Enhanced parathyroid hormone

Yi H, Fukagawa M, Yamamoto H et al. (1995) Prevention of enhanced parathyroid hormone secretion, synthesis and hyperplasia by mild dietary phosphorus restriction in early chronic renal failure in rats. Possible direct role of phosphorus. Nephron 70 242-248... 

Cheung R, Erclik MS, Mitchell J (2005) Increased expression of Gllalpha in osteoblastic cells enhances parathyroid hormone activation of phospholipase C and AP-1 regulation of matrix metalloproteinase-13 mRNA. J Cell Physiol 204 336-343... 

Thiazides enhance parathyroid hormone (PTH)-mediated calcium reabsorption from the distal tubule. Thus, urinary calcium is decreased. This characteristic is especially useful in the treatment and prophylaxis of renal calculi. 

The a ns wer is a. (Hardman, pp 1525-1528.) Pa r a thyroid ho r m o ne is synthesized by and released from the parathyroid gland increased synthesis of PTI1 is a response to low serum Ca concentrations. Resorption and mobilization of Ca and phosphate from bone are increased in response to elevated PTI1 concentrations. Replacement of body stores of Ca is enhanced by the capacity of PTH to promote increased absorption of Ca by the small intestine in concert with vitamin D, which is the primary factor that enhances intestinal Ca absorption. Parathyroid hormone also causes an increased renal tubular reabsorption of Ca and excretion of phosphate. As a consequence of these effects, the extracellular Ca concentration becomes elevated. 

High phosphate diets cause decreased Ca absorption, secondary hyperparathyroidism, accelerated bone resorption and soft tissue calcification in some animals, but not in normal humans. Although phosphates may decrease Ca absorption in man at very high (> 2000 mg/day) Ca intakes, they do not do so at more moderate Ca levels and enhance Ca absorption at very low levels (< 500 mg/day). Phosphates increase renal tubular reabsorption and net retention of Ca. At low Ca intakes, phosphates stimulate parathyroid hormone (PTH) secretion without causing net bone resorption. 

We have tested the hypothesis that insulin inhibits the stimulatory effect of parathyroid hormone (PTH) on calcium reabsorption in the distal nephron. PTH is known to enhance calcium transport in renal cells, probably by stimulation of adenylate cyclase and subsequent increases in 3 5 cyclic AMP productoin. Since insulin had been observed to inhibit PTH-stimulated increases in kidney cyclic AMP levels in vitro (24) we investigated whether insulin-mediated hypercalciuria was dependent on the presence of PTH in vivo. 

Many of the adverse effects of lithium can be ascribed to the action of lithium on adenylate cyclase, the key enz)nne that links many hormones and neurotransmitters with their intracellular actions. Thus antidiuretic hormone and thyroid-stimulating-hormone-sensitive adenylate cyclases are inhibited by therapeutic concentrations of the drug, which frequently leads to enhanced diuresis, h)rpoth)n oidism and even goitre. Aldosterone synthesis is increased following chronic lithium treatment and is probably a secondary consequence of the enhanced diuresis caused by the inhibition of antidiuretic-hormone-sensitive adenylate cyclase in the kidney. There is also evidence that chronic lithium treatment causes an increase in serum parathyroid hormone levels and, with this, a rise in calcium and magnesium concentrations. A decrease in plasma phosphate and in bone mineralization can also be attributed to the effects of the drug on parathyroid activity. Whether these changes are of any clinical consequence is unclear. 

Enzyme induction properties Rifampin has enzyme induction properties that can enhance the metabolism of endogenous substrates including adrenal hormones, thyroid hormones, and vitamin D. Rifampin and isoniazid have been reported to alter vitamin D metabolism. In some cases, reduced levels of circulating 25-hydroxy vitamin D and 1,25-dihydroxy vitamin D have been accompanied by reduced serum calcium and phosphate, and elevated parathyroid hormone. 

Parathyroid hormone is a single-chain polypeptide of 84 amino acids which is produced in the parathyroid glands. It increases serum calcium and decreases serum phosphate. In bone it promotes resorption of calcium. It indirectly increases osteoclastic activity by promoting the action of osteoblasts. It has been shown that in low doses PTH may even increase bone formation without stimulating bone resorption. In the kidney PTH increases resorption of calcium and it increases excretion of phosphate. An other important activity in the kidney is the enhanced synthesis of 1,25-dihydroxyvitamin D. An increased serum calcium level inhibits PTH secretion and increased serum phosphate decreases free serum calcium and thus stimulates PTH secretion. 

The major location of calcium in the body is in the skeleton, which contains more than 90% of the body calcium as phosphate and carbonate. Bone resorption and formation keeps this calcium in dynamic equilibrium with ionized and complexed calcium in blood, cellular fluids and membranes. Homeostasis is mainly regulated by the parathyroid hormone and vitamin D which lead to increased blood calcium levels, and by a thyroid hormone, calcitonin, which controls the plasma calcium concentration J5 Increasing the concentration of calcitonin decreases the blood calcium level, hence injections of calcitonin are used to treat severe hyperalcaemia arising from hyperparathyroidism, vitamin D intoxication or the injection of too high a level of parathyroid extract. High levels of calcitonin also decrease resorption of calcium from bone. Hypocalcaemia stimulates parathyroid activity, leading to increased release of calcium from bone, reduction in urinary excretion of calcium and increased absorption of calcium from the intestine. Urinary excretion of phosphate is enhanced. 

Ryder KD, Duncan RL. 2001. Parathyroid hormone enhances fluid shear-induced [Ca2+]i signaling in osteoblastic cells through activation of mechanosensitive and voltage-sensitive Ca2+ channels. J Bone Miner Res 16 240-8. 

As discussed in Section 2.4.1, there are some data that suggest that aluminum absorption can be enhanced by parathyroid hormone and vitamin D, but the data are inconclusive. 

Soma S, Matsumoto S,Takano-Yamamoto T. Enhancement by conditioned medium of stretched calvarial bone cells of the osteoclast-like cell formation induced by parathyroid hormone in mouse bone marrow cultures. Archs Oral Biol. 1996 42(3) 205-211. 

The physiological role of vitamin D is to maintain calcium homeostasis. Phosphate metabolism is also affected. Vitamin D accomplishes its role by enhancing the absorption of calcium and phosphate from tte small intestines, promoting their mobilization from bone, and decreasing their excretion by the kidney. Also involved are parathyroid hormone and edeitonin. 

When the secretion of parathyroid hormone is excessive, the physiologic effects of this peptide on the gut, the skeleton, and the kidney tubules are enhanced. The percentage of dietary calcium absorbed into the circulation is increased, calcium ions are released from bone and enter the blood more rapidly, and the renal tubules reabsorb more calcium than usual from the luminal urine, all leading to hypercalcemia. Chronic hypercalcemia is associated with vague generalized musculoskeletal pain, fatigue, and eventually, slowed mentation. 

Calcium is essential for the normal growth and development of the body, especially (in the form of calcium phosphate) of the bones and teeth. Its level in the blood is regulated by the opposing actions of the thyroid hormone calcitonin, and the parathyroid hormone parathormone. Its uptake from food is enhanced by vitamin D (calciferol). Forms of calcium used therapeutically include the folinic acid supplement calcium foiinate, and the mineral supplements calcium bicarbonate, calcium carbonate, calcium gluconate and calcium lactate. 

The concentration of ionized calcium is closely regulated by the interactions of parathyroid hormone (PTH), phosphorus, vitamin D, and calcitonin (Fig. 49-9). Parathyroid hormone increases serum calcium concentrations by stimulating calcium release from bone, reducing renal excretion, and enhancing absorption in the gastrointestinal tract secondary to increased renal production of 1,25-... 

A subset of patients with hypercalcaemia related to a malignancy show no evidence of excess parathyroid hormone production or osseous metastases. PG have been implicated in the pathogenesis of malignancy-related hypercalcaemia, since PG enhance bone resorption, and are necessary for the synthesis of osteoclastic activating factor. Some patients with renal cell carcinoma and concomitant hypercalcaemia have been shown to have elevated renal PG levels which can be suppressed with indomethacin. 

---