The Italian Register of primary hypoparathyroidism

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Introduction

Calcium is an important bioinorganic ion performing a variety of intra- and extra-cellular functions and playing an important role in maintaining normal physiologic processes. It is also an im­portant component or co-factor required for the proper function­ing of coagulation factors and adhesion molecules. Homeostasis of calcium and phosphorus is maintained by a combined activity of the calciotropic hormones: parathyroid hormone (PTH), Vitamin D [25 OH₂D₃ and 1-25 (OH)₂D₃], and calcitonin (CT). PTH, the product of the parathyroid glands, regulates serum calcium concentrations and bone metabolism. In turn serum calcium concentrations regulate PTH secretion by means of a calcium-sensing receptor (CaSR) on the surface of parathyroid cells. buy cheap viagra on rx-approved

The term of primary hypoparathyroidism refers to a group of in­herited disorders in which the relative or absolute deficiency of PTH leads to hypocalcemia and hyperphosphatemia (Table I). These disorders may be caused by developmental defects in the parathyroid glands, by autoimmune endocrinopathies, by defects in PTH synthesis, by impaired regulation of PTH secre­tion, and by defective PTH action. The latter forms termed pseudo-hypoparathyroidism are unique in that PTH secretion is increased rather than deficient.

Table I – Categories of primary hypoparathyroidism.

Causes	Diagnosis
Developmental defects in the parathyroid glands	•DiGeorge syndrome •Autosomal recessive hypoparathyroidism •Kenney-Caffey syndrome •Mitochondrial neuromyopathy
Autoimmune disorders	• APS 1
Defects of the parathyroid hormone molecule	• Mutations of PTH gene
Defective regulation of parathyroid hormone	• Activating mutation of the CaSR gene
Defect of the type 1 PTH receptor	•Jansen’s chondrodystrophy •Blomstrand’s chondrodystrophy
Defect of the stimulatory Gsa subunit	•PHP-Ia and PHP-Ib •PPHP

A cause of hypoparathyroidism is represented by an anom­alous development of parathyroid glands. The disease called DiGeorge syndrome can be sporadic or familiarly transmitted as autosomal dominant trait.

The polyglandular disorder called autoimmune polyglandular syndrome type 1 (APS 1) is characterized by autoimmune Ad­dison’s disease, moniliasis, and hypoparathyroidism. A gene encoding for a putative regulator of transcription featuring two PHD-type zinc-finger motifs (AIRE: Autoimmune Regulator) has been discovered as the primary cause of APS 1. Mutations of the prepro-PTH gene are commonly involved in the pathogenesis of familial isolated hypoparathyroidism trans­mitted in autosomal mode. Familial hypoparathyroidism can al­so be X-linked. In other cases, linkage of hypocalcemia to the locus of the CaSR gene has been demonstrated in some forms of familial hypoparathyroidism. Hy- poparathyroidism has been also reported to occur in two disor­ders associated with mitochondrial dysfunctions.

Mutations of the G_sa subunit gene (GNAS1) have been identified in patients with pseudohypoparathyroidism type Ia (PHP-Ia) and with pseudo-pseudohypoparathyroidism (PPHP). PHP is an autosomal dominant disorder characterized by a typical phenotype.