ACTA ENDOCRINOLOGICA (BUC)

Introduction. Abnormal thyroid function affect spermato-genesis and male infertility. For men, the aromatase deficiency can cause infertility. In this study, the aim is to investigate the effect of maternal hypothyroidism on offspring testicular morphology and cytochrome-P450- aromatase (P450arom) immunoreactivity. Materials and Methods. Eighteen Wistar albino pregnant rats were divided into three groups, namely A, B and K groups. Hypothyroidism was induced by adding 0.01% of propyl thiouracil (PTU) in drinking water. Hypothyroid mothers, group A: given PTU for 21 days during pregnancy, group B: given PTU for 21 days prior to pregnancy; control mothers, group K, given only water. Hypothyroid and control group mothers’ pups at postnatal day (PND) 15 and 60 were sacrificed. We determined immunoreactivity intensity of P450arom and mRNA levels by RT-PCR performed in the testis tissues. ELISA method was used for thyroid function tests for T3, T4 and TSH. Structure of seminiferous tubule was evaluated by hematoxylin-eosin staining. Results. It was seen that the aromatase expression in 15-day-old maternal hypothyroid groups was similar to the one in the control group while there was a decline in the aromatase expression of 60-day-old groups. As for mRNA, it was determined that it had a tendency to increase over time in all groups but this increase was not significant. The tubule diameter and Johnsen’s Testicular Biopsy Score diminished in all hypothyroid groups in comparison to the control group. Conclusion. The changes that occur in the early period of testis development due to maternal hypothyroidism negatively affect testis development in the next stages of life. This situation leads to a decline in aromatase expression in the following years.

Introduction. Diabetic chronic kidney disease has more fatal clinical progresses and this situation can be related to volume overload, which is seen more commonly in diabetic chronic kidney disease patients than in non-diabetic chronic kidney disease patients. Therefore, we examined the effect of diabetes mellitus on volume overload in newly diagnosed stage 5 chronic kidney disease patients whose volume overloads were not showing signs of improvement from renal replacement therapy. Method. One hundred and five patients (46 diabetic, 59 non-diabetic) with end-stage chronic kidney disease, who had glomerular filtration rate (GFR) under 15 mL/min for at least three months were enrolled in this prospective study. We determined the body volume overload and configuration using a bioimpedance device. NT-proBNP levels were recorded. Results. There was a statistically significant difference between diabetic and non-diabetic groups according to overhydration (OH, p=0.003), extracellular water (ECW, p=0.045), intracellular water (ICW, p<0.001) and OH/ECW (p=0.003). In addition, there was a statistically significant difference between groups in terms of N-terminal Pro-brain Natriuretic Peptide (NT-proBNP levels, p=0.008). Discussion. We compared diabetic and nondiabetic end-stage chronic kidney disease patients who were not in renal replacement therapy yet. We found more volume overload and extracellular fluid volume in the diabetic group.

The effects of finasteride on insulin resistance and of metformin on hyperandrogenism in patients with polycystic ovary syndrome (PCOS) are not clear. This study therefore compared the effects of finasteride, metformin, and finasteride plus metformin treatments on hormone levels, insulin resistance, and hirsutism score in women with PCOS. Fifty-two patients with PCOS were randomly assigned to receive finasteride 5 mg/day, metformin 1700 mg/day or finasteride plus metformin for 12 months. Body mass index (BMI), Ferriman Gallway score (FGS), serum concentrations of estradiol, sex hormone-binding globulin, free testosterone, dehydroepiandrosterone sulfate (DHEAS), androstenedione, and homeostasis model assessment of insulin resistance (HOMA-IR) index and areas under the curve (AUC) for insulin and glucose were evaluated before and after 12 months of treatment. Reductions in FGS, free testosterone, DHEAS, androstenedione, HOMA-IR, AUCinsulin, and AUC-glucose were significant within each group, whereas BMI and estradiol were not. Comparisons of changes in parameters in the 3 groups did not clearly show the superiority of any treatment modality. The treatment with finasteride alone significantly reduced both androgen levels and parameters of insulin resistance. In addition, metformin alone was effective, and not inferior to finasteride, in the treatment of hyperandrogenism.

Endogenous hyperinsulinemia was found in a 38-yearold female patient with recurrent neuroglycopenic symptoms (the glucose level was 25 mg/dL, insulin 43.9 μ/mL, C-peptide 5.54 ng/mL). No lesion was found on imaging tests including enhanced computed tomography (CT) methods performed with a preliminary diagnosis of insulinoma. A suspicious hyperperfusion was present in the pancreatic tail on the perfusion CT examination performed after obtaining approval. The selective arterial calcium stimulation test (SACST) result was consistent with a diffuse disease in the body and tail. The patient underwent partial (75%) pancreatectomy and is now followed up as a diabetes patient on intensive insulin treatment at the postoperative 38th month. The most common cause of endogenous hyperglycemia in hypoglycemia patients is insulinoma. The noninsulinoma pancreatogenous hypoglycemia syndrome (NIPHS) is rarely seen in the adult age group. Although invasive, SACST seems to be the most suitable test to differentiate diffuse or multiple disease from insulinoma and to guide the surgery when advanced radiological imaging methods are inadequate to detect the presence of insulinoma. Regarding perfusion CT, it would be more appropriate to wait for comparative data to be put forward in a more consistent manner. When no response can be obtained to medical treatment in NIPHS, partial/total pancreatectomy is the most appropriate treatment option as it enables recovery from the hypoglycemic episodes despite leading to a significant condition like diabetes.

Objective. Adrenal incidentaloma are lesions which are stated incidentally by imaging methods when there is no suspicion of any disease in adrenal gland. Inappropriate Jak2 signaling causes some solid and hematological malignancies. But the Jak2 mutation has not been previously evaluated with regard to adrenal tumors. In this study, we aimed to positivity of the Jak2 mutation in patients with non functioning adrenal incidentaloma (NFAI). Methods. 45 (38 female–7 male) patients, who were followed due to NFAI at Tepecik Training and Research Hospital, Department of Endocrinology and Internal Medicine between February 2014 and March 2015, and 45 (31 female–14 male) healthy controls were included in the study. Results. The average age was 54.02±11.7 years and 38 patients were female, 7 were men. All patients underwent the following analyses for excluding a functioning adrenal mass, overnight dexamethasone suppression test, 24 hour urinary metanephrine and normetanephrine, plasma aldosterone/ renin activity ratio. Jak2 mutation of the patients who were diagnosed as NFAI was all negative. Conclusion. We could not identify the JAK2 gene mutation positivity in any sample. Since other possible mechanisms may throw fresh light on the etiology of adrenal incidentaloma, further clinical studies are needed on this subject.

Background. Pomegranate is a rich source of many polyphenolic compounds including ellagitannins (punicalagin, punicalin and others). Aim. The effects of punicalagin and punicalin on adipogenesis were investigated in this study. Materials and Methods. To examine the effect of punicalagin and punicalin on adipocyte differentiation, various concentrations of punicalagin and punicalin (2- 10 μM) were applied to differentiated 3T3-L1 cells. Glyceraldehyde-3-phosphate dehydrogenase (GPDH) activity, Oil red O staining, intracellular triglyceride levels, and gene expressions of transcription factors (Peroxisome proliferator-activated receptor-γ (PPARγ), CCAATenhancer- binding proteins-α (C/EBPα), Sterol regulatory element-binding protein 1c (SREBP-1c)) and lipolysisassociated genes (hormone-sensitive lipase (HSL), Perilipin A, tumor necrosis factor-α (TNF-α)) were examined in order to investigate the effects of punicalagin and punicalin on adipocyte differentiation. Results. Punicalagin and punicalin applications caused a continuous decrease in cell size and intracellular triglyceride accumulation. GPDH activity and transcription gene expressions decreased significantly in groups that were applicated punicalagin and punicalin at high concentrations. Punicalagin, but not punicalin, down-regulated the expression of HSL and perilipin A and up-regulated the expression of TNF-α in a dose-dependent manner. In conclusion, both punicalagin and punicalin were able to inhibit the adipocyte differentiation.

Purpose. Vitamin D insufficiency and age related cataract (ARC) are public health problems. We evaluated serum vitamin D levels in ARC patients. Method. A prospective hospital-based crosssectional study was designed to measure the vitamin D status of patients with ARC. Patients have grouped either presence of any type of posterior subcapsular cataract (PSC) (group 1) or ARC without the PSC component (Group 2). After full ophthalmologic consideration, patients over 40 years of age with no history of ocular trauma, multivitamin supplement ingestion, chronic renal failure, thyroidectomy, parathyroidectomy, skin cancer, and cigarette smoking were included in the study. Results. Totally, 79 subjects of which 26 (32.9%) subjects in group 1 and 53 (67.1%) subjects in group 2 were included in the study. Group 1 had mean vitamin D levels of 17.31±13.30 ng/mL. Vitamin D levels in Group 2 were 13.34±7.87 ng/mL. Group 1 did not show vitamin D insufficiency (P = 0.31; one-sample t-test). However, Group 2 showed a statistically significantly lower vitamin D level compared to the insufficiency level of 20ng/mL (P= 0.00; one-sample t-test). Conclusion. Vitamin D may have an important function in lens metabolism. Vitamin D deficiency and cataract development need further extensive researches.

Objective. Personal discrepancies in gastrointestinal physiology might influence responses to GH suppression during OGTT. We aim to compare growth hormone (GH) response during oral glucose tolerance test (OGTT) and intravenous glucose tolerance test (IVGTT). Methods. Data of 18 healthy volunteers were analyzed in the study. Subjects were firstly evaluated with standard 75-g OGTT. In subjects with serum glucose <100 mg/dL at basal state and <140 mg/dL at 120th minute of oral loading, IVGTT was performed after at least 3 days. Serum glucose, insulin and GH levels were measured during two tests. Results. Basal GH levels had a wide distribution ranging from 0.00005 μg/L to 0.768 μg/L (median 0.0145 μg/L). Mean nadir GH level during OGTT was obtained at 60th minute and it was 0.0376 μg/L(range 0.00011-0.387, median 0.0016 μg/L, SD: 0.095, SEM: 0.038). Nadir GH level during IVGTT was observed at 10th minute and it was 0.112 μg/L(range 0.0005-0.770 μg/L, median 0.0053 μg/L, SD: 0.242, SEM: 0.057). There was a statistically significant difference between nadir GH levels obtained during IVGTT and OGTT (p=0.028). Conclusions. We found that mean nadir GH level was significantly higher during IVGTT in healthy subjects. This is a preliminary study and further large scale studies are required to suggest that IVGTT may be used in the diagnosis and follow-up of patients with acromegaly as an alternative to or instead of OGTT.

Context. Noninvasive encapsulated anaplastic thyroid carcinomas (NE-ATCs) have been described in few case reports, and consistently associated with favorable outcome compared to the classical ATCs. Objective. Our aim is to remark a rare histological finding in ATCs, encapsulation, which has been associated with a favorable outcome. Design. We have documented a rare case of an NE-ATC with its clinical, pathological, and molecular features. We also provided a thorough discussion of all the encapsulated ATCs reported in the literature. Subjects and Methods. A 50-year-old woman with an unremarkable medical history, who presented with a thyroid nodule, and diagnosed as “follicular lesion of undetermined significance” by fine needle aspiration biopsy. The patient was lost to follow-up for six years and revisited upon her neck disturbances and underwent total thyroidectomy. Results. Sections of the right lobe revealed a grossly encapsulated nodular lesion, measuring 75x55x55 mm. Histologically, the tumor consisted of both carcinomatous and sarcomatous components supported by immunohistochemical stains. Necrosis and atypical mitotic figures were evident. Capsular and/or vascular invasion was not identified. There were no BRAF codon 600, KRAS, NRAS mutations and RET/PTC rearrangement. During three-month follow-up, the patient was free of disease without adjuvant therapy. Conclusion. Encapsulated ATCs tend to follow a favorable clinical course and may deserve conservative treatment approaches.

Glucose-6-phosphate dehydrogenase (G6PD) enzyme deficiency is common in the community. The most important clinical manifestation of G6PD deficiency is acute hemolytic anemia due to oxidative stressors. Diabetes Mellitus (DM) can precipitate hemolysis in patients with G6PD deficiency. Here, we described a 15-year-old male with newly diagnosed type 1 DM (T1DM) and unknown G6PD deficiency who suffered from hemolytic anemia during normalization of blood glucose. On admission, the patient did not have ketoacidosis. After the patient's blood sugars were regulated with insulin therapy, he presented five days later with hemolytic anemia. The cause of hemolytic anemia was G6PD deficiency. The patient had no previous episodes of hemolysis and had no relevant family history. Hypoglycemia did not occur during blood glucose regulation. The return of blood sugar to normal after a long period of hyperglycemia was thought to be the possible cause of hemolysis. In conclusion, G6PD deficiency should be considered when there is an episode of hemolysis in newly diagnosed children and adolescents with T1DM, especially in the absence of ketoacidosis and hypoglycemia.