ACTA ENDOCRINOLOGICA (BUC)

Background. There are few data to demonstrate the usefulness of N-terminal pro B-type natriuretic peptide (NT-proBNP) for the left ventricular diastolic dysfunction (LVDD) diagnosis in metabolic syndrome (MSy) patients as the relationship between NT-proBNP and MSy components is still under study. Objectives. The present study aims to determine the influence of MSy components on NT-proBNP concentrations. In this respect, we tried to identify the relationship between NT-proBNP concentrations and LVDD in patients with MSy and preserved LV systolic function. Methods. 68 hospitalized obese patients with MSy (IDF2006 definition) were taken under study. All patients underwent Doppler echocardiography. NT-proBNP was determined using the ELISA method (Biomedica). The data obtained in the study group were compared to those of 70 obese subjects, age and sex matched, without MSy. Results. The median of plasmatic NT-proBNP level in MSy patients was 155 pmol/L significantly (p=0.002) higher than in the control group (120 pmol/L). Median NTproBNP was significantly higher (p=0.0266) in MSy patients presenting LVDD (160 pmol/L) as compared to those with normal left ventricular function (125 pmol/L).In the LVDD subgroup NT-proBNP level was positively and significantly correlated with age (r=0.326, p=0.025), SBP (r=0.508, p=0.0003) and DBP (r=0.396, p=0.005) and negatively correlated with waist circumference (r=-0.380, p=0.008). Dyslipidemia, impaired fasting glucose and body mass index (BMI) did not significantly influence NT-proBNP levels. Conclusions. MSy patients had higher NT-proBNP concentrations as compared to obese subjects without MSy, due to the presence of LVDD and the positive and statistically significant correlation with age, SBP and DBP.

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. Hidradenitis suppurativa (HS) is a chronic, debilitating disease with a profound impact on the quality of life of patients. Objectives. To describe a rare case of HS with postmenopausal onset, to review the literature data regarding late onset HS and to discuss the current knowledge on the role of endocrine abnormalities in the development of HS. Case report. We report the case of a 68-year-old patient in whom HS occurred 10 years after menopause. She was referred to our clinic for the presence of an open fistula on the left groin, fibrotic scars and visible alteration of the vulvar anatomy due to numerous surgical interventions. The patient shared features of the metabolic syndrome (obesity, arterial hypertension, dyslipidemia, aortic atherosclerosis), but showed no signs of virilism and no hormonal abnormality. HS was controlled using antiseptics, topical retinoids and antibiotics. Conclusions. This case is of particular interest given the late onset of HS, long time after menopause. The development of HS requires a complex interaction between genetic predisposing factors, endocrine dysregulation, metabolic alterations, bacterial overgrowth and an aberrant inflammatory response. Evidence points to an important role of sex-hormones in the emergence and progression of the disease, but the underlying mechanisms are still unclear. A better understanding of HS pathogenesis is needed to elucidate the precise way in which endocrine factors influence the disease onset and course. This would guide the way to novel therapies and a better control of this challenging disease.

Context. Orbital pseudotumor (OP) is a benign inflammatory process of the orbit with a large polymorphous lymphoid infiltrate, associated with fibrosis in variable amounts, localized or diffuse. Graves’ ophthalmopathy (GO) is the most common cause of proptosis, unilateral or bilateral. Case report. We report a patient with unilateral proptosis who was initially treated with antithyroid drugs for an euthyroid Graves disease, but the extension of the investigation infirmed this. The MRI findings (inflammation of fat, muscle and the left lacrimal gland) in conjunction with the biopsy infirmed the initial diagnostic and confirmed the OP. Conclusions. Orbital pseudotumor is a rare disorder that can image and clinically mimics some inflammatory disease especialy Graves’ ophthalmopathy. Orbital MRI represents the most important test for diagnostic. A negative TRAb in euthyroid cases of proptosis can be a serious starting point for investigating an OP.

Vitamin D is essential in efficient absorption of calcium and normal mineralization of bone. Severe vitamin D deficiency produces impairment of bone mineralization and osteomalacia. Less severe vitamin D deficiency, called vitamin D insufficiency or inadequacy, causes secondary hyperparathyroidism, increased bone turnover and bone loss. The aims of our study were: the evaluation of vitamin D status and its seasonal variation in postmenopausal women with osteoporosis, from Romania; we studied also the relationship between vitamin D and parathyroid hormone serum concentrations in order to establish the threshold level of vitamin D which determines secondary hyperparathyroidism. The study was performed on 834 postmenopausal (natural or surgical) women who attended the National Osteoporosis Center and were diagnosed with osteoporosis using dual absorptiometry with X ray (DEXA). None was receiving vitamin D supplementation and they were not taking drugs affecting bone and mineral metabolism and were not suffering from such diseases. Estimation of vitamin D and parathyroid hormone status was made by determining 25-hydroxyvitamin D (25OHD) and PTH-intact (PTH) serum concentrations from a single blood sample using immuno-enzyme methods. The results were compared using Student? t test for unpaired values and linear regression to establish the correlation. All data were expressed as mean value ? standard deviation and a value of p<0.05 was considered as statistically significant. In a previous study we reported for premenopausal normal women the mean value for 25OHD at 26.58?10ng/ml. At the same time, we defined the vitamin D deficiency as the levels below 12 ng/mL, and the insufficiency of vitamin D (vitamin D inadequacy) as the values between 12 and 26.58 ng/mL. The mean serum 25OHD concentration for our study group was 20.04?144.22 mg/mL. We defined arbitrary values (using data from international studies) for 25OHD serum levels to estimate the prevalence of vitamin D deficiency and vitamin D inadequacy in our study group. In 834 postmenopausal women with osteoporosis, living in Romania, without vitamin D supplementation or pharmacological therapy to treat or prevent osteoporosis, the prevalence of vitamin D deficiency was 32.2% and the prevalence of vitamin D inadequacy was 42.3%. Seasonal variation of 25OHD was found statistically significant (p<0.05), with lower values at the end of winter. Statistical tests applied to results have shown a significant negative correlation between PTH and 25OHD serum levels (p<0.001) and established the cut-off concentration for 25OHD which determine secondary hyperparathyroidism at 20 ng/mL. Our data underscore the need for adequate vitamin D supplementation in women with osteoporosis.

A 9 member independent panel of endocrinologists and pediatricians was convened to discuss basic issues with respect to definition, diagnosis, and clinical management of children born small for gestational age (SGA). SGA is defined as the situation when birth weight and/or length are at least 2 standard deviations (SD-s) below the mean for gestational age (<2 SD). The seven consensus guidelines agreed by the panel members are as follows: i. Children born SGA have a serious and permanent handicap of growth in adulthood if not treated. ii. Any term newborn lighter than 2500 g (male) or 2000 g (female) may be considered SGA. iii. When 4 years of age, all children born SGA will be evaluated for height, height velocity, bone age. Preterm children and multiplets should be included even if they were AGA. All children having concomitantly a SD score of < -2.5, a HVSD score < -1 and a bone age (Greulich-Pyle) smaller or equal to the chronological age are to be considered candidates to GH therapy. iv. All recognizable short stature syndromes must be extracted from the contingent of SGA by clinical and laboratory thorough evaluation and subjected to their distinctive growth disturbance protocol. v. The rest of candidates will receive GH therapy at 0.35 mg/kg/week daily dosage. A\r\nbiochemical screening including hormonal and IGF I determinations and also hematology should be performed before administering the first injection. GH dynamic tests are not recommended as a rule. vi. Effectiveness of the therapy will be appreciated after 6-12 months of uninterrupted therapy. Annualized growth rates higher than 7 cm/yr are considered proofs in favor of successful therapy. IGF I levels higher than 600 ng/ml should be avoided. vii. After the inclusion in therapy and the first evaluation, the patients follow-up should align to the standard provisions of the national or regional programs of GH therapy.

Objective. To analyze the association between low bone mineral density (BMD), metabolic syndrome (MS) and sex hormones deficiency in men. Methods. We included in this retrospective study 199 men with osteoporosis or osteopenia and 167 men with normal BMD as controls, aged between 55-85 years old. Patients’ evaluation included: medical history and physical examination, X-ray of thoracic and lumbar spine, measuring BMD at hip and lumbar spine, serum glucose and lipid profile, serum levels of total testosterone (tT), free testosterone (fT) and estradiol (E2). Results. The results revealed a significant association between low BMD and MS (p=0.011). Vertebral fractures were more frequently associated with MS (p=0.041). Patients with MS had lower vertebral BMD (p=0.037) and lower E2 levels (p=0.024) compared with those without MS. In men with MS, E2 deficiency can predict the value of vertebral and hip BMD. fT deficiency can predict only the value of hip BMD. Conclusions. A significant association between MS, low BMD, vertebral fractures and sex steroids deficiency, in particular E2 and fT was found. The presence of MS and sex hormones deficit can predict the reduction of BMD.

Our aim was to explore the interactions of intercellular adhesion molecule (sICAM-1), TNF-&#945; (tumor necrosis factor-&#945;), interleukin-1&#945; (IL-1&#945;) and interleukin-6 (IL-6) with\r\ndopamine agonists in a culture of adenomatous cells from an nonfunctional macroadenoma.\r\nMaterials and methods. Tissue specimen from pituitary macroadenoma removed in transsphenoidal surgery was prepared for primary culture. Cells were counted and plated at 105/well into 24-well plates in a final volume of 1ml. Cabergoline in molar doses of 10-6, 10-7, 10-8, 10-9 was added and the cells were incubated for 4 days. sICAM-1, TNF-&#945;, IL-1&#945;, IL-6 were measured from cell-culture supernatants by ELISA kits.\r\nResults. sICAM-1, TNF-&#945;, IL-1&#945; and IL-6 were detected in the untreated control cultures after a 4d period. There was a negative correlation between TNF&#945; and IL-1&#945; (p=0.007).\r\nThe levels of PRL and hGH had measurable values above those found in culture medium without tumor cells. PRL positively correlated with IL-1&#945; ( p=0.05). hGH positively correlated with cell proliferation (p=0.049). Cabergoline treatment showed that IL-6 progressively decreased with the dose, ranging from -27.41% to -76.44%. TNF-&#945; significantly decreased (-65.90%; p<0.03)at the cabergoline 10-7 M dose. IL-1&#945; progressively increased with cabergoline dose, ranging\r\nfrom -2.53% to 345 %. sICAM-1 was significantly reduced by cabergoline at 10-9 (-47.12 %; p=0.045) and 10-6 M (-59.16%; p=0.01) doses. TNF-&#945; positively correlated with PRL (p=0.025); IL-6 positively correlated with hGH (p=0.044); sICAM-1 negatively correlated with hGH\r\n(p=0.009), TNF&#945; (p=0.025) and IL-1&#945; (p=0.044).\r\nConclusions. These data support the existence of an immunoendocrine network in pituitary tumorigenesis; TNF-&#945;, IL-6, IL-1&#945;, sICAM-1 significantly interfered by cabergoline\r\ntreatment in a dose-dependent way. However, future studies on different types of pituitary tumours are needed to confirm these findings.

Background. Genetic variants of the endothelial nitric oxide synthase (eNOS) gene have\r\nbeen reported to be associated with cardiovascular disease. We hypothesized that G894T\r\npolymorphism might trigger many of the endocrine-metabolic changes related to metabolic\r\nsyndrome (MetS).\r\nStudy Design. 148 subjects with MetS and 142 healthy control subjects aged 23-60 years\r\nwere studied. Fasting serum levels of insulin, cortisol, 17-OH Progesterone, DHEA,\r\nandrostendione, IGF1, GH, PRL, CRP, resistin and biochemical profile were evaluated. G894T\r\n(eNOS) polymorphism was assayed by using PCR-RFLP technique.\r\nResults. The frequencies of genotypes and alleles of G894T polymorphism did not deviate\r\nfrom the Hardy-Weinberg equilibrium. In the MetS group the percentages of both GT (51.35 vs.\r\n39.44; OR=2.09; CI=1.27-3.45; p= 0.003) and TT (16.22 vs. 8.45; OR=3.08; CI=1.41-6.74;\r\np=0.003) genotypes and T allele (41.9 vs. 28.2; OR=1.83; CI=1.3- 2.6; p=0.0005) significantly\r\nincreased compared to control group. The G894T polymorphism was more significantly\r\nassociated with the MetS in the presence of cortisol, 17-OH Progesterone, PRL, IGF1 and CRP\r\n(OR= 8.20; 95%CI=2.31-29.08; p=0.001) and significantly stronger in the presence of IGF1,\r\nPRL, 17OHP, resistin and CRP (OR= 10.21; 95%CI=2.42-43.05; p=0.002). The T allele carriers\r\nhad higher values of waist circumference, systolic and diastolic blood pressure, cortisol, 17-OHP,\r\nandrostendione, PRL, resistin and lower values of glucose, HOMA-IR in MetS group; The TT\r\ngenotype carriers had higher values of triglyceride in both control and MetS group.\r\nConclusion. Our results show an interaction between the G894T polymorphism and its\r\nphenotypes in conferring a higher susceptibility to the endocrine changes involved in\r\npathogenesis of MetS suggesting a role of the eNOS gene in the modulation of the molecular\r\nendocrine mechanisms.

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.