DIFFERENT EFFECTS OF PYRIDOSTIGMINE ON THE THYROTROPIN RESPONSE TO THYROTROPIN-RELEASING-HORMONE IN ENDOGENOUS-DEPRESSION AND SUBCLINICAL THYROTOXICOSIS

Primary organic disorders of the thyroid gland must be excluded in int erpreting the thyrotropin (TSH)-releasing hormone (TRH) test in affect ive disease. Both endogenous depression and subclinical thyrotoxicosis are frequently associated with low basal TSH levels and a blunted (<5 mlU/L) TSH response to TRH despite thyroid hormone levels within the normal range. The present study was performed to establish whether a r eduction of the hypothalamic somatostatinergic tone by treatment with the acetylcholinesterase inhibitor pyridostigmine before TRH might be useful to distinguish endocrine from affective diseases. Twelve male d epressed patients (aged 41.4 +/- 3.1 years) and 12 men (aged 43.4 +/- 4.1 years) with subclinical thyrotoxicosis because of autonomous thyro id nodules were selected according to the presence of a low basal TSH level and a blunted TSH response to 200 mu g TRH intravenously (IV) (T SH increment was <5 mlU/L at 30 minutes [peak] after TRH) but thyroid hormone levels within the normal range. All patients were tested again with TRH 60 minutes after treatment with 180 mg pyridostigmine orally , Eleven normal men served as controls. Basal TSH levels were 0.2 +/- 0.2 mlU/L(mean +/- SE) in depression and 0.1 +/- 0.2 in subclinical th yrotoxicosis (normal controls, 1.4 +/- 0,3). In both groups, the mean peak response to TRH was significantly higher than baseline; however, according to selection, the TSH increase was less than 5 mlU/L. Pyrido stigmine did not change basal TSH levels in any group, but significant ly enhanced the TRH-induced TSH increase in normal controls and in dep ressed subjects (TSH increment became >7 mlU/L in all depressed subjec ts). In contrast, no significant change in the TSH response to TRH was observed in subclinical thyrotoxicosis after pyridostigmine treatment . Basal and TRH- and pyridostigmine + TRH-induced TSH levels were sign ificantly higher in the normal controls than in the other groups. Thes e data show a cholinergic involvement in the blunted TSH response to T RH in patients with endogenous depression, but not in subjects with su bclinical thyrotoxicosis, suggesting that these diseases could be sepa rated on the basis of the pyridostigmine + TRH-induced TSH response te st. Copyright (C) 1998 by W.B. Saunders Company.