Hypoparathyroidism, Autosomal Dominant Hypocalcaemia and Pseudohypoparathyroidism in Denmark - Epidemiology, Causes, Symptoms and Prognoses

Hypoparathyroidism (HypoPT) is a relatively rare disease, where the level of parathyroid hormone (parat hormone [PTH]) cannot maintain a physiologically sufficient concentration of plasma calcium (P-Ca). This may be due to neck surgery (most frequently), congenital HypoPT, auto-immune destruction of the parathyroid gland, peripheral resistance to PTH, pseudoHypoPT or magnesium deficiency, by which PTH cannot be released from parathyroid gland.

Low plasma levels of P-Ca are registered by the calcium-sensing-receptors (CaSR) located e.g. in the gld. Parathyroid cell membranes and in the renal tubules, by which the flow of PTH into plasma increases, with normalization of P-Ca and decreasing P-phosphate to follow. By lack of PTH the renal synthesis of 1,25-dihydroxycholecalciferol is dismissed, with decreased bone turnover as a consequence.

Congenital causes of HypoPT are very rare and seen either sporadic or hereditary. The hereditary forms are more frequent in some areas of the world: founder-effect and familial marriages. Autoimmune HypoPT caused by mutations in the AIRE gene results in lack of negative selection of the T-cells in thymus. Autosomal dominant hypocalcaemia is caused by gain-of-function mutations in the G-protein receptor CaRS in the main cells in the parathyroid gland and kidney tubules. PseudoHypoPT is due to resistance in the target organs, despite high concentrations of PTH. The symptoms are shown by Albrights's hereditary osteodystrophy, (AOH), (maternal allel). PseudopseudoHypoPT is characterized by AOH, but without the typical biochemical findings (paternal allel).

The clinical manifestations of HypoPT depend on whether it occurs acute or chronic. The affected systems are the neuromuscular, ectodermal, ocular, cardia and neuropsychiatric system and manifest by increased neuromuscular irritability including weakness, muscle cramps, paresthesias of the lips, tongue, fingers and feet, memory loss, cardiac arrhythmias and heart insufficient headaches, and uncontrollable cramping muscle movements of the wrists and feet (carpopedal spasms) and possibly dry and scaling skin. In severe cases there may be cataract. In children symptoms may include malformations of the teeth. Due to high blood phosphorous levels, intracranial calcifications (basal ganglia), renal stones, and renal failure may develop. Studies have shown that HypoPT patients have reduced quality of life compared to a control group; more often have anxiety, depression and feel somatic. Furthermore, they have more physical symptoms like fatigue, ache, pain in the extremists and heart complaints.

The level of PTH decreases during pregnancy, while the level of 1,25-dihydroxycholecalciferol almost double due to placental and increased renal expression of 1α-hydroxylase with increased intestinal calcium absorption to follow, This improves maters calcium homeostasis why pregnant women should be monitored closely to prevent complications for the fetus.