Parathyroid gland hyperparathyroidism

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... 

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. 

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). 

Cinacalcet is the first representative of a new class of drugs that activates the calcium sensing receptor (CaR). CaR is widely distributed but has its greatest concentration in the parathyroid gland. Cinacalcet blocks PTH secretion by this mechanism and is approved for the treatment of secondary hyperparathyroidism in chronic kidney disease and for the treatment of parathyroid carcinoma. 

Of 12 patients who underwent parathyroid gland resection while maintaining their intake of lithium, only eight remained normocalcemic (679). Nevertheless, the authors recommended that surgery should be considered if there is hyperparathyroidism. 

Hyperparathyroidism Increased parathyroid hormone secretion, usually caused by parathyroid tumors leads to excessive bone resorption and hypercalcemia Usually treated surgically by partial or complete resection of the parathyroid gland... 

The polypeptide parathormone is released from the parathyroid glands when the plasma Ca2+ level falls. It stimulates osteoclasts to increase bone resorption in the kidneys it promotes calcium reabsorption, while phosphate excretion is enhanced. As blood phosphate concentration diminishes, the tendency of Ca2+ to precipitate as bone mineral decreases. By stimulating the formation of vitamin D hormone, parathormone has an indirect effect on the enteral uptake of Ca2+ and phosphate. In parathormone deficiency, vitamin D can be used as a substitute that, unlike parathormone, is effective orally. Teriparatide is a recombinant shortened parathormone derivative containing the portion required for binding to the receptor. It can be used in the therapy of postmenopausal osteoporosis and promotes bone formation. While this effect seems paradoxical in comparison with hyperparathyroidism, it obviously arises from the special mode of administration the once daily s.c. injection generates a quasi-pulsatile stimulation. Additionally, adequate intake of calcium and vitamin D must be ensured. 

Hypercalcemia occurs with hyperparathyroidism, a disease involving the excessive production of PTH by the parathyroid gland. Hypercalcemia can result from cancers that produce l,25-(OH)jDg, Cancer cells produce a variety of other molecules that stimulate osteoclasts this condition is called oncogenic hypercalcemia. 

Of 537 patients who had parathyroid glands excised for hyperparathyroidism, 12 (2.2%) had been taking lithium and 11 (2.0%) had been taking it long-term (mean 15.3... 

A causal relationship between lithium treatment and hyperparathyroidism has been suggested [37]. Lithium seems to induce morphological changes in the parathyroid glands with an increase in parathyroid volume, and an increase in cellular DNA synthesis [37-39], which may explain why its effects may not be completely reversible. It is not rare to find patients with hypercalcemia, usually mild, after discontinuation of prolonged lithium therapy. A number of cases have been reported where hypercalcemia and hypocalciuria persisted even after discontinuation. We also have seen persistence of hypercalcemia and hyperparathyroidism several years after discontinuation of lithium therapy [Batlle et al unpublished, 2000]. 

Primary hyperparathyroidism results from hyperplasia, adenoma, or carcinoma of the parathyroid glands and from ectopic production of the hormone by squamous cell carcinoma of the lung or by adenocarcinoma of the kidney. In about 10% of hyperparathyroidism, hyperplasia or tumors of the parathyroid glands occur due to familial disorders known as multiple endocrine neoplasia (MEN). MEN syndromes consist of three subtypes (I, IIA, IIB) and are... 

Calcium and phosphorus balance is mediated through the complex interplay of hormones and their effects on bone, the Gi tract, kidney, and parathyroid gland. What begins as relatively minor imbalances in phosphorus and calcium homeostasis leads to secondary hyperparathyroidism (sHPT) in the short term and ultimately renal osteodystrophy (ROD) if these metabolic abnormalities are not corrected. 

Hyperparathyroidism results from oversecretion of PTH. This condition leads to excessive bone turnover and demineralization and must be treated by removal of the parathyroid gland. The disorder is classified into primary, secondary, and tertiary hyperparathyroidism. Sporadic primary hyperparathyroidism is the third most common endocrine disorder, after diabetes and hyperthyroidism. It is most common in females older than 55 years of age and the leading cause is a single adenoma, which secretes the hormone constitu-tively, without regulation. Symptoms can include osteopenia and bone fractures, renal stones resulting from hypercalciuria, peptic ulcer disease, and pancreatitis. In milder cases, patients are asymptomatic or suffer only muscle weakness, fatigue, and/or depression. 

Secondary hyperparathyroidism arises from chronic hypocalcemia. This condition can result from renal failure leading to poor reabsorption of calcium from the urinary filtrate. It can also arise from poor nutrition or malabsorption of vitamin D by the intestine. In response, parathyroid glands increase their secretion of PTH. This condition also leads to decalcification of bone. Tertiary hyperparathyroidism is often seen after renal transplantation. In these patients, the parathyroid gland secretes the hormone independently of blood calcium levels. 

Studies of heritable tumor syndromes have provided considerable insight into the molecular basis of the corresponding sporadic tumors. Mutations of the HRPT2 gene are responsible for the development of the hyperparathyroidism-jaw tumor (HPT-JT) syndrome, which is inherited as an autosomal dominant trait. The commonest manifestations of this syndrome include primary hyperparathyroidism, fibro-osseous lesions of the mandible and maxilla, and a variety of renal lesions. In this syndrome, hyperparathyroidism occurs as a result of neoplasms of one or more parathyroid glands, which... 

It is g erally assumed that it is the concentration of ionic calcium in the extracellular fluid which the parathyroid glands control by this action on the skeleton and that the variations in total plasma calcium are strictly proportional. However, Freeman and Breen (Fll) have shown that parathyroidectomy is followed by a rise in the proportion of protein-boimd calcium and that this can be reduced by injection of the hormone. This accords with the observations of Lloyd and Rose in hyperparathyroidism (L6 see Section 4.2) and with the clinical observation that hypo-parathyroid patients may develop tetany at surprisingly high levels of total plasma calcium. The effects of Ae hormone on add-base balance may be concerned in this phenomenon since acidemia reduces the proportion of protein-bound calcium. 

Very occasionally, patients are seen in whom hypercalcemia is apparently due to secondary hyperparathyroidism. This is in a sense a contradiction in terms, since the essence of secondary hyperparathyroidism is the continuous stimulation of the parathyroid glands by a reduced ionic calcium concentration. However, at least two such cases with steatorrhea have now been described (D4, El), and in each case a parathyroid adenoma was discovered. The implication is that parathyroid stimulation can in certain circumstances go on to adenoma formation this also occurs occasionally in prolonged renal failure (G5). 

Calcimimetics mimic the action of calcium via the CaSR to inhibit PTH secretion by the parathyroid glands. Because of this enhanced sensitivity, they decrease PTH secretion for any given level of Ca. The calcimimetic cinacalcet (sensipar) is FDA-approved for the treatment of secondary hyperparathyroidism due to chronic renal disease and for patients with hypercalcemia associated with parathyroid carcinoma (Figure 61-9). In clinical trials, cinacalcet also effectively reduced PTH levels in patients with primary hyperparathyroidism and normalized serum calcium without altering bone mineral density for up to 2 years. 

It is obvious that a variety of disorders would result from a disturbance of the vitamin D endocrine system. Fat malabsorption would result in a deficiency of vitamin D giving rise ultimately to osteomalacia or rickets or secondary hyperparathyroidism. A hepatic disorder such as severe cirrhosis, or biliary atresia, may result in malabsorption of vitamin D and defective vitamin D-25-hydroxylation. Dilantin and phenobarbital cause low plasma 25-OH-D levels resulting in rickets and osteomala-cia246) Qf parathyroid glands would cause a severe hypocalcemia and tetany. 

The parathyroid glands secrete parathyroid hormone (PTH) that regulate calcium levels in the blood. A decrease in serum calcium stimulates the release of PTH. A decrease of PTH is called hypoparathyroidism and an increase in PTH is hyperparathyroidism. 

Hyperparathyroidism is caused by malignancies of the parathyroid glands or ectopic PTH hormone secretion from lung cancer, hyperthyroidism, or prolonged immobility during which calcium is lost from bone. 

In the hyperparathyroid state, the parathyroid gland does not become autonomous, although the regulation of PTH secretion by calcium is altered. Murray and co-workers (18) demonstrated that modulation of serum calcium levels in IHPT patients by EDTA or calcium infusion still resulted in the appropriate changes in PTH secretion. In addition, studies with normal and adenomatous parathyroid cells in culture have shown that IHPT may cause changes in the calcium inhibitory set point as well as an inability for calcium to completely suppress PTH secretion in spite of reduced PTH mRNA levels (3,19). 

In chronic renal failure treated by renal transplantation, hyperparathyroidism may persist, as discussed above. In most cases, the parathyroid glands involute to normal within 3 years (11,59,M,, 66). However, since severe or prolonged hypercalcemia impairs renal function and may cause permanent renal graft injury, subtotal parathyroidectomy must be considered for patients with persistent hypercalcemia or acute hypercalcemic crisis. 

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