Endocrine Abstracts

The past 15 years resulted in a great progress of our understanding regarding the genetic basis, pathogenesis, symptomatology, laboratory diagnosis and differential diagnosis of hypercalcemic disorders both of those occurring seemingly sporadically and of those developing in a familial setting. Since serum calcium measurement takes as part of the routine laboratory screening examinations the number of asymptomatic and also of familial cases of primary hyperparathyroidism are increasing worldwide.

This session will review the most important new knowledge about sporadic primary hyperparathyroidism (PHPT) as well as inherited parathyroid-dependent hypercalcemic syndromes, including the genetic diseases of the calcium-sensing receptor (CaSR).

Nowadays, PHPT is the third most common endocrine disorder after diabetes mellitus and thyroid diseases. Its prevalence is 3–4 per 1000 in northern Europe. Among elderly patients (≥75 years) the prevalence could be as high as 21 per 1000. According to some estimation, 80% of PHPT cases are asymptomatic, while the familial forms represent about 5% of all cases. There are four autosomal dominant hereditary syndromes frequently associating with PHPT: multiple endocrine neoplasia type 1 (MEN1), multiple endocrine neoplasia type 2 (MEN2), hyperparathyroidism–jaw tumor syndrome (HPT-JT) and familial isolated hyperparathyroidism (FIHPT). Until the cloning and sequencing of the putative FIHPT gene(s), the diagnosis of FIHPT rests on the exclusion of other specific endocrine and non-endocrine tumors featuring MEN1, MEN2 and HPT-JT syndromes, as well as CaSR mutations.

The hypercalcemia of familial hypocalciuric hypercalcemia (FHH) is usually mild (<3.0 mmol/l) and asymptomatic, and it associates almost always with low calcium clearance to creatinine clearance ratio. The relative frequency of FHH among patients with PTH-dependent hypercalcemia is not exactly known, it was estimated to be about 7%.