End-Organ Damage in Primary Hyperparathyroidism: Prevalence, Progression, and Treatment Gaps in a National Cohort

Highlight

– Primary hyperparathyroidism (PHPT) is frequently associated with serious end-organ damage affecting bones and kidneys.
– In a large national cohort, 51.3% of patients presented with end-organ complications at diagnosis.
– Among initially unaffected patients, 32% developed end-organ damage within approximately 1.5 years.
– Despite high morbidity, less than 20% of patients with end-organ damage underwent parathyroidectomy.

Study Background

Primary hyperparathyroidism (PHPT) is a common endocrine disorder characterized biochemically by elevated parathyroid hormone (PTH) levels in the context of hypercalcemia. Clinically, PHPT leads to increased calcium levels that adversely affect skeletal integrity and renal function. Chronic elevations in PTH can cause osteoporosis, increase fracture risk, precipitate nephrolithiasis (kidney stones), and promote chronic kidney disease (CKD). While parathyroidectomy offers curative treatment and has been shown to reduce these end-organ complications, many patients are conservatively managed or simply monitored. The real-world prevalence and timing of PHPT-related organ damage and the utilization patterns of parathyroidectomy at a population level remain underexplored, limiting evidence-based guidance on optimizing management strategies.

Study Design

This retrospective cohort study analyzed national electronic health record and insurance claims datasets from 2010 to 2023 to identify adults with a new biochemical diagnosis of PHPT. The diagnosis criteria were stringent, requiring two elevated calcium measurements followed by a PTH level above 65 pg/mL within one month. The cohort included 43,399 patients with demographic and clinical data including age, sex, comorbidities, and follow-up through 2023. The main outcomes measured were clinically coded or laboratory-confirmed PHPT-associated end-organ damage including osteoporosis, atraumatic fractures, kidney stones, or stage 3 or worse CKD, evaluated both at diagnosis and longitudinally after diagnosis. The frequency and timing of parathyroidectomy were also captured. Data were analyzed during August 2025 to April 2026.

Key Findings

The mean age of the cohort was 67.9 years, predominantly female (78%). At the time of PHPT diagnosis, 51.3% (22,279 patients) already had evidence of end-organ damage. The types of damage included skeletal complications such as osteoporosis and fractures, and renal complications like nephrolithiasis and CKD.

Among the 21,120 patients without evident organ damage at diagnosis, 6,762 (32.0%) developed end-organ sequelae after a median follow-up of 516 days (approximately 1.4 years). This indicates significant progression risk in untreated or under-managed cases.

Despite the substantial burden, parathyroidectomy was performed in only 19.9% of patients who had end-organ damage at diagnosis, highlighting underutilization of a potentially curative intervention. Among those who developed organ damage after initial diagnosis, only 19.9% underwent parathyroidectomy subsequently, with surgery occurring at a median of 154 days after organ damage identification.

These findings collectively show that two-thirds (67%) of adults with biochemical PHPT either present with or subsequently develop clinically significant end-organ damage within a relatively short time frame, yet definitive surgical treatment remains uncommon.

Expert Commentary

This study provides compelling population-based evidence of a substantial burden of organ complications associated with PHPT under usual care conditions. The high prevalence of skeletal and renal damage, often present at diagnosis, emphasizes the need for earlier identification and risk stratification. The limited deployment of parathyroidectomy suggests barriers in referral, patient selection, or awareness. It is conceivable that clinical inertia, comorbidities, or perceived surgical risks may contribute to low surgical rates; however, the evidence aligns with existing guidelines recommending surgery for symptomatic patients or those with end-organ effects.

Mechanistically, sustained PTH excess leads to increased bone resorption causing osteoporosis and fracture risk, while hypercalcemia and hypercalciuria promote stone formation and kidney injury. Early surgical intervention can restore calcium homeostasis and reduce morbidity.

Study limitations include reliance on coded EHR data which may underdetect some complications, absence of detailed symptomatology or imaging, and potential selection bias inherent in observational analyses. Nevertheless, the large sample and longitudinal follow-up strengthen generalizability.

Conclusion

In a nationwide cohort study spanning over a decade, a majority of patients diagnosed with PHPT demonstrated or developed end-organ damage affecting bones or kidneys. Despite this clinical burden, parathyroidectomy was underutilized, underscoring missed opportunities to mitigate morbidity through surgical cure. These findings support strategies emphasizing timely diagnosis, systematic assessment for end-organ involvement, and appropriate referral for parathyroidectomy. Future research should focus on elucidating barriers to surgical care and optimizing management pathways to improve patient outcomes in PHPT.

Funding and ClinicalTrials.gov

The study was conducted using national electronic health record and claims data sets; specific funding details and clinical trial registration were not provided.

References

1. Delaney LD, Day HS, Arnow KD, et al. End-Organ Damage Associated With Primary Hyperparathyroidism. JAMA Surg. 2026 Jul 29. PMID: 42525408.
2. Bilezikian JP, Brandi ML, Eastell R, et al. Guidelines for the Management of Asymptomatic Primary Hyperparathyroidism: Summary Statement from the Fourth International Workshop. J Clin Endocrinol Metab. 2014 Oct;99(10):3561-9.
3. Marcocci C, Cetani F. Clinical practice. Primary hyperparathyroidism. N Engl J Med. 2011 Jun 30;364(25):2392-401.