Thyroid Function and Serum Hepatic Enzyme Activity in Dogs after Phenobarbital Administration

Abstract

Phenobarbital is the drug of choice for control of canine epilepsy. Phenobarbital induces hepatic enzyme activity, can be hepatotoxic, and decreases serum thyroxine (T 4 ) concentrations in some dogs. The duration of liver enzyme induction and T 4 concentration decreases after discontinuation of phenobarbital is unknown. The purpose of this study was to characterize the changes in serum total T 4 (TT 4 ), free T 4 (FT 4 ), thyroid-stimulating hormone (TSH), cholesterol and albumin concentrations, and activities in serum of alanine aminotransferase (ALT), alkaline phosphatase (ALP), and gamma-glutamyl transferase (GGT) after discontinuation of long-term phenobarbital administration in normal dogs. Twelve normal dogs were administered phenobarbital at a dosage of approximately 4.4-6.6 mg/kg PO q12h for 27 weeks. Blood was collected for analysis before and after 27 weeks of phenobarbital administration and then weekly for 10 weeks after discontinuation of the drug. The dogs were clinically normal throughout the study period. Serum ALT and ALP activity and TSH and cholesterol concentrations were significantly higher than baseline at week 27. Serum T 4 and FT 4 were significantly lower. Serum albumin and GGT were not changed from baseline at week 27. Changes in estimate of thyroid function (TT 4 , FT 4 , TSH) persisted for 1-4 weeks after discontinuation of phenobarbital, whereas changes in hepatic enzyme activity (ALT, ALP) and cholesterol concentration resolved in 3-5 weeks. To avoid false positive results, it is recommended that thyroid testing be performed at least 4 weeks after discontinuation of phenobarbital administration. Elevated serum activity of hepatic enzymes 6-8 weeks after discontinuation of phenobarbital may indicate hepatic disease.

Influence of Drugs on Thyroid Function in Dogs

“…64 Not only TT4 but also FT4 measurements (determined by equilibrium dialysis) were lowered by phenobarbital therapy in several studies. 55,63,65 This finding supports the hypothesis that phenobarbital influences the steady-state clearance of thyroxine.…”

“…51-54 Increased conversion of T4 to T3 in peripheral tissues also might play a role. 55 Phenobarbital also could have additional central effects on the hypothalamus-pituitary-thyroid axis. 56,57 Most studies in rats report decreased T4 with normal or, more often, increased TSH concentrations.…”

“…Despite the fall in FT4 concentrations, most studies on the effects of phenobarbital administration in dogs identified only minor or no effects on TSH concentrations. 55,63,65 One hypothesis is that phenobarbital also inhibits TSH secretion. Another hypothesis is that T4 clearance is increased by deiodinative and nondeiodinative pathways.…”

“…In one study, thyroid function normalized 1-4 weeks after discontinuation of phenobarbital. 55 Therefore, when possible, thyroid function should be evaluated at least 4-6 weeks after discontinuation of phenobarbital.…”

Computed Tomographic Features of the Normal Canine Thyroid Gland

“…8,[29][30][31] In dogs, various anesthetic agents have an influence on thyroid function. [32][33][34][35] Limited data are also available on the influence of intravenous iodinated contrast medium in dogs on thyroid function. 36 As a precaution we obtained all blood samples before induction of anesthesia and administration of iomeprol.…”