Hyperparathyroidism

Parathyroid hormone increases the release of calcium and phosphate from bone, increases calcium reabsorption by the kidney and increases renal production of 1,25-dihydroxyvitamin D-3 (calcitriol) which increases intestinal absorption of calcium. As well as increasing serum calcium, parathyroid hormone also causes phosphaturia, therefore reducing serum phosphate levels.

• Prevalence of primary hyperparathyroidism is approximately 4 cases in 100,000 persons.
• Primary hyperparathyroidism affects women twice as frequently as men.
• Prevalence increases with age, but can affect any age.
• Familial cases can occur, either as part of the multiple endocrine neoplasia syndromes (ie, type 1 or type 2a) or as familial hyperparathyroidism.

• Single parathyroid adenoma (85% of cases)
• Hyperplasia (14%)
• Carcinoma (less than 1%)

• Parathyroid glands become hyperplastic after long-term stimulation in response to chronic hypocalcaemia.
• Usually seen in renal disease and seen in virtually all patients with dialysis-dependent chronic renal failure.
• It can occur in any condition with chronic hypocalcaemia such as vitamin D deficiency or malabsorption.
• Treatment with calcitriol and calcium can either prevent or minimize secondary hyperparathyroidism. However total parathyroidectomy and autotransplantation is considered the treatment of choice.¹

• Occurs after prolonged secondary hyperparathyroidism.
• The glands become autonomous, producing excessive secretion of PTH (after the cause of hypocalcaemia has been corrected) and results in hypercalcaemia. This occurs in patients with chronic renal failure or after a renal transplant.
• Management is as for primary hyperparathyroidism and total parathyroidectomy with auto-transplantation or subtotal parathyroidectomy is indicated.

• Very rare
• Has been identified with several malignancies, e.g. ovarian cancer, lung cancer, intestinal leiomyosarcoma

Clinical features are due to:

• Excessive calcium resorption from bone causing osteopenia, presenting as bone pain and pathological fractures
• Excessive renal calcium excretion causing renal stones
• Hypercalcaemia:
  • Muscle weakness, fatigue
  • Nausea and vomiting; constipation; abdominal pain; peptic ulcer disease; pancreatitis
  • Polyuria, polydipsia, dehydration
  • Renal colic, haematuria, hypertension
  • Long-standing hypercalcaemia causes corneal calcification, which is usually asymptomatic
  • Neuropsychiatric manifestations are particularly common and may include depression and confusion.
  • Severe cases may lead to coma and death.

Other causes of hypercalcaemia, especially malignancy, but other causes include thyrotoxicosis, sarcoidosis, Paget's disease and Addison's disease.

Most cases are diagnosed by demonstrating persistent hypercalcaemia and elevated parathyroid hormone level.

• Total serum calcium, phosphate and albumin levels; ionized calcium levels if available.
• Renal function, electrolytes, amylase.
• Serum parathyroid hormone.
• 24 hour urinary calcium excretion: to differentiate from familial hypocalciuric hypercalcaemia in which there is a low 24 hour urine calcium excretion. May not be necessary if the diagnosis of primary hyperparathyroidism is not in doubt.
• X-rays: is occasionally helpful to determine end organ damage (but likely to be normal in early cases). Subperiosteal resorption (especially on hand x-ray); chest x-ray and skull x-ray (pepper-pot skull). Consider x-ray's of other joints (chondrocalcinosis, pseudogout).
• DEXA scan: osteoporosis is common.
• Imaging of renal tract: x-ray, ultrasound.
• If neck exploration has failed, ⁹⁹mTc-sestamibi scan, Thallium or Tc subtraction scanning, CT scan, ultrasound, and/or angiography with selective venous sampling may be required.

Multiple endocrine neoplasia type I and IIa.

• Definitive treatment involves surgery but surveillance may be justified in patients whose calcium levels are only mildly elevated and whose renal and bone status are close to normal.² Such patients may continue for long periods without deteriorating.
• Monitor plasma calcium, renal function, blood pressure, regular assessments of bone mineral density and renal ultrasound.
• Avoid dehydration (advise a high fluid intake) and also avoid thiazides; patients should have a moderate calcium intake.
• Treatment hypercalcaemia with appropriate drugs (see related article).
• Surgery: either by removal of an adenoma or carcinoma, or parathyroidectomy with auto-transplantation or subtotal parathyroidectomy for hyperplasia. Surgery is advocated because patients who are unaware of mild hyperparathyroidism may still have an increased prevalence of mild psychiatric symptoms, bone loss, and have increased risk of cardiovascular disease.