The hypothalamic-pituitary-thyroid axis in patients maintained on lithium prophylaxis for years: high triiodothyronine serum concentrations are correlated to the prophylactic efficacy.

Serum concentrations of thyrotropine (TSH), thyroxine (T4), free T4 (fT4), triiodothyronine (T3) and reverse T3 (rT3) were measured 4 x during a 12-month period in 28 patients with major depressive disorder maintained on lithium prophylaxis for 4-23 years (mean = 11.8). The course of illness was carefully monitored and documented for all patients throughout a 3.5-year period. All hormones were also measured in 41 healthy controls matched for age and gender. Patients on lithium had normal serum concentrations of TSH, T4, fT4 and T3 only the levels of rT3 were elevated. The efficacy of the lithium prophylaxis was significantly correlated to the serum concentrations of T3, i.e., the higher the patients' serum levels of T3, the shorter was the overall duration of recurrences of depression within the 3.5-year period. We conclude that: (1) thyrotropine and the thyroid hormones, which are often abnormal during the first weeks or months of lithium treatment, returned to normal when lithium prophylaxis was maintained for years; (2) a possible explanation for the higher T3-serum concentrations in responders might be that lithium interacts with thyroid hormone metabolism in the CNS, leading to enhanced T3 concentrations in the tissue and to a secondary increase in the serum concentrations of T3.