Thyroid Function in Men Taking Carbamazepine, Oxcarbazepine, or Valproate for Epilepsy

Abstract

Summary:Purpose: Antiepileptic drugs (AEDs) may affect serum thyroid hormone concentrations. This study aimed to evaluate thyroid function in men taking carbamazepine (CBZ), oxcarbazepine (OCBZ), or valproate (VPA) for epilepsy.Methods: Ninety men with epilepsy (40 taking CBZ, 29 taking OCBZ, and 21 taking VPA monotherapy) and 25 control subjects participated in the study. After clinical examination, a blood sample for hormone, ␥-glutamyl-transferase (GGT) and antibody (ab) assays was obtained.Results: Serum thyroxine (T 4 ) and free thyroxine (FT 4 ) concentrations were low in men taking CBZ or OCBZ. Forty-five percent of men taking CBZ and 24% of men taking OCBZ had serum T 4 and/or FT 4 levels below the reference range. However, no correlations were found between T 4 or FT 4 and GGT concentrations in men taking CBZ or OCBZ. Thirteen percent of men taking CBZ, 17% of men taking OCBZ, and 6% of control men had increased levels of thyroid peroxidase (TPO)-ab and/or thyroglobulin (TG)-ab, but these were not associated with altered serum thyroid hormone concentrations. Serum triiodothyronine and thyrotropin levels in men taking CBZ or OCBZ were normal. In men taking VPA, the concentrations of thyroid hormones, thyrotropin, and antithyroid ab were normal.Conclusions: Serum thyroid hormone concentrations are low in CBZ-or OCBZ-treated men. However, these low levels do not seem to be due to liver enzyme induction or activation of immunologic mechanisms. Therefore, interference with hypothalamic regulation of thyroid function by CBZ and OCBZ seems possible. VPA does not have any significant effects on thyroid function. Key Words: Epilepsy-Thyroid hormonesCarbamazepine-Oxcarbazepine-Valproate.The endocrine effects of carbamazepine (CBZ) have been well documented. A decrease in serum thyroid hormone levels can already be detected in patients 2 months after starting CBZ (1). However, serum thyrotropin concentrations do not change, and the clinical significance of low serum thyroid hormone concentrations is unclear (1-8). The altered thyroid function during CBZ medication has been attributed to induction of the hepatic P-450 enzyme system and the consequent increase in the metabolism of thyroid hormones (9,10).Oxcarbazepine (OCBZ) is a novel antiepileptic drug (AED) that structurally resembles CBZ. However, the metabolic pathway of OCBZ in the liver is different from that of CBZ. OCBZ is mainly reduced, instead of being oxidized. Consequently, OCBZ does not appear to induce the hepatic P-450 enzyme system (11). Therefore, it has been suggested that OCBZ may not have effects on endocrine function equivalent to those of CBZ, and replacing CBZ with OCBZ resulted in deinduction of liver enzyme levels and short-term restoration of normal endocrine function in men with epilepsy (10,12). However, OCBZ may induce the hepatic P-450 enzyme system when given in high doses, and recent studies have shown that high doses of OCBZ may also affect sex hormone metabolism in men with epilepsy (13). Furthermore, OCBZ is well known to decreas...

Thyroid hormones in children with epilepsy during long-term administration of carbamazepine and valproate

“…These data are in agreement with previous papers that found normal thyroid hormone levels (19,20,25,(28)(29)(30). By contrast, other studies (11,31) found normal thyroid hormone levels while TSH levels were increased.…”

“…The clinical significance of this increase is uncertain but seems to be a compensatory response in at least some of the patients. No association was also found between serum thyroid hormone concentrations and VPA related obesity (30,33).…”

Thyroid Hormone-Induced Seizures A Case Report and Review of Literature

“…Various AEDs, either carbamazepine, or phenytoin, or sodium valproate and additional diazepam or clonazepam were used to treat seizures in the acute phase. In a study of thyroid function in patients who were taking carbamazepine and oxcarbamazepine showed that carbamazepine can lower serum thyroid hormones [23]. Antiepileptic drugs may be useful and justified during the initial treatment of seizures till you reach the diagnostic confirmation and then antithyroid drug alone will be helpful to prevent seizure recurrences except in proved SSS thrombosis where AED may be continued in view of hemorrhagic and thrombotic lesions.…”

The Case of Hypopituitarism in Traumatic Brain Injury

“…Stimulation with thyrotropin releasing hormone (TRH) has given discrepant results (Franklyn, 1997;Hartoft-Nielsen et al, 2004;Lania et al, 2008). The possible confounding by certain antiepileptic drugs is well-described (Cansu et al, 2006;Isojarvi et al, 2001), inducing a biochemical picture mimicking that of secondary hypothyroidism with decreased peripheral thyroid hormone concentrations and a normal TSH.…”