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Key Features

Essentials of Diagnosis

  • Frequently detected incidentally by routine blood testing

  • Kidney stones, polyuria, hypertension, constipation, mental changes

  • Bone pain

  • Parathyroid hormone (PTH), serum and urine calcium, and urine phosphate elevated

  • Serum phosphate low to normal

  • Alkaline phosphatase normal to elevated

General Considerations

  • Primary hyperparathyroidism

    • PTH hypersecretion usually due to parathyroid adenoma, less commonly, to hyperplasia or carcinoma (rare)

    • If age < 30 years, higher incidence of multiglandular disease (36%) and parathyroid carcinoma (5%) responsible for hyperparathyroidism

  • Secondary or tertiary hyperparathyroidism

    • Chronic kidney disease (CKD): hyperphosphatemia and diminished renal vitamin D production decrease serum ionized calcium, thus stimulating the parathyroids

    • Renal osteodystrophy: bone disease of secondary hyperparathyroidism and CKD

  • Multiple endocrine neoplasia (MEN)

    • Hyperparathyroidism is familial in about 10% of cases; parathyroid hyperplasia may arise in MEN types 1, 2A, and 2B

    • In MEN 1, multiglandular hyperparathyroidism is usually the initial manifestation and ultimately occurs in over 90% of affected individuals

    • Hyperparathyroidism in MEN 2A is less frequent than in MEN 1 and is usually milder

  • Hyperparathyroidism-jaw tumor syndrome is autosomal dominant and associated with recurrent parathyroid ademonas (5% malignant), benign jaw tumors and renal cysts

Demographics

  • Most common cause of hypercalcemia, with a prevalence of 1000–4000 cases per 1 million persons

  • Occurs at all ages but most commonly in the seventh decade and in women (74%)

  • Before age 45, the prevalence is similar in men and women

  • More prevalent in blacks, followed by whites, then other races

Clinical Findings

Symptoms and Signs

  • Frequently asymptomatic

  • Symptoms include problems with "bones, stones, abdominal groans, psychic moans, fatigue overtones"

  • Bone pain and arthralgias are common

  • Severe, chronic hyperparathyroidism can cause diffuse demineralization, pathologic fractures, and cystic bone lesions throughout the skeleton, a condition known as osteitis fibrosa cystica

  • Postmenopausal women are prone to asymptomatic vertebral fractures

  • Mild hypercalcemia

    • May be asymptomatic

    • Some patients can have significant symptoms, particularly depression, constipation, and bone and joint pain

  • Hypercalcemia in patients with hyperparathyroidism usually causes a variety of manifestations whose severity is not entirely predictable by the level of serum calcium or PTH

    • Paresthesias, muscular weakness, and diminished deep tendon reflexes

    • Malaise, fatigue, intellectual weariness, depression, increased sleep requirement, progressing to cognitive impairment, disorientation, psychosis, or stupor

    • Hypertension; ECG findings of prolonged P-R interval, shortened Q-T interval, sensitivity to arrhythmic effects of digitalis, bradyarrhythmias, heart block, asystole

    • Polyuria and polydipsia, caused by hypercalcemia-induced nephrogenic diabetes insipidus

    • Anorexia, nausea, vomiting, abdominal pain, weight loss, constipation, and obstipation; pancreatitis (in 3%)

    • Pruritus may be present

    • Calcium may precipitate in the corneas ("band keratopathy"), in extravascular tissues, and small arteries, causing small vessel thrombosis and skin necrosis (calciphylaxis)

Differential Diagnosis

  • Artefactual hypercalcemia

  • Hypercalcemia of malignancy

  • Plasma cell myeloma (formerly multiple myeloma)

  • Vitamin D intoxication

  • Granulomatous diseases (sarcoidosis, tuberculosis)

  • Familial benign hypocalciuric hypercalcemia

  • Immobilization

  • Hyperthyroidism

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