Vitamin and parathyroid hormone

Hypocalcemia results from altered effects of parathyroid hormone and vitamin D on the bone, gut, and kidney. The primary causes are postoperative hypoparathyroidism and vitamin D deficiency. 

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. 

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. 

Endocrine topics not discussed in Chapters 30-34 that are covered elsewhere in the text are as follows gastrointestinal hormones, Chapter 12 eicosanoids, Chapter 18 pancreatic hormones, Chapter 22 parathyroid hormone and vitamin D, Chapter 37 renin-angiotensin system and antidiuretic hormone. Chapters 32 and 39. A list of expanded acronyms appears in Appendix VIIl. 

Hypocalcemia is the result of alterations in the effect of parathyroid hormone and vitamin D on the bone, gut, and kidney (see Fig. 49-9). The primary causes of hypocalcemia are postoperative hypoparathyroidism and vitamin D deficiency. Other causes include magnesium deficiency, thyroid surgery, medications, hypoalbuminemia, blood transfusions, peripheral blood progenitor cell harvesting, tumor lysis syndrome, and mutations in the calcium-sensing receptor. " Parathyroid hormone concentrations are elevated in conditions of hypocalcemia, with the exception of hypoparathyroidism and hypomagnesemia (Fig. 49-11). ... 

Levine, M.A. (2003) Normal mineral homeostasis. Interplay of parathyroid hormone and vitamin D. Endocrine Development, 6, 14-33. 

Mittleman R, Chausmer A, Bellavia J, et al. 1967. Thyrocalcitonin activity in hypercalcemia produced by calcium salts, parathyroid hormone and vitamin D. Endocrinology 81 599-604. 

Spreng P. 1967. Effect of parathyroid hormone and vitamin A on the retention of radiostrontium in the rat. Nature 214 513-514. 

The precise mechanism and the localization of the absorption for orally taken aluminum are not known so far. It is assumed, however, that the aluminum is absorbed in the stomach and the duodenum, possibly in the proximal jejunum as well. The absorbed amount depends on the solubility of the aluminum compound and the respective gastrointestinal pH level. In addition, iron and fluorine increase the enteral absorption. Furthermore, the aluminum intake might be influenced by the parathyroid hormone and vitamin D. The daily aluminum intake via nutrition depends on eating habits and is estimated at an average of 5-10 mg/day less than 1% of this amount is absorbed. 

All these processes are dependent on an adequate supply of calcium from the diet. It is the integrated action of parathyroid hormone and vitamin D3 which supplies the required amounts of calcium for all these processes via a smoothly operating calcium homeostatic mechanism. When serum calcium concentration falls below 10 mg/100 ml, the sequence of events shown in Fig. 2 takes place. 

The level of inorganic phosphate in blood is controlled by a balance of various factors such as phosphatase activity, parathyroid hormone, and vitamin D. 

Although it is being found that vitamin D metaboUtes play a role ia many different biological functions, metaboHsm primarily occurs to maintain the calcium homeostasis of the body. When calcium semm levels fall below the normal range, 1 a,25-dihydroxy-vitainin is made when calcium levels are at or above this level, 24,25-dihydroxycholecalciferol is made, and 1 a-hydroxylase activity is discontiaued. The calcium homeostasis mechanism iavolves a hypocalcemic stimulus, which iaduces the secretion of parathyroid hormone. This causes phosphate diuresis ia the kidney, which stimulates the 1 a-hydroxylase activity and causes the hydroxylation of 25-hydroxy-vitamin D to 1 a,25-dihydroxycholecalciferol. Parathyroid hormone and 1,25-dihydroxycholecalciferol act at the bone site cooperatively to stimulate calcium mobilization from the bone (see Hormones). Calcium blood levels are also iafluenced by the effects of the metaboUte on intestinal absorption and renal resorption. 

Russell J et al Interaction between calcium and 1,25-dihydroxy-vitamin D3 in the regulation of preproparathyroid hormone and vitamin D receptor mRNA in avian parathyroids. Endocrinology 1993 132 2639. 

Check parathyroid hormone (PTH), vitamin D and precursors, magnesium, and phosphate levels ° Pharmacological causes of decreased ionized calcium may include excess infusions of citrate, EDTA, lactate, fluoride poisoning, foscarnet, cinacalcet, bisphosphates, or unrelated increase in serum phosphate or decrease in serum magnesium levels... 

Vitamin D is really a small family of closely related molecnles that prevent the bone disease rickets in children and osteomalacia in adnlts. In both cases, inadeqnate mineralization of bone results in bone deformation and weakness. Calcinm, Ca +, homeostasis is one goal of vitamin D activity, a goal it shares with parathyroid hormone and calcitonin. Calcium is intimately involved in bone mineralization and distnrbances of calcium levels in the blood can resnlt in inadeqnate bone mineralization or excessive calcification of other tissues. 

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. 

Abrams, S. A., Griffin, 1. J., Hawthorne, K. M., Gunn, S. K., Gundberg, C. M., and Carpenter, T. O. (2005b). Relationships among Vitamin D Levels, parathyroid hormone, and calcium absorption in young adolescents. J. Clin. Endocrinol. Metab. 90,5576-5581. 

Calcitonin is a polypeptide hormone which (along with parathyroid hormone and the vitamin D derivative, 1,25-dihydroxycholecalciferol) plays a central role in regulating serum ionized calcium (Ca +) and inorganic phosphate (P,) levels. The adult human body contains up to 2 kg of calcium, of which 98% is present in the skeleton (i.e. bone). Up to 85% of the 1kg of phosphorus present in the body is also found in the skeleton (the so-called mineral fraction of bone is largely composed of Ca3 (P04)2 which acts as a body reservoir for both calcium and phosphorus). Calcium concentrations in human serum approximate to O.lmg/ml and are regulated very tightly (serum phosphate levels are more variable). 

Parathyroid Hormone, Caicitonin, Vitamin D, and Other Compounds Reiated to Minerai Metaboiism 754... 

CLINICAL USES OF PARATHYROID HORMONE, CALCITONIN, VITAMIN D, AND BISPHOSPHONATES... 

Calcium is present in three forms e.g., as free calcium ion, bound to plasma protein albumin and in diffusable complexes. The endocrine system, through parathyroid hormone and calcitonin, helps in keeping the concentration of ionized plasma calcium in normal level. Decrease in plasma levels of ionized calcium leads to increased parathyroid hormone secretion. Parathyroid hormone tends to increase plasma calcium level by increasing bone resorption, increasing intestinal absorption and increasing reabsorption of calcium in kidney. Vitamin D acts by stimulating... 

Table 42-2 Actions of Parathyroid Hormone (PTH), Vitamin D, and FGF23 on Gut, Bone, and Kidney. ...

Uptake of Ca2+ from the intestine is stimulated by vitamin D.447 Vitamin D3 is converted to the 25-hydroxy derivative in the liver (equation 11) by a two component mixed-function hydroxylase.448 The metabolically active 1,25-dihydroxy form is synthesized by further hydroxylation in the kidney. This latter stage involves the renal 25-hydroxyvitamin D3- 1-hydroxylase in a reaction which is controlled by Ca2+, parathyroid hormone and phosphate. This renal hydroxylase contains a flavoprotein, an iron-sulfur protein (with an Fe2S2 cluster) and cytochrome P-450.447... 

Willett AM. Vitamin D status and its relationship with parathyroid hormone and bone mineral status in older adolescents. Proc Nutr Soc. 2005 64 193-203. 

Vitamin D, along with parathyroid hormone and calcitonin, plays a primary role in calcium and phosphorus homeostasis in the body. Intensive research efforts over the past several years have elucidated a role for vitamin D in many other physiological processes as well. The biological actions of this seco-steroid are mediated primarily through the action of its polar metabolite, 1,25-dihydroxy vitamin D3 (l,25(OH)2D3). There is emerging evidence that l,25(OH)2D3 has many more target tissues than those involved in its classical role in the control of mineral metabolism. In addition, some of the actions of l,25(OH)2D3 may be mediated by mechanisms other than the classical steroid-receptor interaction. In this chapter we will provide a brief overview of the multiple actions of vitamin D3 and the pleiotropic mechanisms by which these actions are accomplished. 

Bone is a relatively dynamic organ that undergoes significant turnover that is, hone resorption and deposition it is broken down hy osteoclasts and rebuilt by osteoblasts. Besides an adequate supply of calcium, a close cooperation is required between these two types of cell. Complex signalling pathways achieve proper rates of growth and differentiation these pathways include the action of several hormones, including parathyroid hormone (PTH), vitamin D, growth hormone, steroids and calcitonin, as well as several cytokines. 

The plasma concentration of calcidiol is the most sensitive and usefiil index of vitamin D status, and is correlated with elevated plasma parathyroid hormone and alkaline phosphatase activity (Table 3.4). As shown in Table 3.2, the reference range of plasma calcidiol is between 20 to 150 nmol per L, with a twofold seasonal variation in temperate regions. Concentrations below 20 nmol per L are considered to indicate impending deficiency, and osteomalacia is seen in adults when plasma calcidiol falls below 10 nmol per L. In children, clinical signs of rickets are seen when plasma calcidiol faUs below 20 nmol per L. The plasma concentration of calcitriol does not give a useful indication of vitamin D status. The reference range is between 38 to 144 pmol per L and is maintained because of the stimulation of calcidiol 1-hydroxylation by parathyroid hormone secreted in response to faUing concentrations of calcium (Holick, 1990). 

Haynes RC Jr, Murad F. Agents affecting calcification, calcium parathyroid hormone, calcitonin, vitamin D and other compounds. In Goodman LS, Gilman A, editors. The Pharmacological Basis of Therapeutics. 6th ed. New York MacMillan, 1980 1545. 

---