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 serum 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 an estimated prevalence of 0.89% of the US population, but it is underdiagnosed and undertreated. 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 Black adults than in 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, the retroesophageal space, and the thymus or mediastinum. Hyperparathyroidism is usually caused by a single parathyroid adenoma (80%), and less commonly by hyperplasia or adenomas of two or more parathyroid glands (20%), or carcinoma (less than 1%). 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 5–10% of cases; hyperparathyroidism presenting before age 45 has a higher chance of being familial. Parathyroid hyperplasia commonly arises 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. Hyperparathyroidism-jaw tumor syndrome is a familial autosomal dominant condition with parathyroid adenomas or carcinomas that are associated with tumors of the jaw and renal lesions. Familial isolated hyperparathyroidism refers to familial hyperparathyroidism without the characteristic extraparathyroid features of other more complex hyperparathyroid syndromes. Affected kindreds may harbor an incomplete phenotypic expression of MEN 1 or hyperparathyroidism-jaw tumor syndrome, or germline mutations in other genes, such as CASR (encoding the calcium sensing receptor), CDC73, or GCM2.
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.
Parathyroid carcinoma is a rare cause of hyperparathyroidism, accounting for less than 1% of hyperparathyroidism. However, it occurs in about 15% of patients with hyperparathyroidism jaw-tumor syndrome and is also more common in patients with familial hyperparathyroidism or MEN. Surgical histopathology typically reveals prominent fibrous bands (90%), capsular invasion (60%), vascular invasion (15%), high mitotic index (80%), and ...