Hyperparathyroidism

• • Cinacalcet: reduces PTH secretion and therefore serum calcium. It is used in patients with primary hyperparathyroidism in whom surgery would not be appropriate, has been declined or has been unsuccessful
• • Bisphosphonates: do not affect serum calcium but do preserve bone density and therefore reduce fracture risk
• Hyperparathyroidism occurs when there is an excess of parathyroid hormone (PTH) being secreted from the parathyroid glands in the neck
• hyperparathyroidism is the most common cause of hypercalcaemia, followed by malignancy
• The parathyroid glands sit in the neck, on the posterior surface of the lateral lobes of the thyroid. Most adults have four, which are commonly described in two pairs (the superior and inferior parathyroid glands
• Normally, the role of the parathyroid glands is to regulate serum calcium and phosphate levels via the secretion of PTH.

  The chief cells of the parathyroid glands are responsible for the synthesis and secretion of PTH, as well as the sensing of changes in serum calcium levels via the calcium-sensing receptor
• In response to hypocalcaemia, secretion of PTH is increased. PTH then raises serum calcium levels by acting on various organs throughout the body:

  • Bone: promotes bone resorption and thus release of calcium into the blood
  • Kidneys: stimulates calcium reabsorption in the distal convoluted tubule. It also inhibits phosphate reabsorption, decreasing serum phosphate
  • Small intestine: indirectly increases absorption of calcium by stimulating 1α-hydroxylase, the enzyme that activates vitamin D in the kidneys
• Primary hyperparathyroidism is the most common of the three types and is driven by a pathology of the glands. Here, one or more of the parathyroid glands is over-secreting PTH despite normal serum calcium, which over time leads to hypercalcaemia

  This most commonly occurs due to an adenoma but can be hyperplasia or carcinoma
• Secondary hyperparathyroidism is due to a disorder in calcium-phosphate-bone metabolism.

  In response to low serum calcium levels as a result of another condition, commonly chronic kidney disease or vitamin D deficiency, the parathyroid glands secrete PTH. This may or may not normalise serum calcium levels, depending on the underlying condition
• Tertiary hyperparathyroidism may occur following a prolonged period of secondary hyperparathyroidism. In response to chronic PTH secretion, the glands may become hyperplastic and begin to secrete PTH autonomously. This can lead to hypercalcaemia as in primary hyperparathyroidism, especially if the underlying condition impairing calcium metabolism is treated.
• Malignancy is the 2nd most common cause of hypercalcaemia. It is PTH independent meaning PTH will be low or low-normal
• Symptoms of hyperparathyroidism:

  • Stones - renal stones
  • Bones - bone pain
  • Moans - abdominal pain and constipation
  • Groans - lethargy and depression
  • Polyuria and polydipsia
  • On examination - abdominal and bone tenderness
• Laboratory investigations:

  • Corrected calcium: should be measured in patients with suspected primary hyperparathyroidism
  • Serum PTH: measure serum PTH with a paired corrected calcium. This is helpful in suggesting a cause for hypercalcaemia. Primary hyperparathyroidism will show raised or inappropriately normal PTH. A low PTH suggests a PTH-independent cause of hypercalcaemia such as malignancy.
  • Vitamin D: if low, offer supplements
  • Urea & electrolytes: advanced chronic kidney disease is a common cause of secondary hyperparathyroidism
• Other relevant specialist laboratory investigations may include a 24-hour urinary calcium excretion test or calcium: creatinine clearance ratio to exclude familial hypocalciuric hypercalcaemia 
• Relevant imaging investigations include:

  • DEXA scan: to assess for osteoporosis
  • Ultrasound of renal tract: looking for renal stones 
  • Ultrasound of the neck: pre-operative planning and to identify adenomas (first line)
• Acute, severe hypercalcaemia of any cause requires urgent management in secondary care including the administration of intravenous fluids
• Mild primary hyperparathyroidism may not require any management other than monitoring symptoms and complications. This includes annual tests for corrected calcium and creatinine or eGFR, as well as assessing cardiovascular and fracture risk.
• Medical management includes bisphosphonates and cinacalcet

  Secondary hyperparathyroidism should be managed by treating the underlying cause
• Curative therapy requires a parathyroidectomy to remove the parathyroid gland

  • Symptoms of hypercalcaemia
  • End-organ disease
  • Corrected calcium above 2.85 mmol/litre
• Complications of primary hyperparathyroidism include osteoporosis, renal impairment and calculi, pseudogout, pancreatitis and cardiovascular disease.
• Multiple myeloma is a cause of PTH independent hypercalcaemia
• Cinacalcet is a calcium sensing receptor agonist - signals the body to produce less PTH
• Risk factors:

  • Primary is normally sporadic
  • Post menopausal women
  • Previous radiation exposure to the neck
  • Lithium
  • Inherited disorders such as MEN
  • Secondary and tertiary - conditions affecting calcium metabolism such as chronic kidney disease
• Phosphate binders, calcium and vitamin D supplements may be used in chronic kidney disease
• Squamous cell carcinoma can release parathyroid hormone related protein - leading to hypercalcaemia