Vol 51, No 1 (2005)

Clinical endocrinology
Long-term results of treatment of toxic goiter with radioactive 131I
Fadeyev V.V., Drozdovsky В.Y., Guseva Т.N., Garbuzov P.L., Buziashvili I.I., Melnichenko G.A.

The study included 103 patients with toxic goiter, among whom 75 patients were diagnosed as having Graves' disease (GD) and 28 had thyroid functional autonomy (FA) that was presented with toxic multinodular goiter in most cases. All the patients received 131I therapy, then they were followed up; the duration of the follow-up of the patients in whom euthyroidism was preserved at the moment this paper was being written was 18 [10; 28] months. The treatment of GD in 86.7% of the cases ended either with hypothyroidlsm (53.4%), recurrent thyrotoxlcosls (33.3%), or with euthyroidism (13.3%). In FA, recurrent thyrotoxlcosls developed statistically less frequently (10.7%; p = 0.041) and a euthyrold state was statistically more frequent (46.4%; p < 0.001). It was concluded that the optimal purpose of 131I therapy for GD was to destroy the thyroid gland and to achieve persistent hypothyroidlsm, but, in FA, to achieve either euthyroidism or hypothyroidlsm. The use the relatively low activities of 131I (on the basis of the estimated absorbed dose of 100-200 Gy) was demonstrated to be accompanied by a high (33.33%) risk for recurrent thyrotoxlcosls. The volume of the thyroid gland is the major predictor of the late outcome of 131I therapy; but the high level of free T4 after 1 month of 131I therapy and/or the necessity of temporary use of thyrostatlc therapy Involve a high risk for recurrent thyrotoxlcosis.

Problems of Endocrinology. 2005;51(1):3-9
The role of thin-needle aspiration biopsy in the diagnosis of thyroid nodules
Grineva Y.N., Malakhova T.V., Goryushkina Y.V.

The paper analyzes the results of thin-needle aspiration biopsy (TNAB) performed in 1155 patients with thyroid nodules. The purpose of the paper was to evaluate the efficiency of TNAB in the differential diagnosis of thyroid nodules and in the detection of carcinoma among them. A prospective open uncontrolled study was conducted. According to the data of TNAB, benign, malignant, and suspected malignant masses were found in 808 (69.96%), 49 (4.2%), and 148 (12.8%) patients, respectively. The data of TNAB were compared with the histological findings in 333 patients undergoing surgery. The sensitivity, specificity, and other indices of the efficiency of TNAB were calculated by and without taking into account a group of suspected malignant changes. The sensitivity, specificity, and diagnostic accuracy were 93.9, 97.5, and 96.5%, respectively; the prognostic values as for the presence and absence of cancer were 93.8 and 97.5%, respectively, The presence of a group of suspected malignant changes substantially lowered the efficiency of TNAB. The specificity of TNAB in detecting thyroid cancer, assessed by taking into account this group was 52.5%; the prognostic value as to the presence of cancer was 39.8%. The diagnostic accuracy (63.2%), sensitivity (93.9%), and the prognostic value of TNAB in relation to the absence of cancer (97.5%) substantially unchanged. The presence of a rather large number of unrepresentative aspirates (13.0%), the bulk (74.7%) of which is presented by the contents of a cyst is another disadvantage of TNAB. A histological study revealed thyroid cancer in 6 out of these patients. The high (62%) incidence of cancer in the cystic nodes reasonably warrants the use of surgery in case of the repeated accumulation of the contents with a cystic node.

Problems of Endocrinology. 2005;51(1):10-14
Experience with pioglitasone (actos) in the treatment of polycystic ovary syndrome
Dedov I.I., Pishchulin A.A., Yarovaya I.S., Akmayev I.G.

The paper presents the authors 'data obtained from examinations of 1 7 patients aged 15 to 36 years who had polycystic ovary syndrome (PCOS) and insulin resistance before and after therapy with pioglitasone in a daily dose of 30 mg, regardless of the time of a meal, for 3 months. The study was undertaken to examine the effects of pioglitasone on carbohydrate and lipid metabolic parameters, as well as on the hormonal parameters of ovarian function and on the basic clinical manifestations in patients with PCOS. Elimination of insulin resistance with the sensitizers of the action of insulin, such as pioglitasone, contributes to the normalization of reproductive function in most patients with PCOS and insulin resistance.

Problems of Endocrinology. 2005;51(1):15-18
The preva-lence and pattern of autoimmune thyroid disease in young patients with type 1 diabetes mellitus
Karlovich N.V., Mokhort T.V., Vorontsova T.V.

This study whose purpose was to examine the prevalence and pattern of autoimmune disease of the thyroid gland (TG) in young patients with type I diabetes mellitus (DM1) involved 288 individuals with DM1 whose age was 5.5 to 30years; the average duration of DM1 was 5.5+4.7 years. In all the patients, thyroid ultrasonography was performed, thyroid antibodies (Abs) [thyroid peroxidase antibodies (TPO-Abs) and thyroglobulin antibodies (TG-Abs)] were determined, thyroid function was evaluated by measuring the level of thyroid-stimulating hormone (TSH) and free reactions of thyroid hormones were assessed. The detection rates of TPO-Abs and TG-Abs were 22.2 and 20.5%, respectively, which was substantially greater than those in apparently healthy individuals matched by age and gender. The frequency of positive thyroid Abs was significantly higher in females. Age at the moment of examination and the duration of DM1 were not found to have an impact on the detection rate of thyroid Abs. The ultrasound signs of autoimmune thyroid diseases were revealed in 19.1% of the cases. 10.0% of the patients with DM1 were found to have these or those TG dysfunctions the most common of which was subclinical hypothyroidism (6.60%). A comprehensive TG assessment in the young patients with DM1 demonstrated the typical signs of autoimmune thyroid disease in 14.2% of the examinees. In the patients with autoimmune thyroid disease, the thyroid was significantly larger and the levels of TSH, TPO-Abs, and TG-Abs were higher than the patients without autoimmune thyroid disease and those at risk for the latter. The proportion of females was significantly higher among the patients 19 with concomitant autoimmune thyroid disease than that among those without the signs of this condition. It has been concluded that the high incidence of autoimmune thyroid disease in young patients with DM1 permits the authors to recommend a screening for its early detection, which involves the measurement of the serum level of TPO-Abs and TG ultrasonography in all females with first detected DM1

Problems of Endocrinology. 2005;51(1):19-24
Assessment of the risk of type 1 diabetes mellitus in children with borderline fasting hyperglycemia by determining islet-cell autoantibodies
Yanovskaya E.Y., Odud Y.A., Popenko V.I., Zhuleva L.Y., Timofeyev A.V.

The role of borderline fasting hyperglycemia (BFHG) as a risk factor of type 1 diabetes mellitus was studied in children without a family history of diabetes. A prospective study included 19 children (mean age 10.31±4.53 years; M±σ) with BFHG and 69 children without glucose exchange impairments (mean age 10.78±3.47years). Islet-cell autoantibodies (ICAs) were determined once at the beginning of the study. The three-year cumulative risk of type 1 diabetes mellitus in children without glucose metabolic disorders and in those with BFHG who had no ICAs was equal to zero and that in children with BFHG and ICAs was 100%. It has been established that the presence of ICAs in children with BFHG points to the preclinical period of type 1 diabetes mellitus. It is recommended that ICAs and other markers of autoimmune β-cell destruction should be studied in all children with BFHG. When these markers are detected, it is necessary to make preventive measures aimed at suppressing the progression of the disease and at preventing its sudden manifestation

Problems of Endocrinology. 2005;51(1):25-27
studies in the early diagnosis of Value of noninvasive diabetic angiopathies
Garagan S.F.

Eighty-six patients of both sexes (46 males and 40 females) who had type 1 diabetes mellitus (DM1) in the decompensated state were examined. Moderate and severe DM1 were detected in 66 and 20 patients, respectively. The patients' age ranged from 16 to 46 years. The purpose of the study was to improve early diagnosis and to make a differential diagnosis of diabetic and macroangiopathies of the coronary vessels of the heart and the pulmonary arterial system, by using noninvasive (clinical, instrumental examinations, such as echocardiography, phlebography, apex and right ventricular cardiographies, jugular phlebography, oscillography) and immuno-logical studies. The studies yielded definite calculation criteria (the myocardial viability index (MVI) that characterizes subendocardial blood flow and pulmonary pressure). Diabetic coronary microangiopathies may be stated if MVI is more than 1.3 conventional units. The MVI of less than 1.3 conventional units is indicative of diabetic macroangiopathies (coronary heart disease). The calculation values of pulmonary pressure in patients aged above 40 years who had DM1 in the decompensated state were statistically more sig-nificant than those in these patients in the compensated state, which suggested the presence of diabetic macroangiopathies of the pulmonary arterial system. In diabetic patients aged less than 40 years, the difference in these values was insignificant, which may point to the presence of diabetic microangiopathies. This opens up a way to the early treatment of diabetic microangiopathies and to the prevention of diabetic macroangiopathies.

Problems of Endocrinology. 2005;51(1):28-29
The genetic and biochemical mechanisms of the development of diabetic nephropathy in children
Kondratyeva Y.L., Puzyrev V.P., Sukhanova G.A., Kravets Y.В., Spirina L.V., Kosyankova T.V., Tarasenko N.V., Vaganova T.V.

The mechanisms responsible for the development of microangiopathies in type diabetes mellitus (DM1) are complex and under extensive study. Fresh data on the pathogenesis of DM1 make it possible to direct actual ways to the studies aimed at preventing the complications of this disease. The purpose of this study was to examine the contribution of the polymorphic types of the VNTR polymorphism of endothelial NO-synthase gene (NOS3) and the I/D polymorphism of angiotensin-converting enzyme (ACE), the status of the proteolytic systems and lipid metabolic disturbances to the development of diabetic neuropathy (DN). A total of 197 children Работа выполнена при финансовой поддержке гранта РГНФ № 00-06-00- 162а. who had DM1 in 1996-2002 were examined. Their mean age was 13.1 ±0.3 years. A control group comprised 32 apparently healthy children whose mean age was 12.8±0.1 years. DN was present in 44 children (19 boys and 25 girls). It has been established that allele A of endothelial NO-synthase is less common in diabetic patients with nephropathy (p < 0.05) and that it is a factor that reduces, while insignificantly, the risk for nephropathy (RR = 0.13). Analyzing the association with pathology by using the transmission/disequilibrium test has indicated the association of allele В of the gene NOS3 (TDT = 4.5, p - 0.034) and allele D of the gene ACE (TDT = 3.6, p < 0.05) with DN. The activity of plasma kallikrein was increased at the early stages of nephropathy (hyper-function). The higher activity of angiotensin-converting enzyme (57.0±2.9 μmol/min·l in the patients with nephropathy versus 38.1±2.8 μmol/min·/ in those without this disease) and the substantial suppression of α-proteinase inhibitor (21.1+-1.2 IU/ml in nephropathy at the stage of proteinuria versus 27.6±1.6 IU/ml without nephropathy) make a contribution to the development of nephropathy at the stages of microalbuminuria and proteinuria. ffyperlipidemia that manifests itself by the increased levels of cholesterol, triglycerides, and low-density lipoprotein cholesterol and by the decreased levels of high-density lipoprotein cholesterol is one of the mechanisms responsible for the development of DN in DM1.

Problems of Endocrinology. 2005;51(1):30-33
Prospects of the impact of antihypertensive therapy on the pathogenetic mechanisms of insulin resistance
Ametov A.S., Demidova T.Y., Smagina L.V.

The study was undertaken to evaluate the antihypertensive effectiveness and metabolic safety of the selective imidazoline receptor agonist moxonidine. Thirty patients with mild and moderate arterial hypertension associated with type 2 diabetes mellitus were ex-amined. The patients' mean age was S2.43±4.65 years. The history of diabetes mellitus and arterial hypetension averaged 4.77±2.69 and 6.93±2.98 years, respectively. The duration of the study was 16 weeks. The drug was found to have a positive effect on the 24-hour blood pressure (BP) profile: a long-term significant optimal lowering of DP during 12 hours, a significant reduction in the pressure load index, a decrease of the baseline greater variability, and normalization of a two-phase BP profile. There was a significant improvement of carbohydrate metabolism: a reduction in the level of glycolysated hemoglobin and fasting glycemia, a decrease in the fasting and postprandial immunoreactive insulin levels, which suggests the positive effect of the drug on tissue insulin sensitivity at the level of peripheral tissues and the liver. There was a significant tendency for changing the qualitative composition of blood lipids by lowering the atherogenic fractions of lipoproteins and by elevating the level of high-density lipoproteins. Physiotens is a highly effective antihypertensive drug that may be recommended for the treatment of mild and moderate arterial hypertension in patients with impairments considered within the metabolic syndrome.

Problems of Endocrinology. 2005;51(1):34-39
Case Reports
Functional autonomy in endemic goiter
Sviridenko N.Y.

Diagnostics and treatment of functional thyroid autonomy is more concerned with endocrinologists, however, the consequences of functional thyroid dysfunctions have to be faced by other medical specialists, primarily general pgactitioners and cardiologists, and often not months but years pass before the patient goes to the endocrinologist. We present 2 fairly typical cases of untimely diagnosis of functional autonomy from our clinical practice.

Problems of Endocrinology. 2005;51(1):40-41
Experimental endocrinology
Effects of the recombinant human growth hormone drug biosome on deep skin burn healing in rats
Klebanovas J., Lashas L., Lashiene D., Pangonyte D.

The purpose of the study was to select the parameters of an experimental model of burn and to determine the effects of the recombinant human growth hormone drug biosome ("BIOTECHNA" CJSC, Lithuania) burn wound healing. Wistar rats were randomly divided into 2 groups: 1) those receiving placebo injections and 2) those given daily injections of Biosome in a dose of 2.0 mg/kg. A model of contact burn was used to reproduce a burn wound. The depth of the wound was determined, by morphologically assessing a burn wound tissue specimen on day О of burn application. The process of wound healing was associated with the change in the skin granulation defect area expressed as cm2. A statistically significant difference in the area of wounds in 2 animal groups was observed on healing day 10. On experimental day 22, the rat wound area in Group 2 decreased to an average of 0.26±O.I9 cm2, it was covered by crusts and regarded as healed. In Group I, the wound area achieved the similar one only on healing day 28. The difference in the duration of wound healing between the two groups was 9 days. The copper plate heated up to 240°C and pressed by a force of 1.56 n for 14 sec causes a deep rat skin bum of grade III B. The injections of Biosome reduced the healing of a deep skin burn in Group 2 rats by 27% as compared with Group I ones.

Problems of Endocrinology. 2005;51(1):42-45
Biological effects of thyroxine in experimental carcinogenesis
Abduvaliyev A.A., Gildiyeva M.S., Saatov T.S.

The study was undertaken to examine the in vitro and in vivo effects ofthyroxine Т4 at the concentrations of 10ˉ4 M, 10ˉ6 M, 10ˉ M on the proliferative capacity and apoptosis of tumor cells of various pathogenesis. During the investigations, the authors used the unicellular suspension prepared from the surgical material obtained from 2 patients operated on for thyroid nodules (n = 1) and breast tumors in gynecomastia (n = 1) and evaluated the in vivo antitumor and antiproliferative activities of Т4, by using the melanoma B-16 inoculated in C57B1 mice. In the in vitro experiments, Т4 given in a dose of 10ˉ М produced the highest cytotoxic activity against benign thyroid tumor cells (70±4.58%; p < 0.05). When used in this dose, T4 induced the greatest apoptotic death of the cells (9.0±0.90%; p < 0.05) as compared with the controls (1.0±0.30%). The in vitro effect of T4 in doses of 10ˉ4 M, 10ˉ6 M, 10ˉ M on breast tumor cells in the presence of gynecomastia led to a decrease in levels of the oncogenic protein HER2/neu by an average of 27.25±1.14% (p < 0.001). In the in vivo experiments on a model of the tumor strain of melanoma B-16, T4 at the concentrations of 10ˉ4 M, 10ˉ6 M, 10ˉ M showed a high antitumor activity (59.00±5.54%; p < 0.001 of tumor growth suppression by mass and 74.12±0.26%; p < 0.001 by volume). When given in a dose of 10ˉ M, T4 displayed the highest antiproliferative activity (MI, 1.3±0.16%o, p < 0.001; AI, 10.65±1.39%, p < 0.001) as compared with the control group (MI, 4.96±0.43%o; AI, 4.43+0.40%).

Problems of Endocrinology. 2005;51(1):46-49
Thyroid functional features after diagnostic studies with iodine-containing X-ray contrast substances
Yegorov A.V., Sviridenko N.Y., Platonova N.M.

Iodine-containing radiopaque preparations have been widely used for diagnostic purposes. The absolute amount of iodine introduced in this case is 200,000 to 350,000 times the daily requirement for the element. Throughout life, a person consumes only about 3-5 g of iodine, while during coronary angiography the dose of parenterally administered iodine is about 25-52 g. In this regard, the possibility of development should be taken into account when conducting diagnostic studies using radiopaque drugs iodine-induced conditions, especially in people of an older age group, among which the prevalence of thyroid pathology is especially high. The presence of autonomous formations in the thyroid gland (thyroid gland), often unrecognized, can lead to the development of iodine-induced thyrotoxicosis (IIT) after the introduction of pharmacological doses of iodine, which in turn can lead to deterioration in the course of IHD and the development of arrhythmic complications.

We continue discussion the need for screening for the detection of functional thyroid dysfunctions and an ultrasound of the thyroid gland before the introduction of iodine-containing radiopaque drugs. The controversial issue remains the need for preventive treatment with thyreostatic drugs of people at risk of developing IIT.

Problems of Endocrinology. 2005;51(1):50-52
Replacement therapy for hypothyroidism with thyroid hormonal drugs: one or two hormones?
Morgunova Т.В., Fadeyev V.V.

In recent years, along with a large number of works devoted to the problem of subclinical hypothyroidism, the first studies have appeared that raise the problem that was actively discussed in the 70s at the current methodological level - what is the place of L-T3 drugs in hypothyroidism replacement therapy, and does monotherapy L -T4 advantages over combination treatment. Over the past few years, publications have appeared in the literature in which the authors, citing their own clinical experience in the treatment of patients with hypothyroidism, speak out in favor of the combination therapy of L-T3 and L-T4. This review is devoted to a comprehensive analysis of research results in this area.

Problems of Endocrinology. 2005;51(1):53-56

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