Hyperparathyroidism hypercalcemia

Figure 49-15 Midregion (A) and intact (B) PTH in normal subjects and patients with primary hyperparathyroidism, hypercalcemia associated with malignancy, and hypoparathyroidism. (From Endres DB, Viifanueva R, Sharp CF jr. Singer FR. /Vleasurement of parathyroid hormone. Endocrinol Metab Clin North Am 1989 18 611-29.)...

The ultimate therapeutic goal of managing hyperparathyroid hypercalcemia is returning blood PTH, calcium and phosphate levels to their normal range. In IPTH, when active bone, renal or 61 symptoms are present, surgery is the most effective treatment modality when the offending parathyroid adenoma can be identified. In MENl or hyperplasia, controversy exists as to whether total parathyroidectomy... 

PTH antagonists probably would not be effective in managing 2HPT prior to renal transplantation, but may be quite beneficial for the transient and subacute hyperparathyroid hypercalcemia present after transplantation. The use of PTH antagonists after renal transplantation may reduce the risk of hypercalcemia-associated graft injury. 

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... 

Hepatic encephalopathy Hyperbilirubinemia Hypocalcemia Hypercalcemia Hyperparathyroidism Hypoparathyroidism Thiamine deficiency (Wernicke s) encephalopathy Diabetic ketoacidosis Nonketotic hyperosmolar coma Phosphate depletion Hypoglycemia Hypoxemia Hypercapnia... 

Cancer and hyperparathyroidism are the most common causes of hypercalcemia. The primary mechanisms are increased bone resorption, increased GI absorption, and decreased renal elimination. 

Chronic hypercalcemia (i.e., hyperparathyroidism) is associated with metastatic calcification, nephrolithiasis, and chronic renal insufficiency. 

Pidasheva, S., D Souza-Li, L., Canaff, L., Cole, D. E. C., and Hendy, G. N. (2004) CASRdb Calcium-sensing receptor locus-specific database for mutations causing familial (benign) hypocalciuiic hypercalcemia, neonatal severe hyperparathyroidism, and autosomal dominant... 

Hypercalcemia is a common clinical condition that can accompany a variety of other medical conditions, such as sarcoidosis, vitamin D toxicity, hyperparathyroidism, and malignancy. When calcium levels are exceptionally high, adjunctive measures for the control of plasma calcium levels are necessary, as this is a medical emergency. Various modalities in combination are used to treat this condition intravenous hydration with normal saline and the use of loop diuretics (e.g., furosemide) to induce calcium diuresis are the most important supportive measures. 

A. Although all of the conditions can present as an asymptomatic nodule in the thyroid, the marked hypercalcemia in this patient makes hyperparathyroidism the probable diagnosis. Carcinomas of the thyroid are common, and outcomes are improved with early diagnosis. Medullary carcinoma and hyperparathyroidism caused by hyperplasia may be inherited and are associated with the multiple endocrine neoplasia syndromes. 

Thiazides inhibit NaCI reabsorption from the luminal side of epithelial cells in the DCT by blocking the Na+/Q transporter (NCC). In contrast to the situation in the TAL, in which loop diuretics inhibit Ca2+ reabsorption, thiazides actually enhance Ca2+ reabsorption. This enhancement has been postulated to result from effects in both the proximal and distal convoluted tubules. In the proximal tubule, thiazide-induced volume depletion leads to enhanced Na+ and passive Ca2+ reabsorption. In the DCT, lowering of intracellular Na+ by thiazide-induced blockade of Na+ entry enhances Na+/Ca2+ exchange in the basolateral membrane (Figure 15-4), and increases overall reabsorption of Ca2+. Although thiazides rarely cause hypercalcemia as the result of this enhanced reabsorption, they can unmask hypercalcemia due to other causes (eg, hyperparathyroidism, carcinoma, sarcoidosis). Thiazides are useful in the treatment of kidney stones caused by hypercalciuria. 

This rather common disease, if associated with symptoms and significant hypercalcemia, is best treated surgically. Oral phosphate and bisphosphonates have been tried but cannot be recommended. Asymptomatic patients with mild disease often do not get worse and may be left untreated. The calcimimetic agent cinacalcet, discussed previously, has been approved for secondary hyperparathyroidism and is in clinical trials for the treatment of primary hyperparathyroidism. If such drugs prove efficacious, medical management of this disease will need to be reconsidered. 

In contrast to the hypocalcemia that is more often associated with chronic kidney disease, some patients may become hypercalcemic from two other possible causes (in addition to overzealous treatment with calcium). The most common cause of hypercalcemia is the development of severe secondary (sometimes referred to as tertiary) hyperparathyroidism. In such cases, the PTH level in blood is very high. Serum alkaline phosphatase levels also tend to be high. Treatment often requires parathyroidectomy. 

Two analogs of calcitriol—doxercalciferol and paricalcitol—are approved for the treatment of secondary hyperparathyroidism of chronic kidney disease. Their principal advantage is that they are less likely than calcitriol to induce hypercalcemia for any given reduction in PTH. Their greatest impact is in patients in whom the use of calcitriol may... 

Therapy with hydrochlorothiazide, up to 50 mg twice daily, or chlorthalidone, 50-100 mg daily, is recommended. Loop diuretics such as furosemide and ethacrynic acid should not be used because they increase urinary calcium excretion. The major toxicity of thiazide diuretics, besides hypokalemia, hypomagnesemia, and hyperglycemia, is hypercalcemia. This is seldom more than a biochemical observation unless the patient has a disease such as hyperparathyroidism in which bone turnover is accelerated. Accordingly, one should screen patients for such disorders before starting thiazide therapy and monitor serum and urine calcium when therapy has begun. 

The incidence of acute pancreatitis as a suspected complication of finasteride treatment has been examined in a case-control study in a Danish regional population of 490 000 over 7 years. Of 302 men aged 60 and older with incident acute pancreatitis, three had been exposed to finasteride of 2994 controls 37 had been exposed to finasteride. After adjustment for alcohol-related diseases, gallstone disease, hyperlipidemia, hypercalcemia, and hyperparathyroidism, the authors found no evidence of an increased risk of acute pancreatitis in users of finasteride (48). 

In the last case the authors concluded that the hypercalcemia was due to long-term lithium treatment and cited studies showing that hyperparathyroidism occurs in 5—40% of patients taking long-term lithium, compared with a population frequency of less than 4%. The patient s chief complaint included nausea when he was exposed to food and water, and he therefore refused food and water for 2-3 days before admission. He also had acute renal insufficiency, which was thought to be due to... 

NSHPT in most cases presents within the first six months of life. Affected infants have severe, symptomatic, PTH-dependent hypercalcemia, along with the bony changes of severe hyperparathyroidism. Infants with NSHPT can exhibit polyuria, dehydration, hypotonia, and failure to thrive (Brown et al, 1997 Eftekhari and Yousefzadeh, 1982 Grantmyre, 1973 Heath, 1989a Marx etal, 1985). A prominent feature of the disease is the associated hyperparathyroid bone disease, which can be associated with multiple fractures. Rib fractures can in some cases produce a... 

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