ACTA ENDOCRINOLOGICA (BUC)

Serotonergic 5HT2A receptors constitute the sole subtype identifiable in platelets, their sole location outside CNS. They may intervene in intra-CNS pathways involved in GHRH and GH release, mainly during sleep. To gain information about such a subtype receptor in GH deficiency and, indirectly, on its role in GH release, studies on the platelets membrane binding sites of labelled LSD were undertaken in dwarf, GH-deficient children, assuming that the platelets sites number is parallel to their number in the brain. Five dwarf (Dw) children (3 boys) aged 7-13, having no signs of puberty, with a peak GH level under 5 ng/ml during ITT, no tumor in the hypothalamic and pituitary area and no previous rhGH therapy were compared with ten normally statured, non-obese children serving as controls (C). Fifty mL of platelet membrane preparation of pooled samples were incubated at 25?C with radioiodinated lysergic acid diethylamide ([125I] LSD) in concentrations of 0.35-3.5 nM/L. The reaction kinetics was followed up within 60 min weekly for 4 weeks. Bmax and Kd were calculated as means of 4 repetitions. Competitive inhibition curves were also drawn by using ketanserin (KET), mianserin (MIA) and cyproheptadin (CYP) in concentrations of 10-4 mM- 1nM/L and the inhibition constant (Ki) was calculated. The results showed that Bmax was (mean ? SEM) 33.0 ? 3.06 fmol/mg protein in C group versus 64.06 ? 13.82 fmol/mg protein in Dw group (F test in covar p<.05). Kd was 0.76? 0.166 nM in C and 2.0? 0.48 nM in Dw (t test p<0.01). The earliest time of 100% binding (Tmin) was 20 min in C and 5 min in Dw groups. Ki in C was 0.1 nM for KET, 18 nM for MIA and <0.1 nM/L for CYP. In Dw children Ki was 1.85 nM for KET, 18 nM for MIA and <0.1 nM for CYP. The results indicated that the number of 5HT2A receptors in platelets was significantly greater in GH-deficient children than in controls, as well as Kd. Tmin indicated an earlier steady state in Dw patients. Ki values pleaded to some extent in favour of the presence of excess 5HT2A receptors. In conclusion, excessive binding of labelled LSD and its inhibition by specific antagonists proves excess of 5HT2A receptors in platelets preparations collected from dwarf children.

Background. Multiple endocrine neoplasia type 2B (MEN 2B) is a rare hereditary syndrome caused mainly by Met918Thr germline RET mutation and characterized by medullary thyroid carcinoma (MTC), pheochromocytoma (PHEO), and typical phenotypic features. MEN 2B cases previously reported in the literature have variable clinical course. Objectives. We aimed to discuss the characteristics of four MEN 2B cases with unusual presentations,clinical course and review the recent clinical data on MEN2B Results. All patients had de novo M918T mutation and no family history. The mean age of patients was 38.2 years (27-56). Two patients had typical phenotypic features of MEN 2B; the other two patients had no striking phenotypic features. First detected MEN 2B component was MTC in two, intestinal ganglioneuromatosis in one, and PHEO in one of the cases. Bilateral PHEO was detected in all four cases. Conclusions. MEN 2B is a complex syndrome characterized by wide phenotypic variability and different clinical outcomes. To diagnose sporadic MEN 2B cases, genetic testing should be performed in all cases with suspicious clinical features. Although early diagnosis is the main factor that increases life expectancy, some MEN 2B patients with late diagnosis may exhibit a mild clinical course and better prognosis than expected, with effective treatment.

Context. Despite that the Triglycerides/High Density Lipoprotein Cholesterol (TG/HDL-C) ratio has been associated with insulin resistance and cardiovascular disease, some outcomes differ between populations. Objective. The objective of this study was to evaluate the association between TG/HDL-C ratio and cardio-metabolic risk factors in both obese and normal weight women. Design. Cross sectional, from January to December of 2015. Subjects and Methods. Two hundred and fifty three women aged 40 to 60 years. Anthropometric and laboratory measurements were performed. Insulin resistance was measured by the homeostasis model assessment for insulin resistance (HOMA-IR). All participants underwent a Doppler ultrasound to measure intima-media thickness of carotid artery (cIMT). Results. TG/HDL-C ratio correlated with body mass index (r=0.194, p=0.01), and visceral adipose tissue (r=0.193, p=0.002). Additionally, TG/HDL-C correlated with glucose (r=0.367, p=0.001), insulin (r=0.354, p=0.001) and HOMA-IR (r=0.396 p=0.001). TG/HDL-C was associated with prediabetes, Odds Ratio (OR) was 1.83 (95%CI 1.07-3.13) and insulin resistance 3.27 (95%CI 1.78- 6.01), and this risk remains in normal weight women 4.7 (95%CI 1.2-17.81) for prediabetes and 4.38 (95%CI 1.42- 13.84) for insulin resistance. No significant risk for cIMT. Conclusion. A TG/HDL-C ratio ≥ 3.0 is a potential risk factor for prediabetes and insulin resistance in women 40-60 years, even in normal weight women.

Background. There is no standard definition for goitres extending below the thoracic inlet and no clear guidelines for pre-operative planning of surgery. The aim of this study is a practical classification of retrosternal goitres (RSG) based on the anatomical , radiological shape and size of the thyroid. Methods. Retrospective analysis of all thyroidectomies performed in a referral centre between January 2012 and December 2016. Patients with RSGs had a pre-operative CT scan of neck/thorax. Imaging was reviewed to establish features to predict the difficulty of delivering the goitre through the neck incision and to advise the best surgical approach. Results. 847 thyroidectomies were performed with n=98 involving RSGs. TypeA (n=47) are RSG with a shape of a “cone” or pyramid with the apex pointing down. Cervicotomy is the usual approach. TypeB (n=39) are goitres with a shape of a “pyramid’ with the apex pointing up, cervicotomy with ± manubriotomy or sternotomy ± thoracotomy maybe required. TypeC (n=6) are thyroid enlargements in the mediastinum connected by a pedicle with the thyroid in the neck. A cervical approach ± manubriotomy or sternotomy ± thoracotomy is needed. TypeD (n=6) are true intrathoracic or “forgotten” goitres. Sternotomy is indicated for thyroids in the anterior mediastinum though a thoracic approach for those located in the posterior mediastinum might be needed. Conclusion. The shape and size of goitres is important in carefully planning surgery. CT imaging with cross-sectional reconstruction should be analysed before operation. The proposed classification helps treatment planning and allows comparison of outcomes by anatomical complexity.

Endogenous Cushing’s syndrome is rare, with an incidence of 0.7–2.4 per a million people a year. Clinical presentation of Cushing syndrome can be pleomorphic, and establishing diagnosis can be difficult. Early recognition and rapid control of hypercortisolaemia are necessary to decrease morbidity and mortality in these patients. We report a series of 6 endogenous Cushing’s syndromes of different etiologies (4 Cushing’s disease and 2 adrenal Cushing’s syndrome) assessed in our endocrine department over a decade (2009-2019). In order to highlight the diversity of clinical forms, diagnostic tools and specific management of this condition we labelled each case suggestively: the typical Cushing’s disease, the Pseudo Cushing’s, the elusive Cushing’s disease, the mild autonomous cortisol hypersecretion, Cushing’s syndrome in pregnancy and Cushing’s disease with thromboembolism. We discussed their particularities which were revelatory for the diagnosis, such as dermatologic, cardiovascular, musculoskeletal, neuropsychiatric, or reproductive signs, reviewing literature for each manifestation. We also discuss the commonalities and differences in laboratory and imagistic findings. Therapeutic approach can also differ with respect to the particular condition of each patient and the multiple choices of therapy will be reviewed.

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Introduction. Relative adrenal insufficiency (RAI) is common in the setting of critical illness as well as in hemodynamically instable cirrhotic patients with sepsis. Several studies have also shown that RAI is frequent in patients with stable cirrhosis without sepsis. The aim of this study was to prospectively assess the incidence of RAI in patients with stable cirrhosis. Patients and Methods. Forty-seven patients with hemodynamically stable liver cirrhosis without sepsis were prospectively included. RAI, assessed by using low doseshort Synacthen test (LD-SST), was defined as either a basal total cortisol concentration below 3.6 μg/dL or a peak total serum cortisol ≤ 16 μg/dL at 30 min after stimulation. Results. RAI was present in 10 (21.3%) of 47 cirrhotic patients. Peak cortisol level was negatively correlated with the severity of cirrhosis evaluated by Child- Turcotte-Pugh (CTP) (r=-0.46; P=0.001) and Model for End- Stage Liver Disease (MELD) (r=-0.51; P=0.001) scores. The frequency of RAI increased from CTP-A (10%) to CTP-B (30%) to CTP-C (60%). Conclusion. RAI diagnosed by LD-SST is frequent in patients with stable cirrhosis and is related to the severity of liver disease. Further studies are needed to define clinical importance of RAI in stable cirrhotic patients.

Obesity is an increasing public health problem, the fifth leading risk for global deaths according to WHO. It is associated with major comorbidities, such as type 2 diabetes mellitus, ischemic heart disease, hypertension, dyslipidemia, sleep apnea, osteoarthritis, nonalcoholic fatty liver disease and depression. The obesity pathogenesis increasingly became clearer. It is thought to be the result of a neuroendocrine dysregulation of energy intake and energy expenditure. One of the most studied cytokines involved in obesity, leptin is secreted from adipose tissue, proportional to fat mass. It inhibits neuropeptide Y/Agouti-related peptide neurons and activates pro-opiomelanocortin (POMC)/ cocaine amphetamine-related transcript neurons in the hypothalamus, resulting in an anorectic effect.

Background. The high recurrence rate and low survival rate of ovarian cancer (OC) patients are closely related to an anoxic environment. We aim to study the mechanism of long non-coding RNA (lncRNA) HOXA transcript at the distal tip (HOTTIP) on hypoxia ovarian cancer cells (OCC) and its mechanism was investigated. Methods. Knockdown and overexpression of HOTTIP in human OCC (SKOV-3, OVCAR3) were performed. The expression levels of HOTTIP and HIF- 1α were monitored by qRT-PCR and WB. Transwell was conducted to validate the cell migration and invasion. ELISA was performed to calculate VEGF concentration in cells. Cell viability was monitored by CCK-8. Cell apoptosis and cycle were tested by flow cytometry. RNA pull-down was used to analyze the interaction between HIF-1α and HOTTIP. Results. HOTTIP was highly expressed in OCC. After HOTTIP knockdown, HIF-1α expression and VEGF concentration in OCC were decreased. Cell migration, invasion, and cell viability were decreased. Cell apoptosis rate and G0/G1 phase cells were increased. RNA pull-down indicated a direct interaction between HIF-1α and HOTTIP. Conclusions. HOTTIP formed a positive feedback loop with HIF-1α to promote the development and metastasis of hypoxia ovarian cancer. This study provided theoretical support for the development of new OC treatment strategies.

Background. Type 1 diabetes mellitus is a common disorder which causes a variety of complications such as cognitive deficits in central nervous system. Auditory P300 event related potential is a wellestablished neurophysiologic approach in the assessment of cognitive performance. In this study, we aimed to evaluate the cognitive performance in insulin dependent diabetic patients by auditory event related potentials. Methods. In this descriptive analytical and non-interventional study, auditory P300 event related potential was measured in oddball paradigm by using two tone burst stimuli (1000 & 2000 Hz) on 25 diabetic patients and 25 age, education and sex matched healthy controls, with mean age 28.76±4.1 in patients and 29.68±3.6 in controls. Results. The mean P300 latency of the diabetic patients was significantly prolonged and the mean P300 amplitude of the diabetic patients was significantly lower when compared with that of controls at all electrode sites (p<0.01). Also there was a strong correlation between P300 latency and glucose level, HbA1c and diabetes duration (p<0.01). Conclusion. Auditory information processing is slower and the speed of information categorizing is lower in diabetic patients than in controls.