Effect of TRH on TSH and prolactin levels in affective disorders

The thyrotropin-releasing hormone (TRH) test was studied in 32 patients with acute major depressive disorder, 16 patients with recurrent unipolar ( n=8) or bipolar ( n=8) affective disorder in remission, and 22 healthy control subjects. Twenty-six of the 32 acutely ill patients were also studied when in remission. Outcome in these patients was correlated to serum levels of triiodothyronine (T 3), 3,3',5'triiodothyronine (reverse T 3), thyroxine (T 4), thyroid-stimulating hormone (TSH), prolactin (PRL), melatonin, dexamethasone suppression test (DST) results, and clinical symptoms assessed by the Comprehensive Psychopathological Rating Scale (CPRS). The TSH response to TRH (δTSH) was decreased in the acutely ill patients, but no difference was found between patients in remission and controls. The δTSH was correlated to TSH but not to T 3 and T 4 levels in both acutely ill and control subjects. In the acutely ill group, δTSH did not distinguish between patients with normal and abnormal DST results. Thus, abnormalities in the hypothalamic-pituitary-thyroid (HPT) axis are not correlated to abnormalities in the hypothalamic-pituitary-adrenal (HPA) axis. Moreover, δTSH did not differentiate between melancholic ( DSM-III) and nonmelancholic patients or between patients with primary and secondary depression. No correlation was found between δTSH and CPRS scores. Patients with observable agitation>0.25 points (item range 0–3) had higher levels of δTSH than patients with lower levels. No significant correlation was found between δTSH and seven specific symptom clusters on the CPRS. However, there was a possible relation between low δTSH and violent suicide attempts or suicide. PRL levels did not distinguish acutely ill patients from controls. Finally, there was no significant regression between δTSH and melatonin levels. The decrease in δTSH seen in the acutely ill patients was too small to be of diagnostic value as a laboratory measure differentiating acutely ill and healthy subjects. The mechanism underlying the HPT alterations in acute major depressive disorder may be a desensitization of the TRH receptor in the thyrotrophs secondary to an increased endogenous TRH stimulation.