P.2.d.036 - Lithium-induced parathyroid dysfunction: another approach

Abstract

The past six decades have witnessed the initial clinical descriptions of neonatal severe hyperparathyroidism (NSHPT) and familial hypocalciuric hypercalcemia (FHH), biochemical and physiologic studies suggesting abnormal calcium sensing by parathyroid glands and kidneys, and finally the description of three distinct molecular causes of FHH. FHH1 results from heterozygous inactivating mutations in the extracellular calcium-sensing receptor (CaSR), usually manifesting as mild to moderate resistance of parathyroid and kidney to calcium, mild PTH-dependent hypercalcemia, and relative hypocalciuria. NSHPT is caused by more severe calcium resistance owing to heterozygous, compound heterozygous, or homozygous CaSR mutations. Recent studies have identified the molecular bases for two additional forms of FHH linked to chromosome 19, FHH2 and FHH3, caused by mutations in downstream proteins in the CaSR signaling pathway. Further studies will likely further expand the range of clinical presentations of FHH, enhance our diagnosis of these conditions, and improve therapies for treating NSHPT and the occasional FHH patients requiring medical or surgical therapy.