Causes of spontaneous hypoparathyroidism: 38 patients

Hypoparathyroidism is a rare endocrine disorder characterized by hypocalcaemia and reduced concentrations of parathyroid hormone (PTH). Causes of hypoparathyroidism may be iatrogenic, autoimmune or genetic. The aim of our study was to investigate patients with spontaneous hypoparathyroidism to define the well-known autoimmune or genetic causes and propose diagnosis algorithm taking account of initial clinical data. Between 2000 and 2010, 38 patients consulting in our institution for hypoparathyroidism were studied. Post-surgical or radio-induced forms were excluded. Autoimmune hypoparathyroidism was diagnosed in 9 cases, DiGeorge syndrome in 7 cases, HDR (hypoparathyroidism, deafness and renal dysplasia) syndrome in 3 cases, activating mutations of calcium sensing receptor (CaSR) gene in 3 cases. One case of syndromic hypoparathyroidism was due to a 10p deletion and another to ring chromosome 18. Hypoparathyroidism caused by hypomagnesemia was found in 1 case. Etiology of hypoparathyroidism remained unknown in 13 patients. There were no striking differences between groups in ages of revelation, calcemia and PTH levels. Autoimmune hypoparathyroidism was transient in 2 patients who harbored anti-CaSR autoantibodies while 2 others had undetectable PTH levels indicating parathyroid irreversible damage. Persistent secretion of PTH in subjects with DiGeorge syndrome suggested parathyroid hypoplasia as a mechanism of hypoparathyroidism. Latent hypoparathyroidisms were frequent in this population. Varying phenotypes of HDR syndrome were seen in the 3 members of a same family. The patient with chromosomal 10p deletion showed signs of HDR syndrome (sensorineural deafness) associated with dysmorphic features and retardation. Among the 13 undetermined cases, etiologic diagnosis was suspected in half of them but investigations could not be completed. Causes of spontaneous hypoparathyroidism are various. Meticulous clinical examination has to precede immunological or molecular explorations even if etiological diagnosis might remain undefined in some cases.