Function of the Parathyroid Glands

In humans, there are usually four parathyroid glands that are embedded on the posterior surface of the thyroid gland. Each parathyroid gland is a pea-sized 

Generic Name Trade Name(s) Thyroid Hormone Content Source 

---

Q4 Comment on the function of the parathyroid gland and the actions of its hormone. 

Q13 Magnesium is a major intracellular cation which acts as a co-factor in many intracellular enzyme reactions. Plasma concentration is normally 2 mg dl-1. This ion is abundant in the diet, and hypomagnesaemia is relatively uncommon, unless there is malabsorption or excessive loss via the kidney. However, when present, hypomagnesaemia can lead to hypoparathyroidism. Adjustment to the levels of magnesium can shift the function of the parathyroid glands back to normal. Chronic alcoholism, malnutrition, malabsorption, renal tubular dysfunction and excessive use of diuretics, such as loop and thiazide diuretics, may lead to hypomagnesaemia. Symptoms of magnesium deficiency include depression, confusion, muscle weakness and sometimes convulsions. 

Abnormal levels of blood electrolytes such as sodium and potassium can also cause neuromuscular disturbances. When potassium is too high or too low, the muscles of the trunk, arms, and legs can be very weak, even to the point of paralysis. If the blood calcium is low (as in vitamin D deficiency or inadequate function of the parathyroid gland), twitching may occur. When blood calcium is too high, there may be profound weakness. Normal magnesium levels are also important for proper neuromuscular functioning. 

Capen, C. C., and T. J. Rosol. 1989. Recent advances in the structure and function of the parathyroid gland in animals and the effect of xenobiotics. Toxicologic Pathology 17 333-356. 

CTN Under normal circumstances, the body maintains the required balance between the calcium found in the tissues and the calcium obtained in the diet. The normal value range for total serum calcium varies with the age of the individual. The normal range for adults is 8.6-10.3 mg/dL (2.23-2.57 mmol/L). In certain situations, ionized calcium levels, which in adults should be between 4.65 and 5.28 mg/dL (1.03 and 1.23 mmol/L), provide a better picture of whether or not adequate calcium is present. This is particularly true when a protein deficiency exist because 50 percent of the calcium found in the body is bound to protein. Proper functioning of the parathyroid gland, adequate levels of vitamin D, and normal kidney function also affect calcium levels. An imbalance in calcium metabolism results in either hypocalcemia (calcium levels below 8.6 mg/dL) or hypercalcemia (calcium levels above 10.0 mg/dL). 2... 

The findings of Cox and Imboden (40, 41) were confirmed by Bodansky and Duff (43) who found that the normal calcification of the fetal skeleton depends not only upon the maternal mineral intake but also upon normal function of the parathyroid glands of the mother. 

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. 

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 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. 

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 ... 

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). 

The parathyroid hormone content of blood has not been studied sufficiently to yield any data with regard to variation. The functioning of the glands is so closely related to other factors which regulate calcium and phosphorus metabolism that it is impossible to assign differences in these areas to variation in parathyroid function. The variation of the calcium (and phosphorus) in the blood has been noted (p. 55), and this variation, of course, may be due in a substantial degree to differences in parathyroid functioning. 

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. 

CaR expression is greatest in the parathyroid glands, calcitonin-secreting C-cells of the thyroid gland, and kidney, but the CaR is also found in the two other key organs that participate in calcium homeostasis gut and bone (Brown and MacLeod, 2001). This review will focus on the structure and function of the CaR, its role in normal physiology and in various disorders of Ca -sensing, and the development of CaR-based therapeutics. 

Although bone is not considered a major calcium sensing organ in humans, the cells of bone tissue control over 99% of the human body s calcium content. The principal calcium sensors that regulate bone calcium uptake and release are in the parathyroid glands. Bone function is also modified by vitamin D and by calcium transport in the kidney and intestine. These indirect mechanisms of controlling bone calcium metabolism are beyond the scope of our considerations here. In spite of processing... 

The thyroid and parathyroid glands serve a number of vital endocrine functions. The thyroid gland synthesizes and secretes the thyroid hormones T3 and T4. These hormones are important regulators of cellular metabolism and metabolic rate. Thyroid hormones also interact with other hormones to facilitate normal growth and development. The parathyroid glands control calcium homeostasis through the release of PTH. This hormone is crucial... 

Only one radioactive isotope of selenium is used commercially, selenium-75. This isotope is used to smdy the function of two organs in the body, the pancreas and the parathyroid gland. (The pancreas helps with digestion and the parathyroid gland releases hormones.) The radioactive... 

Aluminum binds diatomic phosphates and possibly depletes phosphate, which can lead to osteomalacia. High aluminum serum values and high aluminum concentration in the bone interfere with the function of vitamin D. The incorporation of aluminum in the bone may interfere with deposition of calcium the subsequent increase of calcium in the blood may inhibit release of parathyroid hormones by the parathyroid gland. The mechanism by which aluminum concentrates in the brain is not known it may interfere with the blood brain barrier. 

A second member of the parathyroid hormone family, parathyroid hormone-related protein (PTHrP), is quite similar to PTH in amino acid sequence and protein structure. Like PTH, it activates the parathyroid hormone receptor causing increased bone resorption and renal tubular calcium reabsorption. Increased serum concentrations of parathyroid hormone-related protein are the predominant cause of hypercalcemia in cancer patients with solid tumors. This observation led to its discovery and to the elucidation of its many cellular functions in normal tissues. In contrast to PTH, which is expressed only in parathyroid glands, PTHrP is detected in many tissues in fetuses and adults it is found in epithelia, mesenchymal tissues, endocrine glands, and the central nervous system. This protein is also the principal regulator of placental calcium transport to the fetus. 

---