parathyroid

Embryologically, the superior parathyroid glands arise from the 4th pharyngeal pouch and the inferior parathyroid glands from the 3rd pharyngeal pouch (paradoxically migrating further than the superior glands, which come from the pouch that develops later). Chief cells within the parathyroid glands secrete PTH in response to low serum ionized calcium, sensed via the calcium-sensing receptor (CaSR). PTH's main actions include: (1) increasing bone resorption via RANKL upregulation on osteoblasts leading to osteoclast activation, releasing calcium and phosphate; (2) increasing renal calcium reabsorption in the distal convoluted tubule; (3) decreasing renal phosphate reabsorption (phosphaturic effect) in the proximal tubule; (4) stimulating 1-alpha-hydroxylase in the kidney, converting 25-hydroxyvitamin D to active 1,25-dihydroxyvitamin D (calcitriol), which increases intestinal calcium and phosphate absorption. Net effect: increased serum calcium, decreased serum phosphate.

Clinical correlations: - Primary hyperparathyroidism: most often due to a parathyroid adenoma, causing hypercalcemia, hypophosphatemia, elevated PTH. Symptoms: "stones, bones, groans, and psychiatric overtones" (nephrolithiasis, bone pain/osteitis fibrosa cystica, abdominal pain, depression). - Secondary hyperparathyroidism: compensatory PTH elevation due to chronic hypocalcemia, commonly from chronic kidney disease (decreased vitamin D activation) or vitamin D deficiency. - Tertiary hyperparathyroidism: autonomous PTH secretion after prolonged secondary hyperparathyroidism, seen in long-standing renal failure, causing hypercalcemia. - Hypoparathyroidism: often iatrogenic (post-thyroidectomy) or autoimmune (e.g., in DiGeorge syndrome, due to 3rd/4th pharyngeal pouch developmental failure), leading to hypocalcemia with symptoms like tetany, Chvostek and Trousseau signs, perioral numbness. - Pseudohypoparathyroidism: end-organ resistance to PTH (Gs-alpha protein defect), causing hypocalcemia despite elevated PTH levels; associated with Albright hereditary osteodystrophy phenotype.

Parathyroid hormone-related peptide (PTHrP) is important in malignancy-associated hypercalcemia (e.g., squamous cell lung cancer), acting on the same PTH receptor but not measured by standard PTH assays.