LONG-TERM RESULTS FOR THE TREATMENT OF PATIENTS WITH THE APPLICATION OF ORGAN-PRESERVING OPERATIONS IN PAPILARY THYROID CANCER

Іn order to analyse the changes in the structural and functional state of the thyroid gland, a group of 185 patients (67.8 %) were examined after the surgical treatment of papillary thyroid cancer. Of these, 94 patients belonged to the first group – the comparison group where thyroidectomy was performed, and 91 to the second – the main group where, mainly, organ-preserving operations were performed. The average follow-up was 6.5 ± 5.1 years (varied from 2 to 11 years. Hypoparathyroidism in patients receiving replacement therapy was observed in 20 (16.4 %) patients after thyroidectomy and only in 4 (6.3 %) patients after organ-preserving techniques (the differences are significant, p < 0.05). Side effects of replacement therapy were observed in 21 (17.2 %) patients after thyroidectomy and only in 4 (6.3 %) patients after organ-preserving techniques (the differences are significant, p < 0.05). Disease recurrence was detected in 4 (3.3 %) patients after thyroidectomy and in 1 (1.6 %) patient after organ-preserving techniques (the differences are not significant, р > 0.05). The use of organ-preserving approaches in the main group allowed improving functional results by reducing the frequency of hypothyroidism and side effects of replacement therapy, due to the preservation of thyroid secretion and its regulation, without worsening the results of relapse-free survival.

Functional activity of the thyroid gland, the thyrotropic function of the hypophysis and the level of cortisol in patients with new-onset pulmonary tuberculosis depending on the clinical forms

The degree of disbalance of interleukin-6, depending on the functional activity of the thyroid gland, has been studied on the basis of a survey of 55 patients with newly diagnosed pulmonary tuberculosis with preserved sensitivity to anti-TB drugs and 36 patients with drugresistent pulmonary tuberculosis (case-control) using ELISA research. Results of the study showed that patients with preserved thyroid secretion, regardless of the variant of the sensitivity an increase of interleukin-6 can be observed, and in patients with disorder of thyroyid homeostasis its level is significantly lower (p<0,05) than in the group with preserved thyroid activity.

Atypical Expression of Type 2 Iodothyronine Deiodinase in Thyrotrophs Explains the Thyroxine-Mediated Pituitary Thyrotropin Feedback Mechanism

T4, the main product of thyroid secretion, is a critical signal in plasma that mediates the TSH-negative feedback mechanism. As a prohormone, T4 must be converted to T3 to acquire biological activity; thus, type 2 iodothyronine deiodinase (D2) is expected to play a critical role in this feedback mechanism. However, the mechanistic details of this pathway are still missing because, counterintuitively, D2 activity is rapidly lost in the presence of T4 by a ubiquitin-proteasomal mechanism. In the present study, we demonstrate that D2 and TSH are coexpressed in rat pituitary thyrotrophs and that hypothyroidism increases D2 expression in these cells. Studies using two murine-derived thyrotroph cells, TtT-97 and TαT1, demonstrate high expression of D2 in thyrotrophs and confirm its sensitivity to negative regulation by T4-induced proteasomal degradation of this enzyme. Despite this, expression of the Dio2 gene in TαT1 cells is higher than their T4-induced D2 ubiquitinating capacity. As a result, D2 activity and net T3 production in these cells are sustained, even at free T4 concentrations that are severalfold above the physiological range. In this system, free T4 concentrations and net D2-mediated T3 production correlated negatively with TSHβ gene expression. These results resolve the apparent paradox between the homeostatic regulation of D2 and its role in mediating the critical mechanism by which T4 triggers the TSH-negative feedback.

Impact of Gene Cloning, Disruption and Over-Expression of Iodothyronine Deiodinases on Thyroid Hormone Homeostasis

Thyroxine (T4) is the main product of thyroid secretion, a pro-hormone that must be activated by deiodination to T3 in order to initiate thyroid hormone action. This deiodination reaction occurs in the phenolic-ring (outer-ring deiodination, ORD) of the T4 molecule and is catalyzed by two selenocysteine-containing deiodinases, i.e. D1 and D2. As a counter point to the activation pathway, both T4 and T3 can be irreversibly inactivated by deiodination of the thyrosyl-ring (inner-ring deiodination, IRD), a reaction catalyzed by D3, the third member of the selenodeiodinase group. Due to its substantial physiological plasticity, D2 is considered the critical T3-producing deiodinase in humans. Recently, the observations made in the D1-deficient C3H mouse mice were expanded by the development of mice with generalized targeted disruption or cardiac-specific over-expression of the D2 gene. The results obtained indicate that the selenodeiodinases constitute a physiological system contributing with the thyroid hormone homeostasis during adaptation to changes in iodine supply, cold exposure, in patients with thyroid dysfunction and perhaps during starvation and illness.