Endocrine Abstracts

Context: Normocalcemic hyperparathyroidism (NHPT) is considered as an earlier or milder phenotype compared to traditional primary hyperparathyroidism (PHPT). To make a correct diagnosis, secondary hyperparathyroidism due to low calcium intake must be excluded. Whether calcium intake might affect presentation of PHPT vs NHPT has never been addressed consistently.

Objective: To describe patients with a diagnosis of NHPT or PHPT in relation to their calcium intake, through three standard validated questionnaires.

Design: Cross-sectional study.

Setting: Outpatient, single academic medical center.

Patients: 44 consecutive women recruited from March through December 2021. 22 patients with mild primary hyperparathyroidism (PHPT or NHPT) were age-matched with 22 women undergoing bone mineral evaluation for the first time due to recently diagnosed hormone-positive breast cancer. NHPT diagnosis was based on multiple determinations of both total calcium and albumin-corrected calcium within normal limits, as per current international guidelines.

Interventions: Administration of all the following: a validated local food-frequency questionnaire (LOC), International Osteoporosis Foundation Calcium Calculator (IOF) and National Osteoporosis Foundation Calcium Calculator (NOF).

Main outcome measures: Any association with biochemistries or clinical features.

Results: All three questionnaires confirmed that NHPT patients had similar calcium intake as compared with PHPT or controls. Calcium intake evaluated with all three questionnaires was not correlated with any biochemical index in NHPT nor PHPT, although it showed an association with hip T-scores in PHPT patients (r=-0.821,P=0.027 for total hip T-scores). Maximum serum calcium reached over time (CaMax), SCa ranges and 24-Hour Urinary Calcium were significantly greater in PHPT than in NHPT. The remaining biochemistries and bone turnover markers were similar, even when compared with controls. Age positively correlated with calcium intake only in PHPT patients (r=0.630,P=0.038). Multivariate analysis investigating predictors of CaMax (age, BMI, albumin-corrected SCa, serum phosphate, GFR, calcium intake, PTH and 25(OH)vitamin D) showed that only albumin-corrected SCa predicted CaMax. GFR was a much milder positive predictor.

Conclusions: NHPT appears to represent a milder phenotype of PHPT. Presentation of NHPT is independent of calcium intake, when this is sufficient. The setpoint of albumin-corrected serum calcium probably determines the subtype of primary hyperparathyroidism, with greater values having greater chances of reaching calcium levels above normal, independent of other biochemistries.