ACTA ENDOCRINOLOGICA (BUC)

A 38 years old, heavy smoker, was admitted in our thyroid unit in August 1993 with left eye proptosis (21 mm), right eye prosthesis and euthyroidism. Orbital CT scan revealed inferior rectus muscle hypertrophy in the left orbit and possible residual (postoperative) lateral rectus muscle hypertrophy in the right orbit. Left eye proptosis was treated with both glucocorticoids and orbital radiotherapy.\r\nSeven years before (1986) the patient developed right eye proptosis, without clinical features of hyperthyroidism. Being suspected of a sphenoid ring meningioma and since orbital CT scan was not available at that time, a right orbit exploration was performed in November 1987; soon after orbital exploration, clinical features suggesting right orbital cellulitis occurred, followed by right eye evisceration and right eye prosthesis. After 18 years of Graves ophthalmopathy with euthyroidism, in February 2004 an autoimmune hyperthyroidism was diagnosed (suppressed TSH, high TT3, positive TRAb), being successfully treated with radioiodine. One year after the ablative therapy the patient is still euthyroid. A patient with euthyroid Graves ophthalmopathy should be monitored indefinitely, since a thyroid dysfunction may occur even after more than a decade.

Epidemic of obesity is ongoing and did not slow down. Causes of obesity are numerous and very complex. Among them, the concept of bidirectional signaling within the brain-gut-microbiome axis was recently proposed as possible pathophysiological mechanism and become a hot topic in the explanations for the control of food intake. Discoveries of new anti-obesity drugs that are analogs for the receptors for some hormones derived from gastrointestinal tract contribute to the investigations in this area. The human gut microbiota plays a fundamental role in human health and disease and it is considered that it represent an endocrine organ that participate in energy homeostasis and host immunity. Role of gut microbiome has been investigated in metabolic diseases such as obesity, type 2 diabetes and non-alcoholic fatty liver disease. Gut microbiome participate in regulation of various mechanisms inside the gastrointestinal tract due to its production of different bacterial metabolites. In our manuscript we present current knowledge about microbiota in the gut; the relation between gut microbiota and brain; neuroendocrine system and gut-brain axis; immune system and gut-brain axis; endocrine system and gut-brain axis; the role of gut microbiota in obesity development and possible use of gut microbiota for the treatment of obesity.

Background. Weight loss associated with long-term lifestyle changes has significant beneficial effects on metabolic syndrome (MetS) features on obese patients; unfortunately, the weight recidivism rate is high and the weight fluctuations could increase the cardiovascular and metabolic risk. On the other hand, there are many data about the endocrine role of adipose tissue. Objective. Taking into account the imbalance between pro-inflammatory and anti-inflammatory cytokines secreted by adipose tissue on obese patients, this study assessed the effects of one month-long supervised lifestyle change (SLC) program without weight loss on the MetS-associated inflammatory status. Methods. The study included 29 obese adults with MetS. The SLC program included supervised moderate physical activities and diet for one month. The levels of adipocytokines, lipids and inflammatory markers were analyzed before and after one month SLC program, and 2 months later at follow-up. Results. At follow-up, the leptin, vascular endothelial growth factor (VEGF), and hsCRP levels decreased, whereas the interleukin-4 (IL-4) and high-density lipoprotein (HDL) cholesterol levels increased from their baseline levels. So, an SLC program, even in the absence of weight loss, could have an extended antiinflammatory effect by decreasing the proinflammatory adipocytokines. Conclusion. Our data furthermore emphasize the importance of the adipocytokines gender-related variation for a more personalized evaluation protocol on obese patients.

Metabolic syndrome may have direct myocardial effects in addition to their atherogenic effects, and this has been related to left ventricular systolic and diastolic dysfunction, as well as left ventricular remodelling. The aim of the study was to analyze the correlation between the metabolic syndrome clustering components (individual and additive) and heart failure severity in patients with prior myocardial infarction. We performed a cross-sectional study including 65 patients with heart failure post-myocardial infarction (31 men and 34 women) with a mean age at 64.1 (9.1). We evaluated the metabolic syndrome parameters (individual and additive) and analyzed their impact on heart failure severity by comparing NYHA I+II and NYHA III+IV groups. The elements of metabolic syndrome independently correlated with heart failure severity were identified by means of logistic regression method. The frequency of metabolic syndrome in our study group was high (49.23%). High blood pressure, fasting glucose, central obesity and low HDL-Cholesterol levels were significantly associated with severe heart failure (NYHA III and IV classification) in univariate logistic regression analyses. The only two independent variables: hyperglycaemia and reduced HDL-Cholesterol returned high enough levels of OR and 95%CI (1.79; 1.45-2.89 and 0.83; 0.67-0.91 respectively) to reach statistical significance beyond adjustment risk factors. In our study it was identified a significant correlation between presence of complete metabolic syndrome criteria and heart failure severity, measured in either NYHA IV categories (p=0.002), or by means of echocardiographical parameters such as: left ventricular ejection fraction (p=0.026), left ventricular masse index (p=0.006), peak E velocity (p=0.011), peak A velocity (p=0.037), Mitral E/A ratio (p=0.001) and E-deceleration time (0.021). Conclusions: Among the criteria for metabolic syndrome, hyperglycaemia and reduced HDLCholesterol levels had a strong association with heart failure severity. Our findings are relevant for\r\nclinical practice and intervention, and the aggressive treatment for conventional risk factors has also been effective in the prevention of heart failure.

Primary hyperaldosteronism is the cause of approximately 0.05 to 2.2% of all\r\nunselected cases of hypertension. It was first described in 1955 by Conn in conjunction with\r\naldosterone-producing adrenal adenoma, which is the most frequent aetiology, in 65% of\r\ncases. Clinical features are usually non-specific and result from potassium depletion. We\r\nreport here the case of a 54-year-old woman who was admitted to the emergency department\r\ndue to coma (Glasgow score 6). The presence of severe potassium depletion (1.2 mmol/L)\r\nand metabolic alkalosis (PH=7.76, base excess>30 mmol/L) in a hypertensive patient\r\ndetermined the clinicians to search for a secondary cause of hypertension. This was\r\nconfirmed by localizing on computer tomography a right adrenal adenoma of 31-mm\r\ndiameter and on endocrine measurements that showed mineralocorticoid excess (plasma\r\naldosterone=764 pg/mL;N=14-193). Clinical evolution was slowly favourable after\r\nrestoring the electrolyte balance, with increasing of serum K up to 3.05 mmol/L. The patient\r\nbecame asymptomatic in 3 weeks and underwent laparoscopic right adrenalectomy. The\r\npatient had a good postoperatory evolution. Two weeks after laparoscopic right\r\nadrenalectomy, blood pressure normalized after the discontinuation of the antihypertension\r\ntreatment and the aldosterone measurement was normal (102 pg/mL).

The nuclear receptor coding PPARγ2 (PEROXISOME PROLIFERATORACTIVATED RECEPTOR-GAMMA; *601487) gene influences the lipid and carbohydrate metabolism via multiple pathways and is a candidate for the metabolic syndrome. In this paper we studied the relationship of the CCG (Pro) → GCG (Ala) polymorphism of the gene with the metabolic syndrome diagnosed according to the criteria recommended by the International Diabetes Federation (IDF) in 2005, in a population from central Romania. We have carried out a case-control study on 144 patients and 73 control subjects. Routine biochemical assays have been carried out, fasting insulinemia was measured by ELISA, and insulin sensitivity was assessed by calculating the HOMA and QUICKI indices. Genetic analysis was done by PCR followed by digestion with the restriction enzyme BstU I. The results show that the Pro12 allele had a higher frequency in the group of patients as compared to the healthy controls (76 vs. 65.7%, p<0.05). The risk for developing the metabolic syndrome in the presence of the Pro12 allele in a homozygous combination was found to be low but statistically significant (PP vs. PA + AA: OR = 1.98, CI 95% 1.04 -3.78, p = 0.046). In conclusion, in the local population, the Pro12 allele of the PPARG2 gene seems to contribute to the hereditary predisposition of the metabolic syndrome diagnosed according to the recommendations of the IDF, most likely as part of a polygenic system. Probably the absence of the protective Ala12 allele increases the risk for developing the disease.

Context. Vitamin D is a steroid hormone that acts by binding to the vitamin D receptor (VDR) found in many tissues. According to the long-term mechanism, vitamin D causes the proliferation and differentiation of muscle cells by gene transcription. Objective. We aimed to evaluate the relationship between muscle strength and serum vitamin D levels in elderly men. Design. Cross-sectional study. Subjects and Methods. Male patients over age 50 were included in the study. Study population was divided into 2 groups with handgrip strength according to body mass index, either as subjects with weak or with normal handgrip strength test (HGST). Vitamin D levels and other variables compared between weak and normal groups. Results. Vitamin D level of weak and normal groups were 7.5 (3-19.9) μg/L, and 11.6 (11.6-34.9) μg/L, which means significant reduced vitamin D levels in weakness group (p=0.01). Vitamin D levels were significantly correlated with HGST levels (r:0.362, p=0.001). Vitamin D levels were found to be an independent predictor of weakness according to HGST in logistic regression analysis (OR: 0.453, 95% Cl:0.138-0.769, p=0.05). Conclusions. Low vitamin D level is an independent risk factor for muscle weakness in men aged more than 50 years. Therefore, vitamin D levels should be screened and early replacement should be initiated for the sake of improvement of muscle strength in elderly subjects that vulnerable for frailty.

The pharmacokinetic characteristics of a compound as well as the immediate consequences of its physicochemical behavior during interactions with biological structures,\r\nrepresent the key issues for its pharmacodynamic profile, starting from the most fundamental global aspects (i.e. central and / or peripheral action) to the most detailed ones (i.e. molecular mechanism of action).\r\nSuccessive metabolic reactions lead to either bioactivation or bioinactivation of themolecular entity. A particular importance is currently assigned to several molecular\r\nphysicochemical descriptors, for instance the polarity degree (mirroring the changes of partition coefficients and of the permeability of biological structures), and emphasizing on distribution and renal excretion rate.\r\nThe active metabolite (9-hydroxy-risperidone) of the atypical antipsychotic agent risperidone has an increased polar character and, consequently, its pharmacokinetic profile is modified compared to the parent drug: especially the penetration through the bood brain barrier and the efflux pump mediated transport were considered. In this context, the kinetic characteristics and their correlation with the pharmacodynamic properties for the two active\r\nentities, as well as the consequences dealing with the antipsychotic efficacy, the safety and efficacy profiles can be anticipated. The present approach critically asseses the available data from literature corroborated with the personal findings over the last years.

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