Further insights into the pathogenesis of primary hyperparathyroidism: a nested case-control study

Area of Science:

• Endocrinology
• Biochemistry

Background:

• The underlying causes of primary hyperparathyroidism (PHPT) remain poorly understood.
• Early detection of PHPT is crucial for timely intervention and management.

Purpose of the Study:

• To investigate plasma levels of calcium, parathyroid hormone (PTH), and 25-hydroxyvitamin D (25OHD) in individuals before a clinical PHPT diagnosis.
• To identify biochemical markers indicative of latent PHPT.

Main Methods:

• Analysis of three population-based cohorts with identified PHPT cases (n=117) and matched controls (n=233).
• Comparison of biochemical profiles, including calcium, PTH, and 25OHD levels, between cases and controls prior to PHPT diagnosis.

Main Results:

• A significant proportion of PHPT cases (63%) had undiagnosed PHPT at cohort inclusion, with a median of 5.6 years before diagnosis.
• Individuals later diagnosed with PHPT exhibited lower 25OHD levels and distinct patterns of normocalcemic hyperparathyroidism or normoparathyroid hypercalcemia compared to controls.
• Plasma calcium levels >2.52 mmol/liter showed a 95% positive predictive value for later PHPT diagnosis.

Conclusions:

• Calcium homeostasis is disturbed years before clinical PHPT diagnosis.
• Latent PHPT can manifest as normocalcemic hyperparathyroidism or normoparathyroid hypercalcemia.
• Long-term follow-up of individuals with these biochemical profiles is recommended to confirm early-stage PHPT.