ACTA ENDOCRINOLOGICA (BUC)

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.

Calciphylaxis, also known as calcific uremic arteriolopathy (CUA), is usually observed in women and it is a serious complication of hyperparathyroidism secondary to chronic renal failure. CUA is characterized by ischemic tissue loss secondary to progressive vascular degeneration. Although it is rare, it may end up with sepsis and organ failure and can be fatal. Its pathogenesis is not fully understood, but it is thought that it occurs secondary to increased calcification activators such as oxidized LDL, TNF- α, calcitriol, fibronectin, collagen-I, and TGF-1α. The most effective treatment is managing underlying pathology and decreasing serum calcium and phosphorus levels. In this report, we aimed to present an end stage renal failure case with coexisting hyperparathyroidism, hyperthyroidism and calciphylaxis in whom cutaneous manifestations were healed 6 months after parathyroidectomy.

Abstract Objective. The aim of the present study is to evaluate the effects of methimazole (MTZ) and propylthiouracil (PTU) treatments on osteopontin (OPN) and oxidative stress in Graves’ disease (GD). Material and Methods. The study included 60 cases with GD in hyperthyroid state and taking no antithyroid treatment, and 30 healthy volunteers. GD patients were randomly separated into two groups; 30 of them took PTU, and the other 30 took MTZ treatments. Blood samples were taken from the patients with GD before the treatment, and three months after the treatment was begun, when they were in the euthyroid state; blood samples of the healthy control subjects were also taken at these times. Results. TAS and OSI levels before treatment were significantly higher in the GD group, when compared to the control group (p<0.001, for each). GD subjects taking PTU treatment had significantly higher TAS levels (p=0.001), and significantly lower TOS and OSI levels (p=0.008 and p=0.001, respectively). TAS levels significantly decreased in the patients taking MTZ treatment (p=0.029), but TOS and OSI levels did not change significantly (p>0.05). Pretreatment OPN levels were significantly higher in GD patients, when compared to the control group (p=0.014). OPN level significantly decreased in the GD group taking PTU treatment; however OPN levels in the group taking MTZ treatment did not change significantly when compared to the pretreatment value. Conclusion. PTU treatment is more effective in decreasing OPN and oxidative stress in GD patients, when compared to the MTZ treatment.

The most common cause of hypercalcemia is parathyroid hyperplasia and carcinoma. Tuberculosis(TB) and sarcoidosis are the most common granulomatous diseases of the parathyroid. We report a case of parathyroid adenoma that can mimic many lesions. A 46-year-old woman on continuous ambulatory peritoneal dialysis (CAPD) with symptoms and signs of hypercalcemia. Laboratory findings were consistent with tertiary hyperparathyroidism. She underwent elective parathyroidectomy due to high PTH values despite effective treatment including calcimimetics and vitamin D receptor activators. Subtotal thyroidectomy and three and a half of parathyroid adenomas were removed. Histopathological examination revealed features of parathyroid adenoma with granulomatosis infection that supports tuberculosis. In order to confirm the pathological findings, the PCR study was performed on the pathology specimens. After obtaining a negative result, the treatment was stopped. We have reported a case of parathyroid adenoma that mimicking tuberculosis.

Background. Congenital adrenal hyperplasia (CAH) is an autosomal recessive inherited disorder caused by congenital deficiency of enzymes involved in cortisol biosynthesis from cholesterol in the adrenal cortex. In this article, we aimed to present a 29-year-old female patient with I2 splice point mutation detected in one allele and P453S mutation on the other allele of CYP21A2 gene associated with 21-hydroxylase deficiency. Her further investigation revealed that her mother had P453S mutation and her father had I2 splice mutation. Case report. A 29-year-old woman with CAH was admitted to our clinic with the request of pregnancy. Her physical examination revealed a height of 151 cm, weight 59 kg, body mass index 25.8 kg/m2. According to Tanner staging, she had Stage 3 breast development and pubic hair. Her laboratory test results were as follows: Glucose: 79 mg/dL (70-100 mg/dL), Creatinine: 0.6 (0.5-0.95 mg/ dL), Sodium: 138 mEq/L (135-145 mEq/L), Potassium: 4.4 mEq/L (3.5-5.1 mEq/L), Cortisol: 0.05 μg/dL, ACTH: <5.00 pg/mL (5-46 pg/mL), 17-OH progesterone: 7.67 ng/mL (0-3 ng/mL). Chromosome analysis revealed a 46, XX karyotype. CYP21A2 gene mutation analysis was performed for the patient whose clinical history and laboratory results were compatible with congenital adrenal hyperplasia. During the reverse dot blot analysis, I2 splice mutation in one allele and P453S mutation in the other allele were detected. Conclusion. Although the I2 splice mutation detected in our case was mostly associated with a saltwasting form of CAH, it was thought that the other P453S mutation detected may explain the relatively good clinical course in our case.

Denosumab,a monoclonal IgG2 antibody directed against RANK-L,is used as a neoadjuvant therapy for inoperable or metastatic giant cell tumor of bone. Many side effects like as hypocalcemia during treatment and rarely severe hypercalcemia especially in children after discontinuation of denosumab occurred. The unpredictable onset and recurrent episodes of severe hypercalcemia increase the duration of hospitalization and the risk of complications. Persistent hypercalcemia and difficulties in management have prompted the search for different more effective therapeutic options. Objectives. To share our experience with the use of oral bisphosphonate in acute and long-term therapy of severe hypercalcemia following high-dose denosumab therapy and to review the literature on this subject Case. We report the management of a case of severe hypercalcemia that developed 4 months after the completion of 18-month denosumab treatment in a 9-year-old girl who was followed up with a giant cell bone tumor for 6 years. Based on an evaluation aiming to determine etiology, hypercalcemia was considered as "rebound-linked" upon denosumab discontinuation. Severe hypercalcemia attacks recurring with an interval of 2 weeks were treated with IV bisphosphonate, but when mild hypercalcemia developed again, treatment with 70 mg per week of oral bisphosphonate was planned. After the second dose of alendronate, the calcium level always remained below 10.5 mg/dl. In the 14-month follow-up, no hypercalcemia attack was observed again. Results. Rebound hypercalcemia can occur as an unpredictable recurrent episode at any time after denosumab cessation. Thus, the patient should be closely monitored especially in childhood due to rapid bone cycle. In longterm follow-up, oral biphosphonates can be used effectively to reduce hospitalization time and the management of especially life-threatening recurrent attacks.

An 81-year-old woman presented with a history of essential hypertension for eight years and an asymptomatic multinodular goiter that had been incidentally discovered on neck ultrasonography two years ago and an-isohypoechoic mass lesion located adjacent to the right lobe inferior pole of the thyroid gland. Parathyroid adenoma or lymphadenopathy were the differential diagnosis. After two years, the endocrine surgeon decided to operate her multinodular goiter and her probably benign lesion. Intraoperatively, the blood pressure and pulse rate increased markedly and intravenous antihypertensive treatment was administered. She was discharged after blood pressure control. A 2 mm micromedullary thyroid carcinoma with C-cell hyperplasia located on the left lobe of the thyroid was detected. The aforementioned mass lesion was also reported as typical cervical paraganglioma. Because of concomitant medullary thyroid carcinoma with C-cell hyperplasia and paraganglioma the patient was subjected to genetic counseling and molecular testing for hereditary cancer syndromes. A variation of the succinate dehydrogenase gene D (SDHD) NM_003002.3: c.325C> T (Gln109Term) has been reported as the disease-causing mutation. Herein we present a case diagnosed for neck paraganglioma and medullary thyroid carcinoma after an intraoperative hypertensive crisis.

Branched chained amino acids (BCAA) are essential components of the human diet and important nutrient signals, which regain particular interest in recent years with the avenue of metabolomics studies suggesting their potential role as biomarkers. There is now compelling evidence for predictive role of BCAA in progression of diabetes, but causality relationship is still debated concerning insulin resistance and genetic versus nongenetic pathogenesis. Mendelian randomization studies in large cohorts of diabetes indicated pathogenic role of PPM1K (protein phosphatase Mg2+/Mn2+ dependent 1K) on Chr 4q22.1 gene, encoding for a phosphatase that activate BCKDH (branched chain keto acid dehydrogenase) complex. Recent studies indicated that insulin rapidly and dose-dependently regulates gene expression of the same complex, but the relationship with systemic insulin resistance and glucose levels is complex. Rare genetic syndromes due to Mendelian mutations in key genes in BCAA catabolism may be good models to understand potential role of gene of BCAA catabolism. However, in studying complex disorders geneticists are faced to complete new aspects of metabolic regulation complicating understanding genetics of obesity, diabetes or metabolic syndrome. A review of genetic syndromes of BCAA metabolism suggests that insulin resistance is not present, except rare cases of methylmalonic aciduria due to MUT (methylmalonyl-coA mutase) gene on Chr 6p12.3. Another aspect that complicates understanding is the new role of central nervous system (CNS) in insulin resistance. For long time the hypothalamic hunger/satiety neuronal system was considered a key site of nutrient regulation. Genes may also affect the brain rewarding system (BRS) that would regulate food intake by modulating the motivation to obtain food and considering hedonic properties. Nutrigenomic and nutrigenetic investigations taking into account concurrently BCAA intake, metabolic regulation and gene variation have large perspectives to merge genetic and nutritional understanding in complex disorders.