ACTA ENDOCRINOLOGICA (BUC)

Context. It is a challenge to determine the origin of Cushing syndrome (CS), especially in patients with low-normal adrenocorticotropic hormone (ACTH) concentrations. Objective. To evaluate the reliability of the corticotropin-releasing hormone (CRH) stimulation test in patients with CS whose origin of disease was not clearly identified using ACTH values, the high-dose dexamethasone suppression test (HDDST), and imaging in a single tertiary referral center. Design and Methods. Twenty-one patients with CS who were admitted to the endocrinology-metabolism clinic between 2004 and 2016 whose ACTH concentrations were 5-20 pg/mL and needed CRH stimulation test were retrospectively assessed. Results. Nine out of 21 patients were diagnosed as having Cushing’s disease (CD) and 12/21 had adrenal CS. The CRH stimulation test had a sensitivity and specificity of 100% and 8%, and positive and negative predictive values of 100% and 45% according to the current diagnostic criteria, respectively. An increase in ACTH ≥115% at 15 minutes and cortisol ≥86% at 60 minutes after CRH were associated with the highest likelihood ratio. The sensitivity and specificity of ACTH was 67% and 83% (AUC=0.75±0.12, 95% CI: [0.5-0.9]; p=0.03), and for cortisol it was 75% and 78% (AUC=0.71±0.15, 95% CI: [0.5-0.9]; p=0.03). Cortisol suppression of more than 64% from basal level in the HDDST suggested CD with the highest likelihood ratio. When these cut-off values were used together, both tests were negative in the patients with CD. Conclusion. The CRH stimulation test has low specificity to localize CS in patients with ACTH concentrations of 5-20 pg/mL according to the current diagnostic criteria. Different diagnostic criteria may be used in the CRH stimulation test and also in the HDDST in this group of patients.

Background and aim. Antithyroid drugs are first treatment for Graves hyperthyroidism worldwide. Although remission can be achieved in approximately 40-50% of patients in 12-18 months with antithyroid drugs, this period can be extended up to 24 months. We aimed to evaluate the effect of individual clinical/biochemical variables and GREAT score in predicting response to antithyroid drug in Graves disease. Material and methods. This is a retrospective single-center study including 99 patients with the first episode of Graves disease treated for at least 18 months. The patients were classified into two groups as those who responded to antithyroid medication at 18-24 months (group 1) and those who did not respond at 24 months and continued with low-dose antithyroid medication (group 2). Results. Medical treatment response was obtained in 38 (38.3%) of the patients at 18 months, and in 19 (19.1%) patients at 24 months. Long-term medical treatment (>24 months) was given to the remaining 43 patients due to the lack of response to medical treatment. Thyroid volume and free T4 levels were higher in those followed up with longterm antithyroid drugs, and orbitopathy was more common in this group. Median anti TPO value was significantly higher in group 1 when compared to group 2 (593 U/l and 191.6 U/l respectively). More patients were classified as GREAT class 3 in group 2 when compared to group 1 (46.5% and 12,5% respectively). We analyzed the Thyroperoxidase Antibody(anti TPO) titers, which we divided into three levels, according to groups 1 and 2. Post-hoc Chi-Square analysis revealed that falling into the highest anti TPO category was significantly associated with response to medical therapy in 24 months (p <0.05). Conclusion. According to our study, GREAT score and anti TPO Ab titers at presentation may help predict response to ATD in Graves disease

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.

Background. Plasma level of ghrelin is possibly reduced in Helicobacter pylori infection and may account for the resultant failure to thrive. Objective. To investigate relationships between Helicobacter pylori infection, and plasma level of ghrelin, anthropometric measurements, appetite, educational and economical status of parents. Methods. Ninety-four children were screened for Helicobacter pylori infection with C-14 urea breath test. Anthropometric measurements were performed in Helicobacter pylori (+) and (-) groups. Plasma ghrelin was measured. Parents were asked to fill out the questionnaire prepared by the researcher on the number of family members, parents’ level of education, monthly income and children’s status for appetite. Results. Plasma ghrelin was lower in Helicobacter pylori (+) group (20.00 ± 22.10 ng/mL), compared to Helicobacter pylori (-) group (79.72 ± 78.13 ng/mL). The percentiles of measurements for height, weight and body mass index were higher in Helicobacter pylori (-) group. Results of C-14 urea breath test were negatively correlated with height, weight and body mass index; however, no correlation was detected between the results of C-14 urea breath test, and plasma ghrelin, number of family members, levels of parents’ education and income. A negative correlation was observed between the results of C-14 urea breath test and appetite. Conclusions. Helicobacter pylori infection is considered to play a restricting role in growth potential by decreasing ghrelin level in children. Moreover, the existence of a negative correlation between the results of C-14 UBT, and weight, height and body mass index suggests a possible link between Helicobacter pylori infection and poor growth.

Context. Primary hyperparathyroidism is one of the most common endocrinological disorder and surgery of parathyroid glands is the main therapy of this disease. Minimally invasive surgery is getting more prominent in these days and its success in parathyroid surgery mostly depends on accuracy of the localization studies. Objective. The aim of this study is to understand the relationship between preoperative biochemical tests, intraoperative findings and Technetium-99mmethoxyisobutylisonitrile (MIBI) scan results. Design. Retrospective clinical study. Subjects and Methods. A total of 185 patients, who have been diagnosed with primary hyperparathyroidism (PHPT) and operated between January, 2010 and October, 2018, were included to the study. Patients with less than 6 months of follow up are excluded from the study. Results. Patients were divided into two groups according to their scintigraphy results; with positive scintigraphy findings as group 1 (n:135) and negative scintigraphy findings as group 2 (n:50). Mean preoperative serum parathyroid hormone (PTH) values were significantly different between the two groups (p<0.02). Mean preoperative serum calcium, creatinine, magnesium, phosphorus, alkaline phosphatase, 25-OH Vitamin D3 levels of both groups were analyzed and there were no statistical differences between the two groups considering these parameters. Also, mean diameter and mean volume of parathyroid adenomas were significantly higher in group 1 (2.1±1.0 cm vs. 1.55±0.72 cm, respectively, p<0.0001; 2.66±5.35 cm3 vs. 1±1.9 cm3, respectively, p<0.0001). Optimal cut-off values of parathyroid adenoma diameter for MIBI scan positivity were 1.55 cm, parathyroid volume for MIBI scan positivity were 0.48 cm3, preoperative serum PTH for MIBI scan positivity were 124.5 ng/L. Conclusions. Preoperative serum PTH levels, diameter and volume of adenomas might be helpful for the prediction of MIBI scan accuracy and possible need of another localization studies.

Aim is to evaluate atherosclerotic risk factors and carotid intima media thickness [CIMT] in offspring of type 2 Diabetes Mellitus [DM] patients with normal glucose tolerance. Methods. We evaluated 96 offspring of Type 2 DM patients and 39 healthy control who were in similar age, sex and body mass. We measured fasting blood glucose [FBG], postprandial blood glucose [PBG], insulin, uric acid, homocystein, fibrinogen, HOMA-IR, lipid profile, hsCRP, microalbuminuria, glycosylated hemoglobin A1c and CIMT by Doppler ultrasonography. Results. FBG was found higher in study group [p<0.001]. The HOMA-IR was 1.7±0.98 and 1.2±0.58 mg/dL x uUI/mL for study and control group, respectively [p=0.007]. TCholesterol, triglycerides, HDL-C, LDL-C and homocystein levels were not different. HsCRP and fibrinogen levels were higher in study group [p=0.014 and p=0.035, respectively]. Microalbuminuria levels were higher in study group but not significant [p=0.111]. CIMT in study group increased distinctively [p<0,001]. In regression analysis, being in study group causes a significant increase on the mean CIMT level by 0.057 mm [0.029-0.086] Conclusion. Our study demonstrated that various atherosclerotic risk factors are aggregated in offspring of Type 2 DM patients having NGT even before they develop glucose intolerance. Having a diabetic family alone might be effective in developing increased CIMT.

Introduction. The functions of CD36 membrane receptor include removal of oxidized low-density lipoproteins from\r\nplasma. The aim of our study was to search association between the IVS3-6 C allele and hypercholesterolemia in overweight children.\r\nMaterial and Methods. The study groups comprised 55 Caucasian children with (33) and without hypercholesterolemia (22). Amplicons of exon 4 including\r\nfragments of introns 3 and 4 were studied using denaturing high-performance liquid chromatography (DHPLC).\r\nResults. Polymorphism detected by DHPLC was single nucleotide substitution in intron 3 (IVS3-6 T/C - rs3173798). The IVS3-6 T/C polymorphism is located in the\r\nregion encoding the oxidized LDL binding domain, at a conserved splice site. Total serum cholesterol concentrations were significantly lower in the IVS3-6 TC\r\nheterozygotes than in the TT patients. Furthermore we found tendency (p=0.06) to lower LDL-cholesterol level in IVS3-6 TC heterozygotes than in wild-type homozygotes.\r\nConclusion. The results of our preliminary study suggest that the IVS3-6 C allele of CD36 rs3173798 polymorphism\r\nmay be associated with lower serum total and LDL-cholesterol in overweight children diagnosed with hypercholesterolemia.

Objective. This research aim was to evaluates the role of the pre-ablation neutrophil-to-lymphocyte ratio (NLR) and lymphocyte-to-monocyte ratio (LMR) as predictors of distant metastases in patients with differentiated thyroid cancer (DTC). Methods. A retrospective analysis was given to 140 patients with DTC who received 131I remnant ablation after surgery. The patients were divided into two groups based on the existence of distant metastasis. Results. The two groups showed no significant difference in age, gender, WBCs, neutrophils, monocytes, eosinophils, basophils and whether the tumor was multifocal. In the univariate analysis, significant differences were found in tumor size (p=0.021), lymphocyte (p=0.012), NLR (p=0.027), and LMR (p=0.007). According to the ROC curves, NLR had an AUC of 0.612 ± 0.097 with a cut-off value of 1.845, sensitivity of 60.0%, and specificity of 66.2% (p=0.027). LMR had an AUC of 0.638 ± 0.095 with a cutoff value of 4.630, sensitivity of 84.6%, and specificity of 35.4% (p=0.007). In the multivariate analysis, larger tumor size (OR=5.246, 95% CI 1.269-10.907, p=0.009) and higher NLR (OR=2.087, 95% CI 0.977-4.459, p=0.034) were statistically significant for distant metastases. Conclusion. This research reveals that pre-ablation NLR and tumor size are significantly statistically correlated with distant metastases in patients with DTC.

Aim. There is no data for platelet distribution width (PDW) levels as a marker of platelet activation in patients with\r\nmetabolic syndrome (MetS). The present study tested the hypothesis that PDW levels may be elevated in MetS patients. Based on this hypothesis, PDW levels in patients with MetS were compared with those of patients without MetS. The relation between PDW levels and cardiometabolic risk factors was also evaluated.\r\nMaterials and Methods. Two hundred and nineteen non-diabetic MetS patients (MetS group; 155 females, 64 males) and 155 non-diabetic patients without MetS (Control group; 123 females, 32 males) were included consecutively. The primary endpoint of the study was to compare the PDW levels between the groups, while the secondary endpoint was to evaluate the relationship between PDW and cardiometabolic risk factors.\r\nResults. PDW levels were 16.75?1.73%, and 16.89?1.92% in MetS patients and control subjects, respectively (p>0.05). In correlation analysis, insulin and homeostasis model assessment of insulin resistance (HOMA-IR) (r:0.193, p:0.004, and r:0.215, p:0.001, respectively) were associated with the PDW.\r\nConclusion. Although there is a weak positive correlation between PDW and insulin and HOMA-IR, these findings do\r\nnot support our hypothesis that PDW levels may be elevated in MetS patients.

Anaplastic thyroid cancer (ATC) is a highly uncommon (less than 2% of thyroid malignancies) and aggressive type of cancer, with aggressive behavior and, therefore, exhibiting poor prognosis. ATC tumors are automatically labeled as stage IV disease regardless of standard criteria such as tumor burden or metastasis. ATC tumors require a diversified treatment approach that includes surgical resection, followed by a complete an aggressive combination of radiation and chemotherapy and/or palliative care. Despite best efforts, 1-year overall survival of patients is 20% to 40% with nearly universal mortality rate. Consequently, novel approaches (targeted therapy, immunotherapy) have been studied, alone or in combination, to improve the dire prognosis of these patients. BRAF V600E mutation is the most common genetic mutation found in ATC. We report the case of a 57-year-old man diagnosed with stage IVc (undifferentiated) ATC with hepatic and osseous metastases. The molecular analysis of the tumor revealed a V600E BRAF-mutation. The patient was treated with Dabrafenib and Trametinib, and achieved remission 5 weeks after starting the treatment. Subsequently, he had a thyroidectomy, and pembrolizumab was added to the two tyrosine kinase inhibitors. 9 months later he is still in remission. This case illustrates the importance of obtaining molecular information in anaplastic thyroid cancer and the urgent need of studies investigating the combination of tyrosine kinase inhibitors and check-point inhibitors in patients with V600E BRAF- mutations.