ACTA ENDOCRINOLOGICA (BUC)

Introduction. The definition of severity and activity of Graves' ophthalmopathy (GO)comprises different parameters.\r\nThe aim of this study is to select the most appropriate severity and activity criteria, respectively scores and to investigate a possible correlation among them.\r\nSubjects and methods. The study included 51 patients with GO (43 females, 8 males), mean age 46.8?11.2 years. The patients were evaluated by: clinical exam, laboratory\r\nparameters (TSH, FT4, FT3, thyroid autoantibodies) and imagistic means, performed in selected cases (CT or MRI).\r\nResults. The GO activity was assessed by the clinical activity score (CAS). We quantified the EUGOGO severity criteria, by allotting points for each selected parameter.\r\nAccording to the recommended criteria, the cases were divided into active (n=26) and inactive forms (n=25). There were no significant statistical differences regarding CAS\r\nbetween euthyroid cases (n=14) and dysthyroid cases (n=37). Serum thyroid receptor antibodies (TRAb) levels did not correlate with CAS or severity scores. Severity scores\r\ncorrelated significantly with CAS (Pearson correlation index 0.546, r2=0.290, p=0.0001).\r\nConclusion. Active forms of GO showed higher severity scores than the inactive ones. The severity scores correlated significantly with CAS scores. Neither CAS, nor severity scores correlated significantly with the severity of thyrotoxicosis.

Prader Willi syndrome is a complex disease caused by the lack of expression of paternally inherited imprinted genes on chromosome 15q11.2-q13. Typical clinical features are hypotonia and feeding difficulties in infancy, followed by hyperphagia and progressive obesity, distinctive dysmorphic features, intellectual disability and behavioural problems. In this paper we present clinical, metabolic and endocrine aspects in five genetically confirmed patients with PWS. Data about thyroid dysfunction, GH deficiency, adrenal insufficiency, and LH/FSH disorder caused by hypothalamic dysfunction in PWS were collected and analyzed. Cardiovascular metabolic profile was also assessed, based on plasma lipids, blood glucose, HbA1c values, and measurements of body weight and blood pressure. Clinical features present in all our patients were marked hypotonia and feeding difficulties in infancy, obesity, dysmorphic face, viscous saliva, small hands and feet, intellectual disability and characteristic behaviour. Adrenal function appeared to be normal in all patients; mild hypothyroidism was identified in one patient; sex development abnormalities were present in three patients and GH levels were within lower normal range in all patients. GH therapy was initiated in two patients, both with unevolutive skeletal anomalies, with good results and no side-effects. Only one patient had a normal lipid profile, underlying the importance of early detection and treatment of cardiovascular risk factors. Our study also illustrates the challenges raised by some features very rarely described in PWS (Blount disease and multiple allergies).

Metformin, a biguanide, remains the most widely used first-line type 2 diabetes drug. It is generally considered weight-neutral with chronic use and does not increase the risk of hypoglycaemia. Most patients eventually require more than one antihyperglycemic agent to achieve target blood glucose levels. The primary objective of this non-interventional study was to describe and compare the main criteria used by physicians from regular outpatient setting in selecting the add-on therapy in patients with inadequately metformincontrolled type 2 diabetes in 2 time points at 1-year distance by assessment of patient, and/or agent characteristics and/or physician decision. At the end of phase one of the study, the mean duration of type 2 diabetes was 6.8 years. The majority of patients included in the study were overweight (32%) and obese (62%), and presented diabetes complications (59.6%). In 50% of the cases, the major reason for selecting the second-line therapy was related to patient characteristics, while agent characteristics and physician decision were the main categories in 38% and 12%, respectively. Importance to achieve glycemic control and estimated treatment efficacy were selected in 73.9% and 82.4% of patients, calculated as percentage in the respective categories.

49, XXXXY karyotype syndrome has an incidence of between 1/85 000 and 1/100 000 live births. Typical clinical features include hypogonadism, mental retardation with severe learning difficulties, craniofacial and skeletal abnormalities, but also congenital heart disease. We report on a 4 year-old boy diagnosed with severe generalized hypotonia during his first year of life. Behavioural and cognitive profiles of the case are presented. MRI shows apart from global volume loss and atrophy, scattered punctate foci of T2 signal hyperintensity in the white matter. Endocrine investigations revealed impaired GH concentration during clonidine test, low IGF-1 concentration and cryptorchidism. Long term follow-up of patients with polysomy X by a team of specialists in pediatric neurology, endocrinology and cardiology is mandatory.

Context. Papillary thyroid carcinoma(PTC)s are the indolent progressive tumours. Survivin is a unique bifunctional protein with cell cycle regulation and apoptosis inhibition. The expression of this protein has been shown to be increased in thyroid tumours correlated with aggressive behavior from well differentiated to anaplastic. Objective. In this study, we aimed to investigate the relationship between immunohistochemically survivin expression and tumour-associated prognostic factors in papillary thyroid carcinomas. Design. In patients with thyroidectomy, we compared the clinicopathological findings and immunohistochemical positivity for survivin. Subjects and Methods. In 109 patients, sex, age, tumour size, histological tumour variant, tumour focality, tumour border pattern, tumour peripheral/intratumoural lymphocytic and stromal response, intraglandular spread, extrathyroideal spread, lymph node metastases, lymphocytic tiroiditis and relationships of these findings with survivin positivity were investigated. Results. When we indicated the tumour size and compared it with survivin expression, tumour size correlates with, survivin expression (p = 0.016). Survivin expression was correlated statistically significant with lymphovascular invasion, without stromal response and with intraglandular extension respectively (p<0.001, p = 0.043, p<0.001). No significant correlation was found between other clinicopathological parameters and survival. Conclusion. Few studies have investigated the relationship of survivin expression with prognosis in thyroid papillary carcinomas and showed that survivin was a poor prognostic marker. If its expression is detected in preoperative cytology smears, it may affects the surgical treatment strategy. When it is detected in the tissue, postoperative radioactive iodine treatment plan may be modified and the need for more aggressive follow-up may be considered.

Thyroid carcinoma is rare in children and adolescents and has a relatively favorable prognosis. As in adults, the incidence in girls is double than in boys. It has a little risk of mortality, but a high risk of recurrence. Patients younger than 15 years old at diagnosis are considered more likely to have more extensive tumor at diagnosis than patients who are 15 years and older. We report two patients: an 11 years old girl with Fallot tetrallogy and papillary thyroid cancer and a 13 years old girl with Graves&#8217; disease treated with antithyroid drugs for three years and thyroidectomized at 17 years old with an incidental thyroid microcarcinoma. Those unusual associations are discussed regarding therapy and follow-up issues.

Purpose. We checked the advantage of intraoperative quick PTH (iqPTH) for improving cure rate of patients operated for primary hyperparathyroidism (PHPTH) by using minimally invasive surgery. Methods. We compared two groups of patients diagnosed with PHPTH by preoperatory localized single parathyroid adenoma (PA) submitted to minimal invasive surgery with histological confirmation. Patients from a control group (C) were operated without measuring intraoperative PTH, whereas in the second group iqPTH was assessed after adenoma excision and before wound suture. When quick PTH dropped less than 50%, conversion to open surgery and bilateral exploration followed. Results. Six of the 40 patients from the C group (15%) had persistently elevated postoperative PTH, needing reintervention. High intraoperative PTH levels persisted in two of the 13 patients from the iqPTH group (15.4%), but conversion to open surgery allowed localizing and excision of preoperatory undetected supplementary PA, increasing success rate to 100% (p < 0.05). Conclusions. Assessment of iqPTH in PHPTH before wound suture provides reliable confirmation of accurate adenoma removal. Persistence of high PTH levels after adenoma removal suggests multiple gland disease and requires conversion to bilateral neck exploration in order to increase cure rate.

Background. We describe a case of denosumab-related osteonecrosis of the jaw in a 58-year-old patient with a diagnosis of osteoporosis, treated with Denosumab and a short-time course of bisphosphonates. This case illustrates that use of anti-RANKL agents can lead to a type of osteonecrosis resembling bisphosphonate-related osteonecrosis of the jaws, so this medical condition can be categorized as of antiresorptive - induced osteonecrosis of the jaw. The consensus of present day medical opinion is that the benefits of antiresorptive therapy outweigh the disadvantages. However, to provide optimal management for individual patients, the risk-benefit ratio of osteoporosis therapy must be repeatedly assessed at all stages of a patient’s treatment, and therapeutic decisions taken in the light of the ratio as it applies to the individual.

Background. Heterozygous gain-of-function mutations in the glucokinase (GCK) gene cause hyperinsulinaemic hypoglycaemia (GCK-HI), while lossof- function mutations lead to a monogenic type of diabetes (GCK-MODY). We, herein, report a heterozygous GCK gene mutation in a large family with GCK-MODY and insulinoma in one individual from the same family. Patients and methods. The proband, an 11-yearold male, was referred for asymptomatic mild hyperglycemia (fasting glucose:121 mg/dL) and HbA1c of 6.1%. Segregation analysis of the family revealed multiplex members with asymptomatic fasting hyperglycaemia or non-insulindependent diabetes and 33-year-old maternal uncle of the proband case had a history of distal pancreatectomy due to the diagnosis of insulinoma. His preoperative investigations were revealed fasting glucose of 31 mg/dL, insulin: 7μU/ mL, C-peptide: 2.6 mg/dL, and a low HbA1c(4.0%) which was suggestive for recurring hypoglycaemia episodes. Postpancreatectomy he developed mild fasting hyperglycemia (115-136 mg/dL). Results. Genetic analysis revealed heterozygous p.Ser453Leu(c.1358C> T) mutation in the GCK gene in the proband. In segregation analysis, the identical heterozygous p.Ser453Leu(c.1358C> T) GCK gene mutation was detected in all of the other affected family members for whom a DNA analysis was applicable. The maternal uncle was first diagnosed with insulinoma and underwent a pancreatectomy. He also had an identical mutation in a heterozygous state. Conclusion. We, to the best of our knowledge, firstly identified these two entirely distinct phenotypes of glucose metabolism, GCK-MODY and GCK-HI, due to an identical heterozygous p.Ser453Leu (c.1358C> T) mutation in the GCK. Further studies required to elucidate this new phenomenon and understanding the genotype-phenotype relationship of GCK gene mutations.

Background. There have been a number of reports on the relationship between the PPARγ2 Pro12Ala genotype and the development of obesity. Objective. A case-control survey was designed to investigate the potential association between a Pro12Ala polymorphism in the PPARγ2 gene and obesity and/or obesity-related phenotypes in a population from Turkey. Materials and methods. The polymerase chain reaction and restriction enzyme digestion were used to genotype the Pro12Ala polymorphism of the PPARγ2 gene in 149 unrelated obese and 105 non-obese control subjects from Turkey. The data were analyzed statistically. Results. We found that the overall minor allele frequency was 0.12 in cases and 0.095 in controls. In terms of genotype distribution and allele frequencies among the cases versus controls in the population studied, only the genderstratified analysis revealed a significantly higher frequency of Pro/Ala genotype within males. The polymorphism was associated with significantly higher weight, height, waist circumference, central adiposity (waist-to-hip ratio, WHR), lean body weight as well as dry body weight, but not overall adiposity (total body fat percentage, TBF) in cases carrying Ala allele (Pro/Ala or Ala/Ala). However, in the subjects carrying Ala allele of the control group, WHR values were found significantly lower. Conclusion. Our results showed that the Pro12Ala polymorphism in the PPARγ2 gene is associated with obesity in the studied adult population from Turkey. These data suggest that the Pro12Ala polymorphism in PPARγ2 may be a potential genetic risk factor for central obesity.