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For further information, see CMDT Part 26-15: Hyperparathyroidism

Key Features

Essentials of Diagnosis

  • Often found incidentally by routine blood testing.

  • Renal calculi, polyuria, hypertension, constipation, fatigue, mental changes.

  • Bone pain; rarely, cystic lesions and pathologic fractures.

  • Elevated serum 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 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 5–10% 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: a familial autosomal dominant condition with parathyroid adenomas or carcinomas that are associated with tumors of the jaw and renal lesions

  • Familial isolated hyperparathyroidism: familial hyperparathyroidism without the characteristic extraparathyroid features of more complex hyperparathyroid syndromes


  • Most common cause of hypercalcemia, with a prevalence of 0.1 to 0.4% of the population

  • 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

  • Skeletal manifestations

    • Low bone density: most prominent at the distal third of the radius

    • Postmenopausal women are prone to asymptomatic vertebral fractures

    • Severe bone demineralization is uncommon in mild cases

    • Arthralgias and bone pain, particularly involving the legs, are more common than severe bone demineralization

    • Osteitis fibrosa cystica

      • Seen in severe chronic hyperparathyroidism

      • Calcified bone matrix is replaced with fibrous tissue forming cystic brown tumors of bone that can be palpable in the jaw

      • The skeleton become weaker with bowing of the long bones and pathologic fractures

  • Hypercalcemia manifestations

    • Level of serum calcium or PTH may not reliably predict severity of symptoms

    • Mild cases may be asymptomatic or manifest significant symptoms, particularly

      • Depression

      • Constipation

      • Bone and joint pain

    • Neuromuscular manifestations

      • Paresthesias

      • Muscle cramps and weakness

      • Diminished deep tendon reflexes

    • Neuropsychiatric manifestations

      • Malaise, fatigue, insomnia

      • Headache

      • Irritability, depression

      • Cognitive impairment can vary from intellectual weariness to more severe disorientation, psychosis, or stupor

    • Cardiovascular manifestations

      • Hypertension

      • Palpitations

      • Prolonged P-R interval, shortened Q-T interval

      • Bradyarrhythmias, heart block, asystole

      • Sensitivity to digitalis

    • Renal manifestations

      • Polyuria and polydipsia

      • Calcium-containing renal calculi

    • Gastrointestinal symptoms


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