Causes of hypercalcemia are generally divided into two types; primary and secondary. Primary causes are excessive parathormone secretion, and secondary causes include disease processes that directly affect bone metabolism and calcium excretion. The most common cause of primary hyperparathyroidism (PHPT) is a solitary parathyroid adenoma, accounting for approximately 80% of cases. Multiple adenomas are found in 2% to 4% of cases. The second most common cause of PHPT (15%) is parathyroid hyperplasia of multiple (usually >4) parathyroid glands. The etiologies for these include a mix of congenital and familial diseases (MEN-I, MEN-IIA). Less than 1% of PHPT is caused by primary parathyroid malignancy (Silverberg and Bilezikian, 2006) (Box 35-12).
Primary hyperparathyroidism does not present with classic symptoms. Symptoms may be as nonspecific as generalized weakness in the proximal muscles, fatigue, headache, weight loss, and constipation or as profound as renal failure, hypovolemic shock, and death (usually in patients with malignancy, although sometimes previously undiag-nosed). Patients rarely present with signs and symptoms immediately suggesting hypercalcemia. PHPT is usually uncovered through routine nonspecific screening laboratory tests, during evaluation for nephrolithiasis, or occasionally in a patient with accelerated osteoporosis and pathologic fracture.
There is a classic "quadrad" of symptoms associated with hypercalcemia that, although seen in many disease processes, may be helpful in a patient with hypercalcemia, irrespective of etiology. The mnemonic taught to medical students is "bones, stones, moans, and abdominal groans," representing the four symptoms of the classic quadrad: bone pain, renal calculi, psychiatric disorder, and nausea and vomiting (Silverberg and Bilezikian, 2006).
The primary dysfunction in PHPT is an excess of circulating parathormone. However, with bony metastases, PTH levels will be appropriately suppressed in the presence of elevated serum calcium levels caused by osteolytic metastases. When the cause of hypercalcemia is malignancy, the patient usually has a history; an exception is unsuspected multiple myeloma, which may present with chronic low back pain and elevated serum calcium. Calcium levels in malignancy are typically higher (>14 mg/dL) than those found with parathyroid adenomas (<13 mg/dL), although this is not always the case (Table 35-10).
Thiazide diuretics, lithium, and calcium carbonate are common medications seen in primary care that, if not properly
Cholecalciferol (vitamin D3) Liver
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