Endocrine Abstracts

Background: Thyroid hormones participate in maturation, differentiation and triggering of immunity, but little is known about the modulating role of thyroid hormones on intracellular enzymatic reactions of immune cells and their role in immunopathogenesis of Graves’ disease (GD).

Methods: The activity of NAD(P)-dependent dehydrogenases in lymphocytes and neutrophils ofperipheral blood was studied in a group of 145 women with GD, 53 (36.5%) patients with a first episode and 92 (63.4%) with relapse of hyperthyroidism, mean age 43.14 ± 13.81 years, and, also, 73 age- and gender matched healthy controls were determined. The diagnosis of GD had to be established by a low TSH, a high fT4 or fT3 and positive TRAb. The activity of glycerol-3-phosphate dehydrogenase (Gly3PhD), glucose-6-phosphate dehydrogenase, NAD-lactate dehydrogenase (LDH), NADH-lactate dehydrogenase (NADH-LDH), NAD–malate dehydrogenase (MDH), NADH–malate dehydrogenase, NAD-glutamate dehydrogenase (GDH), NADH--glutamate dehydrogenase (NADH-GDH), NAD(P)--isocitrate dehydrogenases (ICDH and NADP-ICDHrespectively), NADP(H)-glutamate dehydrogenases (-NADP-GDH and NADPH-GDH respectively), NADP-malate dehydrogenase and glutathione reductase were measured usingbiochemiluminescence method.

Results: Studying the activity ofNAD(P)-dependent dehydrogenases in lymphocytes we found the reduction of MDH and NADPH–GDH (P < 0.001). In neutrophils ofperipheral blood in patients with manifestation of GD increased the activity of ICDH (P < 0.01) and reverse reaction of LDH (P < 0.05). In patients with GD relapsing in peripheral blood lymphocytes we observed low activity of LDH (P < 0.05), MDH (P < 0.01), ICDH and NADPH–GDH (P < 0.01). Studying intracellular metabolism of blood neutrophils patients with recurrence of the disease showed significantly high activity of NADP-MDH, NADP-GDH, NADP-ICDH, GDH, NADH-GDH, but inhibiting reverse reactions of LDH and MDH (P < 0.05). The comparative analysis of the studied NAD(P)-dependent dehydrogenases demonstrate, that in group with newly diagnosed GD compared to patients with recurrent disease in lymphocytes of peripheral blood increase the level of Gly3PhD, NADH-GDH (P < 0.05). Intracellular metabolism of blood neutrophils in patients with manifestation of GD compare to GD relapse group vary by decreasing activity of Gly3PhD,GDH and NADP-MDH (P < 0.05).

Conclusion: The main features oflymphocyte metabolism in GD relapse patients were the reduction of intermediates formation for macromolecular synthesis reactions and aerobic processes, the low intensity of glycolysis, nitrogen metabolism,and in neutrophils – activation in the system of malate-aspartate hydrogen shunt. Further exploration of immunological mechanisms has the potential to improve treatment of GD, with more targeted treatment strategies based on the different physiopathological concepts of this heterogeneous disease.