Parathyroid Carcinoma

A number sign (#) is used with this entry because of evidence that parathyroid carcinoma can be caused by mutation in the CDC73 gene (607393) on chromosome 1q.

Parathyroid carcinomas are an uncommon and often devastating cause of primary hyperparathyroidism (145000) (Wang and Gaz, 1985; Shane, 2001).

Shane (2001) reviewed the clinical features of parathyroid carcinoma and provided a summary of features that might lead one to suspect parathyroid cancer in a patient with hypercalcemia and elevated parathyroid hormone (PTH; 168450) levels. There is no association of gender with parathyroid carcinoma. The average age of the patient with parathyroid carcinoma is in the fifth decade, approximately 10 years younger than typical patients with primary hyperparathyroidism, who most often present in their fifties or sixties. The serum calcium level of most patients with parathyroid carcinoma is much higher than that seen in patients with primary hyperparathyroidism. This more severe hypercalcemia is almost invariably associated with the typical signs and symptoms of hypercalcemia. The most frequent complaints are fatigue, weakness, weight loss, anorexia, nausea, vomiting, polyuria, and polydipsia. Other common presenting symptoms characteristic of a severely hyperparathyroid state include bone pain, fractures, and renal colic. When reported, PTH levels have ranged from 3 to 10 times above the upper limit of normal for the assay employed. Patients with parathyroid carcinoma may have elevated levels of alpha- and beta-subunits of chorionic gonadotropin (see 118860), whereas patients with primary hyperparathyroidism do not. A palpable neck mass, an unusual finding in primary hyperparathyroidism, had been reported in 30 to 76% of patients with parathyroid carcinoma. Shane (2001) stressed that it is of great importance that parathyroid carcinoma be considered in the differential diagnosis of PTH-dependent hypercalcemia, as the morbidity and mortality associated with this diagnosis are substantial, and optimal outcomes are associated with complete resection of the tumor at the time of the initial operation.

Shattuck et al. (2003) identified somatic and germline mutations in the CDC73 gene (607393) in patients who had no known family history of primary hyperparathyroidism (HPRT1, 145000) or the hyperparathyroidism-jaw tumor syndrome (HPRT2, HPT-JT; 145001), also caused by mutation in the CDC73 gene, at presentation.

Weinstein and Simonds (2003) suggested that it is possible that CDC73 is almost always mutated in parathyroid carcinoma. In most of the tumors studied by Shattuck et al. (2003), there was evidence of biallelic inactivation of the gene, although in many cases the second hit was a mutation, rather than loss of heterozygosity.