Hyperparathyroidism

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 adenomas (5% malignant), benign jaw tumors and renal cysts

Demographics

• 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 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 ...