Clinical Trial: Characterization of Patients With Non-surgical Hypoparathyroidism and Pseudohypoparathyroidism

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Observational

Official Title: Characterization of Patients With Idiopathic Hypoparathyroidism, Autosomal Dominant Hypocalcaemia and Pseudohypoparathyroidism

Brief Summary:

Hypoparathyroidism (hypoPT) and pseudohypoparathyroidism (Ps-hypoPT) are rare diseases, characterized by low levels of parathyroid hormone [PTH] and plasma calcium or high plasma PTH and low plasma calcium, respectively. A recently study by the investigators' group, identified 123 living persons with idiopathic hypoPT and 62 living persons with Ps-hypoPT, only few of these have been genetic tested.

The aim of the study is to perform a detailed clinical and genetic characterization of Danish patients with idiopathic hypoPT and Ps-hypoPT. Patients will be examined by questionnaires, biochemistry, scans, bone biopsies and genetic tests. Furthermore the investigators aim to perform family tracing for the hereditary forms. The prevalence of magnesium depletion will be assessed as well.

In addition to providing new information on symptoms, co-morbidity, and prognosis for this group of patients, the investigators presume that the study may improve their understanding on calcium homeostasis and bone metabolism in general.

Detailed Summary:

Background:

Hypoparathyroidism (HypoPT) is a group of rare clinical disorders characterized by hypocalcaemia and hyperphosphatemia with inappropriate low levels of parathyroid hormone (PTH). Due to the lack of PTH, the renal production of 1α,25-dihydroxycholecalciferol (1,25(OH)2D) is reduced. Most often, HypoPT is caused by accidental removal of the parathyroid glands during neck surgery (postsurgical hypoPT). However, in rare in-stances HypoPT is caused by autoimmune disorders with immune mediated destruction of the parathyroid glands, or a variety of genetic mutations, including the CATCH-22 (DiGeorge) Syndrome, familial isolated HypoPT or an activating mutation in the gene encoding the calcium-sensing receptor (CaSR), termed autosomal dominant hypocalcaemia (ADH).

The CaSR is not only found in the parathyroid glands, but is also expressed by other tissue including the renal tubules. Low plasma levels of ionised calcium (Ca2+) are registered by the calcium sensing receptors (CaSR) located e.g. in the cell membranes of the parathyroids and in the renal tubules. Low levels of Ca2+ increases the release of PTH from the parathyroids, which normalises plasma Ca2+ and decrease P-phosphate. Lack of PTH decreases the renal synthesis of 1,25-dihydroxycholecalciferol, witch in combination with low PTH decreases bone turnover. Although, large-scale meta-analysis of genome wide association data incorporating 150 candidate genes did not link the CaSR to bone mineral density or osteoporotic fracture risk, no specific data are available on whether BMD in patients with an activating mutation in their CaSR gene (ADH patients) differs from the general population. The largest case series of patients with ADH so far reported included 25 patients and did not report BMD within this group.

A detailed clinical characterization of Danish patients with idiopathic HypoPT, ADH and Ps-HypoPT including genetics of patients with idiopathic HypoPT and Ps-HypoPT.