Decreased neuropeptide Y (NPY) expression in the infundibular nucleus of patients with nonthyroidal illness

In patients with a variety of illnesses, serum concentrations of T3 decreas e without giving rise to elevated serum levers of TSH, a phenomenon known a s the sick euthyroid syndrome or nonthyroidal illness (NTI). Our previous s tudies in postmortem brain material showed decreased thyrotropin-releasing hormone (TRH) messenger RNA (mRNA) in the paraventricular nucleus (PVN) of patients with NTI, suggesting a role for TRH cells in the persistence of lo w TSH levels in NTI. In the present study, we hypothesized that changes in neuropeptide Y (hTPY) input from the infundibular nucleus (IFN) to TRH cells in the PVN might he a determinant of decreased TRH expression in NTI. We investigated the hypo thalamus of nine patients whose endocrine status had been assessed in a ser um sample taken less than 24h before death and we examined NPY expression i n the IFN by means of immunocytochemistry and mRNA in situ hybridization us ing an image analysis system. Then was a negative correlation (r = -0.88; p = 0.01) between serum leptin concentrations and total NPY mRNA in the IFN. The total amount of NPY immunoreactivity in the lFN correlated with total NPY mRNA (r = 0.69; p = 0.04). In contrast to the situation in food-deprive d rodents, total NPY immunoreactivity in the IFN showed a positive correlat ion with total TRH mRNA in the PVN (r = 0.77; p = 0.02). The results sugges t a role for decreased NPY input from the IFN in the resetting of thyroid h ormone feedback on hypothalamic TRH cells in NTI. (C) 2001 Elsevier Science Inc. AU rights reserved.