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For further information, see CMDT Part 26-16: Hyperparathyroidism

Key Features

Essentials of Diagnosis

  • Frequently detected incidentally by routine blood testing

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

  • Bone pain

  • Elevated serum parathyroid hormone (PTH), serum and urine calcium, and urine phosphate

  • Serum phosphate low to normal

  • Alkaline phosphatase normal to elevated

General Considerations

  • Primary hyperparathyroidism

    • PTH hypersecretion usually caused by a single parathyroid adenoma (80%), less commonly to hyperplasia or adenomas of two or more parathyroid glands (20%), or carcinoma (rare)

    • When hyperparathyroidism presents < 30 years, higher incidence of multiglandular disease (36%) and parathyroid carcinoma (5%)

  • Parathyroid carcinoma

    • Accounts for < 1% of hyperparathyroidism

    • Occurs in about 15% of patients with hyperparathyroidism jaw-tumor syndrome and is also more common in patients with familial hyperparathyroidism or multiple endocrine neoplasia (MEN)

  • Secondary or tertiary hyperparathyroidism

    • Chronic kidney disease (CKD): hyperphosphatemia and decreased renal production of vitamin D frequently result in decreased ionized calcium

      • Parathyroid glands are stimulated by the hypocalcemia (secondary hyperparathyroidism)

      • Over time the parathyroid glands may become enlarged and autonomous (tertiary hyperparathyroidism)

    • Renal osteodystrophy: bone disease of secondary hyperparathyroidism and CKD

  • MEN

    • Hyperparathyroidism is familial in about 5–10% of cases; parathyroid hyperplasia may arise in MEN types 1, 2 (2A), and 4

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

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

    • Hyperparathyroidism-jaw tumor syndrome is a familial autosomal dominant condition with parathyroid adenomas or carcinomas associated with tumors of the jaw and renal lesions


  • Most common cause of hypercalcemia, with an estimated prevalence of 0.89% of the population in the United States

  • 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 Black adults than in other individuals

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

    • However, symptom severity is not entirely predicted by the level of serum calcium or PTH, so even mild hypercalcemia can cause significant symptoms, particularly depression, constipation, and bone and joint pain

  • Hypercalcemic manifestations include

    • Neuromuscular: paresthesias, muscle cramps and weakness, and diminished deep tendon reflexes

    • Neuropsychiatric: malaise, headache, fatigue, insomnia, irritability, depression, intellectual weariness, cognitive impairment, disorientation, psychosis, or stupor

    • Cardiovascular: hypertension; palpitations; ECG findings of prolonged P-R interval, shortened Q-T interval, sensitivity to arrhythmic effects of digitalis, bradyarrhythmias, heart ...

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