Treatment of Obesity with Thyroid hormones in Europe. Data from the THESIS* Collaboration.

PURPOSE: The use of thyroid hormones (TH) to treat obesity is unsupported by evidence as reflected in international guidelines. We explored views about this practice, and associations with respondent characteristics among European thyroid specialists. METHODS: Specialists from 28 countries were invited to a survey via professional organisations. The relevant question was whether "Thyroid hormones may be indicated in biochemically euthyroid patients with obesity resistant to lifestyle interventions". RESULTS: Of 17,232 invitations 5695 responses were received (33% valid response rate; 65% women; 90% endocrinologists). Of these, 290 (5.1%) stated that TH may be indicated as treatment for obesity in euthyroid patients. This view was commoner among non-endocrinologists (8.7% vs. 4.7%, p < 0.01), private practice (6.5% vs. 4.5%, p < 0.01), and varied geographically (Eastern Europe, 7.3%; Southern Europe, 4.8%; Western Europe, 2.7%; and Northern Europe, 2.5%). Respondents from Northern and Western Europe were less likely to use TH than those from Eastern Europe (p < 0.01). Gross national income (GNI) correlated inversely with this view (OR 0.97, CI: 0.96-0.97; p < 0.001). Having national guidelines on hypothyroidism correlated negatively with treating obesity with TH (OR 0.71, CI: 0.55-0.91). CONCLUSIONS: Despite the lack of evidence, and contrary to guidelines' recommendations, about 5% of respondents stated that TH may be indicated as a treatment for obesity in euthyroid patients resistant to life-style interventions. This opinion was associated with (i) respondent characteristics: being non-endocrinologist, working in private practice, treating a small number of hypothyroid patients annually and (ii) national characteristics: prevalence of obesity, Eastern Europe, low GNI and lack of national hypothyroidism guidelines.

[Psychopathological syndromes with sleep disorders in patients with type 2 diabetes mellitus]. / Psikhopatologicheskie sindromy s rasstroistvami sna u patsientov s sakharnym diabetom 2-go tipa.

Sleep disorders are very common in patients with type 2 diabetes (T2DM) and psychiatric disorders. Sleep disturbances can be both an independent condition and are one of the symptoms in the structure of a psychopathological syndrome. The negative impact of sleep disorders and mental disorders on the course of T2DM is known from numerous publications. This article presents current information on the mutual influence of mental disorders and sleep disorders on the course and prognosis of T2DM.

[Manifestation of Graves' disease, resulting from radiosurgical treatment of acromegaly, in a patient with panhypopituitarism].

Cases of thyrotoxicosis associated with a previous case of secondary hypothyroidism are extremely rare. This article presents a rare clinical case of Graves' disease manifestation in a patient with secondary hypothyroidism after radiosurgical treatment of acromegaly. A 38-year old woman presented with acromegaly and endo-supra-laterosellar pituitary adenoma. After non-radical removal of the pituitary adenoma, radiosurgical treatment of the of the residual tissue of the pituitary tumor in the cavernous sinus area was performed. After 14 months of radiation therapy, the acromegaly was in remission; after 24 months of radiation therapy, panhypopituitarism developed (secondary hypothyroidism, adrenal insufficiency, hypogonadism, and growth hormone deficiency). Furthermore, 1.5 years after the panhypopituitarism was diagnosed, the manifestation of Graves' disease was also noted, requiring thyrostatic and radioactive iodine treatments. Diagnostic criteria for secondary hypothyroidism are low levels of the thyroid hormones free T4 and free T3, with a reduced, normal or slightly elevated level of thyroid stimulating hormone (TSH). The criterion for the development of thyrotoxicosis in the context of the secondary hypothyroidism was the persistent increase in the level of free T4 despite adequate drug therapy with levothyroxine. In the case report, the patient's diagnosis of Graves' disease was confirmed by the presence of a high level of antibodies to the TSH receptor.

[Pretibial myxedema: pathogenetic features and clinical aspects].

Pretibial myxedema (PTM) or thyroid dermopathy is a rare extrathyroidal manifestation of Graves' disease. The condition is accompanied by mucinous skin changes, mainly in the anterior tibial surface. Severe forms may lead to lymphatic congestion and disability. Prolonged and intense autoimmune aggression is supposed to be necessary for PTM manifestation. However, data on the role of TSHR antibodies in the development of thyroid dermopathy are very ambiguous; evidence of IGF-1 receptor involvement in the pathogenesis was reported recently. Typically, PTM is localized on the anterior and lateral surfaces of both tibias and can be represented by diffuse, tumorous, plaque-like, or elephantiasic forms. Currently, early diagnostics involves regular preventive examination of the pretibial area. A diagnostic biopsy is indicated only in complex cases. Maintaining euthyroidism, smoking cessation, preventing injuries, and avoiding tight shoes that disturb lymphatic drainage are measures reducing the risk of PTM in GD patients. Currently, there are no accepted clinical guidelines for the diagnosis and treatment of thyroid dermopathy. This review provides the recent scientific data on etiopathogenesis and management of patients with PTM.

[Virilizing ovarian tumor: the challenges of differential diagnosis].

SertoliLeydig cell tumor is a rather rare type of ovarian neoplasms belonging to the group of sex cordstromal tumors. This malignancy is characterized by androgen overproduction, which results in the so-called virilization and can be accompanied by various metabolic disorders such as abdominal obesity, disturbances of carbohydrate and protein metabolism, and high blood pressure. During differential diagnosis, it is important to identify the source of androgen overproduction. An androgen-secreting ovarian tumor needs to be differentiated from androgen-secreting adrenal tumor, ovarian stromal thecomatosis (hyperthecosis), and endogenous hypercorticism (the Cushings syndrome). In most cases, the SertoliLeydig cell tumor is associated with DICER1 mutation carriership. If a patient is found to carry the DICER1 mutation, patients relatives need to undergo genetic testing as the individuals with mutations in this gene have an elevated risk of developing a broad range of benign and malignant tumors (most of these tumors are relatively rare in the overall population). The awareness of this rare ovarian neoplasm among medical specialists (obstetriciansgynecologists, endocrinologists, and oncologists) is supposed to ensure timely diagnosis and adequate treatment of this disease.

[Dynamics of prevalence of functional thyroid dysfunctions among pregnant women in Moscow from 1999 to 2008].

The objective of this study was to study dynamics of prevalence of functional thyroid dysfunctions among pregnant women. The levels of TSH, free T4, and antithyroid peroxidase antibodies (ATP-AB) were measured in randomly selected women of different gestational age who applied to be registered in a maternity welfare centre in 1999-2003 (n = 215) and 2006-2008 (n = 325). The available data indicate that iodine consumption by the study populations increased during the above periods even if still remains subnormal. No statistically significant decrease in the occurrence of ATP-AB and hypothyroidism was recorded. Women carrying ATP-AB in the first and seconds trimesters of pregnancy had significantly higher TSH levels compared to those without ATP-AB. A change of diagnostic criteria for hypothyroidism (lowering the reference TSH threshold from 4.0 to 2.5 mU/l accounts for a several-fold rise (by a factor of 2-7) in the prevalence of hypothyroidism among pregnant women.

[Postpartum thyroiditis: risk factors, differential diagnosis, clinical features].

Postpartum thyroiditis (PT), one of the commonest causes of disturbed thyroid function (TF), is believed to occur in 5% of the women. The present study involving 57 patients with PT was designed to study risk factors and clinical features of this pathology as well as approaches to its diagnosis. Two control groups comprised female carriers of anti- thyroid peroxidase antibodies (TPO-AB) without PT and women having symptoms of Graves disease (GD) in the postpartum period, respectively. Patients with PT were shown to have significantly elevated TPO-AB levels during pregnancy compared with controls. Postpartum GD manifested itself later than PT, it was associated with a significantly higher freeT4 level and a greater thyroid volume. In twenty of the 57 women with PT, it was manifest in the thyrotoxic phase and in the remaining 37 in the hyperthyroid state. The TSH level in the first half of pregnancy was significantly higher in the women that eventually developed a monophasic hypothyroid variant of PT. In the same group, the TPO-AB level at the time of PT diagnosis was significantly higher than in the biphasic variant of PT. Forty (70%) of the 57 women with PT recovered to an euthyroid state by the end of the study whereas in 17 (30%) hypothyroidism persisted. The biphasic variant of PT was manifest starting from the thyrotoxic phase and more frequently ended in the recovery to the euthyroid state (90%) than the monophasic one, the difference being statistically significant. In contrast, the monophasic hypothyroid variant more frequently resulted in persistent hypothyroidism (40%).

Analysis of extended human leukocyte antigen haplotype association with Addison's disease in three populations.

OBJECTIVE: Addison's disease is an organ-specific autoimmune disorder with a polygenic background. The aim of the study was to identify non-class II human leukocyte antigen (HLA) susceptibility genes for Addison's disease. DESIGN AND METHODS: Addison's disease patients from three European populations were analysed for selected HLA-DR-DQ alleles and for 11 microsatellite markers covering approximately 4 Mb over the HLA region. Subjects were 69 patients with Addison's disease from Estonia (24), Finland (14) and Russia (31). Consecutively recruited healthy newborns from the same geographical regions were used as controls (269 Estonian, 1000 Finnish and 413 Russian). Association measures for HLA-DRB1, DQB1, DQA1 and 11 microsatellites between D6S273 and D6S2223 were taken. A low-resolution full-house typing was used for HLA class II genes, while microsatellite markers were studied using fluorescence-based DNA fragment sizing technology. RESULTS: We confirmed that the HLA-DR3-DQ2 and the DQB1*0302-DRB1*0404 haplotypes confer disease susceptibility. In Russian patients, we also found an increase of DRB1*0403 allele, combined with DQB1*0305 allele in three out of six cases (P<0.0001). Analysis of 11 microsatellite markers including STR MICA confirmed the strong linkage in DR3-DQ2 haplotypes but DRB1*0404-DQB1*0302 haplotypes were diverse. MICA5.1 allele was found in 22 out of 24 Estonian patients, but results from Finnish and Russian patients did not support its independent role in disease susceptibility. CONCLUSION: HLA-DRB1*0403 was identified as a novel susceptibility allele for Addison's disease. Additionally, we found no evidence of a non-class II HLA disease susceptibility locus; however, the HLA-DR3-DQ2 haplotype appeared more conserved in patient groups with high DR-DQ2 frequencies.

[Risk factors of thyrotoxic cardiomyopathy].

A retrospective study covered 272 patients (mean age 54 years) admitted for different forms of toxic goiter concurrent with cardiac arrhythmias and/or sings with heart failure (HF), which was undertaken to explore risk factors of thyrotoxic cardiomyopathy (TTCM). Cardiac arrhythmias following the pattern of sinus tachycardia and/or supraventricular extrasystole without signs of HF were observed ПРОБЛЕМЫ ЭНДОКРИНОЛОГИИ. 2007. Т. 53, № 4. in S3 (19.5%) out of the 272 patients (a mild TTCM group - TTCM-1) whereas cardiac arrhythmias as atrial fibrillations and/or flutters and/or the devebpment of HF In the presence of thyrotoxicosis (TT) were detected in 219 (80.5%) of the 272 patients (a severe TTCM group - TTCM-2). Indices, such as admission age, an interval between TT detection and the initiation of treatment, a history of endocrine ophthalmopathy and cardiovascular pathology, were examined in the regression analysis considering the severe course of TTMC as a poor predictor. Comparison of the groups revealed statistically significant differences in such Indices, as the interval between TT identification to therapy (OR = 1.8; 95% CI = 1.06-3.13; p = 0.02) and the patients' age at the moment of admission (OR = 1.1, 95% CI = 1.02-1.15; p= 0.01).

[Medical treatment for Graves' disease: principles, markers of a relapse and remission].

Graves' disease (diffuse toxic goiter) is a systemic autoimmune disease that develops as a result of the production of antibodies to the thyroid stimulating hormone receptor (AT-rTSH), which is clinically manifested by thyroid damage with the development of thyrotoxicosis syndrome in combination with extrathyroid pathology (pretibial endocrine) myxedema, acropathy). The disease was first described by S. Ives in 1722, then Peri in 1786 and Flayani in 1802. In 1835, R. Graves associated the occurrence of the described symptom complex, now known as thyrotoxicosis syndrome, with thyroid pathology. In 1840, K. Bazedov singled out a triad in the clinical picture: goiter, buccalis, tachycardia.

[Long-term results of treatment of toxic goiter with radioactive 131I].

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.

[Replacement therapy for hypothyroidism with thyroid hormonal drugs: one or two hormones?]

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.

[Thyroid-stimulating hormone receptor antibodies in the differential diagnosis of toxic goiter].

The production of stimulating thyroid-stimulating hormone (TSH) receptor antibodies (TSHR-Ab) whose level measurement has come into clinical use underlies the pathogenesis of Graves'disease (GD). This paper deals with the diagnostic and differentially diagnostic value of measurement of TSHR-Ab levels using two first-generation techniques (with heterological TSH): radioreceptor assay ("CIS bio international", France) and enzyme immunoassay ("Medizym" T.R.A."). The levels of TSHT-Ab, as well as thyroid peroxidase antibodies (TH-Ab) and thyroglobulin antibodies (TG-Ab) were studied in 206 patients among whom 176 patients were diagnosed as having GD and 30 had clinical thyroid functional autonomy (FA) generally appeared as multinodal toxic goiter. A comparative analysis of these two assays did not reveal some advantages of them and their results showed a significantly positive correlation (r = 0.91; p < 0.001). The diagnostic sensitivity of the assays was about 80-88% and their specificity was 60-70%. The findings led to the conclusion that in the absence of significant endocrine ophthalmopathy (EOF), clinical and routine instrumental and laboratory studies fail to differentiate GD and throid FA to sufficient accuracy whereas the measurement of the levels of TSHR-Ab substantially makes diagnosis easier. Moreover, it has been shown that the determination of the level of TBII using the test systems containing heterological TSH may not be used for the evaluation of the course of EOF.

[Thyroid cancer].

The prevalence of nodular lesions of the thyroid gland (thyroid gland), according to various researchers, ranges from 3 to 7%]. The widespread introduction of ultrasound (ultrasound) in clinical practice, as well as the results of autopsy studies, showed that the prevalence of nodular lesions of the thyroid gland is much higher and is about 50%, especially at the age of over 50. In women, thyroid nodes are detected 2-4 times more often than in men. Children suffer from nodular lesions extremely rarely. The incidence of nodular goiter is directly proportional to age. The increase in the incidence of nodular goiter is approximately 0.1% per year at a young age and gradually reaches 2%. The prevalence of thyroid cancer (thyroid cancer) among nodular goiter, according to various authors, is from 1 to 6%. It should be noted that the prevalence in the population of nodular goiter is so high both in the regions of iodine deficiency and with normal iodine supply, but in the first case it is slightly higher. The incidence of thyroid cancer in absolute terms does not depend on the level of iodine supply. Thus, in a situation of a slightly higher incidence of banal nodular colloid goiter in the regions of iodine deficiency, the proportion of cancer among all cases of nodular goiter will be less. It is important to note that these data make it possible to equally use the results of studies on thyroid cancer obtained in regions with different iodine supply.

[Clinical guidelines developed by the Russian Association of Endocrinologists for the diagnosis and treatment of nodular goiter].

The guidelines presented do not pretend to be a systematic presentation of all aspects of the diagnosis and treatment of nodular goiter and are not intended to replace guidelines for various medical disciplines. In real clinical practice, situations may arise that are beyond the scope of the recommendations presented, in connection with which the final decision regarding a specific patient and responsibility for him lies with the attending physician.The recommendations presented are mainly devoted to the diagnosis and treatment of nodular (multinodular) euthyroid colloid, differently proliferating goiter in adults (over 18 years of age) and are the agreed opinion of the RAE experts who developed them. Nodular (multinodular) toxic goiter, tumors (malignant and benign), as well as other diseases that can manifest themselves by nodular formations of the thyroid gland (thyroid gland), are discussed mainly in the context of differential diagnosis. The recommendations also do not affect the features of diagnosis and treatment of nodular goiter in children and adolescents.

Prevalence of thyroid disorders in pregnant women with mild iodine deficiency.

To assess the prevalence of thyroid disorders in a region with mild iodine deficiency, this study was undertaken in a randomized sample of pregnant women during different gestational periods. Evaluations were performed in 215 women: thyroid ultrasound scanning, thyroid stimulating hormone (TSH), free thyroxine (T4) and thyroid peroxidase (TPO) antibodies. At the time of participation in the study, some women (90/215) had been receiving 150-200 micrograms iodine. Hypothyroidism was found in four women (1.86%). Positive TPO antibodies were seen in 34 of 215 women (15.8%), and TPO antibody level over 150 mU/l was found in 9.8% (21/215). There was no significant difference between TSH levels in women with positive or negative TPO antibodies. There were no differences in TSH level between the women receiving and those not receiving iodine prophylaxis. The prevalence of goiter in 211 euthyroid women was found to be 24.2% (51/211). in the group with iodine prophylaxis, thyroid volume was found to be significantly lower (t = 2.5; p = 0.02) than in women who had not received it, or had started it during the second trimester. By comparison of history data on the prevalence of aborted pregnancy between the group with positive (26.5%; 9/34) and the group with negative TPO antibodies (14.3%; 26/181), no significant differences were found. We conclude that, in mild iodine deficiency, pregnancy is related to a high risk of goiter, which can be prevented by iodine prophylaxis. TPO antibody carrier status in pregnant women is probably not associated with a significant risk of thyroid dysfunction or spontaneous abortion.

Branching fraction and photon energy spectrum for b --> s gamma.

We have measured the branching fraction and photon energy spectrum for the radiative penguin process b-->s gamma. We find Beta(b-->s gamma) = (3.21+/-0.43+/-0.27(+0.18)(-0.10))x10(-4), where the errors are statistical, systematic, and from theory corrections. We obtain first and second moments of the photon energy spectrum above 2.0 GeV, = 2.346+/-0.032+/-0.011 GeV, and -(2) = 0.0226+/-0.0066+/-0.0020 GeV(2), where the errors are statistical and systematic. From the first moment, we obtain (in the modified minimal subtraction renormalization scheme, to order 1/M(3)(B) and beta(0)alpha(2)(s)) the heavy quark effective theory parameter Lambda = 0.35+/-0.08+/-0.10 GeV.

Hadronic mass moments in inclusive semileptonic B meson decays.

We have measured the first and second moments of the hadronic mass-squared distribution in B-->X(c)l nu, for P(lepton)>1.5 GeV/c. We find = 0.251+/-0.066 GeV(2), <(M(2)(X)-)(2)> = 0.576+/-0.170 GeV(4), where M macro(D) is the spin-averaged D meson mass. From that first moment and the first moment of the photon energy spectrum in b-->s gamma, we find the heavy quark effective theory parameter lambda(1) (in the modified minimal subtraction renormalization scheme, to order 1/M(3)(B) and beta(0)alpha(2)(s)) to be -0.24+/-0.11 GeV(2). Using these first moments and the B semileptonic width, and assuming parton-hadron duality, we obtain absolute value of V(cb) = 0.0404+/-0.0013.

Novel AIRE mutations and P450 cytochrome autoantibodies in Central and Eastern European patients with APECED.

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare recessive disorder that results in several autoimmune diseases due to the mutations in the AIRE (autoimmune regulator) gene. APECED patients develop several autoimmune endocrine disorders and are characterized by the high titer autoantibodies to organ-specific antigens such as the steroidogenic P450 cytochromes. So far, 38 mutations have been identified in the AIRE gene. We report here the genetic and autoantibody analysis of 27 APECED patients of Eastern and Central European origins and one Egyptian patient. From 54 analyzed APECED chromosomes, eight mutations were detected, four of which (T16M, W78R, IVS1_IVS4, 30-53dup23bp) are novel. The most prevalent reason for APECED in these populations was the occurrence of R257X (36 chromosomes) that has been described earlier as a common and recurrent mutation in several other populations. The analysis of humoral immunity to steroidogenic P450 cytochromes by the immunoblotting of E. coli expressed antigens in the 18 APECED patients showed that 67%, 44%, and 61% of the Eastern and Central European APECED patients had autoantibodies to P450c17, P450c21, and P450scc, respectively.