Pseudohypoparathyroidism: A Variation on the Theme of Hypoparathyroidism

Pseudohypoparathyroidism is characterized by an inability of the body to respond appropriately to parathyroid hormone (PTH), the principal hormone that regulates calcium and phosphorous levels in the body. PTH is made by the parathyroid glands in the neck. There are usually four parathyroid glands, but we probably only need one or two of the glands. PTH is missing, or too low, in patients with hypoparathyroidism. Therefore, the fundamental difference between hypoparathyroidism and pseudohypoparathyroidism is that PTH is absent in hypoparathyroidism, but the body will respond to it; and PTH is plentiful in pseudohypoparathyroidism, but the body cannot respond to it! PTH acts directly on the bone and kidneys to control blood levels of calcium and phosphorous, and to regulate bone mass and strength. PTH also acts indirectly on the intestine and skeleton by stimulating production of the active form of Vitamin D (calcitriol) in the kidney. Calcitriol stimulates absorption of calcium and phosphorous from the intestine and also increases the release of calcium and phosphorous from storage pools in the skeleton (Figure 1). In the bone, PTH stimulates specific bone cells called osteoclasts to break down or "resorb" bone to release the minerals calcium and phosphorus into the blood stream. Osteoclasts resorb bone when extra minerals are needed in the blood or when it is necessary to remodel bone, such as during growth or repair of a fracture. Working closely with the osteoclasts are osteoblasts, the cells that create new bone tissue after osteoclasts remove old or damaged bone. PTH also acts in the kidney, where it increases calcium reabsorption (prevents loss into the urine) and increases urinary phosphate excretion (loss into the urine) to avoid elevated levels of phosphorous in the blood. The kidney is a very important control valve to maintain normal levels of blood calcium and phosphorous. The kidney filters the blood, like a colander, and keeps large particles such as blood cells. The filtered "water" contains both waste products and minerals. The kidney reclaims or reabsorbs the important things, such as water and minerals, and gets rid of, or excretes, what it does not need, such as waste products and extra minerals. It knows how much of each mineral to excrete by signals from hormones such as PTH. An increase in PTH saves, or reabsorbs, the calcium and excretes extra phosphorus.