Parathyroid disorders

On the basis of strong evidence, parathyroid hormone (PTH) is a peptide hormone that signals through a G-protein-coupled receptor (1) and is regulated primarily by changes in serum calcium. (3) On the basis of strong evidence, PTH acts through bone and kidney to raise serum calcium concentrations (6)(7) and lower serum phosphorus concentrations. (9) In hypoparathyroidism, low PTH levels result in low serum calcium, causing tetany and seizures. Clinical signs include Chvostek and Trousseau signs. Among the variety of causes for inherited hypoparathyroidism are specific gene defects, Barakat syndrome, Sanjad-Sakati syndrome, Kenny-Caffey syndrome, gain-of-function calcium-sensing receptor mutations, PTH gene mutations, and DiGeorge syndrome. On the basis of strong evidence, acquired hypoparathyroidism can result from surgical removal of the parathyroid glands, iron overload, magnesium disorders, Wilson disease, or autoimmune polyglandular syndrome type 1. Treatment of hypoparathyroidism is with calcium and activated Vitamin D (calcitriol). On the basis of strong evidence, pseudohypoparathyroidism is characterized by low calcium despite high PTH concentrations, indicating resistance. Type Ia is caused by mutations in the GNAS1 gene and is known as Albright hereditary osteodystrophy. Type Ib is caused by defects in GNAS1 methylation and does not result in osteodystrophy. (8) In primary hyperparathyroidism, high serum calcium occurs with inappropriately high PTH levels. Clinical signs and symptoms of primary hyperparathyroidism include abdominal pain, constipation, nausea and vomiting, flank pain, hematuria, polyuria, stupor, coma, weakness, loss of reflexes, and bradycardia. Bone lesions called brown tumors can be seen on radiography. The broad differential diagnosis of primary hyperparathyroidism includes neonatal severe hyperparathyroidism and familial benign hypocalciuric hypercalcemia, both of which are caused by inactivating mutations of the calcium-sensing receptor. Parathyroid gland hyperplasia or parathyroid adenomas can cause PTH overproduction, which is common in adults but rarer in children. Parathyroid carcinoma is extremely rare and often fatal. Parathyroid adenomas can occur as part of a syndrome such as multiple endocrine neoplasia (MEN)1, hyperparathyroidism-jaw tumor syndrome, or MEN2A. Evaluation for hyperparathyroidism includes neck ultrasonography and sestamibi scan to detect and localize parathyroid adenomas. Treatment of hyperparathyroidism is surgical removal. If the PTH is elevated in response to hypocalcemia, this is termed secondary hyperparathyroidism. In tertiary hyperparathyroidism, hyperplastic parathyroid tissue loses responsiveness to calcium signaling. On the basis of strong evidence, secondary hyperparathyroidism is commonly seen with Vitamin D deficiency. Chronic kidney disease can also cause secondary hyperparathyroidism, which can progress to tertiary hyperparathyroidism when it is longstanding.