During the fifth week of embryologic development, the parathyroid glands develop from the ectoderm of the dorsal third and fourth branchial pouches. There are usually four parathyroid glands, but more may be present. The superior parathyroid glands are derivatives of the fourth branchial pouch. The inferior glands arise from the third branchial pouch, which also gives rise to the thymus gland. Each gland weighs 30 to 40 mg, and the gross appearance is sometimes likened to a lentil bean with a pinkish complexion. The superior parathyroid glands are usually located behind the superior pole of the thyroid, close or posterior to the level of the recurrent laryngeal nerve at its entrance to the larynx in the cricothyroid area, or in the retroesophageal position. The inferior parathyroid glands are usually located close to the inferior thyroid pole, alongside or behind a plane anterior to the recurrent laryngeal nerve. The superior glands do not migrate and, therefore, generally are more consistent in location than the inferior glands that may migrate along with the thymus gland. Aberrant parathyroid tissue occurs in 15% to 20% of cases. The blood supply is primarily from the inferior thyroid artery, which gives rise to the inferior parathyroid and superior parathyroid arteries. The principal innervation of the parathyroid glands is from the autonomic nervous system.

The parathyroid glands contain chief and oxyphilic cells that synthesize and secrete parathyroid hormone (parathormone; PTH). PTH is a straight-chain peptide that contains 84 amino acids with the biologic activity residing in the N terminal. The primary role of PTH is regulation of serum calcium and phosphorus levels. PTH releases calcium from bone, prevents calcium from being excreted in the urine, stimulates renal enzymes to produce active vitamin D for additional calcium absorption from the gastrointestinal tract, and increases excretion of phosphorus in the urine. The net effect is to raise serum calcium level and decrease serum phosphorus levels. Thus, the hallmarks of hyperparathyroidism are hypercalcemia and hypophosphatemia.

Hyperparathyroidism can be classified into three main categories. Primary hyperparathyroidism is excessive PTH production by a single or multiple parathyroid glands. The actions of excessive PTH on bone and kidney usually cause hypercalcemia, which does not normally inhibit PTH secretion. Secondary hyperparathyroidism occurs when partial resistance to the metabolic actions of PTH leads to excessive production of the hormone. Resistance to the normal level of hormone leads to hypocalcemia, which leads to parathyroid gland hyperplasia. Secondary hyperparathyroidism occurs among patients with
renal failure, osteomalacia, and psuedohypoparathyroidism (PTH receptor disorder). Tertiary hyperparathyroidism is demonstrated by autonomous function of the parathyroid glands and irrepressible PTH production. Before attributing clinical findings solely to one disease, the physician must address the differential diagnosis of hypercalcemia (Table 35-1).