| If the pituitary-thyroid axis is normal, there is usually little effect from medications that enhance hepatic thyroid hormone clearance. However, there may be profound effects when an individual is dependent on a fixed dose of oral T4. Hepatic T4 and T3 metabolism can probably be enhanced by a wide range of agents that may stimulate the cytochrome p450 system through low-specificity "orphan" members of the steroid/thyroid hormone super-family of receptors (Blumberg et al, 1998). In addition to the known effects of drugs such as rifampicin, phenytoin, carbamazepine and barbiturates (Curran & DeGroot, 1991), it is possible that a wider range of agents that can have this effect, for example, antibiotics, psychotrophics and non-therapeutic xenobiotics. Of interest is the report that sertraline can markedly impair the effectiveness of oral T4 in hypothyroidism, by a so far unidentified mechanism (McCowen et al, 1997). It remains to be established whether unexplained 2-4 fold increases in T4 dosage requirement in critically-ill thyroidectomized patients receiving multi-drug therapy, may be due to accelerated T4 clearance. |
