What are the causes of hyperparathyroidism?

What are the causes of hyperparathyroidism?

Primary hyperparathyroidism is most commonly due to hyperplasia of a single gland. This isolated hyperplasia is usually a benign adenoma. The inferior parathyroid glands are the most common sites for adenomas. Some adenomas present in and around the thyroid and thymus, and even behind the esophagus. Locating these adenomas during surgery can be difficult. Parathyroid carcinoma is a rare cause of hyperplasia. Familial forms of hyperparathyroidism tend to have multiple glands involved.

The multiple endocrine neoplasia (MEN) syndromes are the most common causes of hereditary hyperparathy-roidism. MEN 1 consists of hyperparathyroidism, tumors of the pituitary, and tumors of the pancreas. MEN 2A consists of hyperparathyroidism, medullary carcinoma of the thyroid, and pheochromocytoma. The various disorders can present at different times, so the associated disorders should be considered in patients with familial hyper-parathyroidism.

Chronic renal failure causes secondary hyperpara-thyroidism. Renal failure leads to chronically elevated phosphate levels. Increased deposition of calcium and phosphate in bone, because of the increased phosphate concentrations, leads to hypocalcemia. 

The lack of 1,25(OH)₂D, which is produced in normal kidneys and stim-ulates gastrointestinal absorption of calcium, exacerbates the hypocalcemia. This chronic hypocalcemia leads to chronic stimulation and hyperplasia of the parathyroid glands.

Long-standing secondary hyperparathyroidism can cause the parathyroid glands to become unresponsive to correction of hypocalcemia. This condition is referred to as tertiary hyperparathyroidism, and is treated surgically. Typically, the parathyroid glands are resected, and a portion of one is auto-transplanted into the forearm.

A rare cause of reversible hyperparathyroidism is treat-ment with lithium. There appears to be a high incidence of parathyroid adenomas with chronic lithium treatment. The mechanism for this is not clear.