ACTA ENDOCRINOLOGICA (BUC)

Objective. Metabolic syndrome (MetS) is a metabolic condition with high prevalence worldwide. This study aims to examine the relationship between serum concentrations of gastrointestinal hormones such as cholecystokinin (CCK), ghrelin, peptide YY (PYY), and high sensitive C-reactive protein (hs-CRP) and the ingredients of MetS in obese population. Subjects and Methods. This case-control study included 40 obese subjects (20 with MetS and 20 BMI and age-matched control individuals). The age range of the participants was 20-50 years and the participants’ anthropometric characteristics were measured. Serum lipids and the concentrations of oxidized low density lipoprotein (Ox-LDL), insulin, hs-CRP, CCK, PYY, and ghrelin were assessed with commercial ELISA kits. Results. Serum levels of hs-CRP, total cholesterol (TC) and triglycerides (TG) in patients with MetS were significantly higher while CCK and insulin concentrations were higher in obese non- MetS group (P <0.05). PYY had a negative association with waist circumference (WC) and high density lipoprotein cholesterol (HDL-C) and ghrelin had a positive association with systolic blood pressure (SBP) and TC in obese control group (P < 0.05). In obese patients with MetS, hs-CRP had a strong positive association with TG. Conclusion. The current study revealed the possible role of hs-CRP and several GI- hormones in the pathogenesis of obesity-associated diseases and MetS. Additional works are needed to elucidate the possible underlying mechanisms and clarify several controversies in this issue.

Context. The effects of COVID-19 on the adrenocortical system and its hormones are not well known. Objectives. We studied serum cortisol, serum adrenocorticotropic hormone (ACTH), and their ratio in hospitalized non-critically ill COVID-19 patients. Design. A prospective case-control study. Methods. The study participants were divided into 2 groups. Group 1 consisted of 74 COVID-19 patients. The second group consisted of 33 healthy persons. Early admission above hormones levels was determined and compared between the study groups. Besides that, COVID-19 patients were grouped according to their Glasgow Coma Score (GCS), CURB-65 score, and intensive care unit (ICU) requirement, and further sub-analyses were performed. Results. There were no significant differences in the mean age or gender distribution in both groups. In the patients’ group, the serum ACTH concentration was lower than in the healthy group (p<0.05). On the other hand, the serum cortisol levels and cortisol/ACTH ratio of the patients’ group were significantly higher than of the healthy controls (p<0.05, all). Further analyses showed that, although serum cortisol and ACTH levels were not high, the cortisol/ACTH ratio was higher in COVID-19 patients with low GCS (<15) than patients with normal GCS (=15) (p<0.05). In COVID-19 in patients with different CURB-65 scores, the cortisol/ACTH ratio was significantly different (p<0.05), while serum cortisol and ACTH were not different in groups (p>0.05). Serum cortisol levels and cortisol/ACTH ratio were higher but ACTH level was lower in the ICU needed COVID-19 patients than in patients who do not need ICU (p<0.05). Conclusion. Our pilot study results showed that the cortisol/ACTH ratio would be more useful than serum cortisol and/or ACTH levels alone in evaluating the adrenocortical system of COVID-19 patients. Still, further detailed studies are needed to confirm these.

Background. Hashimoto’s thyroiditis is in coexistence with many autoimmune disorders, especially celiac disease. There are a limited number of studies evaluating the prevalence of celiac-related antibodies in patients with Hashimoto’s thyroiditis. Objective. This study aimed to further investigate the prevalence of undiagnosed celiac disease in patients with Hashimoto’s thyroiditis and the relationship between these two autoimmune disorders in these patients Subjects and methods. This study was performed on 82 women aged 20-50 years including 40 patients with Hashimoto’s thyroiditis and 42 healthy age-matched individuals. Anthropometric assessments were performed and biochemical parameters including thyroid hormones (TSH, T3 and T4), antithyroid antibodies, anti-tissue transglutaminase and anti-gliadin antibodies were measured by enzyme linked immunosorbent assay (ELISA). Results. The prevalence of IgG and IgA anti-tissue transglutaminase antibodies and IgA anti-gliadin antibody was higher in Hashimoto’s thyroiditis patients compared with control group (15% vs. 7%, 22.5% vs. 17% and 15% vs. 12% respectively). In ordinal regression model, serum IgG anti-tissue transglutaminase and IgA anti-gliadin antibodies were significant predictors of antithyroid antibodies in patients with Hashimoto’s thyroiditis (P < 0.05). A significant relationship between serum TSH and IgG antigliadin antibody were also found (P = 0.003). Conclusion. To our findings, a high prevalence of anti-tissue transglutaminase and IgA anti-gliadin antibodies and their positive relationship with antithyroid antibodies in patients with Hashimoto’s thyroiditis were reported. These findings further warrant the need for interventions to reduce the prevalence of these antibodies in Hashimoto’s thyroiditis for preventing the occurrence of celiac disease in these patients.

Objectives. We aimed to determine lipodystrophy frequency according to insulin treatment regimen and insulin injection frequency in type 2 diabetic patients. Methods. A total of 345 type 2 diabetic patients under insulin treatment for at least one year were included in this cross-sectional study. Patients were examined for presence of lipodystrophy, insulin injection frequency and dosage. Lipodystrophy was evaluated with visual inspection and palpation of all injection sites. Patients were evaluated into three categories according to daily insulin dose requirement: Group 1= Standard-dose insulin users 0.6 U/ kg/day; Group 2= Medium-dose insulin users 0.61-1.9 U/kg/ day, Group 3= High-dose insulin users ≥2 U/kg/day. Results. Lipodystrophy was seen in 28% of the patients. Lipodystrophy was significantly higher in group 3. There was no significant difference between the groups in terms of lipodystrophy size. Duration of insulin treatment, daily total insulin dose, daily insulin dose per weight and number of daily insulin injections were significantly higher in the group with lipodystrophy. Daily injection number of long-acting, rapidly-acting analog and total insulin injections were significantly higher in group 3 than group 1 and 2. Number of daily insulin injections and lipodystrophy frequency were significantly higher in basalbolus insulin user group. Multivariate analysis showed that insulin injection frequency is the independent risk factor for lipodystrophy. Conclusion. Lipodystrophy is still a clinical problem in patients with high-dose insulin requirement and frequent insulin injections. Reducing daily insulin requirement and daily number of injections should be given priority in the management of patients to prevent the development of lipodystrophy.

Introduction. Pituitary adenomas (PA) are the third most common intracranial tumors, with an incidence rate of 10-15%. More than half are invasive, infiltrating adjacent structures. The primary objective of this project was to determine whether MGMT expression is associated with the invasiveness of PA. Material and Method. All patients who underwent surgical decompression consecutively between 2007- 2012 were included. All data were obtained from the case records. Formalin-fixed paraffin-embedded (FFPE) tissue specimens were stained with hematoxylin and eosin (HE) and then examined via light microscope. Paraffin blocks that lacked necrosis and hemorrhage were chosen for histologic examination. In addition to an immunoprofile battery that consisted of Ki-67 and p53, MGMT, S-100 and Pan-CK were evaluated as well. Results. The subjects included 25 women and 15 men. The mean age was 48.9 ± 14.5 years. Of these, 63% of cases involved the invasion of adjacent structures. Of the PA, 17 (42%) were non-functioning pituitary adenomas (NFPA). There was a statistically significant relationship between the invasiveness and Ki-67, p53, MGMT expression, and prolactinoma. Gonodotropinomas were mostly non-invasive. FPAs presented invasive features more frequently than NFPAs. Pan-CK was positive in GH-secreting adenomas but negative in FSH- and LH-secreting adenomas. Conclusion. Ki-67 and p53 in lower expression level can be used for evaluating invasiveness but not for recurrence. MGMT expression can be a useful IHC indicator for invasiveness. However, Pan-CK cannot be used for invasiveness or aggressiveness.

Introduction. The pituitary gland serves as the center of the endocrine system. Stem cells are typically found in a specialized microenvironment of the tissue, called the niche, which regulates their maintenance, self-renewal, fate determination, and reaction to external influences. The aim of this study is to elucidate the role of stem cells in the initiation, invasion, and progression of pituitary adenomas. Materials and methods. All specimens were collected between January 2007 and April 2015. Radiological classification (invasiveness) for all cases was performed according to the Wilson-Hardy classification system. Immunohistochemical staining was performed to all specimens for CD133, Oct4, Sox2 and nestin. Results. The study included 48 patients. Of 48 patients, 17 (35.4%) were male and 31 (64.6%) were female. Mean age is 47.10±14.14 (17–86 yrs.). According to the Wilson-Hardy classification system, 27 (56.3%) were noninvasive adenomas. There was no statistical significance between the expression of pituitary stem cell markers (CD133, OCT4, SOX2, nestin) and invasiveness. Conclusion. All stem cell markers are stained extensively in pituitary adenomas, except for SOX2 which was stained weakly. However, there is no effect of stem cells on invasiveness of pituitary adenomas because we cannot find a difference of the staining level between invasive and non-invasive adenomas. Nestin was stained extensively in functional adenomas, especially for GH, PRL, and gonadotropin secreting adenomas. SOX2 was stained extensively for ACTH-secreting adenomas.

Context. A persistently elevated thyroid stimulating hormone (TSH) level is a common clinical problem in primary hypothyroidism patients treated with levothyroxine (LT4). “Pseudomalabsorption”, which is characterized by poor adherence,should be considered in cases of refractory hypothyroidism after excluding other causes, such as malabsorption. Objective. We reviewed the features of the patients with persistently elevated TSH despite high-dose LT4 therapy. Design. Symptom evaluation, medications, comorbid diseases and physical examination features of five patients who applied to our outpatient clinic between 2016- 2019 and diagnosed with LT4 pseudomalabsorption were retrospectively analyzed. Subjects and methods. The LT4 loading test was performed with an oral dose of 1,000 μg LT4. Demographic parameters, BMI, thyroid function tests, laboratory parameters for malabsorption were recorded. Results. We observed at least two-fold increase of free thyroxine levels during the test, which was considered pseudomalabsorption. Euthyroidism was achieved in two patients by increasing the LT4 dosage and in one patient with a change in the preparation. TSH decreased significantly after being informed about compliance in one patient. Another one was given LT4 twice weekly, but TSH remained elevated because of nonadherence. Conclusion. The LT4 loading/absorption test is a valuable tool to confirm the diagnosis of pseudomalabsorption. Informing patients, changing the preparation, increasing the dose, supervised intake of daily/weekly LT4 forms are treatment options for managing these cases.

Background. Although diseases such as diabetes, hypertension, obstructive sleep apnea and hyperlipidemia are clearly documented as obesity associated diseases, it is not wellknown whether obesity causes renal pathologies. The aim of the present study was to evaluate the effect of weight loss following laparoscopic sleeve gastrectomy on clinical, renal parameters and urinary Neutrophil gelatinase-associated lipocalin (NGAL) levels in diabetic and non-diabetic obese patients. Methods. Nineteen morbidly obese patients (10 diabetic and 9 non diabetic) who underwent laparoscopic sleeve gastrectomy were evaluated clinically (anthropometric measurements) and biochemically before surgery and at 6 months from surgery. Results. Significant decreases in weight, BMI, FPG, PPG and HbA1c levels were observed in the diabetic group when the baseline and 6th month parameters of the patients were compared. There was also a significant decrease in SBP and DBP. At 6th month following laparoscopic sleeve gastrectomy, renal parameters such as creatinine, mAlb/creatinine, NGAL/ creatinine did not differ in the diabetic group. In the nondiabetic group, serum creatinine levels were significantly decreased, but other renal parameters such as mAlb/creatinine and NGAL/ creatinine were not significantly different. Conclusions. Our findings revealed significant decreases in weight, body mass index and glycemic parameters after sleeve gastrectomy in diabetic and non-diabetic patients, while no significant alteration was noted in renal functions, urinary NGAL and microalbumin levels.

Introduction. Disorders of sexual development can present isolated or as a part of complex genetic syndromes. Case presentation. A newborn with ambiguous genitalia and prenatally diagnosed brain malformations was referred to our hospital. Prenatal ultrasound examination and MRI showed lissencephaly and absence of the corpus callosum. At admission, physical examination revealed microphallus, hypospadia and complete fusion of labioscrotal folds with nonpalpable gonads, normal blood pressure and serum biochemistry. Cortisol level was normal (201 nmol/L), testosterone elevated (14.4 nmol/L), FSH 0.1 IU/L, LH 0.7 IU/L, estradiol 241 pmol/L. Seizures were noted on the 2nd day and the child was started on anticonvulsives. When 17-OHP level results came back elevated (200 nmol/L), ACTH test was performed and the child was started on hydrocortisone and fludrocortisone treatment. Congenital adrenal hyperplasia became unlikely when karyotype result showed normal male karyotype (46, XY, SRY+) with no Mullerian structures seen on ultrasonographic exam. As association of ambiguous genitalia and lissencephaly strongly suggested a mutual genetic background, diagnosis of X-linked lissencephaly with ambiguous genitalia (X-LAG) became apparent. Conclusions. The presented case highlights the importance of looking at the whole clinical picture instead of separate isolated findings with emphasis on patient-centered approach guided by clinical findings and patient history.

Context. Pancreatic neuroendocrine tumours (PanNETs) are rare pancreatic neoplasms. PanNETs can be treated by multimodal approach including surgery, locoregional and systemic therapy. Objective. The aim of the present study is to evaluate predictive factors of overall survival in patients with PanNETs surgically treated at a single center. Subjects and methods. The study group consisted of 120 patients with PanNETs who had undergone surgery at the Center of Digestive Diseases and Liver Transplantation of Fundeni Clinical Institute, Bucharest, Romania. Surgical resection of the primary tumor was performed in 110 patients. Results. Tumor size > 2 cm (p=0.048) (90% CI) lymph node involvement (p=0.048), ENET grade (p<0.001), distant metastases (p<0.001), Ki 67 index (<2%, 2-5%, 5-10%, 10-20%, >20%) (p<0.001) were identified as significant prognostic factors for OS on univariate analysis. Using multivariate Cox proportional regression model we found that distant metastases and Ki 67 index were independent risk factors for the survival outcome. Conclusions. Surgery with curative intent should be considered in all cases if clinically appropriate and technically feasible. High grade (Ki67 index ≥10%) tumours were associated with a 2- fold increase in risk of death as compared to those with a Ki67 <10%