Clearly, the high mortality rate in patients with T4 under 4ug/dl suggests that this is a target group in whom thyroid hormone administration should be considered. In this group of patients there appears to be no obvious contraindication to replacement therapy, with the possible exception of people who have cardiac decompensation or arrhythmias. Even here the evidence is uncertain. There is no clear evidence that administration of replacement doses of T3 to patients with low cardiac output is disadvantageous, and in fact current studies using intravenous T3 in these patients indicate it is well tolerated and may be beneficial ( 139). Arrhythmias obviously also raise a question, but again, there is no evidence that replacement of thyroid hormone to a normal level would cause trouble in control of arrhythmias. Thus, even in this group of patients, it is reasonable to suggest therapy. It should also be noted that among patients with NTIS there will certainly be patients who are clearly hypothyroid based on known disease, treatment with dopamine, or elevated TSH, who need replacement therapy by any standard.

If therapy is to be given, it cannot be thyroxine alone, since this would fail to promptly elevate T3 levels ( 49). Treatment must be with oral, or if this is impractical, intravenous T3, and probably should be at the replacement level of approximately 50 ug/day given in divided doses. It may be appropriate to give slightly higher doses, such as 75 ug/day for 3 - 4 days to increase the body pool more rapidly, followed by replacement doses as described. Coincidentally, it is appropriate to start replacement with T4. Serum levels of T4 and T3 should be followed at frequent intervals (every 48 hours), and dosages adjusted to achieve a serum T3 level approximating at least low normal, 70-100ng/dl, prior to the next scheduled dose. If treatment is successful, T3 administration can gradually be reduced, and thyroxine administration increased to replacement levels as deiodination increases. Because of the marked diminution in T4 to T3 deiodination, and shunting of T4 toward reverse T3, replacement with T4 may initially only lead to elevation of reverse T3 and have very little effect upon T3 levels, or physiologic action. In this situation, continued administration of T3 would be preferred.