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

Demographics

• 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

    ...