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helpful clinically The serum phosphate is often low (< 25 mg/dL) The urine calcium excretion may be high or normal (averaging 250 mg/g creatinine) but it is usually low for the degree of hypercalcemia There is an excessive loss of phosphate in the urine in the presence of hypophosphatemia (25% of cases) to low-normal serum phosphate (In secondary hyperparathyroidism due to renal failure, the serum phosphate is high) The alkaline phosphatase is elevated only if bone disease is present The plasma chloride and uric acid levels may be elevated Vitamin D deficiency is common in patients with hyperparathyroidism, and it is prudent to screen for vitamin D deficiency with a serum 25-OH vitamin D determination Low serum 25-OH vitamin D levels (< 20 mcg/L; < 50 nmol/L) can aggravate hyperparathyroidism and its bone manifestations; vitamin D replacement may be helpful in treating patients with hyperparathyroidism (See below) Elevated serum levels of PTH confirm the diagnosis of hyperparathyroidism The best immunoassay recognizes the intact molecule at two different sites the amino terminal and the carboxyl terminal ends with two different antibodies This assay, known as IRMA, is specific and sensitive, making it easier to distinguish primary hyperparathyroidism from other causes of hypercalcemia All patients with apparent hyperparathyroidism should be screened for familial benign hypocalciuric hypercalcemia with a 24-hour urine for calcium and creatinine Patients should discontinue thiazide diuretics prior to this test Calcium excretion of < 50 mg/24 hours (or < 5 mg/dL on a random urine) is not typical for primary hyperparathyroidism and indicates possible familial benign hypocalciuric hypercalcemia (See below)

Parathyroid carcinoma is a rare cause of hyperparathyroidism but is more common in patients with severe hypercalcemia About 50% of parathyroid carcinomas are palpable

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Hypercalcemia is typically discovered accidentally by routine chemistry panels Most patients are asymptomatic Parathyroid adenomas are usually so small and deeply located in the neck that they are almost never palpable; when a mass is palpated, it usually turns out to be an incidental thyroid nodule Although many patients with mild hypercalcemia offer no complaints, symptomatic patients are said to have problems with bones, stones, abdominal groans, psychic moans, with fatigue overtones The manifestations are categorized as skeletal, urinary tract, and those associated with hypercalcemia 1 Skeletal manifestations Hyperparathyroidism causes a loss of cortical bone and a gain of trabecular bone Significant bone demineralization is uncommon in mild hyperparathyroidism, but osteitis fibrosa cystica may present as pathologic fractures or as brown tumors or cysts of the jaw More commonly, patients have bone pain and arthralgias 2 Urinary tract manifestations Polyuria and polydipsia may be present and are due to hypercalcemia-induced nephrogenic diabetes insipidus Calcium-containing kidney stones are reported in about 18% of those with newly discovered primary hyperparathyroidism Nephrocalcinosis and renal failure can occur 3 Manifestations of hypercalcemia Mild hypercalcemia is often asymptomatic In more severe cases, thirst, anorexia, nausea, and vomiting are present Constipation, fatigue, anemia, weight loss, and hypertension are commonly found Pancreatitis occurs in 3% Some patients have neuromuscular disorders such as muscle weakness, easy fatigability, or paresthesias Depression, intellectual weariness, and increased sleep requirement are common Pruritus and psychosis or even coma may accompany severe hypercalcemia Calcium may precipitate in the corneas ( band keratopathy ) or soft tissue (calciphylaxis) 4 Hyperparathyroidism during pregnancy About 67% of women with primary hyperparathyroidism during pregnancy experience complications such as nephrolithiasis, hyperemesis, pancreatitis, muscle weakness, cognitive changes, and hypercalcemic crisis About 80% of fetuses experience complications of maternal hyperparathyroidism, including fetal demise, preterm delivery, low birth weight, postpartum neonatal tetany, and permanent hypoparathyroidism.

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