ACTA ENDOCRINOLOGICA (BUC)

Polycystic ovary syndrome (PCOS), the main cause of androgen excess in women of reproductive age, is a multifaceted, dynamic and clinically heterogenic disorder. Rotterdam 2003 ESHRE/ASRM definition criteria were recently reinforced at the NIH Consensus Meeting 2012. Concomitant identification of the clinical phenotypes of the syndrome is mandatory in medical care and clinical studies, as these are strongly related to reproductive, cardiovascular and metabolic outcomes. Documentation of polycystic ovarian morphology (PCOM) is challenging, with the AE/PCOS Task Force 2014 suggesting a threshold of ≥25 follicles/ovary in 18- 35 years old women when using high-frequency transducers. Elevated levels of total testosterone and/or free testosterone and/or low sex hormone-binding globulin (SHBG) stand for androgen excess in women, as stated by the ESE Position Statement 2014. Despite evidence of increased metabolic and cardiovascular risk, increased prevalence of cardiovascular events linked to PCOS status per se is still insufficient documented, mainly because of the clinical heterogeneity of studies populations and lack of prospective data. First-line therapy in the medical management of PCOS is metformin, at least 1.5 g/d, in all patients with documented insulin resistance and hyperinsulinemia. According to Endocrine Society Guidelines 2013, other insulin-sensitizers (e.g. thiazolidinediones) raise safety concerns on the long-term, whereas statins need further evaluation to demonstrate their benefits in the treatment of PCOS, however, are indicated in dyslipidemic patients. Anti-androgens and combined oral contraceptives (COC) are targeting androgen excess, particularly in non-insulin resistant patients, with an overall benefit to risk ratio in PCOS favoring benefits.

Context. Besides its typical features, hypothyroidism comes to notice sometimes with neurologic features like reversible cerebellar ataxia, dementia, peripheral neuropathy, coma, etc. Therefore hypothyroidism should be suspected in all cases of cerebellar ataxia, as it is easily treatable. Objective. Here we illustrate a case of hypothyroidism initially reported with cerebellar ataxia. Case report. A 40 year-old male presented with history of gait-ataxia. His investigations revealed frank primary hypothyroidism with positive anti-TPO antibody. The patient was put on thyroxine and he improved completely within eight weeks. Conclusions. This case report emphasizes that hypothyroidism can present with ataxia as one of the initial features. Therefore, hypothyroidism should be considered in all cases of cerebellar ataxia as it is a reversible cause of ataxia

Alzheimer’s disease(AD) is the leading cause of dementia and is characterized by the presence of extensive plaque deposition and neurofibrillary pathology. The aim of the present study was to make an update regarding the influence of estrogens and SERMs on inflammation and on the resolution of inflammation, respectively, focusing on these most important features implicated in the pathophysiology of AD. Several hypothesised mechanisms of action of estrogens and SERM are exposed and also some relevant clinical studies on this subject are analysed. The analyzed studies have a high heterogeneity of preparations used, of administration routes, of the female population included and of the periods of time from the appearance/ induction of menopause to the therapeutic intervention and also of follow-up periods of patients and of the means of evaluating their cognitive decline. One can say that all the ways of pharmacological influence on the membrane or intracellular signalling system associated to estrogens that may have clinical importance in the prevention and possibly in the treatment of AD have not been exhausted. Estrogens with selective ERα or G protein-coupled estrogen receptors (GPER1 or GqMER) effects could be used to influence the resolution of inflammation process, with positive effects on AD evolution.

Radioiodine treatment of hyperthyroidism is easy to perform, has a low cost and presents a low risk adverse effects.\r\nDespite many reports on the efficiency and results, the number of studies investigating the efficiency of radioiodine treatment in subclinical hyperthyroidism is limited.\r\nAim. Therefore, this study aimed to investigate the efficiency of radioiodine treatment in subclinical hyperthyroidism.\r\nMethods. The study involved 50 patients with subclinical hyperthyroidism (42 females, 8 males, mean age: 60.3?10.8)\r\ntreated by radioiodine in our department. Thirtyfour (68%) of the 50 patients had multinodular hyperplasia; 9 (18%) had diffuse hyperplasia, and 7 (14%) had solitary nodule.\r\nThe patients were applied I-131 treatment with a dose of 5-20 mCi (mean 11.52?3.63 mCi) based on the thyroid gland volumes, TSH levels, age, any clinical findings, and\r\nalso, the type of hyperplasia (diffuse or nodular hyperplasia). The patients were followed for 5.13 to 46.5 months (mean: 24.62?11.47).\r\nResults. Forty-three (86%) of the 50 patients were euthyroid after a mean of 2.36?1.18 months following radioiodine\r\ntreatment. The mean dose of radioiodine was 11.91?3.73 mCi. Only 5 (10%) of 50 patients developed hypothyroidism 1-5 months (mean: 2.8?1.48) after radioiodine therapy with 8-10\r\nmCi (mean: 8.4?0.89) I-131 administration. When hypothyroidism is also considered as a criterion for cure in addition to euthyroidism, the success rate of radioiodine treatment was 96% (48/50) in the patients with subclinical\r\nhyperthyroidism.\r\nConclusion. Radioiodine treatment provides quick and high efficiency of recovery, easy application, and quick\r\nadaptation by patient; thus, it can be a preferred choice of subclinical hyperthyroidism treatment, particularly for the\r\nelderly patients who cannot adapt treatment with antithyroid tablets easily.

A 63-years old patient with severe thyrotoxicosis with cachexia and high frequency atrial fibrillation showed an inadequate secretion of TSH. A pituitary macroadenoma was revealed by computed tomography. Acute octreotide administration decreased serum TSH\r\nfrom 2.48 mU/mL to 0.06 mU/mL and T3 from 3.1 ng/mL to normal values (0.93 ng/mL) in 3 days; at the same time serum T4 remained unchanged (raised).The response to octreotide supported the diagnosis of TSH-secreting adenoma. T3 suppression test is no longer useful at present for diagnosis.Administration of long- acting somatostatin analogues (lanreotide) together with antithyroid drugs (ATD) was initially necessary. However, after removal of pituitary tumor the clinical symptoms (including atrial fibrillation) disappeared.ATD administration was no longer necessary, nor was octreotide or lanreotide. Immunohistochemistry certified that the pituitary tumor was a pure thyrotropinoma (without plurihormonal expression). Complete cure of severe thyrotoxicosis due to a TSH-secreting pituitary adenoma by pituitary surgery is possible. Thyroidectomy is not indicated.

Aim. To evaluate the malignancy rates of Atypia of undetermined significance /follicular lesion of undetermined significance (AUS/FLUS) cases in the light of clinical and sonographic features. Material and Methods. The percentage of AUS/ FLUS cases, second fine needle aspiration cytology (FNAC) results, cyto-histopathological correlations and risk of malignancy were analyzed. Results. 113 out of 1461 thyroid FNAC samples (7.7%) were diagnosed as AUS/FLUS and included in the study. Seventy three out of 113 cases (64.6 %) underwent repeat biopsies or surgery. From 45 cases repeat biopsies were taken and 28 had thyroidectomy or lobectomy. There was a significant relation between nodule size and underwent surgery or repeat FNAC (p=0.036). Malignancy rate was 24.6% for cases which had any managements. The malignancy rates were higher in AUS/FLUS cases with cytological atypia (28.8%). After surgery the most common malignancy was papillary thyroid carcinoma, followed by follicular carcinoma. Conclusion. The risk of malignancy of AUS/ FLUS cases is quite high because of the heterogeneity of the group. The sub-classification of this category according to cytological or/and architecture atypia may be more useful in predicting malignancy risk. Further larger studies with ancillary techniques including molecular analysis may be more useful in determining the malignancy risk and appropriate management of this heterogeneous category.

Context. Pheochromocytomas and paragangliomas (PCC/PGLs) are diagnosed variously with increasing incidence and changing clinical and pathology pattern. Objective. The aim was to further characterize PCC/PGLs in a stable population. Methods. A retrospective, single institution study analysed adrenalectomies for PCC/PGLs between January 2010 - January 2019. Demographics, symptoms, blood pressure, preoperative hormones, imaging, histology, hospital stay, complications and three subgroups [based on the modality of diagnosis - incidentaloma group (IG), genetic group (GG) and symptomatic group (SG)] were noted. Results. 86 patients included IG 51 (59.3%), GG 10 (11.62%) and SG 25 patients (29.06%). Incidence was 5.30 cases/1 million population. 33.34% of the IG had a delayed diagnosis with a mean interval of 22.95 months (4- 120 months). Females presented more often with paroxysmal symptoms (PS) (p=0.011). Patients with PS and classic symptoms were younger (p=0.0087, p=0.0004) and those with PS required more inotropes postoperatively (p=0.014). SG had higher preoperative hormone levels (p=0.0048), larger tumors (p=0.0169) and more likely females. GG are younger compared with those from the IG (p=0.0001) or SG (p= 0.178). Conclusion. Majority of patients had an incidental and delayed diagnosis. If symptomatic, patients are more likely to be young females with higher hormone levels and larger tumors.

Hyperosmolar hyperglycemic non-ketotic state is a life-threatening emergency manifested by a marked elevation of blood glucose, hyperosmolarity, and little or no ketosis. It most frequently develops in middle-aged or elderly patients, often in the setting of previously mild type 2 diabetes and in the presence of one of the established risk factors (e.g. infection, cerebrovascular accident, myocardial infarction). We present the case of a 48 years old woman with no past history of diabetes who developed hyperosmolar hyperglycemic nonketotic state after transsphenoidal surgery for a large macroprolactinoma. Despite having symptoms (secondary amenorrhoea and galactorrhoea) for many years the patient only had inconsistent medical follow-up and eventually she developed optic chiasm syndrome. She was referred for pituitary surgery performed by transsphenoidal route. After surgery there was marked improvement of the visual signs but few days after intervention the patient presented with polydipsia, polyuria and paresthesiae. Based on laboratory tests that showed a markedly elevated blood glucose level (1088 mg/dl), hyperosmolarity, no acidosis therefore, a diagnosis of hyperglycemic hyperosmolar state was made. With rehydration and insulinotherapy she recovered and the evolution was favourable over weeks with discontinuation of insulin administration. The patient still had high prolactin level after surgery (3060.3 ng/dl) so we also initiated dopamine agonist bromocriptine treatment. In addition to the well known effects of dopamine agonist upon prolactinoma it also has beneficial effects on glycemic control in diabetics (it reduces insulin resistance, both fasting and postprandial plasma glucose levels and HbA1c levels). We discuss the possible explanations of the syndrome and the effects of bromocriptine treatment.

INTRODUCTION: Sleep apnea syndrome is a common manifestation of acromegaly. Although the obstructive type of apnea was thought to be predominant there are some reports suggesting that central apneic episodes show a high rate and are related to abnormalities of central respiratory control.\r\nAIM: The present study determines the presence and severity of central sleep apnea syndrome in patients with acromegaly compared with obese subjects.\r\nMATERIALS AND METHODS: 35 consecutive acromegalic patients (min GH (growth hormone) during oral glucose tolerance test (OGTT) 6.6 ng/ml) and 19 obese subjects (BMI=44 kg/m2) were polisomnographically recorded between 10 p.m and 6 a.m. Sleep and respiratory disturbances were manually staged according to standard criteria.\r\nRESULTS: The prevalence of sleep apnea syndrome in acromegaly group was 45.7% (16 out of 35 patients). The median of minimum GH level during OGTT was 8.3 ng/ml in apnea group and 5.16 ng/ml in nonapneic group (p>0.05). In acromegaly group with severe sleep apnea syndrome central apnea rate was greater than 10% in 6 out of 7 subjects with REM sleep and in 7 out of 10 with NREM sleep whereas in obesity group this percent was present in 6 out of 18 (REM sleep), respectively 7 out of 19 (NREM sleep).\r\nCONCLUSIONS: The study confirms the high prevalence of sleep apnea in acromegaly. GH serum level is not an indicator for the presence and severity of sleep apnea. Although the total time of central apnea per hour of sleep did not differ between the two groups, the percent (rate) of central apnea was significantly greater in acromegaly group.

Background The cardiovascular risk in obese patients is very high and is the main cause of mortality and morbidity. While many studies have focused on obese patients who already developed cardiovascular pathologies few tried to address the prevention of atherosclerosis in healthy young adults. Objectives In the present study we assessed the effect of weight loss on atherosclerosis risk factors and on vascular stiffness. While no important clinical events were expected our goal was to show that weight loss in obese patients will lower the vascular risk. Subjects and methods 159 obese patients with no cardiovascular pathology were assigned, for 6 months, to either weight loss program or a weight maintenance recommendation. The intensive care group subjects participated to weekly visits consisting of counseling on hypocaloric diets and physical exercise programs. We have measured BMI, lipid profile, adipokines levels, glycemia as well as markers of arterial stiffness (CAVI, BP, ABI). Results At the study endpoint, we found a clinically and statistically significant (p<0.001) difference between the lipid and the adipokines profiles, and, in univariate analysis, this difference correlates with weight loss: for total cholesterolemia decrease r= 0.63, LDL decrease r= 0.65, HDL increase r= -0.48, adiponectin increase r= -0.59, leptin decrease r=0.6 and also with abdominal circumference decrease. We also found correlation between vascular stiffness parameters (CAVI, diastolic blood pressure) and the adipose tissue loss (r = 0,71; p < 0,001 for CAVI and r = 0,4; p = 0,001 for DBP). Conclusions : We found that using a moderate hypocaloric diet and encouraging physical exercise, even after a short period of time, subjects can lose weight, mainly by losing fat mass. The weight loss improved the lipid and adipokines levels and had reduced vascular stiffness