ACTA ENDOCRINOLOGICA (BUC)

Urinary Bladder paraganglioma accounts for 0.06% of all bladder tumors and 1% of all pheochromocytoma. Most tumors are localized at the dome or trigone and are unifocal. The presenting complaints are painless hematuria, micturition syncope. It may be sporadic or associated with hereditary predisposition syndromes such as Hereditary Paraganglioma-Pheochromocytoma Syndrome.

Aim. The purpose of this study was to examine various hormonal, biochemical and environmental factors (i.e., smoking and alcohol intake) and to investigate their possible correlation to the development of polycystic ovary syndrome (PCOS). The main objective was to evaluate the associations between hormonal profile and the antimüllerian hormone (AMH) levels in PCOS patients and their relation to environmental factors. Patients and Methods. In two gynecological clinics, 38 women with PCOS (defined according to the Rotterdam criteria) were enrolled and observed in relation to AMH, follicle stimulating hormone (FSH), luteinizing hormone (LH), testosterone (T), Δ4-androstendione (Δ4- A), dehydroepiandrosterone sulfate (DHEA-S) and glucose plasma concentrations. Obesity, smoking and alcohol exposure were also studied. Results. AMH, T, Δ4-Α, DHEA-S, LH and FSH were increased in 76.3%, 50%, 31.8%, 23.7%, 21% and 18.4% of the patients, respectively. The LH/FSH ratio and glucose concentrations increased abnormally in 18.4% and 15.8% of the patients, respectively. AMH and T levels were both increased in 47.4% of the patients whereas both AMH and LH levels increased in 21% of the patients. Smoking, alcohol intake, obesity and glucose concentrations were not associated with AMH concentrations. On the contrary, high levels of T and LH were linked to higher levels of AMH. FSH concentrations were not increased in these patients. Conclusion. AMH is an important hormonal parameter for the diagnosis of PCOS. Larger clinical controlled studies are necessary in an effort to further investigate the inclusion of AMH measurement in the diagnostic criteria of PCOS.

Surgery plays a major role as a first-line treatment of the different etiologies of Cushing’s syndrome (CS) and bilateral adrenalectomy (BA) is extremely effective as a second line, so that there seems to be little room for medical treatment (MT). However, during the past years several drugs acting either on ACTH secretion or cortisol synthesis have been developed, so that MT of CS might be reassessed. After briefly analyzing the efficiency and tolerance of surgical and medical treatments of CS we try to distinguish consensual and controversial indications for MT. We believe the former include “pre-operative treatment” in rare patients in whom the severity of CS is likely to increase the risks of surgery; “inoperability” for rare patients who cannot be operated even when CS is controlled and “surgical failure or recurrence”, mainly in patients Cushing’s disease (CD) not in remission after TSS. Controversial indications include “unavailability of an expert surgeon”, which we believe does not make sense when the cost of MT is taken into consideration. Finally in patients with the “surgical failure or recurrence” indication the balance between efficacy and side effects of MT should be balanced with the efficacy and side effects of BA.

This is a rare disease, which is often diagnosed at a late stage, and which has no fully efficacious medical treatment; hence its dismal prognosis. Yet its clinical presentation is changing (more and more as an "incidentaloma"), new insights have emerged on its\r\npathophysiological mechanisms (through the genetic elucidation of familial syndromes), and Reference Centers within National and European Networks are now offering more\r\nstandardized and efficient multidisciplinary clinical management to these difficult patients. There are three important messages:\r\n-The single best likelihood of "cure" is when a localized tumor can be subjected to\r\n"complete" surgical removal. An early diagnosis is crucial. In front of an adrenal tumor, an endocrinologist must always ask two questions: could it be a pheochromocytoma? Could it be an adrenal cortical carcinoma? In both cases, it can be a vital question which can make the difference between a fatal issue or cure! A thorough biological and imaging work-up is mandatory for a proper diagnosis. An expert endocrinologist will recognize a suspicious\r\nadrenal "incidentaloma", diagnose steroid hypersecretion, suspect a familial disease, communicate with the pathologist and surgeon, and, when necessary, manipulate difficult drugs like O,p' DDD, participate in multidisciplinary discussions with oncologists,\r\nradiotherapists, molecular biologists?.\r\n-Research, both basic and clinical, is key to further progress: a better understanding of the biology of these tumors has already shed some light on the role of signaling pathways, on some familial syndromes, on new prognostic markers. There is some hope that these approaches will provide us with targeted therapies. Alternatively, progress in our understanding on the general mechanisms of tumor growth might help us design new therapeutic tools using antiangiogenic agents and/or immunotherapy.\r\n-Reference Centers and National (and European) Networks are essential to optimize individual patient management, as well as to organize basic research and multicenter clinical\r\ntrials in this rare disease. For an individual patient, difficult therapeutical options are best offered by a multidisciplinary team (endocrinologist, oncologist, surgeon, radiologist, pathologist, radiotherapist) In order to boost scientific exchange, to facilitate and harmonize\r\nanalyses of biological samples, to allow the design of epidemiologic studies or prospective therapeutic trials, several European countries have developed their national networks dedicated to the study of adrenal tumors: COMETE in France, NISGAT in Italy,\r\nGANIMED in Germany. These national networks have merged into the European network ENS@T (European Network for the Study of Adrenal Tumors): its goal is to create a\r\nnetwork large enough to allow the recruitment of patients with rare diseases to harmonize diagnostic and therapeutic procedures at the European level.

Background. Coronary artery disease (CAD), often asymptomatic, is the most common cause of morbidity, mortality and costs in diabetes. Early detection of CAD in patients with diabetes may be of paramount importance and substantially improve the outcome in diabetic patients. Objective. The aims of the current study were to determine if there are significant differences concerning the prevalence of occult CAD in asymptomatic type 2 diabetic patients compared to asymptomatic nondiabetic patients. Design, subjects and methods. The authors retrospectively reviewed a group of 120 non-diabetic (77 men, 43 women, mean age 61±10.2 years) and 120 diabetic (81 men, 39 women, mean age 58±11.4 years) asymptomatic patients that underwent coronary computed tomography angiography (CCTA) for various reasons between January 2013 and January 2014. Results. Coronary plaques were identified in 105 diabetic patients (87.5%) and in 75 non-diabetic patients (62.5%) the prevalence being significantly different (p=0.023). Regarding plaque composition and degree of stenosis, we found a higher prevalence of calcified (p=0.016) and significantly stenotic (≥50% luminal narrowing) plaques (p=0.008) in the diabetic group. Agatston calcium score, relevant for atherosclerotic plaque load, was higher (p=0.005) in type 2 diabetic patients (350.3) compared to non-diabetic patients (158.7). Conclusion. CCTA could represent a screening method able to detect silent atherosclerotic plaques thus contributing to the prevention of acute coronary syndrome (ACS) by an early and adequate treatment of CAD. Obstructive atherosclerotic plaques can be accurately identified using CCTA, limiting the use of invasive imaging methods and selecting patients that could benefit of coronary revascularization.

Branched chained amino acids (BCAA) are essential components of the human diet and important nutrient signals, which regain particular interest in recent years with the avenue of metabolomics studies suggesting their potential role as biomarkers. There is now compelling evidence for predictive role of BCAA in progression of diabetes, but causality relationship is still debated concerning insulin resistance and genetic versus nongenetic pathogenesis. Mendelian randomization studies in large cohorts of diabetes indicated pathogenic role of PPM1K (protein phosphatase Mg2+/Mn2+ dependent 1K) on Chr 4q22.1 gene, encoding for a phosphatase that activate BCKDH (branched chain keto acid dehydrogenase) complex. Recent studies indicated that insulin rapidly and dose-dependently regulates gene expression of the same complex, but the relationship with systemic insulin resistance and glucose levels is complex. Rare genetic syndromes due to Mendelian mutations in key genes in BCAA catabolism may be good models to understand potential role of gene of BCAA catabolism. However, in studying complex disorders geneticists are faced to complete new aspects of metabolic regulation complicating understanding genetics of obesity, diabetes or metabolic syndrome. A review of genetic syndromes of BCAA metabolism suggests that insulin resistance is not present, except rare cases of methylmalonic aciduria due to MUT (methylmalonyl-coA mutase) gene on Chr 6p12.3. Another aspect that complicates understanding is the new role of central nervous system (CNS) in insulin resistance. For long time the hypothalamic hunger/satiety neuronal system was considered a key site of nutrient regulation. Genes may also affect the brain rewarding system (BRS) that would regulate food intake by modulating the motivation to obtain food and considering hedonic properties. Nutrigenomic and nutrigenetic investigations taking into account concurrently BCAA intake, metabolic regulation and gene variation have large perspectives to merge genetic and nutritional understanding in complex disorders.

Hematopoietic stem cell transplantation (HSCT) is an effective treatment for various types of hereditary hematologic disease, hematological malignancy, primary immunodeficiency and metabolic disease. Thyroid dysfunction is a common complication of HSCT, which situation is mainly manifested as hypothyroidism and rarely as hyperthyroidism. This report presents a 28-yearold man who developed hyperthyroidism 9 years after sibling allogeneic HSCT, which was most likely caused by chronic GVHD. In the meantime, the patient also suffered from liver dysfunction and pancytopenia, for which he was inappropriate to take antithyroid drugs (ATD) for treatment of hyperthyroidism. The patient was orally administered 259 MBq 131I, an individualized dose. The symptoms of hyperthyroidism were mitigated by 131I treatment.

Objective. To examine the prevalence of laryngopharyngeal reflux disease (LPRD) in patients with hypothyroidism.\r\nMaterials and Methods. A total of 85 patients with hypothyroidism vs 31 matched controls were recruited. Demographic data was collected and an RSI questionnaire\r\nfilled. A score > 10 was considered diagnostic of LPRD. The average score of every question was computed for all patients and compared to the corresponding average score in controls.\r\nResults. Mean age of hypothyroidism patients was 44.92 ? 13.77 years (83% females). One third of subjects were smokers and 10% had allergy. In 78.8% of the cases Hashimoto?s disease was the etiological factor and 22.4% patients had history of thyroidectomy. At the time of examination, only 30% had a TSH > 4.2 mU/L. There was\r\na borderline significance where more patients than controls had a RSI > 10 (24.7% patients vs. 9.1% controls), but with non-significant difference (p = 0.077). Similarly, closer\r\nexamination of those with TSH > 4.2mU/L compared to those with controls revealed a higher prevalence in the former group, but statistically non-significant (p = 0.275). A\r\ncomparison between those with TSH > 4.2 mU/L and cases diagnosed with hypothyroidism and normal TSH revealed no\r\nsignificant difference in the prevalence of LPRD. All laryngopharyngeal questions had a score higher in the hypothyroid group than controls.\r\nConclusion. LPRD is more prevalent in hypothyroidism patients compared to normal individuals, but with nonstatistically significant difference. The prevalence of symptoms should alert physicians to the possibility of LPRD and prompt further diagnostic tests and therapeutic intervention.

Objective. Antithyroid drugs, surgical excision, and radiation therapy with 131I are the common treatment modalities thyrotoxicosis. The medical treatment of\r\nthyrotoxicosis has approximately 0.35% serious complications which consist of agranulocytosis, liver necrosis and failure. Therapeutic plasma exchange is an effective\r\npreoperative preparation method in thyrotoxicosis patients who are candidates for surgery and unable to manage an euthyroid state with medical treatment.\r\nPatients and Methods. This study was constructed between 2002-2009 in 9 patients who were resistant or had complications with medical treatment of thyrotoxicosis. The\r\ntherapeutic plasma exchange procedures were performed with discontinuous flow cell separator devices.\r\nResults. Seven patients were females and 2 patients were males. The mean age was 51.22 years (32-78 years). The mean duration of the disease was 35.4 months (3-120 months). The patients underwent 3.3 (2-6 sessions) session of therapeutic plasma exchange before surgery. The mean volume of\r\nplasma exchange was 10549 mL (7150-18372 mL). The plasma is exchanged with %10 albumin and/or fresh frozen plasma. The\r\ncomplication rate was 22% during therapeutic plasma exchange. Four patients underwent near total thyroidectomy and five patients underwent total thyroidectomy. The mortality rate was zero. Neck hematoma causing acute\r\nrespiratory compromise and requiring urgent evacuation developed in one patient.\r\nConclusions. Total plasma exchange is an effective and safe procedure in preoperative preparation of the patients with thyrotoxicosis who were resistant or complicated with\r\nantithyroid drug in which a high level of concern and steady supervision is mandatory to prevent life threatening preoperative and postoperative complications.