Primary hyperparathyroidism: just how 'primary' is it really?

Abstract

Hyperparathyroidism: causes and definitions Hyperparathyroidism (HPT) is a biochemical diagnosis defined by the serum level of intact parathyroid hormone (PTH) above laboratory reference range. It has long been subclassified into three forms. Primary hyperparathyroidism (PHPT), whose management is discussed in the elegant and informative review by Ayuk and colleagues [Ayuk et al. 2010], results from a primary defect of autonomous PTH secretion and is defined biochemically when HPT is accompanied by hypercalcaemia and, depending on vitamin D sufficiency, hypercalciuria. It is almost invariably an acquired disease (even if genetically programmed, for example, due to mutations in MENIN, RET, HRPT2 and HNF1B) [Oram et al. 2010; Sharretts and Simonds, 2010], resulting from parathyroid gland hyperplasia or neoplasia (typically adenoma, but rarely carcinoma) [Ayuk et al. 2010]. Severe neonatal HPT can occur with biallelic or severe heterozygous inactivating mutations of the extracellular calcium sensing receptor (CaSR) [Pearce et al. 1995]. Most CASR heterozygotes manifest milder hypercalcaemia with HPT, familial benign hypercalcaemia with hypocalciuria (FBHH), which can be mistaken for PHTP if the calcium/creatinine clearance ratio (to evidence/refute hypercalciuria) has not been ascertained. Crucially, FBHH does not exhibit the adverse skeletal and extraskeletal manifestations of PHPT, nor does it respond to subtotal parathyroidectomy.