The effects of chronic ingestion of spironolactone on serum thyrotropin and thyroid hormones in the male rat

Toxicology and Applied Pharmacology
D E SemlerF M Radzialowski

Abstract

Male rats were fed spironolactone admixed with feed at doses of 6, 50, and 200 mg/kg/day for up to 13 weeks. After 13 weeks of treatment, there were dose-related increases in thyroid weight and follicular hypertrophy. Serum thyrotropin (TSH) concentrations were significantly increased throughout the treatment period. Serum thyroxine (T4) and triiodothyronine (T3) were significantly decreased at Weeks 2 and 4, but returned to control concentrations by Week 13. The TSH increase and transient T4 decrease suggested that the thyroid hypertrophy was a compensatory reaction to lowered thyroid hormone levels. To determine the effect of spironolactone ingestion on T4 synthesis and metabolism, male rats were fed spironolactone admixed with feed at 200 mg/kg for 2 weeks. The decrease in T4 was not due to decreased synthesis, since iodide uptake and organification were significantly increased by spironolactone treatment. Since uridine diphosphate glucuronosyl transferase activity was significantly increased by spironolactone treatment, it appears that, by increasing hepatic clearance of T4, spironolactone causes a decrease in the serum concentration of this hormone. The lower T4 level causes a release of feedback inhibition and an increase...Continue Reading

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Citations

Nov 15, 2011·Inflammatory Bowel Diseases·Laura A JohnsonPeter D R Higgins
May 1, 2010·Environmental Toxicology and Pharmacology·Olfa TebourbiKhémais Ben Rhouma
Nov 21, 2001·Toxicology and Applied Pharmacology·N R Vansell, C D Klaassen
Sep 16, 2006·Molecular Nutrition & Food Research·Stefanie Knerr, Dieter Schrenk
Jan 1, 2006·Toxicology Mechanisms and Methods·David E Amacher
Oct 20, 2006·Critical Reviews in Toxicology·Stefanie Knerr, Dieter Schrenk
Feb 21, 2002·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Nichole R Vansell, Curtis D Klaassen

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