Effect of renal failure on hormones
Pathophysiological mechanisms on endocrine function
1: Increased concentration of hormones or hormone fragments
- impaired degradation eg insulin, PTH, calcitonin
- increased secretion eg insulin, PTH
2: Decreased concentration due to reduced production
- renal hormones eg erythropoetin, 1,25 vitamin D3
- extrarenal hormones eg oestradiol, testosterone
3: Disturbances of hormone action
- disturbed prohormone activation eg T4 to T3
- multimolecular forms eg glycosylation isoforms eg LH
- altered binding to carrier proteins eg somatomedins
- altered target organ sensitivity eg GH, insulin
Thyroid function in CRF
Approximately 50% euthyroid patients with CRF have an enlarged thyroid gland if not a palpable goitre. The prevalence of hypothyroidism varies between studies at 0-9.5%. This increased (2.5 fold) prevalence matches an increase in the finding of thyroid peroxidase antibodies.
Routine TFTs in CRF
- TSH is normal and is probably the best guide of thyroid status.
- total T4 and T3 are low especially when GFR > 50%.
- Thyroid hormone binds to pre-albumin, albumin & TBG. These are normal in patients on haemodialysis but low in those on CAPD probably due to peritoneal protein loss.
- Analytical differences: in equilibrium dialysis fT4 / fT3 are normal or high, whereas direct assays of total or free hormones show low values.
- TRH testing shows a blunted but prolonged TSH response probably due to delayed clearance of TSH and TRH.
- Overall there is experimental data to suggest interference with all levels of the hypothalamo-pituitary-thyroid axis with an alteration of the 'thyrostat'.
Pituitary-adrenal axis in CRF
Clinical features of excess cortisol (osteopenia, proximal myopathy, hypertension & glucose intolerance) and reduced cortisol (hypotension, weakness & hypokalaemia) are also features of chronic renal failure and the diagnosis of Cushings syndrome or adrenal insufficiency may depend on biochemical tests.
- Conventional high dose Synacthen (ACTH) tests give normal cortisol responses (Ramirez et al 1988).
- Uraemic patients may show sub-optimal plasma cortisol suppression after oral dexamethasone. It is unknown if this is due to poor intestinal absorption of dexamethasone or increased plasma clearance (Ramirez et al 1982)
- Ramirez G, Gomez-Sanchez C, Meikle WA, Jubiz W. Evaluation of the hypothalamic hypophyseal adrenal axis in patients receiving long-term dialysis. Arch Intern MEd 1982;142:1448-52.
- Ramirez G, Brueggemeyer C, Ganguly A. Counterregulatory hormone responses to insulin-induced hypoglycaemia in patients on chronic hemodialysis. Nephron 1988;49:231-6.