ACTA ENDOCRINOLOGICA (BUC)

Introduction. Obesity was considered to protect against osteoporosis. Recent studies indicate the opposite.\r\nThe study aimed to see if adipose tissue has a protective effect on bone mass and if adipocytokines can explain the\r\nrelationship between obesity and osteoporosis.\r\nSubjects and methods We designed a study enrolling 83\r\npostmenopausal women, aged over 60, without diagnosed or treated osteoporosis and no secondary osteoporosis. We formed 3 groups- group 1- osteoporosis and metabolic syndrome (MetSyn), group 2- osteoporosis, group 3- MetSyn.\r\nWe evaluated the hematological, biochemical profile, bone turnover markers and adipocytokines. DXA of the spine and\r\nthe hip (left) was performed on all the enrolled women. Insulin resistance was appreciated using HOMA index. Metsyn\r\nwas defined using the International Diabetes Federation?s criteria.Results were statistically analyzed using SPSS program, version 15.\r\nResults. All groups were vitamin D insufficient with lower vitamin D, osteocalcin and adiponectin levels in the\r\ngroups with MetSyn and higher leptin levels. BMI correlated positively with spine BMD, while leptin correlated positively with hip BMD, pointing out to the protective effect of obesity against osteoporosis due to leptin?s involvement.\r\nConclusion. Obesity seems to have a protective effect against osteoporosis, probably due to leptin.

Context. Nonalcoholic fatty liver disease (NAFLD) includes simple steatosis, steatohepatitis (NASH) which can evolve with progressive fibrosis, cirrhosis and hepatocellular carcinoma. As liver biopsy cannot be used as a screening method, noninvasive markers are needed. Objective. The aim of this study was to test if there is a significant association between vitamin D deficit and the severity of NAFLD. Design. The patients were divided into two groups (vitamin D insufficiency/deficiency) and statistical analyses were performed on the correlation of clinical and biochemical characteristics with histopathological hepatic changes. Subjects and methods. We prospectively studied 64 obese patients referred for bariatric surgery between 2014 and 2016 to our Surgical Unit. Anthropometric, clinical measurements, general and specific biological balance were noted. NAFLD diagnosis and activity score (NAS) were evaluated on liver biopsies. Results. Increased serum fibrinogen was correlated with NASH (p=0.005) and higher NAS grade. T2DM was positively correlated with liver fibrosis (p=0.002). 84.37% of the patients had vitamin D deficit and 15.62% were vitamin D insufficient. Lobular inflammation correlated with vitamin D deficit (p=0.040). Fibrosis (p=0.050) and steatohepatitis (p=0.032) were independent predictors of low vitamin D concentration. Conclusions. Vitamin D status in conjunction with other parameters - such as T2DM - or serum biomarkers – namely fibrinogen level and PCR level - may point out the aggressive forms of NAFLD and the need for liver biopsy for appropriate management.

The study comments unusual associations between thyroid and cutaneous autoimmunity: Graves-Basedow disease (GBD), vitiligo and alopecia areata (AA) starting from two cases. In the first case, a woman with systemic lupus erythematosus (SLE), data were recorded from 38 to 49 years as follows: vitiligo (at 38 ys), alopecia areata (4-6 months afterwards), SLE (after 2 ys) and then GBD (after 8 ys). After 3 years, hyperthyroidism has spontaneously vanished, but vitiligo, AA, leucothrichia, SLE, goiter and ophthalmopathy persisted. In the second case, a man, data were recorded from 26 to 70 years and the disease was associated with psoriasis. The sequence of diseases was: vitiligo (at 26 ys), AA and GBD (after 8 ys), followed by iatrogenic 131I hypothyroidism, and psoriasis (after 33 ys). Vitiligo and AA have spontaneously vanished before GBD began. These multiple immune syndrome associations bring up the question: ?Are these diseases multiple associations or a unique immune disease?? A possible point of view, related to immune network, suggests that these multiple associations represent in fact only one process, therefore they represent not many diseases, but different expressions in time (sequence) and space (organ-lesion) of the disease of the immune network.

Background. Atypical antipsychotics proved efficacy in monotherapy and more so in\r\nassociation with mood stabilizers, but choosing the atypical antipsychotic requires special\r\ncautions due to metabolic adverse effects. The aim: to verify if Quetiapine-valproate\r\ncombination improves rapidly acute depressive symptoms and has a good endocrinemetabolic\r\ntolerability. Case presentation. A 49 years male, bipolar patient, admitted for a\r\nmajor depressive episode. The patient also has type 2 DM for which he takes oral antidiabetics.\r\nWhen inpatient, he had persistent hyperglycemia (>250mg/dL). DM&#8217;s\r\ncomplications (poly-neuropathy, retinopathy and right bundle-branch block). Diabetic status\r\noriented us to choose quetiapine (600 mg/day) for both antidepressive effect and its safe\r\nmetabolic profile associated with valproate (1000 mg/day). Antidiabetic medication was\r\nadjusted following the clinical outcome. Instruments. for depression we used Montgomery-\r\nAsberg Rating Scale (MARS), for mania Young Mania Rating Scale (YMRS), Clinical\r\nGlobal Impression for Bipolar Disorder (CGI-BP), for diabetes (glycemia, HbA1c,\r\nglycosuria, body weight, adverse events and relapse were followed-up for 6 months. The\r\nevaluations were performed weekly during hospitalization (6 weeks) and then monthly, for\r\n6 months quetiapine together with valproate therapy led to remission of depressive\r\nsymptoms (MADRS <50% vs. baseline). At the same time DM was compensated with\r\nglimpirid and metformin (glycemia < 120mg/dL). These results maintained till the end of\r\nthe follow-up period. Conclusion. Quetiapine associated to valproate in acute and chronic\r\nmanagement of bipolar depression proved to be efficient and well tolerated, along 6 months,\r\nin patient with type 2 diabetes.

Diabetes mellitus is a complex disorder of the energy metabolism of the human body. In the last WHO/ADA classification, the main forms of this disease are Type 1 (T1DM) and Type 2 (T2DM) diabetes mellitus. According to the same classification, the pathogenesis of T2DM is considered to include a progressive insulin secretory defect on the background of insulin resistance. Recently, controversies surround the concept of peripheral insulin\r\nresistance emerging in the 70's as an attempt to explain the differences from the T1DM phenotype whose autoimmune nature was as that time revealed. The insulin resistance\r\nhypothesis was based on the supposition that high plasma insulin levels are the result of a primary molecular defect against which the normal beta cells will react with an increased insulin secretion. This hypothesis has been\r\nused to explain both the pathogenesis of T2DM and the metabolic syndrome, named also for a short period of time "the insulin resistance syndrome". We will try to argue\r\nthat what it is attributed to peripheral insulin\r\nresistance belongs in fact to obesity. Special emphasis is put on the role of the adipocytes, including the secretion of different adipokines with the secondary lipotoxicity, oxidative stress and pro-inflammatory reaction, explaining the complex relationship between obesity and diabetes.

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Aims. To investigate the historical changes in survival with diabetes in patients treated with insulin from diagnosis.\r\nMethods. We analyzed 2811 deaths, 51.5% males, registered at ?I. Pavel? Bucharest Diabetes Centre, aged 40-64 years and deceased between 1943 and 2009. We split the analysis in three time periods according to year of death: 1943-1965,\r\n1966-1988 and 1989-2009.\r\nResults. The mean age at diabetes onset was 51.4?6.8 years, with mean disease duration at death of 17.7?11.6 years\r\nand mean age at death of 69.1?11.2 years. The mean survival after diabetes onset was 13.9?9.8 years in 1943-1965, and rose to 17.3?9.6 years (p<0.001) in 1989-2009. There was a significant increase for coronary heart diseases and cancer and a significant decrease for infections and endstage\r\nrenal disease as causes of death.\r\nConclusions. We found no significant changes in age at onset, which combined with an increase in survival with diabetes lead to a significant increase in age at death.\r\nMajor historical events have a strong impact over survival after the onset of diabetes.

We present a 18 year old phenotypic female patient who presented for primary amenorrhea. Pelvic ultrasound revealed a hypoplastic uterus and CT scan showed a hypoplastic right gonad and a left gonadal tumor with extrapelvic location. Karyotype was 46XY. Hormonal assessment indicated hypergonadotropic hypogonadism: FSH was 39.69 mUI/ml, estradiol was 28.07 pg/ml, testosterone was 0.17 ng/ml. DHEA level was high &#8211; 21 ng/ml. Gonadectomy was performed at 15 years and histologic examination diagnosed left gonadoblastoma and right teratoma in a dysgenetic gonad. The patient had a good postoperatory evolution. Menses were induced with estrogenic and then estroprogestogenic treatment. Plastic breast surgery was performed at 18 years. Establishing the genotypic sex in patients with primary amenorrhea represents a crucial step knowing that intersex disorders bearing Y chromosomal material have a high risk for gonadoblastoma and germ cell tumors.

Based on epidemiological, clinic, biochemical and hormonal data (both personal and\r\ninternational), our personal view is that natural history of autoimmune type 1 diabetes could\r\ninclude the following stages: 1) The presence of a complex genetic predisposition towards ?\r\ncell autoimmunity (possibly &#8220;latent&#8221; until death); 2) The &#8220;initiation&#8221; of autoimmunity in\r\nsubjects carrying a defect in the post-translational processing of pre-proinsulin/ proinsulin/\r\ninsulin, manifested precociously as increased proinsulin-to-insulin ratio; 3) Stimulation by the\r\nincreased proinsulin of the plasmacytoid dendritic cell clones capable to capture the natural\r\nantigens (proinsulin/insulin, Glutamic Acid Decarboxylase, etc.) from the pancreatic beta\r\ncells; 4) Activation of the process generating reactive T cell clones (Teffs) in the detriment of\r\nprotective immuno-regulatory T cell clones (Tregs), triggering the anti-beta cell attack,\r\nexpressed as autoimmune insulitis and/or the presence of circulating anti beta cell antibodies;\r\n5) The onset of the beta cell apoptosis process mediated by pro-inflammatory cytokines (IFN\r\n?, TNF ?, IL6) or by the direct contact between Teffs and the beta cells; 6) Identification of\r\nthe first secretory beta cell defects (the loss of the first phase insulin response followed by the\r\nprogressive decrease of the area under the insulin curve and the progressive increase of the\r\narea under the blood glucose curve) while fasting glycemia is still normal; 7) The progressive\r\nloss of the beta cell mass. All these processes take place during the pre-hyperglycemic stage\r\nof diabetes, with a higher or lower speed depending on the genetic background. The overt\r\nclinical stage of diabetes, marked by the presence of hyperglycemia, occurs rather late, when\r\nmore than 90% of the beta cell function/mass is irreversibly lost.

Context. Despite CT being generally used in thymic pathology, in the case of regions with the same tissue density, only functional radioisotopic imaging can hint towards malignity. Objectives. To assess the usefulness of 99mTc MIBI scintigraphy for diagnosis and treatment planning in thymoma, in relation with the radiotracer uptake mechanism. Patients and methods. 99mTc MIBI thymic scans for 19 patients diagnosed with thymic disorders were assessed using tumor uptake ratio (UR). Specimens of thymectomies were examined and cytological assessments were correlated with the UR. Results. The UR of all surgical patients was higher than 1.2, with a 1.5 cutoff between lymphoid hyperplasia and thymoma. The UR values were correlated with the histopathologic diagnosis (Pearson correlation 0.91, significant at p<0.01). The highest UR was 3.24, found in the case of an AB thymoma where the rate lymphocytes/ epithelial cells (L/E) was 1.6. In B1 thymoma UR was 1.14 and L/E was 2.46. Conclusion. Phenotype differences between thymoma types correlate with 99mTc MIBI cellular uptake: lower rate L/E corresponds to higher UR, higher malignity potential and invasiveness. A thymic 99mTc MIBI UR higher than 1.5, corresponding to a CT tumoral image, is suggestive for a thymoma, requiring surgical treatment first.