Abstract

Chronic renal failure affects thyroid function in multiple ways, including low circulating thyroid hormone concentration, altered peripheral hormone metabolism, disturbed binding to carrier proteins, possible reduction in tissue thyroid hormone content, and increased iodine store in thyroid glands. Both plasma triiodothyronine (T(3)) and thyroxine (T(4)) are reduced. The low serum T(3) is not due to increased T(3) degradation or to decreased thyroidal T(3) secretion but is a result of impaired extrathyroidal T(4) to T(3) conversion. The reduction in T(4) is attributed to the presence of circulating inhibitors, which impair binding of T(4) to thyroxine-binding globulin. Despite decreased circulating T(4) and T(3), thyroid-stimulating hormone (TSH) is not elevated. This absence of TSH elevation is not due to dysfunction of the hypothalamo-pituitary axis, because truly hypothyroid renal failure patients can mount a high TSH response. Thyroid hormone losses during hemodialysis and peritoneal dialysis are trivial and do not require replacement. Serum inorganic iodide and thyroidal iodine content are increased in renal failure patients, and thyroid gland enlargement is frequently encountered. Experiments performed to correct the low serum T(3) level by administration of small doses of LT(3) to renal failure patients resulted in lesser nitrogen balance, greater leucine flux, and protein degradation. We speculate that the low thyroid state in uremia serves to defend against protein wasting and that misguided attempts to replete thyroid hormone stores may worsen protein malnutrition.