Background: Primary hyperparathyroidism classically presents with elevated serum calcium and elevated, or unsuppressed, parathyroid hormone. Normocalcemic primary hyperparathyroidism is characterized by normal serum calcium with an elevated parathyroid hormone. Most patients are asymptomatic but decreased bone mass, nephrolithiasis, and neuropsychiatric symptoms can be observed. Normocalcemic primary hyperparathyroidism (NCpHPT) has recently become a topic of interest with more patients meeting diagnostic criteria for the disorder. To our knowledge, no meta-analysis on laboratory values or co-morbidities of NCpHPT has been performed.
Objective: To compare baseline laboratory values and co-morbidities of NCpHPT to classic, hypercalcemic primary hyperparathyroidism (HCpHPT).
Methods: A literature search was performed using the PubMed database. Studies were included if laboratory values were reported for subjects diagnosed with NCpHPT. The following diagnostic criteria for NCpHPT was used: (1) persistently normal serum calcium, (2) elevated PTH, and (3) causes of secondary hyperparathyroidism were excluded. Standardized mean difference (SMD) was applied to quantitative variables (e.g., calcium, PTH). Odds ratio (OR) was used to determine incidence of co-morbidities.
Results: One hundred and ninety-four studies were identified. Thirty-six studies met inclusion criteria. Of those, 17 studies reported a mean serum calcium of 9.25 mg/dL in subjects with NCpHPT (n=732). Fifteen studies reported a mean serum calcium of 11.23 mg/dL in subjects with HCpHPT (n=4,882). Eight studies compared total serum calcium for both groups and a significantly lower serum calcium was seen in NCpHPT (SMD 3.96; 95% CI: 0.45 – 7.47). In 27 studies, mean PTH for NCpHPT was 98.28rg/mL, whereas 18 studies reported a mean PTH of 157.44 rg/mL in HCpHPT. On further analysis of studies that compared the two groups (n=12), PTH was marginally lower in NCpHPT (SMD 0.57; 95% CI: 0.14 – 0.99). Patients with NCpHPT had a mean 25-OHD of 28.16 ng/mL (25 studies) compared to 27.97 ng/mL in HCpHPT (14 studies). No statistically significant difference in 25-OHD was seen in 11 studies that compared both groups. Mean 24hr urine calcium was 211.59 mg/day in NCpHPT (15 studies) and 316.57 mg/day in HCpHPT (9 studies). Six studies reported urinary calcium for both groups. A lower urinary calcium excretion was seen in NCpHPT (SMD 1.00; 95% CI: 0.04 – 1.97).
Seventeen studies reported incidence of nephrolithiasis in NCpHPT, which was observed in 23.08% of subjects. Seven studies reported decreased bone mineral density (BMD) in NCpHPT, seen in 44.42% of subjects. When compared to co-morbidities of HCpHPT, no statistically significant difference was found.
Conclusions: Patients with NCpHPT have normal serum calcium with PTH and 25-OHD values comparable to HCpHPT. Urinary calcium excretion was lower in NCpHPT. Nephrolithiasis and decreased BMD was commonly reported, but no significant difference in incidence was found when compared to HCpHPT.