Hypercalcemia causing

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

The delicate balance maintained by these factors is altered in patients with cancer by two principal mechanisms tumor production of humoral factors that alter calcium metabolism (humoral hypercalcemia) and local osteolytic activity from bone metastases.27 Humoral hypercalcemia causes around 80% of all hypercalcemia cases and is mediated primarily by systemic secretion of parathyroid hormone-related protein... 

Hypercalcemia causes central nervous system depression, including coma, and is potentially lethal. Its major causes... 

The authors suggested that this was the first report of exogenous calcitonin causing hypercalcemia. There were several unknowns in this case, including the calcium concentration before treatment and the concentration of PTHrp, which would have helped to determine the cause of the hypercalcemia. Calcitonin is usually associated with a reduction in calcium concentration rather than a rise. The authors postulated that calcitonin could alter PTHrp concentrations, with different effects depending on cell type. They also provided evidence of hypercalcemia caused by calcitonin in non-human models (14). 

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. 

Rickets was more or less eradicated as a nutritional deficiency disease dur-ingthe 1950s, as aresultofwidespread enrichment ofinfantfoods with vitamin D. The level of supplementation was reduced as a result of the development of hypercalcemia caused by vitamin D intoxication (Section 3.6.1) in a small number of especially susceptible infants. As a result, rickets has reemerged, especially in northern cities in temperate countries. 

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. 

Renal effects of hypercalcemia include reduced glomerular filtration rate (GFR), polyuria, nephrocalcinosis, and renal stone disease. Hypercalcemia causes renal vasoconstriction which may contribute to decreased GFR. The hypercalcemia-induced polyuria results from 1) an impairment of active transport of NaCl in the loop of Henle, distal tubule and collecting duct and 2) an inhibition of vasopressin-facilitated absorption of water in the distal nephron. As a direct result of the polyuria, many side effects including polydipsia, thirst, nocturia and dehydration are common. Precipitation of calcium salts within the kidney leads to chronic inflammatory reactions (nephrocalcinosis), fibrosis, renal impairment, nephrolithiasis and urolithiasis. Further renal damage may occur indirectly from hypertension. 

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... 

Sodium and water retention may also occur with androgen or anabolic steroid administration, causing die patient to become edematous, hi addition, otiier electrolyte imbalances, such as hypercalcemia, may occur. The nurse monitors the patient for fluid and electrolyte disturbances (see Chap. 58 for signs and symptoms of electrolyte disturbance). 

Hematologic malignancies such as multiple myeloma and, rarely, lymphomas are other causes of hypercalcemia. 

PTHrP). This protein mimics the action of endogenous parathyroid hormone on bones. Local osteolytic activity causes 20% to 30% of hypercalcemia cases, although local osteolytic activity also may have a humoral component. Local production of various factors directly stimulates osteoclastic... 

Although not as common as hypercalcemia, tumor lysis syndrome may cause significant morbidity and mortality if adequate prophylaxis and treatment are not instituted. Tumor lysis syndrome is the result of rapid destruction of malignant cells with subsequent release of intracellular contents into the circulation. 

I 12. The answer is b. (Hardman, pp 1264-1265J Dactinomycin s major toxicities include stomatitis, alopecia, and bone marrow depression. Bleomycin s toxicities include edema of the hands, alopecia, and stomatitis. Mitomycin causes marked bone marrow depression, renal toxicity, and interstitial pneumonitis. Plicamycin causes thrombocytopenia, leukopenia, liver toxicity, and hypocalcemia. The latter may be of use in the treatment of hypercalcemia. Doxorubicin causes cardiotoxicity, as well as alopecia and bone marrow depression. The cardiotoxicity has been linked to a lipid peroxidation within cardiac cells. 

The answer is d. (Kntzung, pp 254—256J Thiazide diuretics raise serum Ca, possibly through a direct effect on Ca reabsorption in the distal tubule While rarely caused by the diuretic alone, hypercalcemia can occur when the patient has a history of carcinoma. 

Vitamin D and its analogs inhibit keratinocyte differentiation and proliferation and have antiinflammatory effects by reducing IL-8, IL-2, and other cytokines. Use of vitamin D itself is limited by its propensity to cause hypercalcemia. 

Hypercalcemia has been associated with causing depression, stupor, and coma. 

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... 

Ora/ - May cause constipation and headache. Mild hypercalcemia (Ca" " greater than 10.5 mg/dL) may be asymptomatic or manifest itself as Anorexia, nausea, and vomiting. More severe hypercalcemia (Ca 12 mg/dL) is associated with confusion. 

Breast cancer Androgen therapy may cause hypercalcemia by stimulating osteolysis. 

Hypercalcemia from any cause predisposes the patient to digitalis toxicity. Calcium, particularly when administered rapidly by the IV route, may produce serious arrhythmias in digitalized patients. On the other hand, hypocalcemia can nullify the effects of digoxin in humans thus, digoxin may be ineffective until serum calcium is restored to normal. 

About 15% of orally administered Ca + is absorbed which can cause problems in patients with uremia. NaHCOs and CaC03 can then lead to hypercalcemia and further deteriorate renal function. 

Calcipotriol is a vitamin D3 derivative which is used as a topical agent in the treatment of psoriasis. Although not completely elucidated its mechanism of action seems to be based on inhibition of the proliferation and stimulation of the differentiation of epidermal keratinocytes. Adverse effects include irritation of the skin but also urticarial reactions. Calcipotriol has 100 fold less vitamin D activity as its active vitamin D3 metabolite calcitriol. However, calcipotriol in overdose can cause symptoms of hypercalcemia. 

A variety of adverse effects have been reported following the use of antacids. If sodium bicarbonate is absorbed, it can cause systemic alkalization and sodium overload. Calcium carbonate may induce hypercalcemia and a rebound increase in gastric secretion secondary to the elevation in circulating calcium levels. Magnesium hydroxide may produce osmotic diarrhea, and the excessive absorption of Mg++ in patients with renal failure may result in central nervous system toxicity. Aluminum hydroxide is associated with constipation serum phosphate levels also may become depressed because of phosphate binding within the gut. The use of antacids in general may interfere with the absorption of a number of antibiotics and other medications. 

Calcipotriene (Dovonex), a synthetic vitamin D3 derivative, is indicated for the treatment of moderate plaque psoriasis. Its mechanism of action is unknown, although it competes for calcitriol receptors on keratinocytes and normalizes differentiation. It also has a variety of immunomodulatory effects in the skin. Although the drug can cause local irritation, the most serious toxicities are hypercalciuria and hypercalcemia, which are usually reversible. 

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. 

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