Background Hypercalcaemia in primary hyperparathyroidism (PHPT) is thought to be due to increased bone resorption, renal calcium conservation, and increased 1,25-dihydroxyvitamin D (1,25(OH)2D) production, which in turn increases gastrointestinal calcium absorption. Data regarding serum 1,25(OH)2D concentrations in PHPT is, however, very limited.
Aim To examine mechanisms of hypercalcaemia in patients with PHPT.
Methods We studied 88 consecutive patients with PHPT diagnosed on fasting metabolic bone studies (based on venous blood and spot urine samples after overnight fast) at PathWest, QEII Medical Centre. Bone resorption was assessed using urine N-telopeptide/creatinine ratio (NTx) and urine calcium excretion calculated in umol/L of glomerular filtrate (GF). Serum 1,25(OH)2D was measured using Liason chemiluminescent immunoassay, using the manfuacturer’s reference range (48-190 pmol/L). Patients with eGFR <60 ml/min or on anti-resorptive treatment were excluded, leaving 73 patients for analysis.
Results Patients were predominantly female (79%), with median age 68.5 y. Median values for analytes (with IQR) were: ionised calcium 1.35 mmol/L (1.33-1.41), PTH 9.5 pmol/L (7.5-12), 25(OH)D 67 nmol/L (53-88nmol/L), 1,25(OH)2D 132 pmol/L (107-164), NTx 40 nmol BCE/mmol creatinine (29-69) and urine calcium excretion 18 umol/L GF (IQR 13-37). Of 73 patients, 40 (55%) had reduced urine calcium excretion, 30 (41%) had increased NTx, and 12 (16%) had elevated serum 1,25(OH)2D. By regression analysis, PTH was positively correlated with 1,25(OH)2D (r=0.306, p=0.008) and negatively correlated with 25(OH)D (r=-0.391, p=<0.001); 1,25(OH)2D was positively associated with NTx (p=0.027) but not significantly correlated with ionized calcium.
Conclusions In this cohort of patients with PHPT, higher PTH was associated with lower 25(OH)D and higher 1,25(OH)2D. Higher serum 1,25(OH)2D was associated with increased bone resorption but not with ionized calcium and was frankly elevated in only a minority of patients. Hypercalcaemia was predominantly attributable due to renal calcium conservation and increased bone resorption.