Plasma parathyroid hormone

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). 

Mg deficiency induces a drop in plasma calcium levels in a variety of animals (mice, dogs, monkeys) but not in the rat. Apparently, the hypocalcemia that occurs in humans and in some animals results from impairment of the process of bone xeabsorption. Mg deficiency seems to result in a decrease in the sensitivity of the osteoclasts to parathyroid hormone. In addition. Mg deficiency may result in a decrease in the rate of secretion of this hormone, leading to low plasma parathyroid hormone levels. 

Levin O, Morris LF, Wah DT, Butch AW, Yeh MW. Falsely elevated plasma parathyroid hormone level mimicking tertiary hyperparathyroidism. Endocr Pract 2011 17 e8-ell. 

A major regulator of bone metabolism and calcium homeostasis, parathyroid hormone (PTH) is stimulated through a decrease in plasma ionised calcium and increases plasma calcium by activating osteoclasts. PTH also increases renal tubular calcium re-absorption as well as intestinal calcium absorption. Synthetic PTH (1-34) has been successfully used for the treatment of osteoporosis, where it leads to substantial increases in bone density and a 60-70% reduction in vertebral fractures. 

More than 99% of total body calcium is found in bone the remaining less than 1% is in the ECF and ICE Calcium plays a critical role in the transmission of nerve impulses, skeletal muscle contraction, myocardial contractions, maintenance of normal cellular permeability, and the formation of bones and teeth. There is a reciprocal relationship between the serum calcium concentration (normally 8.6 to 10.2 mg/dL [2.15 to 2.55 mmol/L]) and the serum phosphate concentration that is regulated by a complex interaction between parathyroid hormone, vitamin D, and calcitonin. About one-half of the serum calcium is bound to plasma proteins the other half is free ionized calcium. Given that the serum calcium has significant protein binding, the serum calcium concentration must be corrected in patients who have low albumin concentrations (the major serum protein). The most commonly used formula adds 0.8 mg/dL (0.2 mmol/L) of calcium for each gram of albumin deficiency as follows ... 

Calcium is freely filtered along with other components of the plasma through the nephrons of the kidney. Most of this calcium is reabsorbed into the blood from the proximal tubule of the nephron. However, because the kidneys produce about 1801 of filtrate per day, the amount of calcium filtered is substantial. Therefore, the physiological regulation of even a small percentage of calcium reabsorption may have a significant effect on the amount of calcium in the blood. Parathyroid hormone acts on the Loop of Henle to increase the reabsorption of calcium from this segment of the tubule and... 

Phosphate, which is also freely filtered with plasma through the nephrons of the kidney, is reabsorbed into the blood from the proximal tubule. Parathyroid hormone acts on this segment to decrease phosphate reabsorption and increase the amount excreted in the urine. 

The mechanism of this effect was addressed in a study in which 2-5 days treatment of female cynomolgus monkeys with relacatib transiently caused a 2-3-fold increase in plasma levels of parathyroid hormone (PTH, a bone anabolic agent) post-dosing compared to vehicle-treated animals [24]. 

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. 

Calcitriol and parathyroid hormone, on the one hand, and calcitonin on the other, ensure a more or less constant level of Ca "" in the blood plasma and in the extracellular space (80-110 mg 2.0-2.6 mM). The peptide parathyroid hormone (PTH 84 AA) and the steroid calcitriol (see p. 374) promote direct or indirect processes that raise the Ca "" level in blood. Calcitriol increases Ca "" resorption in the intestines and kidneys by inducing transporters. Parathyroid hormone supports these processes by stimulating calcitriol biosynthesis in the kidneys (see p. 330). In addition, it directly promotes resorption of Ca "" in the kidneys (see p. 328) and Ca "" release from bone (see B). The PTH antagonist calcitonin (32 AA) counteracts these processes. 

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... 

Regulation of 25-hydroxycholecalciferol 1-hydroxylase 1,25-diOH D3 is the most potent vitamin D metabolite. Its formation is tightly i regulated by the level of plasma phosphate and calcium ions (Figure 28.24). 25-Hydroxycholecalciferol1 -hydroxylase activity is I increased directly by low plasma phosphate or indirectly by bw I plasma calcium, which triggers the release of parathyroid hormone I... 

Plasma phosphate appears to be homeostahcally controlled. The primary organ concerned appears to be the kidney, although the skeleton also may play a role. Parathyroid hormone, by way of its direct action on the kidney and bone, is a significant hormonal factor. 

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. 

Fox, J, Fowe, SH, Petty, BA and Nemeth, EF, 1999, NPS R-568 a type II calcimimetic compound that acts on parathyroid cell calcium receptor of rats to reduce plasma levels of parathyroid hormone and... 

Calcitonin acts to decrease plasma [Ca2+], an effect opposite to that of parathyroid hormone. 

Further evidence that C-25 and C-l hydroxylation are the activation steps of vitamin D3, and that C-24/C-23 and C-23/C-26-lactone metabolic conversions do not produce physiologically important products is with the use of side-chain fluoridated analogues of 25-OH-D3 [87, 88], Studies with these analogues were prompted by assertions that 24-hydroxylated or lactone metabolites are involved or required for such biological actions as mineralization of bone [89], suppression of parathyroid hormone secretion [90], cartilage metabolism [91], and embryonic development in the chick [92]. It is well established that plasma 24,25-(OH)2D3 concentrations (2-5 ng/ml) are approximately 50 times greater than those of l,25-(OH)2D3. Even so,... 

Q2 The hormones that are normally involved in the control of calcium balance are parathyroid hormone (PTH) from the parathyroid gland calcitonin, which is secreted by the thyroid gland and 1,25-dihydroxycholecalciferol (1,25-DHCC, or calcitriol), which is produced in the kidneys. Calcitonin reduces the level of plasma calcium by attenuating its release from bone and by increasing its excretion. The PTH and 1,25-DHCC increase the level of plasma calcium by two mechanisms (1) a combination of an increase in calcium absorption by the gut and an increase in the release of calcium from bone and (2) a reduction in both bone formation and calcium excretion. The three hormones act together to maintain the physiological level of calcium and normal bone turnover. Over 95% of body calcium is located in bone as hydroxyapatite. 

Parathyroid Hormone Parathyroid hormone raises plasma calcium by direct effects on bone resorption and renal reabsorption of calcium, and indirectly by regulating the metabolism of vitamin D. It is a peptide and acts via cell surface G-protein receptors linked to adenylate cyclase. The parathyroid glands have G-protein cell surface calcium receptors linked to phospholipase G, and parathyroid hormone is secreted in response to hypocalcemia. Magnesium is required for secretion of the hormone, which may explain the development of hypocalcemia in premature infants who are magnesium deficient. 

The U.S./Canadian report (Institute of Medicine, 1997) discussed requirements only in terms of bone density and maintenance of a plasma concentration of calcitriol above that associated with elevated parathyroid hormone and alkaline phosphatase. Vieth (1999) noted that intakes above 5 /xg per day are required to prevent osteoporosis (Section 3.4.3) and secondary hyperparathyroidism, and suggested that normal sunlight exposure may provide the... 

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