Background and Epidemiology
Hyperparathyroidism is a common disorder of calcium, phosphorus, and bone metabolism caused by increased circulating levels of parathyroid hormone (PTH). This disease is important to geriatricians because it occurs with increasing frequency in older patients. Widespread use of multiphasic biochemical screening tests led to an increase in the incidence of cases of primary hyperparathyroidism. In the population in Olmstead County, Minnesota, which is served by the Mayo Clinic, the annual incidence rose from 16 per 100 000 people before 1978 to a peak of 112 per 100 000 people 7 years later, then the rate declined. Now such screening tests are used less frequently and the incidence has fallen to 4 per 100 000 people. It is not clear why the incidence of hyperparathyroidism is decreasing, but it is postulated that there is a decreased exposure to ionizing radiation, or better supplementation with vitamin D.
Primary hyperparathyroidism may occur at any age but is found most commonly between the ages of 40 and 65 years. The incidence is approximately 1 per 1000. The disease affects women more than men by almost 2:1, and in women, this usually occurs in the first decade after menopause. In the United States, approximately 80% of patients with primary hyperparathyroidism have no signs or symptoms that are referable to their disease. With the development of sophisticated and specific technologies during the past 15 years, it has become feasible to evaluate patients with asymptomatic primary hyperparathyroidism in ways that have helped to establish prudent guidelines for surgical or medical management.
In hyperparathyroidism, PTH is inappropriately secreted by single or multiple glands in the presence of increased serum calcium levels. The disease is considered primary when autonomous hypersecretion of PTH is caused by a single adenoma, diffuse hyperplasia, multiple adenomas, or, rarely, a parathyroid carcinoma. Secondary hyperparathyroidism occurs when there is a prolonged hypocalcemic stimulus, as in cases of vitamin D deficiency or chronic renal failure. Tertiary hyperparathyroidism occurs in patients with chronic secondary hyperparathyroidism who develop autonomous hypersecretion of PTH and hypercalcemia, e.g., patients who undergo successful kidney transplants. This chapter focuses on primary hyperparathyroidism only.
The etiology of primary hyperparathyroidism is unknown. When calcium is infused into hypercalcemic hyperparathyroid patients, there is a failure to suppress the PTH levels. Furthermore, when cells from hyperparathyroid glands are incubated in vitro, higher levels of ionized calcium in the medium are required to suppress PTH release than are required to suppress PTH release from cells from normal glands. These data suggest that, in part, the abnormality occurring in the parathyroid gland is an elevation of the set point at which ionized calcium levels suppress PTH release. The receptor that is responsible for calcium-sensing in parathyroid glands has been cloned; it is a guanosine triphosphate (GTP)-binding protein that has a seven-amino-acid transmembrane domain. Mutations in this receptor are rare in primary hyperparathyroidism.