In severe hypercalcemia, precipitates can occur in the renal interstitium and incite an inflammatory reaction (nephrocalcinosis). By the time interstitial calcium deposits are visible on radiography, renal function is already considerably reduced. Hypercalcemia also decreases the capacity to concentrate urine, which frequently leads to polyuria and dehydration (if compensatory fluid intake does not compensate for this fluid loss). Pancreatitis and peptic ulcers, although rare, may occur with hyperparathyroidism. Gastrin-secreting tumors associated with hyperparathyroidism may cause ulcers in patients with multiple endocrine neoplasia (MEN) syndromes. Prolonged or severe hypercalcemia often results in calcium deposits in the medial and lateral edges of the cornea (band keratopathy).

TREATMENT

Surgical excision of the single, enlarged parathyroid gland is the treatment of choice for patients with an adenoma. Treatment of hyperplasia is subtotal parathyroidectomy, or removal of all but one or one-half gland. However, excision of too little tissue leads to persistent hypercalcemia and removal of too much tissue causes hypoparathyroidism. Asymptomatic disease is a conundrum in clinical practice. When to intervene surgically is the topic of many guidelines published through the years.

Three familial autosomal dominant syndromes of hyperparathyroidism have been identified among patients with parathyroid hyperplasia. In two of these syndromes, MEN I and II, neoplasms occur in other endocrine glands. MEN I is characterized by pituitary adenomas and islet cell tumors in the pancreas, whereas MEN II is characterized by a high incidence of pheochromocytoma and medullary carcinoma of the thyroid. Patients with familial hypocalciuric hypercalcemia, the third and rarest syndrome, exhibit lifelong asymptomatic hypercalcemia that persists even after subtotal parathyroidectomy. This syndrome is distinguished from typical hyperparathyroidism by an absence of hypercalciuria and a high familial incidence of asymptomatic hypercalcemia without other endocrinopathies. This disorder is due to abnormalities in the calcium-sensing receptors in the kidney that fail to excrete appropriate amounts of calcium, thereby raising the serum level.

Cancer of the parathyroid glands can rarely be cured by surgical excision because it has metastasized by the time it is detected. Patients with parathyroid carcinoma usually die of uncontrollable hypercalcemia.