Hypoparathyroidism, the impaired secretion of parathyroid hormone (PTH) from the parathyroid glands, is the most common cause of hypocalcemia. The inadequate parathormone (PTH) secretion causes failure to mobilize calcium from bone, reabsorb calcium from the distal nephron, or stimulate renal I α-hydroxylase activity. The decreased 1,25[OH] ₂ vitamin D leads to inefficient absorption of calcium from the gut ( Figure 34-1 ). Hypoparathyroidism occurs as a result of congenital (inherited) or acquired (secondary) disorders. DiGeorge’s syndrome, type I autoimmune polyglandular syndrome, X-linked or autosomally inherited hypoparathyroidism, and PTH gene mutations are the most frequent causes of congenital hypoparathyroidism. In DiGeorge’s syndrome, a defect in the development of the third and fourth pharyngeal pouches leads to agenesis of parathyroid gland. Type I polyglandular syndrome is characterized by hypoparathyroidism, adrenal failure, and mucocutaneous candidiasis and develops from circulating antibodies against parathyroid, thyroid, and adrenal glands. Parathyroid glands are absent in X-linked (or autosomally) inherited hypoparathyroidism. PTH is deficient in PTH gene mutations.

Control of mineral metabolism by parathyroid hormone. Levels of serum ionized calcium (Ca ²⁺ ) are tightly controlled through the action of parathyroid hormone (PTH) and 1,25-dihydroxyvitamin D (1,25[OH] ₂ D). Both the rate and magnitude of changes in the serum ionized Ca ²⁺ concentration are detected by extracellular calcium-sensing receptors (CaSRs) expressed on parathyroid cells. When ionized Ca ²⁺ levels decrease, PTH secretion is triggered. Conversely, when ionized Ca ²⁺ levels increase, PTH secretion is suppressed. PTH stimulates bone resorption, which delivers calcium and phosphorus (PO ₄ ³⁻ ) into the circulation. In the kidney, PTH stimulates renal reabsorption of calcium and promotes phosphate excretion. PTH also enhances the conversion of 25-hydroxyvitamin D (25[OH]D) to the active vitamin D metabolite 1,25(OH) ₂ D, which increases the transepithelial transport of calcium and PO ₄ ³⁻ through actions in intestinal cells. In concert, these steps restore ionized Ca ²⁺ levels to the normal range and, through the actions of PTH and other factors (e.g., fibroblast-derived growth factor 23) in the kidney, reset the level of serum PO ₄ ³⁻ within the normal range. When the actions of PTH are reduced or lost, all subsequent steps in the maintenance of homeostasis are impaired, resulting in hypocalcemia, hyperphosphatemia, and hypercalciuria.

(From Shoback D: Hypoparathyroidism, N Engl J Med, 359:391, 2008.)

Damage to the parathyroid glands can lead to secondary hypoparathyroidism. Postsurgical hypoparathyroidism is the most frequent cause of prolonged hypocalcemia and is seen after thyroid and other head and neck surgeries. Infiltration of the parathyroid glands may develop subsequent to several disorders including hemochromatosis, thalassemia major (iron overload due to numerous blood transfusions), Wilson’s disease, and rarely, metastases. Radiation and radioactive iodine thyroid ablation are other secondary causes.

Pseudohypoparathyroidism (PHP) is an inherited disorder resulting from mutations in the end-organ PTH receptors leading to PTH resistance. Similar to hypoparathyroidism, the ultimate outcome would be the absence of PTH action on end organs. In contrast to hypoparathyroidism, in pseudohypoparathyroidism the serum level of PTH is high due to of the lack of negative feedback on the parathyroid glands. Besides the radiographic manifestations of hypoparathyroidism, specific findings are also noticed in pseudohypoparathyroidism as described below.