Hyperparathyroidism causes hypercalcemia as a result of increased resorption of bone, reabsorption of calcium in the renal tubule, and absorption of calcium from the gut. PTH also decreases reabsorption of phosphate in the renal tubule, and in moderate-to-severe hyperparathyroidism the serum phosphate level is reduced; in the mild form of the disease, the serum phosphate level is often normal. Another form of the disease, although less often appreciated, is the entity called normocalcemic or eucalcemic hyperparathyroidism.

CLINICAL MANIFESTATIONS

Hyperparathyroidism is a chronic indolent disorder that slowly increases serum calcium levels over many years and may be evident for decades before it produces significant clinical problems. It was considered a rare disorder until 2 decades ago, but routine screening of serum by automated techniques greatly increased recognition of increased serum calcium in many patients and the suspicion for this disorder. Most patients have mild hypercalcemia (serum calcium level < 12 mg/dL) and have few or no symptoms. The most common clinical complaint in newly diagnosed hyperparathyroidism is no complaint at all. Those patients with clinical manifestations may show a spectrum of problems such as fatigue, lethargy, constipation, nocturia, abdominal discomfort, changes in mental status of minor degree (e.g., poor concentration, forgetfulness, depression) osteoporosis, bone pain, fractures, renal colic and stones, unexplained anemia, and weight loss. With severe hypercalcemia (>12 mg/dL), confusion and coma may supervene along with anorexia, nausea, vomiting, and dehydration. It is a clinical observation that older patients tolerate high serum calcium levels poorly and may manifest these later problems more often than younger patients. In a small number of patients there is clinical or radiographic evidence of hyperparathyroid bone disease. Typical findings include serum calcium levels greater than 12 mg/dL, serum PTH levels several times higher than normal, high serum alkaline phosphatase, and diffuse bone pain.

In patients with severe hyperparathyroidism and bone disease, radiographs may show subperiosteal bone resorption (highly specific to hyperparathyroidism) around the phalanges and distal ends of the clavicles and diffuse decalcification of the skull (salt-and-pepper skull) that resembles multiple myeloma. Bone cysts (also called brown tumors), if present, are often the sites of pathologic fractures. With bone loss in the spine, the intervertebral discs herniate into the vertebral bodies, creating a “codfish” appearance on radiographs. Even if there is no radiographic evidence of bone disease, excessive, PTH-mediated bone resorption may increase the risk of osteoporosis, a situation of particular concern in postmenopausal women who display the greatest incidence of this problem and already are at high risk for primary osteoporosis. This problem is often diagnosed as osteoporosis from a low bone density test. Histologically, the bone changes are more complex than simple osteoporosis. PTH activates osteoclastic resorption of bone, which can lead to significant bone loss. There is also a compensatory increase in osteoblastic bone formation; however, resorption ultimately exceeds formation, leading to bone loss. Osteoblasts release alkaline phosphatase, and serum levels may be elevated in patients with significant bone involvement. In severe cases of hyperparathyroidism, cystic areas of skeletal erosions may appear along with areas of fibrous tissue in adjacent bone marrow (osteitis fibrosa cystica).