26-15: Hypoparathyroidism & Parahypoparathyroidism

GENERAL CONSIDERATIONS

Acquired hypoparathyroidism is most commonly caused by anterior neck surgery, occurring after total thyroidectomy in about 25% of patients transiently, and in about 4% of patients permanently. The risk of hypoparathyroidism is higher (1) for patients undergoing total thyroidectomy (especially large goiters) or surgery for Graves disease, (2) for patients over age 50, and (3) when fewer than 2 parathyroid glands are identified at surgery. The risk of permanent postoperative hypoparathyroidism can be reduced during thyroid surgery by taking parathyroid glands with suspected vascular damage and autotransplanting them into the sternocleidomastoid muscle. Permanent hypoparathyroidism may occur after the resection of multiple parathyroid adenomas. It also occurs transiently after the surgical removal of a single parathyroid adenoma for primary hyperparathyroidism due to suppression of the remaining normal parathyroids and accelerated remineralization of the skeleton. This is known as “hungry bone syndrome.” In such cases, hypocalcemia can be quite severe, particularly in patients with preoperative hyperparathyroid bone disease and vitamin D or magnesium deficiency. All patients undergoing thyroidectomy or parathyroidectomy must be observed closely overnight. Neck irradiation is a rare cause of hypoparathyroidism.

Autoimmune hypoparathyroidism may be isolated or combined with other endocrine deficiencies. Autoimmune polyendocrine syndrome type I (APS-I) is also known as autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED). It is an autosomal recessive condition that is caused by a mutation in the autoimmune regulator (AIRE) gene (21q22.3). It is a rare condition but is found more commonly in Scandinavia, Sardinia, and Iranian Jews. In APS-I, the following conditions may develop: (1) mucocutaneous candidiasis, which appears in the newborn period; (2) hypoparathyroidism, which is the most frequent and often the only endocrine deficiency; (3) Addison disease, which may present anytime from childhood to young adulthood; (4) hypothyroidism; (5) type 1 diabetes mellitus; (6) pituitary deficiency; (7) cataracts; (8) uveitis; alopecia; (9) vitiligo; (10) autoimmune gastrointestinal manifestations; and (11) fat malabsorption, which occurs in 20% of patients. Treatment of hypocalcemia can be challenging in patients with APS-I, since vitamin D₃ is fat-soluble. The fat malabsorption may be due to a deficiency in the jejunal enteroendocrine cells that produce cholecystokinin, causing a reduction in bile acid secretion. Hypoparathyroidism can also occur in SLE caused by antiparathyroid antibodies.

Parathyroid deficiency may also be the result of damage from heavy metals such as copper (Wilson disease) or iron (hemochromatosis, transfusion hemosiderosis), granulomas, Riedel thyroiditis, tumors, or infection.

Magnesium deficiency causes functional hypoparathyroidism. Hypomagnesemia is most commonly caused by alcoholism, diuretics, intestinal malabsorption, and proton pump inhibitors (the reduced stomach acidity also decreases calcium absorption). Hypomagnesemia can also be caused by aminoglycosides, amphotericin, pentamidine, and epithelial growth factor inhibitors (panitumumab, cetuximab). Although mild hypomagnesemia stimulates ...