ACTA ENDOCRINOLOGICA (BUC)

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.

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.

Intracranial germ cell tumors (GCT) are rare brain tumors that typically arise in the pineal or suprasellar regions. Germinomas are highly radiosensitive among pediatric CNS tumors. Suprasellar GCTs most commonly present with hypothalamic/ pituitary dysfunctions. We report a case of an 18 year old boy with particularly long term evolution from the onset of symptoms to the positive diagnosis of suprasellar germinoma. At 9 years he was diagnosed with idiopathic central diabetes insipidus and started DDAVP therapy. In the subsequent years he presented delay in longitudinal growth and delayed pubertal development. At 16 years he was referred to our institute with relatively good general condition despite an extremely severe hypernatremia of 186 mEq/L, serum osmolality of 405 mOsm/kg and impaired thirst sensation. He developed sinus thrombosis as a consequence of hyperosmolality and presented intermittent rises of temperature, but no septic episodes. During a long term follow neuroimaging eventually revealed a thickening of the pituitary stalk, mimicking as an infiltrative lesion. Finally, two supracentimetric tumor nodules were shown on contrast enhanced MRI in the suprasellar region and at the floor of the left lateral ventricle. Stereotactic biopsy concluded a pure germinoma, and craniospinal irradiation was performed. At present he has an infracentimetric suprasellar tumor remnant, reperfused sinus veins, optochiasmatic syndrome sequelae. He benefits from L-Thyroxin and testosterone replacement, and maintains hydro-electrolytic balance on DDAVP and controlled oral fluid intake.

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.

Background. Hashimoto thyroiditis (HT) is an autoimmune disease and the most common cause of hypothyroidism. The widespread lymphocyte infiltration in the thyroid gland and intolerance of the body against its thyroid antigens leads to the destruction of thyroid cells and impaired thyroid function. Granulysin (GNLY) is a cytolytic antimicrobial peptide that has been associated with a wide range of diseases such as various infections, cancer, transplantation, and skin problems. However, there are a few studies investigating the relationship between HT and granulysin. Aim. Our study aims to investigate whether granulysin levels and GNLY gene polymorphism contribute to the damaged immune response leading to HT. Material and Methods. 100 unrelated patients diagnosed with HT and 140 healthy individuals were included in our study. Frequencies of GNLY rs10180391 and rs7908 gene polymorphisms were determined using PCR- RFLP method and serum granulysin levels were determined using ELISA. Results. There is no statistical significance between patient and control groups in terms of genotype and allele frequencies of GNLY gene polymorphisms and serum levels of granulysin. Conclusion. In conclusion, granulysin and GNLY gene polymorphisms do not appear to relate to HT disease.

Objective. To compare results of treatment of primary hyperparathyroidism (PHPT) in two teaching hospitals (eastern and western Europe) and to establish conclusions regarding quality of surgery for PHPT in Romania. Methods. We reviewed two prospectively collected databases of patients submitted to open minimally invasive parathyroidectomy (OMIP) for symptomatic PHPT in two centers from Romania and the United Kingdom (UK). We included patients with biochemically proven PHPT and positive pre-operative localization studies. We excluded patients with negative localization studies, suspected multiglandular disease, concomitant thyroid disorders and chronic renal failure. Results. 60 patients were included, 27 in group A (Romanian cohort) and 33 in group B (UK cohort). We noted significant differences between groups in pre-operative serum calcium and phosphorus levels (p<0.5). There were no differences between groups regarding the presence of symptoms; in group A we had significantly more patients with renal calculi history (p=0.02), digestive symptoms (p=0.006) and osteitis fibrosa cystica (p=0.01). Two patients from the UK group had lithium associated hyperparathyroidism and 2 patients had genetic disease. Intraoperative parathyroid hormone measurement (ioPTH) was available only for group B and frozen sections were selectively used in both groups. Both the adenoma size and weights were significantly higher in group A. The median operative time was significantly longer in Romanian group (p=0.001); in this group we noted the single conversion to traditional cervicotomy (3.7%) from all studied patients. In group A we noted two patients (7.4%) with failed parathyroidectomy and persistent PHPT; the cure rate was 92.5% for Romanian group and 97% for the UK group. Conclusions. OMIP can be performed safe with a high cure rate in “small” volume endocrine centres with results comparable to western experienced endocrine centres. Romanian patients presented with more severe PHPT with more frequent end-organ damage, due probably to late diagnosis.

Despite several attempts to establish the role of QUS in clinical practice, issues such as definition of osteoporosis based on QUS, screening strategy and therapy efficacy for patients identified by QUS as having high risk of fracture remain a matter of debate. The present study aimed to evaluate the diagnostic agreement between two QUS techniques (heel QUS and proximal phalanges QUS) and DXA in an unselected population of Romanian women aged 24- 80 years, as well as to offer cut-off levels for QUS to distinct between women with or without osteoporosis identified by DXA. In women measured by both DXA and calcaneus QUS (c- QUS), bone mineral density (BMD) moderately correlated with stiffness index (SI) (L1-L4: r=+0.51, p<0.001; femoral neck: r=+0.53, p<0.001; hip: r=+0.57, p<0.001), while in women examined by both DXA and phalanx QUS (ph-QUS), BMD was positively related to amplitude-dependent speed of sound (Ad-SoS) (L1-L4: r=+0.47, p<0.001; femoral neck: r=+0.50, p<0.001; hip: r=+0.38, p<0.001) and ultrasound bone profile index (UBPI) (L1-L4: r=+0.44, p<0.001; femoral neck: r=+0.50, p<0.001; hip: r=+0.38, p<0.001). At a T-score cutoff level of -2.5SD, the high specificity but low sensitivity suggests a low false positive rate of c-QUS as a diagnostic test; still, several patients with the disease may not be correctly diagnosed. At the same cut-off level, ph-QUS showed higher sensitivity and lower specificity. Diagnostic agreement between DXA and QUS was poor, with k-scores ranging from 0.33 to 0.39 for c-QUS and from 0.14 to 0.29 for ph-QUS, respectively. Lowering c-QUS T-score cutoff for lumbar spine osteoporosis screening to -1.5SD and ph-QUS T-score cut-off to -1.9SD, respectively, improved sensitivity and had a minor effect on diagnostic agreement. Regardless of the evaluated site, neither c-QUS nor ph-QUS does represent an adequate predictor of BMD in Romanian women. Changing the diagnostic T-score threshold from -2.5 SD to -1.5 SD and -1.9 SD in subjects examined by c-QUS or ph-QUS, respectively, is followed by improved sensitivity and diagnostic agreement in the identification of patients with vertebral osteoporosis. Cut-off values may allow QUS to be used as a screening tool for spine and femur osteoporosis.

Context. Atrial fibrillation (AF) is the most common sustained arrhythmia in clinical practice. The increasing evidence supports links between inflammation and AF. There is evidence showing that obesity is a major cause of adipose tissue (AT) inflammation. Ghrelin (GHRL), through its growth hormone secretagogue receptor (GHS-R) present on adipose tissue macrophages (ATMs), could modulate AT inflammation. Objective. Our study aimed to evaluate the role of adipose tissue macrophages (ATMs) and their GHS-R in adipose tissue samples of right atrial appendages (RAA) biopsies. Subjects and Method. We obtained RAA biopsies from 10 obese patients, undergoing cardiac surgery for coronary artery bypass graft (CABG) and developing postoperative atrial fibrillation (POAF). The epicardial tissue samples were examined using immunohistochemistry to visualize and quantify CD68 and GSH-R expression of the ATMs. Results. Histologically, the mean adipocyte diameter (MAD) of epicardial adipose tissue (EAT) was larger in EAT samples with inflammation as compared to EAT without inflammation (84.2 μm vs. 79.6 μm). The expression of CD68 was lower in EAT without inflammation as compared to EAT with inflammation in adipose tissue samples. Similarly, the expression of GSH-R was lower in EAT samples without inflammation as compared to EAT samples with inflammation in adipose tissue. Conclusions. Increased epicardial fat area, macrophage infiltration, and GHS-R expression in epicardial ATMs appeared to be associated with postoperative atrial fibrillation in obese patients.

There are no new national growth references for the Romanian population and the current recommendations for short stature evaluation is the use of the Swiss growth charts developed based on a longitudinal study. The aim of the present paper is to present the new synthetic growth references for Romanian children. Material and methods. We used local Romanian data from 9 studies with information on height and weight obtained between 1999 and 2016. Based on their plausibility and methodology six studies were selected for generating the National Synthetic Growth References for Romanian Children based on the specific methodology described previously. The selected studies included 8407 subjects measured in schools/kindergartens. Age is reported in years covering a range from 3-18 years. Height and weight were measured at a precision of 0.1 cm and 0.1 kg. All children were measured at normal temperature, in light clothes, without footwear. Results. We present the charts and tables with the common centiles for height, weight and body mass index for boys and girls. Conclusion. We suggest synthetic growth references based upon recent growth data from 6 different Romanian regions as new National Growth Charts for Romanian children.

This study was performed to search the effect of a fiber rich dietary product on anthropometric measurements and some biochemical parameters of obese adult women. A total of 25 adult women (12 were in study and 13 were in control group, all randomly selected) volunteered in this study. At the beginning of the study, height, weight, waist and hip circumferences of all women were measured, and blood samples were collected for fasting blood glucose (FBG), insulin, triglycerides (TG), total cholesterol, HDL-C, LDL-C, VLDL-C levels. Patients having endocrine and metabolic disturbances and who need to use anti-obesity medications were not enrolled. A low calorie weight losing diet consisting of 50-55% carbohydrate, 15-20% protein and <30% fat was given to all cases, but women in the study group were given a specific dietary product rich in apple and wheat fiber as an exchange of one slice of bread every day. Patients were checked monthly with respect to their weight loss and diet adhesion during the three months of treatment period. Although biochemical parameters did not show any significant differences between the two groups at the beginning of the study, FBG and insulin levels were significantly lower in the study group than in the control group at the end of the treatment period. There were also significant decreases in insulin, triglyceride, total cholesterol and VLDL-C levels in the study group after 3 months of treatment, but not in the control group. Women in both groups lost weight, and their waist and hip circumferences decreased significantly. This concludes that the fiber rich, fat, sugar and salt free dietary product could be a useful dietary treatment not only in obesity, but also in dislipidemia and insulin resistant states.