PTHs

PTHs, or parathyroid hormones, are a family of peptide hormones that regulate calcium and phosphate homeostasis. The principal member is parathyroid hormone (PTH), produced by the chief cells of the parathyroid glands. A related peptide, parathyroid hormone-related peptide (PTHrP), is widely expressed in tissues and acts in an autocrine/paracrine fashion, sharing activity with PTH at the same receptor but typically serving different physiological and pathological roles.

Physiologically, PTH acts on bone and kidney to raise serum calcium. In bone, PTH stimulates osteoblasts to increase production of RANKL, promoting osteoclast formation and bone resorption, which releases calcium and phosphate into the bloodstream. In the kidney, PTH enhances calcium reabsorption in the distal tubule and decreases phosphate reabsorption in the proximal tubule, increasing phosphate excretion. It also stimulates 1α-hydroxylase in the proximal tubule, raising calcitriol (active vitamin D) levels, which increases intestinal absorption of calcium and phosphate.

Regulation of PTH secretion is primarily governed by serum calcium through the calcium-sensing receptor on parathyroid cells: low calcium increases PTH release, while high calcium suppresses it. Vitamin D status, phosphate load, and, in some contexts, calcitonin and FGF23, modulate PTH as well. Calcitriol provides negative feedback by inhibiting PTH synthesis. PTHrP can mimic PTH actions at the PTH1 receptor but is mainly produced in non-parathyroid tissues and plays roles in development and humoral hypercalcemia of malignancy.

Clinical relevance includes primary and secondary hyperparathyroidism, hypoparathyroidism, and pseudo-hypoparathyroidism. Diagnosis uses intact PTH measurements alongside calcium and phosphate levels. Therapies range from calcium and vitamin D supplementation to PTH analogs such as teriparatide and abaloparatide for osteoporosis, which are given intermittently to favor bone formation. PTHrP is implicated in malignancy-associated hypercalcemia.