Parathyroid gland

The parathyroid glands are four tiny glands embedded in the back of the thyroid gland. 

The parathyroid glands secrete parathyroid hormone (PTH) when calcium levels in the body are low. 

together with vitamin D, raises plasma calcium levels by increasing activity of osteoclasts, which results in release of calcium from bone by increasing reabsorption of calcium by the kidney and by increasing absorption of calcium from the intestine. 

Deficiency of PTH is treated with injections of calcium and calcitriol (a vitamin D analogue). 

High levels of calcium in blood plasma cause the release of calcitonin from the thyroid gland, which inhibits the reabsorption of calcium from bone by inhibiting osteoclasts. 

Four small parathyroid glands are embedded on the posterior surface of the thyroid gland as it wraps around the trachea. Parathyroid hormone (PTH, parathormone) is the principal regulator of calcium metabolism. Its overall effects include  

Parathyroid hormone carries out these effects through multiple mechanisms of action  

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. 

Parathyroid hormone stimulates bone resorption by increasing the number and activity of osteoclasts. This demineralization process in the bone releases calcium and phosphate into the blood. Although the action of PTH on the bone appears to increase blood phosphate, its action on the kidney, which increases phosphate excretion in the urine, more than compensates for this increase and the net effect is a decrease in serum phosphate. 

When thyroidectomy was introduced as a therapeutic procedure, tetany commonly accompanied the ablation of the gland. Later tetany was established to result from hypocalcemia, and the calcium content of the body fluids was found to be controlled by a hormone secreted by the parathyroid gland [20-23]. 

Humans usually have four parathyroid glands— small, bean-shaped yellow organs at the posterior surface of the thyroid. Occasionally, accessory parathyroid glands are found. The total weight of the parathyroid mass does not exceed 300 mg except in cases of hyperplasia. The glands are so small that an unexperienced prosector might find it difficult to localize them, especially when the glands are deeply embedded within the thyroid tissue. 

The most striking advance in our knowledge of parathormone results from the purification and study of the chemical properties of the hormone. For a long time, only crude extracts of parathormone were used, but later a method of purifying the hormone that involved extracting the active protein with phenol from 

Although the purest preparations are not homogeneous on electrophoretic analysis, they have yielded important information on the chemical properties of the hormone. Parathormone is a small polypeptide with an average molecular weight of 9,000. It contains 17 common amino acids, but cystine is conspicuously absent from the polypeptide chain. Only one N-ter-minal amino acid—alanine—has been identified, suggesting that the hormone is a single-chain polypeptide. 

These encouraging results led to further attempts to purify the hormone. Sephadex filtration, first on G50 and later on GlOO, followed by chromatographic analysis on a carboxymethyl-cellulose column, and finally electrophoresis on polyacrylamide gel yielded two different polypeptides. Enough of the two polypeptides could be obtained to compare their properties. Although the polypeptides differed by their mobilities and amino acid composition, their biological and immunological properties were identical. 

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Blood Calcium Ion Level. In normal adults, the blood Ca " level is estabhshed by an equiUbrium between blood Ca " and the more soluble intercrystalline calcium salts of the bone. Additionally, a subtle and intricate feedback mechanism responsive to the Ca " concentration of the blood that involves the less soluble crystalline hydroxyapatite comes into play. The thyroid and parathyroid glands, the fiver, kidney, and intestine also participate in Ca " control. The salient features of this mechanism are summarized in Figure 2 (29—31). 

Parathyroid hormone, a polypeptide of 83 amino acid residues, mol wt 9500, is produced by the parathyroid glands. Release of PTH is activated by a decrease of blood Ca " to below normal levels. PTH increases blood Ca " concentration by increasing resorption of bone, renal reabsorption of calcium, and absorption of calcium from the intestine. A cAMP mechanism is also involved in the action of PTH. Parathyroid hormone induces formation of 1-hydroxylase in the kidney, requited in formation of the active metabolite of vitamin D (see Vitamins, vitamin d). 

Three hormones regulate turnover of calcium in the body (22). 1,25-Dihydroxycholecalciferol is a steroid derivative made by the combined action of the skin, Hver, and kidneys, or furnished by dietary factors with vitamin D activity. The apparent action of this compound is to promote the transcription of genes for proteins that faciUtate transport of calcium and phosphate ions through the plasma membrane. Parathormone (PTH) is a polypeptide hormone secreted by the parathyroid gland, in response to a fall in extracellular Ca(Il). It acts on bones and kidneys in concert with 1,25-dihydroxycholecalciferol to stimulate resorption of bone and reabsorption of calcium from the glomerular filtrate. Calcitonin, the third hormone, is a polypeptide secreted by the thyroid gland in response to a rise in blood Ca(Il) concentration. Its production leads to an increase in bone deposition, increased loss of calcium and phosphate in the urine, and inhibition of the synthesis of 1,25-dihydroxycholecalciferol. 

A form of hypoparathyroidism (hypofimction of the parathyroid glands) caused by the presence of activating mutations in the CaR, usually in the heterozygous state. 

PTH is the most important regulator of bone remodelling and calcium homeostasis. PTH is an 84-amino acid polypeptide and is secreted by the parathyroid glands in response to reductions in blood levels of ionised calcium. The primary physiological effect of PTH is to increase serum calcium. To this aim, PTH acts on the kidney to decrease urine calcium, increase mine phosphate, and increase the conversion of 25-OH-vitamin D to l,25-(OH)2-vitamin D. PTH acts on bone acutely to increase bone resorption and thus release skeletal calcium into the circulation. However, due to the coupling of bone resorption and bone formation, the longer-term effect of increased PTH secretion is to increase both bone resorption and bone formation. 

The parathyroid glands in FHH are reset to maintain a higher than normal serum calcium concentration owing to impaired suppression of PTH release in the face of hypercalcemia (e.g., resistance to CaQ+) (Fig. 2). Similarly the kidneys show a reduced calciuric response to hypercalcemia, which contributes to the hypercalcemia by promoting inappropriately reabsorption of calcium. Mouse models of FHH and NSHPT result from targeted inactivation of one or both CaR alleles, respectively [1,3]. These animals have provided valuable insights into the alterations in tissue function resulting from loss of the receptor. 

A common cause of PTH-dependent hypercalcemia results from benign, or occasionally malignant, enlargement of one or more parathyroid glands, a condition known as primary hyperparathyroidism (PHPT). Although many patients with PHPT present in an asymptomatic state that does not require medical intervention, some are afflicted with excess bone loss, kidney stones, or other complications. If patients are... 

In the periphery, dopamine receptor levels are generally lower than those observed in brain, particularly in comparison to striatal dopamine receptor levels. Due to these low levels, knowledge of receptor distribution in the periphery is not yet comprehensive. Nevertheless, Dl-like receptors have been reported in the parathyroid gland and in the tubular cells of the kidney. D2-like dopamine receptors have also been observed in the kidney. In addition, dopamine D2 and D4 receptors have been found in the adrenal cortex, where they modulate aldosterone secretion. The... 

A form of PTH-dependent hypercalcemia caused by enlargement and hyperfunction of one or more parathyroid glands. 

As renal function declines in patients with CKD, decreased phosphorus excretion disrupts the balance of calcium and phosphorus homeostasis. 0 The parathyroid glands release PTH in response to decreased serum calcium and increased serum phosphorus levels. The actions of PTH include ... 

As kidney function continues to decline and the GFR falls less than 60 mL/minute/1.73 m2, phosphorus excretion continues to decrease and calcitriol production decreases, causing PTH levels to begin to rise significantly, leading to secondary hyperparathyroidism (sHPT). The excessive production of PTH leads to hyperplasia of the parathyroid glands, which decreases the sensitivity of the parathyroid glands to serum calcium levels and calcitriol feedback, further promoting sHPT. 

Metabolic acidosis, a common complication of CKD, also contributes to ROD by altering the solubility of hydroxyapatite, promoting bone dissolution. Additionally, metabolic acidosis inhibits the activity of osteoblasts, which promote bone formation, while stimulating osteoclasts to promote bone resorption. Finally, metabolic acidosis can worsen sHPT by reducing the sensitivity of the parathyroid gland to serum calcium levels.38... 

Cinacalcet is a calcimimetic that increases the sensitivity of receptors on the parathyroid gland to serum calcium levels to reduce PTH secretion. Cinacalcet maybe beneficial in patients with an increased Ca-P product who have elevated PTH levels and cannot use vitamin D therapy. Because the effects of cinacalcet on PTH can reduce serum calcium levels and result in hypocalcemia, cinacalcet should not be used if serum calcium levels are below normal. 

Secondary hyperparathyroidism Increased secretion of parathyroid hormone from the parathyroid glands caused by hyperphosphatemia, hypocalcemia, and vitamin D deficiency that result from decreased kidney function. It can lead to bone disease (renal osteodystrophy). 

Sites of production Adrenal cortex, testes, ovaries, placenta Hypothalamus, pituitary gland, thyroid gland, parathyroid glands, pancreas Thyroid gland Adrenal medulla... 

A nontrophic hormone acts on nonendocrine target tissues. For example, parathormone released from the parathyroid glands acts on bone tissue to stimulate the release of calcium into the blood. Aldosterone released from the cortical region of the adrenal glands acts on the kidney to stimulate the reabsorption of sodium into the blood. 

The final mechanism of action of PTH involves the activation of vitamin D3 through the stimulation of la-hydroxylase in the kidney. In the gastrointestinal tract, vitamin D3 is essential for the absorption of calcium. Enhanced absorption of calcium from dietary sources serves to further increase the concentration of calcium in the blood. Many foods, in particular, dairy products, which are rich in calcium, are fortified with vitamin D. The release of PTH from the parathyroid glands is regulated by plasma calcium levels through negative feedback. A decrease in the level of calcium in the blood stimulates the secretion of PTH and an increase in the calcium level in the blood inhibits it. 

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. 

Calcium-phosphorus balance is mediated through a complex interplay of hormones and their effects on bone, GI tract, kidney, and parathyroid gland. As kidney disease progresses, renal activation of vitamin D is impaired, which reduces gut absorption of calcium. Low blood calcium concentration stimulates secretion of parathyroid hormone (PTH). As renal function declines, serum calcium balance can be maintained only at the expense of increased bone resorption, ultimately resulting in renal osteodystrophy (ROD) (Fig. 76-7). 

Symptomatic hypocalcemia commonly occurs because of parathyroid gland dysfunction secondary to surgical procedures involving the thyroid, parathyroid, and neck. 

Various factors may be associated with variations in calcium needs differences in vitamin D supply, differences in absorption and excretion, differences in activity of the parathyroid glands, differences in steroid hormone production, differences in thyroid function, differences in phosphate supply and utilization. 10 These we will not discuss, although these considerations may make it possible, in individual cases, to circumvent extra needs for calcium by removing the basis for the augmented need. We are here concerned primarily with the fact that individual people, under prevalent conditions, require amounts of calcium which may vary from individual to individual by a factor of 5. 

The CASR functions as an extracellular calcium sensor for the parathyroid gland and the kidney. CASR serves to maintain a stable calcium concentration, without which many aspects of homeostasis are adversely affected. For example, the effect of CASR variants on seizure threshold in the brain is reviewed in Subheading... 

Families affected by ADH, autosomal dominant hypoparathyroidism, and hypocal-cemic hypercalcinria have each been defined by gain-of-function mutations in the CASR gene (44). ADH is associated with the expression of constitutively activated CASR, which serves to suppress PTH secretion from the parathyroid gland. In the kidney it induces hypercalciuria, which further contributes to the hypocalcemia. 

The suppression of PTH secretion from the parathyroid gland that accompanies the constitutive activation of the CASR makes the disorder difficult to recognize and treat. In some cases, it has been reported that seizures can be intractable. The abnormal set point of calcium regulation complicates treatment with calcitriol and dietary calcium supplementation because the CASR expressed in the kidney controls calcium excretion. The constitutively activated CASR mutant induces hypercalciuria, which may compound the hypocalcemia (42). 

Atwal, O. S., and T. Wilson. Parathyroid gland changes following ozone inhalation. A morphologic study. Arch. Environ. Health 28 91-100, 1974. 

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