevalence; PTX utilization and outcomes; all-cause mortality.

RESULTS

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.

CONCLUSIONS

PHPT is prevalent, profoundly under-evaluated, and undertreated in sarcoidosis. Routine iPTH measurement and timely surgical referral are essential.