Effects of long-term phenobarbital treatment on the thyroid and adrenal axis and adrenal function tests in dogs

Phenobarbital can interfere with the thyroid axis in human beings and rats by accelerating hepatic thyroxine metabolism because of enzyme induction. I n human beings, it also can interfere with the low-dose dexamethasone suppr ession test (LDDST) used to assess adrenal function by accelerating dexamet hasone metabolism. This effect can cause a lack of suppression of pituitary ACTH and subsequent adrenal cortisol release after dexamethasone administr ation. The effects of phenobarbital on the thyroid axis, the adrenal axis, and adrenal function tests were prospectively investigated in 12 normal, ad ult dogs. Phenobarbital was administered at 5 mg per kilogram of body weigh t (range, 4.8-6.6 mg/kg) PO q12h for 29 weeks, resulting in therapeutic ser um concentrations (20-40 mu g/mL). Serum total thyroxine (TT4), free thyrox ine (FT4) by equilibrium dialysis, total triiodothyronine (TT3), thyrotropi n (TSH), and cholesterol were determined before and during phenobarbital tr eatment. LDDST ACTH stimulation tests, and ultrasonographic evaluation of t he adrenal glands were performed before and during treatment. TT4 and FT4 d ecreased significantly (P less than or equal to.05). TT3 had minimal fluctu ation, TSH had only a delayed compensatory increase, and cholesterol increa sed during phenobarbital treatment. The delayed increase in TSH, despite pe rsistent hypothyroxinemia, suggests that accelerated hepatic thyroxine elim ination may not be the only effect of phenobarbital on the thyroid axis. Th ere was no significant effect of phenobarbital on either of the adrenal fun ction tests. With the methods employed, we did not find any effects of the drug on the hormonal equilibrium of the adrenal axis.