Summary

          Hyperthyroidism is a thyroid disease most common among women’s, in which thyroid gland is over activated and produce too much thyroid hormone. The present study was designed to investigate the effect of hyperthyroidism on endothelin-1 (ET-1) level, hemodynamic parameters and relationship between them. Renal and liver function tests were investigated, too. Furthermore, effects of induced-hyperthyroid on ET-1 receptor and their antagonists were investigated.

          In the present study two main experiments were carried out. The first case study experiment included 129 female subjects divided into three groups, 46 subjects with normal thyroid function test (control), 40 patients with hyperthyroid disease and 43 subjects with carbimazole treated hyperthyroid disease. Their mean age range: 32.36 (22.2-55), 35.93(20-60) and 38.33(20-60) years, respectively.

          Serum ET-1, triiodothyronine (T₃), thyroxine (T₄) and glucose levels significantly increased in hyperthyroid patients compared with control subjects. Carbimazole treatment significantly reduced the level of ET-1, T₃, T₄ and glucose level compared with hyperthyroid patients. The hemodynamic parameters: systolic blood pressure (SBP), mean arterial pressure (MAP) and heart rate (H.R) as well as the oxidative stress marker, Malondialdehyde (MDA) significantly raised in hyperthyroid patients in comparison with control subjects. While, carbimazole treatment significantly decreased them. Hyperthyroidism markedly raised the activity of liver enzymes: aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) compared to control subjects, meanwhile, carbimazole treatment only decreased ALP activity corresponding to hyperthyroid value. 

Although, significant decrease in serum creatinine and increase in estimated glomerular filtration rate (eGFR) were found in hyperthyroid patients in comparison with control subjects in contrast carbimazole treatment increased creatinine level and decreased GFR. On the other hand, serum nitric oxide (NO) level reduced in both hyperthyroid and carbimazole treated hyperthyroid subjects.

          The second experiments carried out with two group of female rats: control and induced-hyperthyroidism. Induced-hyperthyroidismin rats occurred by administration of L-thyroxin (0.4 mg/100g food) for four weeks. The results confirmed the induction of hyperthyroidism because L-thyroxine-treated rats were associated with increased serum levels T₃ and T₄.  Moreover SBP, H.R, and serum MDA significantly elevated in induced-hyperthyroid rats.

          In an in vitro study,  the dose response curve (DRC) of ET-1 were found in isolated intact and denuded aortic rings of both control and induced-hyperthyroid groups. The results of these experiments showed that inducing-hyperthyroidism did not chang the E_max, while non-significanty reduced the pD₂ value of ET-1 compared with control. On the other hand, denudation of aortic rings shifted the DRC of ET-1 to the left and the pD₂ increased non-significantly in control group. The pD₂ significantly increased in induced-hyperthyroid aortic rings and shifted the DRC of ET-1 to the left.  Furthermore, pre-incubation with selective endothelin A (ET_A) receptor antagonist (BQ-123) shifted the DRC of ET-1 to right in both groups and significantly reduced pD2 in control aortic rings.

          Selective endothelin B (ET_B) receptor antagonist (BQ-788) pre-incubation significantly raised the pD₂ value in both group and shifted the DRC to the left in induced-hyperthyroid aortic rings, while it decreases E_max in the control and increased in induced-hyperthyroid aortic rings. Furthermore, pre-incubation of denuded aortic rings with ET_A receptor antagonist (BQ-123) shifted the DRC to the right and significantly decreased the pD₂ in induced-hyperthyroid group. While in control group, it non-significantly reduced pD₂ and slightly shifted the curve to the right.

          In conclusion, these results indicate that blood pressure and H.R were markedly increased in patient subjects and animal induced-hyperthyroidism. An increase in ET-1 and its receptor activity, oxidative stress and reduction in NO levels might be the reason behind these increase in blood pressure. Regarding ROC curve analysis ET-1 could be used as a biomarker for hyperthyroid patients.

posted:12-4-2017