ESSENTIALS OF DIAGNOSIS
Often found incidentally by routine blood testing.
Renal calculi, polyuria, hypertension, constipation, fatigue, mental changes.
Bone pain; rarely, cystic lesions and pathologic fractures.
Elevated PTH, serum and urine calcium, and urine phosphate; serum phosphate low to normal; alkaline phosphatase normal to elevated.
Primary hyperparathyroidism is the most common cause of hypercalcemia, with a prevalence of 1000 to 4000 cases per 1 million persons. It occurs at all ages but most commonly in the seventh decade and in women (74%). Before age 45, the prevalence is similar in men and women. It is more prevalent in blacks, followed by whites, then other races.
Parathyroid glands vary in number and location and ectopic parathyroid glands have been found within the thyroid gland, high in the neck or carotid sheath, in the retroesophageal space, and within the thymus or mediastinum. Hyperparathyroidism is caused by hypersecretion of PTH, usually by a single parathyroid adenoma (80%), and less commonly by hyperplasia of two or more parathyroid glands (20%), or carcinoma (less than 1%). However, when hyperparathyroidism presents before age 30 years, there is a higher incidence of multiglandular disease (36%) and parathyroid carcinoma (5%). The size of the parathyroid adenoma correlates with the serum PTH level.
Hyperparathyroidism is familial in about 10% of cases; hyperparathyroidism presenting before age 45 has a higher chance of being familial. Parathyroid hyperplasia may arise in MEN types 1, 2 (2A), and 4. (See Table 26–12.) In MEN 1, multiglandular hyperparathyroidism is usually the initial manifestation and ultimately occurs in 90% of affected individuals. Hyperparathyroidism in MEN 2 (2A) is less frequent than in MEN 1 and is usually milder. Familial hyperparathyroidism can also occur in the hyperparathyroidism-jaw tumor syndrome, a rare autosomal dominant familial condition in which parathyroid cystic adenomas or carcinomas are associated with ossifying fibromas of the mandible and maxilla as well as renal lesions (cysts, hamartomas, Wilms tumors). Affected individuals usually present with severe hypercalcemia as teenagers or young adults; the pathology is usually a single parathyroid adenoma.
Hyperparathyroidism results in the excessive excretion of calcium and phosphate by the kidneys. PTH stimulates renal tubular reabsorption of calcium; however, hyperparathyroidism causes hypercalcemia and an increase in calcium in the glomerular filtrate that overwhelms tubular reabsorption capacity, resulting in hypercalciuria. At least 5% of renal calculi are associated with this disease. Diffuse parenchymal calcification (nephrocalcinosis) is seen less commonly. Hyperparathyroidism causes demineralization of cortical bone and a gain of trabecular bone. Severe, chronic hyperparathyroidism can cause pathologic fractures, and cystic bone lesions throughout the skeleton, a condition known as osteitis fibrosa cystic (eFigure 26–16, eFigure 26–17).
Osteitis fibrosa cystica with resorption of the distal phalanges. (Used, with permission, from C Grunfeld, MD.)
Radiographs of index finger of ...