242. Thyroid axis activity in depressed inpatients

Dysfunction of the thyroid axis is one of the most consistent findings in neuroendocrine studies of major depression. We have reported that, owing to chronobiological influences, the thyrotropin (TSH) response to protirelin (TRH) challenge at 11 PM is more sensitive than at 8 AM and that the difference in TSH response between 11 PM and 8 AM TRH tests (ΔΔTSH) is an even more sensitive measure. We evaluated the serum levels of TSH, free thyroxine (FT4), and free triiodothyronine (FT3) before and after 8 AM and 11 PM TRH challenges (200 μg IV), on the same day, in 108 drug-free DSM-IV euthyroid major depressed inpatients and 50 hospitalized controls. Compared with controls, depressed patients showed lower basal levels of TSH (at 8 AM: p < 0.006; at 11 PM: p < 0.000001); lower ΔTSH values (at 8 AM: p < 0.0002; at 11 PM: p < 0.000001); lower ΔΔTSH values (p < 0.000001); higher basal levels of FT4 (at 8 AM: p < 0.01; at 11 PM: p < 0.004) and higher basal levels of FT3 (at 8 AM: p < 0.08; at 11 PM: p < 0.01). Eighty six patients (80%) had a blunted ΔΔTSH test (i.e. <2.5 μU/ml). ΔΔTSH values were correlated 1) positively with basal levels of TSH (at 8 AM: r = 0.40; p < 0.000001; at 11 PM: r = 0.47; p < 0.000001) and ΔTSH values (at 8 AM: r = 0.25; p < 0.002; at 11 PM: r = 0.66; p < 0.000001), and 2) negatively with FT4 (at 8 AM: r = 0.24; p < 0.006; at 11 PM: r = 0.25; p < 0.003) and FT3 (at 8 AM: r = 0.29; p < 0.0007; at 11 PM: r = 0.31; p < 0.0003). However, FT4, FT3 and TSH values (basal and after TRH) were not correlated with post-DST cortisol levels. These data indicate that ΔΔTSH, which is independent of HPA axis activity, is a chronobiological index and may be the first sign of thyroid axis dysfunction in depression. Moreover, the thyroid hormone negative feedback to the pituitary is preserved in depression and is a significant factor in the blunting of TSH response to TRH.