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Aetiology

Last reviewed dd mmm yyyy. Last edited dd mmm yyyy

Authoring team

Secondary hyperparathyroidism is due to chronic hypocalcaemia associated with:

  • chronic renal failure - defective absorption of calcium in the gut due to reduced levels of 1, 25 dihydroxy cholcalciferol
  • malabsorption and vitamin D deficiency

Mechanism in renal disease:

  • development of secondary hyperparathyroidism in people with impaired renal function is complex

    • occurs as a result of failure of the excretory function of the kidney (impaired excretion of phosphate and impaired reabsorption of calcium) and of the endocrine function of the kidney (reduced hydroxylation of inactive forms of vitamin D to the active form, calcitriol [1,25-dihydroxyvitamin D])

      • in the early stages of renal impairment, phosphate excretion is reduced. Initially, this does not lead to high levels of phosphate in the blood (hyperphosphataemia) because increased secretion of PTH stimulates the kidneys to excrete more phosphate

      • when renal impairment progresses to the moderate stage, the kidneys can no longer eliminate more phosphate in response to increased PTH secretion, and phosphate levels begin to rise
        • hyperphosphataemia suppresses the renal hydroxylation of inactive calcidiol (25hydroxyvitamin D) to calcitriol
        • low levels of calcitriol lead to reduced intestinal absorption of calcium, leading in turn to hypocalcaemia
        • hypocalcaemia, low calcitriol levels and hyperphosphataemia all independently stimulate PTH synthesis and secretion
        • as these chronic stimuli persist, the parathyroid glands become enlarged and begin to function autonomously, continuing to secrete PTH even if hypocalcaemia is corrected. This condition is referred to as 'refractory' hyperparathyroidism and is also sometimes called 'tertiary' hyperparathyroidism
          • PTH levels become extremely elevated and this causes calcium and phosphate to be released from bone. Hyperphosphataemia is exacerbated and hypercalcaemia may occur

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