Hyperparathyroidism hypercalcemia caused

Hypercalcemia causes central nervous system depression, including coma, and is potentially lethal. Its major causes (other than thiazide therapy) are hyperparathyroidism and cancer with or without bone metastases. Less common causes are hypervitaminosis D, sarcoidosis, thyrotoxicosis, milk-alkali syndrome, adrenal insufficiency, and immobilization. With the possible exception of hypervitaminosis D, these latter disorders seldom require emergency lowering of serum calcium. A number of approaches are used to manage the hypercalcemic crisis. 

Alterations in systemic calcium-to-phosphorus ratios are another known cause of band keratopathy. This includes hypercalcemia caused by conditions such as hyperparathyroidism, sarcoidosis, and vitamin D intoxication, as well as the elevated serum phosphorus commonly foimd with kidney feilure. Gout can also cause band keratopathy. 

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... 

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

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... 

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. 

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. 

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... 

Blum M, Kirsten M, Worth MH Jr. Reversible hypertension. Caused by the hypercalcemia of hyperparathyroidism, vitamin D toxicity, and calcium infusion. JAMA 1977 237(3) 262-3. 

Hypercalcemia is commonly encountered in clinical prac-results when the flux of calcium into the extracellular fluid compartment from the skeleton, intestine, or Iddney is greater than the efflux. For example, when excessive resorption of bone mineral occurs in malignancy, hy-percalciuria develops. When the capacity of the kidney to excrete filtered calcium is exceeded, hypercalcemia develops. Hypercalcemia can be caused by increased intestinal absorption (vitamin D intoxication), increased renal retention (thiazide diuretics), increased skeletal resorption (immobilization), or a combination of mechanisms (primary hyperparathyroidism). 

Common and many of the uncommon etiologies of hypercalcemia are listed in Box 49-2. Primary hyperparathyroidism is the most common cause in outpatients, whereas mahgnancy is the most common cause in hospitalized patients. Together, these two disorders account for 90% to 95% of all cases of hypercalcemia. 

Hypercalcemia occurs in 10% to 20% of individuals with cancer. Tumors most commonly cause hypercalcemia by producing PTHrP, which is secreted into the circulation and stimulates bone resorptions and/or by invasion of the bone by metastatic tumor, which produces local factors that stimulate bone resorption. PTHrP binds to the PTH receptor and is the principal mediator of humoral hypercalcemia of malignancy (HHM). Cytokines such as lymphotoxin, interleukin-1, tumor necrosis factor, and PTHrP appear to be important mediators of hypercalcemia in multiple myeloma and other hematological malignancies. Some lymphomas associated with acquired immunodeficiency syndrome or HTLV [ infections cause hypercalcemia by producing 1,25(0H)2D. It is estimated that 5% of patients with hypercalcemic cancer have coexisting primary hyperparathyroidism. 

The common N-terminal explains the ability of PTHrP to interact with the PTH/PTHrP receptor, mimicking the biological actions of PTH in classic target tissues, including bone and kidney. Like PTH, PTHrP causes hypercalcemia and hypophosphatemia t and increases urinary cyclic AMP. However, when compared with patients with primary hyperparathyroidism, patients with PTHrP-induced hypercalcemia have lower concentrations of l,25(OH)2D and more typically have metabolic alkalosis (instead of hyperchloremic metabolic acidosis), reduced distal tubular calcium reabsorption, and reduced and uncoupled bone formation. 

Parathyroid hormone (PTH) Primary hyperparathyroidism causes hypercalcemia, hypophosphatemia, and increased urinary cAMP hypoparathyroidism causes hypocalcemia and hyperphosphatemia, often with soft-tissue calcification and tetany and convulsions. Binds to cell-surface receptors and activates adenylate cyclase increases bone mineralization and activity of renal lot-hydroxylase in kidney, reabsorption of Ca " " increases and reabsorption of phosphate decreases. 

Hypercalcemia (total serum calcium >10.5 mg/dL) may be induced by a multitude of causes (Table 49-5). The most common causes of hypercalcemia are cancer and primary hyperparathyroidism. The incidence of primary hyperparathyroidism is approximately 270 new cases per million persons per year. Hypercalcemia of cancer occurs in approximately 20% to 40% of cancer patients at some time during the course of their disease. Cancer-associated hypercalcemia is predominantly encountered in hospitalized patients, while primary hyperparathyroidism accounts for the vast majority of cases in the outpatient setting. ... 

In this condition the renal tubules are unresponsive to antidiuretic hormone and, as such, the subject has polyuria. The condition may be congenital or acquired. Acquired nephrogenic diabetes insipidus can result from several causes, such as chronic renal disease, potassium deficiency including primary aldosteronism, drugs such as lithium, systemic diseases such as multiple myeloma, and chronic hypercalcemias, including hyperparathyroidism. The damage to the renal tubules... 

The diagnosis of primary hyperparathyroidism should not be made until the following causes of hypercalcemia have been excluded. 

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