ACTA ENDOCRINOLOGICA (BUC)

The mechanism underlying anovulation in the polycystic ovary syndrome (PCOS) remains unclear, although an excessive number of small antral follicles at ultrasound scans and discrepancies with selected follicles sustain the hypothesis of altered follicular development. Anti-M?llerian (AMH) hormone is a member of TGF-b super family of growth factors produced by granulosa cells of pre- and small-antral follicle. The 2 to 3 fold increase in the number of growing follicles in the ovary from PCOS women is reflected by an increase in serum concentration of AMH and thus, this hormone may be a good marker of PCOS.\r\nAim. This study was intended to implement ultra-sensitive ELISA measurement of serum AMH from PCOS women and search for a potential correlation with clinical and laboratory parameters.\r\nSubjects and methods. Sera from patients with PCOS (n = 42) and control women (n = 22) were used for ELISA measurement of AMH (AMH-EIA, Beckman Coulter) with sensitivity of 0.7 pmol/L.\r\nResults. We found a serum concentration of AMH almost 3 folds higher in patients with PCOS compared to controls (73.7 ? 7.5 vs. 25.7 ? 3.9 pmol/L, P < 0.0001). Differences were even higher in lean subjects. A positive correlation was found between total testosterone and LH levels, but not with serum FSH or insulin. Moreover, AMH concentration was correlated to more hyperandrogenic PCOS and with amenorrhea, and thus to the severity of the syndrome.\r\nConclusion. Measurement of serum AMH may be used as a valuable marker for PCOS to confirm diagnosis and evaluate the extent of follicular dysfunction in relation with hyperandrogenism and menstrual disturbances.

Introduction. Surgery for thyroid cancer carries a higher risk of morbidity given the region’s complicated anatomy, the setting of malignancy and extent of the surgery. Aim. To investigate the rate of complications related to the recurrent nerve and parathyroid glands lesions in patients with thyroid carcinoma that undergo thyroid surgery and lymph node dissection. Patients and Methods. The data of 71 patients who underwent total thyroidectomy and 19 patients who underwent total thyroidectomy and central neck dissection with various associated neck dissection techniques were investigated using appropriate statistical tests. Results. As expected, the rate of recurrent nerve injury observed in the neck dissection group was higher than in the total thyroidectomy group (15.7% vs. 2.8%, p=0.05). As for postoperative hypocalcemia, the rate observed in the neck dissection group, both for postoperative day 1 (p<0.0001) and day 30 (p=0.0003) was higher than in the total thyroidectomy group (68.4% vs. 19.7% postoperative day 1, 31.5% vs. 4.2% postoperative day 30). Conclusions. The risk of morbidity concerning the recurrent nerve injury and postoperative hypoparathyroidism increases with the extent of surgery. Extensive surgery may achieve proper oncologic outcomes but increases the risk of postoperative morbidity and decreases quality of life. In deciding for extensive surgery, both patient and medical team need to understand these risks.

Anaplastic thyroid carcinoma (ATC) is the most aggressive type of thyroid\r\ndedifferentiation. Rarely, ATC associates rhabdoid characteristics and only few cases have been\r\npresented to date. We present a case of a thyroid papillary carcinoma which shifted to an\r\naggressive anaplastic form with rhabdoid dedifferentiation and concomitant leukemic reaction\r\nwith eosinophilia. A 76 years old man with a long standing history of a thyroid nodule, noticed\r\nwithin months a rapid growth of the nodule associating marked compression phenomena with\r\nleft deviation of the trachea and esophagus and mild dysphonia. Palliative surgery was\r\nperformed, but the evolution was unfortunate with further health deterioration (fatigue, dyspnea,\r\ndysphagia, loss of appetite and weight loss). Laboratory tests proved leukocytosis with\r\nneutrophilia and left deviation of leukocytes formula, with major eosinophilia. The pathology\r\nshowed a thyroid papillary carcinoma with anaplastic changes. By immunohistochemistry,\r\nit was confirmed the thyroid origin of the tumor (thyreoglobulin positive areas) but also the\r\nepithelial nature of the undifferentiated areas (positive areas for cytokeratin and epithelial\r\nmembrane antigen). Moreover, in the anaplastic areas, rhabdoid differentiation was\r\nidentified by positive coloration against vimentin, protein S100 and desmin. The tumor was\r\naggressive by its anaplastic transformation, confirmed by a high proliferation index (Ki67:\r\n40% positive). The computed tomography was concordant with the phenotype predicted by\r\nhistological description showing a malignant thyroid tumor, invading cervical and mediastinal\r\nareas with secondary lung disseminations. Unfortunately, the outcome was fatal even though\r\nadditional treatment methods have been tried: radiotherapy and chemotherapy. The\r\nparticularities of this case reside in the very rare dedifferentiation of a papillary thyroid\r\ncarcinoma towards an anaplastic thyroid carcinoma harboring the rhabdoid phenotype and\r\nalso its association with eosinophilia.

OBJECTIVE: To report an unusual cause of respiratory failure in a 33-year old Caucasian woman, diagnosed at 26 years with pulmonary lymphangioleiomyomatosis (LAM) and treated with gonadoliberin analogs (aGnRH) four years.\r\nMETHODS: The respiratory failure was diagnosed on functional tests (spirometry, oxymetry, diffusing capacity of carbon monoxide). High resolution chest computed tomographic (HRCT) scan and open lung biopsy with specific immunohistochemistry certified the diagnosis.\r\nRESULTS: The diagnosis of pulmonary LAM was established after one year on chest HRCT and lung biopsy which revealed the proliferation of smooth muscle of pulmonary vessels, positive for actin, desmin, vimentin, estrogen- and progesterone- receptors. Spirometry revealed mixed obstructive and restrictive dysfunction. A correlation between worsening of dyspnea and estradiol peaks occurred during three gestation periods. Despite a short treatment with medroxyprogesterone 10 mg/day and tamoxifen (20 mg/day), the patient?s symptoms and pulmonary function tests worsened. aGnRH treatment improved both symptoms and pulmonary function tests during the first year and was associated with a slow decline in pulmonary function tests and stabilization of the cystic lesions during the following 3 years. The patient did not develop LAM-complications such as: pneumothorax, chylothorax, or hemoptysis.\r\nCONCLUSION: Treatment with aGnRH is effective in slowing the evolution of pulmonary LAM.

In response to increasing interest of the European Commission on large-scale\r\ngenotyping for complex diseases, including variability in ethnic minorities in\r\nEurope (HEALTH-2009-4.3.3-1), at the end of 2008 we composed the\r\nHAPLOGENDIS consortium with partners from Russia and European countries. A\r\nfirst program (SICA) was proposed in cooperation with Russian Federal Agency for\r\nScience and Innovation, focusing on comparative population genetics on diseases\r\naccompanied by insulin resistance. Beside the specificity in analyzing the human\r\ngenome with SNP (single nucleotide polymorphism) and defining haplotype\r\nstructure of genes, the program rises new hypotheses which directly link\r\ncolonization of Europe at the Neolithic period from Eastern Ukraine or Anatolia\r\nwith the development of agriculture and major dietary and life style changes that\r\nmay have an impact on the genome. Although there will be many occasions to\r\nreview both genetic and clinical detailed aspects, this short note will expose some\r\nunifying ideas that joint these partners.

Aims: To assess if amiodarone maintains its antiarrhythmic efficacy in the presence of amiodarone-induced hyperthyroidism (AIT) and to identify the tri-iodothyronine (T3) threshold for atrial fibrillation in patients with AIT versus common hyperthyroidism.\r\nPatients and methods. Study group A consists in 49 patients (25 M/24 F) with AIT (220.83 ? 71.33 mg/day along 2.36 ? 2.25 years) and severe cardiopathies (9 valvulopathies, 40 ischaemic, dilatative and hypertensive cardiomyopathies), aged 57.87?12.63 years. Control group B consists in 51 hypothyroid (B1) or euthyroid patients (B2) treated with amiodarone (222.55 ? 68.78 mg/day along 2.67 ? 1.84 years) and also in 100 patients (23M/77F) with overt hyperthyroidism (B3), without major heart diseases, aged 52.74?12.85 years; TSH, total T3, total T4, free T4 were measured by radioimmunoassay. All were clinically, ECG and echocardiography evaluated.\r\nResults. Prevalence of arrhythmias recurrence was 59.2% (29/49 patients) in group A, significantly higher than in each control subgroups B: B1- 28% (7/25), B2- 15.45% (4/26) and B3- 20% (20/100), P< 0.001. Patients from study group A with AIT and T3 levels >250 ng/dL developed significantly more frequent atrial fibrillation (p= 0.04). However, in control group B3 with common hyperthyroidism, no T3 threshold for arrhythmias could be identified. Overall, there were no significant differences in total T3 levels with respect to the presence of atrial fibrillation in both study group A and subgroup B3 with common hyperthyroidism (p=ns).\r\nConclusion. Amiodarone antiarrhythmic efficacy is surpassed in AIT by the increased arrhythmic susceptibility of damaged myocardial tissue to minimally increased thyroid hormones levels. A tri-iodothyronine level > 250 ng/dL superimposed on preexistent proarrhythmic substrate in amiodarone-induced hyperthyroidism should be avoided.

Chronic transfusion regimen and chelating therapy has dramatically improved the life expectancy of thalassemic patients. The aim of this study was to assess the prevalence of endocrine disturbances in patients with beta-thalassemia major. Subjects were 64 patients with a mean age of 19.45 ? 6.82 years found in haematological care at the National Institute of Transfusional Haematology. All the patients were evaluated clinically and biologically. LH, FSH, estradiol, testosterone, TSH, free T4, insulin were measured by chemiluminescence; mean ferritin value was used to assess iron overload. Fifty one patients (79.68%) -27 male and 24 female in our group were at pubertal or adult age. Eleven boys (40.74%) had delayed puberty, 10 (37%) arrested puberty and 4 (14.8%) had reached complete sexual maturation. In the female group, 6 (25%) had delayed puberty, 4 (16.66%) arrested puberty and 14 (58.32%) reached full sexual development. Half of both the male and female patients with complete sexual maturation had hypogonadotropic hypogonadism at the evaluation moment. Moreover, 34 (53.12%) of our patients had pathological short stature, 11 (17.18%) primary hypothyroidism, 5 (7.8%) hypoparathyroidism, 3 (4.68%) diabetes mellitus and 6 (9.37%) insulin resistance. We found a significantly higher mean ferritin value in patients with endocrine disturbances of any type compared to subjects without endocrinopathies. In conclusion, our data showed that hypogonadism and short stature were the most frequently found endocrine disturbances. Early form of hypogonadism had a major clinical impact on sexual development and final height. These results suggest that early endocrine evaluation and treatment are necessary in order to improve the quality of life of these patients.

Aim: to evaluate the impact of hyperthyroidism on glycemic control among patients with diabetes mellitus (DM).\r\nResearch design and methods: This retrospective study included patients with hyperthyroidism and DM admitted in Endocrinology, Nutrition Diseases and Diabetes Department of Elias University Emergency Hospital. We evaluated 37 patients (35 women/ 2 men), with a mean age of 54.7?15.3 years and duration of diabetes 8.1?7.49 years; 20 patients with Graves diseases (54%), 10 with toxic multinodular goiter (27%), 5 with autonomous hyperfunctioning adenoma (13%) and 2 with amiodarone induced hyperthyroidism (5.4%). Clinical data were recorded for all our patients, as well as thyroid ultrasound exploration, laboratory analyses (glycosylated hemoglobin, free thyroxine FT4, triiodothyronine T3, thyroid stimulating hormone TSH).\r\nResults: Diabetes control was achieved with: insulin in 23 (62%) patients, antidiabetic oral agents in 9 (24%) and solely diet in 5 patients (13.5%). Hyperthyroid patients had a mean value of glycosylated hemoglobin of 9.3%?2.4% (poor glycemic control) versus 7.2%?1.6% after the treatment of hyperthyroidism. Among insulin-treated patients, the average need of insulin in hyperthyroid status was 0.72 u/kg versus 0.55 u/kg when the patients became euthyroid (p<0.01). We found a significant association between type 1 diabetes mellitus and Graves&#8217; disease compared to toxic multinodular goiter (80% vs 50%, p<0.01).\r\nConclusions: The presence of hyperthyroidism aggravates glycemic control of the patients with diabetes mellitus and increases insulin need in insulin-treated patients. Once the thyroid function was stable, the insulin need decreased significantly (p<0.01). Hyperthyroidism should be radically treated to obtain a good glycemic control. Type 1 diabetes is significantly associated to Graves&#8217;s disease by an autoimmune mechanism.

The incidence of type 2 diabetes is continuously growing worldwide, with enormous costs for individuals as well as for society. In the last decades, bariatric surgery has emerged as a possible solution for ameliorating metabolic control or even obtaining diabetes remission. Observational trials and metaanalyses demonstrate consistent improvement of type 2 diabetes following various bariatric procedures, but they are generally uncontrolled or they use historic controls as comparators. In recent years, several randomized trials studying the effectiveness of bariatric surgery in type 2 diabetes have been conducted and they all show substantial benefits, with the observation that the majority are shortterm trials. With the increased popularity of diabetes surgery, concerns about its immediate and long-time safety have also grown. The most frequent peri-operative are ulcers or stenosis, obstruction, venous thrombosis, pulmonary embolism and other pulmonary complications, with a mortality of less than 1%. Gastro-intestinal diseases, nutritional deficiencies and psychiatric disorders are the most important longterm problems to be addressed. The uncertainty regarding the long-term effects of bariatric surgery, together with its potential for morbidity and mortality, underline the necessity of large, long-term, randomized clinical trials comparing the best medical therapy with bariatric surgery in patients with type 2 diabetes.

Aims. To investigate the effect of sulphonylurea (SU) treatment on all-cause and cardiovascular mortality as compared with metformin (MET), when used in combination with insulin (INS) in type 2 diabetes. Methods. All type 2 diabetes patients aged ≥40 years were included at their first prescription of INS+MET or INS+SU, during 2001-2008. They were considered at risk until death or December 31st, 2011. Mortality rates were calculated per 1000 person-years. Crude and adjusted rate ratios (RR) were calculated using time dependent analysis with INS+MET as reference. Results. There were 7122 patients (60.8% women) included in the analysis, with a mean age at baseline of 62.0±9.9 years. During the 11 years of study, patients on INS+MET contributed 13620 person-years and 330 deaths (mortality rate 24, CI95% 22-27), while those on INS+SU contributed 8720 person-years and 393 deaths (mortality rate 45, CI95% 41-50). Adjusted all-cause mortality RR were: SU 1.6 (CI95% 1.21-2.11, p<0.001), glimepiride 1.18 (CI95% 0.73-1.91, p=0.51), gliclazide 1.78 (CI95% 1.07-2.95, p=0.024), glibenclamide 1.66 (CI95% 0.71-3.88, p=0.23), glipizide 1.24 (CI95% 0.68-2.27, p=0.49), and gliquidonum 2.32 (CI95% 1.54-3.50, p=0.001). Conclusions. When combined with insulin as dual therapy, patients treated with SU were at increased mortality risk as compared with insulin + MET.