Hypothyroidism as a cause of tacrolimus intoxication and acute renal failure: a case report

The nephrotoxic side effects of cyclophilin-binding agents like cyclosporine A and tacrolimus are well characterized. In severe cases nephrotoxicity may profoundly deteriorate kidney function and even induce acute renal failure. In this report we describe the first case of excessive tacrolimus intoxication caused by hypothyroidism. The patient had undergone single-lung transplantation 6 months earlier, developed hypothyroidism, and was admitted with acute anuric renal failure. Thyroxin is a potent activator of the cytochrome P-450- CYP 3A enzyme system, which is crucial for tacrolimus metabolism. Hence, hypothyroidism reduces cytochrome P-450 activity and may result in drug accumulation. Rapid reversal of toxic drug levels could be achieved by reducing drug intake and increasing thyroxin levels by substitution therapy. In conclusion, it is important to consider thyroid function when prescribing medications with a narrow therapeutic range, which are metabolized by the cytochrome P-450 system such as tacrolimus, and the possible devastating effect of impaired drug metabolism during hypothyroidism.