Normocalcemic and Normohormonal Primary Hyperparathyroidism: Laboratory Values and End‐Organ Effects

Abstract

Objective Variants of primary hyperparathyroidism (pHPT), described as normocalcemic (NC) and normohormonal (NH), can confuse the diagnosis of classic pHPT. Data Sources A MEDLINE search was performed for variants of pHPT using the PubMed database (last queried October 2019). Review Methods The search was restricted to articles published after 1960 that were specific to humans. Studies were included in our analysis if laboratory values and incidence of end-organ involvement were reported for NCpHPT and NHpHPT variants. The search returned 189 articles; 27 additional studies were identified and included for a total of 216. Non-English-language studies were excluded. Abstracts were screened, full-text articles were then assessed, and 82 articles were excluded. Data were pooled using a random-effects model in studies that compared NC or NH pHPT to classic pHPT. Comparative laboratory values are presented. Conclusion This analysis compares NCpHPT and NHpHPT to classic pHPT. Nephrolithiasis was 21.7% (NCpHPT), 15.9% (classic pHPT), and 25.4% (NHpHPT). Decreased bone mineral density was 49.7% (NCpHPT), 39.7% (classic pHPT), and 40.3% (NHpHPT). Fractures in the NCpHPT group were not significantly different from the classic pHPT. Hypertension in the NCpHPT group was significantly less than classic pHPT (odds ratio, 0.59; 95% CI, 0.40-0.88). Implications for Clinical Practice This information may serve to inform clinicians of the laboratory subtleties of these variants that are being seen with greater frequency in contemporary practice.

Intraoperative Parathyroid Hormone Monitoring In Normohormonal Primary Hyperparathyroidism: How Low Do You Go?

“…Importantly, these "mild" forms of HPT are still often associated with significant end-organ complications. 17 Normocalcemic hyperparathyroidism presents with elevated PTH levels and normal-range calcium. The precise etiology and nature of this entity are still unclear.…”

“…Fewer patients present with dramatic laboratory derangements or severe symptoms. Importantly, these “mild” forms of HPT are still often associated with significant end‐organ complications 17 . Normocalcemic hyperparathyroidism presents with elevated PTH levels and normal‐range calcium.…”

Advances in the diagnosis and the management of primary hyperparathyroidism

“…Rates of nephrolithiasis and decreased bone mineral density were higher in the normocalcemic and normohormonal PHPT groups, but this could be selection bias, as these are the symptoms that that caused them to be referred for evaluation; still, due to these endorgan effects, surgery is still recommended as treatment of these more subtle variants of PHPT. 25 Diagnostic challenges. In any hyperparathyroidism work-up, it is important to rule out benign FHH, an autosomal dominant disorder that is due to inactivating mutations in the calcium-sensing receptor gene (CASR) causing decreased receptor activity.…”

“…Rates of nephrolithiasis and decreased bone mineral density were higher in the normocalcemic and normohormonal PHPT groups, but this could be selection bias, as these are the symptoms that that caused them to be referred for evaluation; still, due to these end-organ effects, surgery is still recommended as treatment of these more subtle variants of PHPT. 25…”