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The aim of this study was to evaluate the efficacy of cabergoline in normalizing plasma IGF-I levels in acromegaly patients with elevated IGF-I levels after surgery and/or SRL therapy. Acromegaly patients (n: 143) were evaluated retrospectively. Patients with elevated IGF-I levels after surgery and/or SRLs therapy and a fixed dose of SRLs treatment for the last six months with no history of radiotherapy in the last three years were included in the study (n: 12). Previous treatment regimens, baseline PRL and IGF-I levels (ULNR), sella MRI, and immunohistochemical findings were evaluated. Cabergoline was used as an add on (n: 11) or single medical treatment (n: 1). The median duration of treatment with SRL alone was 12 months (range 6–48 months). The mean IGF-I value before cabergoline therapy was 1.45±0.4 ULNR. The mean cabergoline dose and duration of treatment were 1.55±0.75 mg/week and 9±6.3 months, respectively. IGF-I normalization was only achieved in patients with serum IGF-I concentration

Following Roux-en-Y gastric bypass (RYGB), positive alterations are observed in gut microbiota and intestinal peptides. Previous studies demonstrated similar alterations observed in cases when pre-probiotics are used without surgery. The aim of this trial was to evaluate the effectiveness of early use of pre-probiotics after RYGB. The operation and follow-up of the patients were performed at Istanbul University Medical Faculty. Thirty-two patients who had undergone RYGB were randomized to pre-probiotic group (PreProBG, n = 16; 200 g/day yogurt plus 10 g/day inulin+oligofructose) and probiotic group (ProBG, n = 16; 200 g/day yogurt only) for 6 months. Blood samples (glucose, insulin, A1c, GLP-1, PYY), anthropometric measurements, and appetite ratings have been evaluated at baseline and 3 (m3) and 6 (m6) months after RYGB. Initial anthropometric measurements and appetite ratings decreased significantly after surgery and there were no significant differences between the groups. The decrease of area under the curve(insulin) was less and has a positive correlation with the changes in anthropometric measurements in PreProBG. GLP-1 and PYY which increased dramatically after surgery in all patients were higher in PreProBG. But this increase had a negative correlation with the changes in anthropometric measurements during the study. Increased insulin, GLP-1, and PYY secretion was more enhanced by pre-probiotic use in early postoperative period. But this increase not only in anthropometric measurements but also in appetite ratings affects negatively, contrary to expectations. In summary, it should be investigated with new studies that use of pre-probiotics in the late postoperative period may be more effective in patients with weak insulin and incretin response and therefore insufficient weight loss. Trial Registration clinicaltrials.gov Identifier: NCT03517345.

No Abstract Available. 34825555

Introduction Gastroesophageal reflux disease (GERD) is more frequent in patients with diabetes mellitus (DM).The aim of the present study was to evaluate gastroesophageal reflux (GER) in asymptomatic patients with DM using 24-h pH impedance. Materials and Methods 19 healthy controls and 35 patients with DM without typical GERD symptoms were enrolled in the study. A 24-h pH-impedance study, esophageal manometry and gastroscopy were performed on all patients with DM. In the control group, an impedance study was performed on all subjects, and gastroscopy and esophageal manometry were performed on those who consented to the procedures. Patients with diabetes were categorized as obese [body mass index (BMI)>30 kg/m2] or non-obese (BMI Results The mean BMI was similar in the control group (27.3±2.6 kg/m2) and the diabetic group (28.7±5 kg/m2) (p>0.05).Erosive esophagitis was found in 7.5% of the DM group. Esophageal dysmotility was higher in diabetics compared to the control group (45.5 vs. 11%, p=0.04). Neuropathy was found to be an independent risk factor for dysmotility. The mean DeMeester score (DMS) (25.6±32.5 vs. 11.2±17, p=0.01) and bolus exposure time (2.1±1.3 vs.1.3±1.3 min, p=0.009) were higher in the DM group compared with the control group.The difference was mainly observed between obese diabetics and the control group (p Conclusion Acid reflux is common in patients with diabetes.GER is associated with the existence of obesity rather than hyperglycemia.

High GH and IGF I levels increase tubular phosphate reabsorption in patients with acromegaly. We aimed to investigate the utility of serum phosphorus levels as an indicator for predicting chance of remission in acromegaly patients. Fifty-one patients (n: 51; F: 24, M: 27) with diagnosis of acromegaly were included in the study. Plasma IGF-1, Phosphorus (P) and nadir GH levels on oral glucose tolerance test (OGTT) at the time of diagnosis were analysed retrospectively. Patients were classified into two groups according to their plasma P levels; P ≤ 4.5 mg/dl (Group-1, n: 23, 45.1%), P > 4.5 mg/dl (Group-2, n: 28, 54.9%). Two groups were compared according to remission status; remission (n: 27) and non-remission (n: 24). Remission was defined with absence of clinical symptoms, normal plasma IGF-1 (adjusted for age and gender) and GH levels (

Introduction Genetic mutations such as C599T polymorphism in glutathione peroxidase [GPX1] gene and polymorphisms in potassium channel (KCNJ11) genes have recently been proposed in the etiopathogenesis of new onset diabetes mellitus after renal transplantation (NODAT). We aimed to examine the association of GPX1 and KCNJ11 polymorphisms in NODAT. Materials and Methods This is a monocenter case-control study with a total of 118 renal transplant recipients who were divided into 2 groups; NODAT and normal glucose tolerance. Relation of GPX1 and KCNJ11 polymorphisms were investigated between these groups. PCR-RFLP method was used for genotyping of polymorphisms in the GPX1 (rs1050450) and KCNJ11 (rs1805127) genes. Two alleles were visualized for each gene (C/T for GPX1 and A/G for KCNJ11). Results NODAT was correlated with age at transplantation (p Conclusions In addition to several diabetogenic risk factors, C599T polymorphisms in GPX1 gene might also contribute to the development of NODAT. Further studies on larger patient series are necessary in order to reach definitive suggestions.

Paget's disease is a disorder of aging bone which occurs in the setting of accelarated bone remodelling. In the presented case we discuss the difficulties in the diagnosis of Paget's disease in a 77 year old patient with coexisting endometrium carcinoma. The patient was initially diagnosed with metastatic bone disease due to endometrium adenocarcinoma when she was admitted to oncology clinic with pelvic pain. Bone scintigraphy with Tc99 and (18)F fluorodeoxyglucose positron emission tomography/CT revealed an increased uptake on the bone lesions which were reported as metastatic bone involvement. Although the (18)F-FDG uptake was much higher than the levels that would generally be anticipated in a case with Paget's disease, high levels of bone turnover markers indicated further evaluation in the differential diagnosis and the definitive diagnosis of Paget's disease was established with the pathological evaluation of bone biopsy.

Objective Familial partial lipodystrophy (FPLD) is a rare genetic disorder characterized by partial lack of subcutaneous fat. Methods This multicenter prospective observational study included data from 56 subjects with FPLD (18 independent Turkish families). Thirty healthy controls were enrolled for comparison. Results Pathogenic variants of the LMNA gene were determined in nine families. Of those, typical exon 8 codon 482 pathogenic variants were identified in four families. Analysis of the LMNA gene also revealed exon 1 codon 47, exon 5 codon 306, exon 6 codon 349, exon 9 codon 528, and exon 11 codon 582 pathogenic variants. Analysis of the PPARG gene revealed exon 3 p.Y151C pathogenic variant in two families and exon 7 p.H477L pathogenic variant in one family. A non-pathogenic exon 5 p.R215Q variant of the LMNB2 gene was detected in another family. Five other families harbored no mutation in any of the genes sequenced. MRI studies showed slightly different fat distribution patterns among subjects with different point mutations, though it was strikingly different in subjects with LMNA p.R349W pathogenic variant. Subjects with pathogenic variants of the PPARG gene were associated with less prominent fat loss and relatively higher levels of leptin compared to those with pathogenic variants in the LMNA gene. Various metabolic abnormalities associated with insulin resistance were detected in all subjects. End-organ complications were observed. Conclusion We have identified various pathogenic variants scattered throughout the LMNA and PPARG genes in Turkish patients with FPLD. Phenotypic heterogeneity is remarkable in patients with LMNA pathogenic variants related to the site of missense mutations. FPLD, caused by pathogenic variants either in LMNA or PPARG is associated with metabolic abnormalities associated with insulin resistance that lead to increased morbidity.

In this study, we aimed to investigate whether HDL-C levels of non-diabetic and type 2 diabetic Turks are as low as those of non-diabetic Turks reported in Turkish Heart Study (THS) and Turkish Adult Risk Factor Sudy (TEKHARF).

Precocious adrenarche (PA) refers to the clinical onset of excess androgen in girls before the age of 8. It is associated with an increased risk of functional ovarian hyperandrogenism after puberty. PA may be associated with polycystic ovary syndrome (PCOS). We compared pelvic ultrasound (US) findings of girls with PA born appropriate for gestational age (AGA) to healthy body mass index (BMI)-matched peers to determine whether US findings in AGA-born PA girls are associated with PCOS antecedents.We conducted a cross-sectional study on 56 AGA-born girls with PA (6·9 ± 0·6 years) and 33 BMI-matched prepubertal AGA-born peers (7·1 ± 1·0 years). Hormonal data, homeostasis model assessment of insulin resistance (HOMA-IR), insulin sensitivity index (ISIcomp ) and pelvic US findings were compared. Associations of pelvic US findings with clinical and metabolic data were investigated.Precocious adrenarche girls had greater height and bone age-adjusted uterine length (UL; P = 0·01) and UL standard deviation score (SDS) (P = 0·02) than BMI-matched peers. Mean ovarian volume (MOV), MOV SDS, uterine volume, uterine cross-sectional area and ovarian morphology were similar between the groups (P0·05). MOV and MOV SDS correlated with ISIcomp (r = -0·683, P0·001; r = -0·760, P0·001; respectively). Correlations of pelvic US findings with other biochemical data did not reach significance (P0·05). Multivariate regression analysis revealed that in girls with PA, ISIcomp had the most significant effect on MOV SDS (R(2) = 0·731, β = -4·784, P = 0·001).Appropriate for gestational age-born PA girls have greater UL measurements than AGA-born BMI-matched peers. In AGA-born girls with PA, decreasing insulin sensitivity is strongly and independently associated with an increase in MOV. Longitudinal follow-up of our cohort after menarche will allow us to establish how many AGA-born girls with PA will ultimately develop PCOS.

Distant metastasis may be the initial sign of differentiated thyroid carcinoma in rare cases. In this instance, the treatment approach is usually individualized. Unlike most other cancers, local treatment of the primary tumor (total thyroidectomy) is preferred as ablative surgery; so that radioactive iodine therapy should be more effective. Repeated doses of I-131 and radiotherapy for metastatic lesions may be needed. We report a female who presented with bone metastasis with fatal progression. Turk Jem 2013; 17: 71-4

Aims To describe the phenotype associated with a novel heterozygous missense PPARG mutation discovered in a Turkish family and to compare the fat distribution and metabolic characteristics of subjects with the peroxisome proliferator activator receptor -γ (PPARG) mutation with those of a cluster of patients with familial partial lipodystrophy with classic codon 482 Lamin A/C (LMNA) mutations. Methods The study involved four subjects with familial partial lipodystrophy who had a novel PPARG mutation (H449L) and six subjects with classic codon 482 LMNA mutations (R482W). Results Compared with subjects with LMNA R482W mutation, fat loss was generally less prominent in subjects with the PPARG H449L mutation. Partial fat loss was limited to the extremities, whilst truncal fat mass was preserved. The PPARG H449L mutation was associated with insulin resistance, hypertriglyceridaemia and non-alcoholic fatty liver disease in all affected subjects, but the severity was variable. Three out of four mutation carriers had overt diabetes or impaired glucose tolerance. Pioglitazone therapy in these three individuals resulted in a modest improvement in their metabolic control, and regular menstrual cycles in the two female subjects. Conclusions We suggest that relatively modest fat loss in patients with PPARG mutations may render the recognition of the syndrome more difficult in routine clinical practice. The PPARG H449L mutation is associated with insulin resistance and metabolic complications, but their severity is variable among the affected subjects.

One form of prolactin (PRL) is macroprolactin with high molecular mass. Many macroprolactinemic patients have no pituitary adenomas and no clinical symptoms of hyperprolactinemia, it is controversial whether macroprolactinemia is a benign condition that does not need further investigation and treatment. In this study, we aimed to compare macroprolactinemic patients (group I) with the true hyperprolactinemic patients (group II) for the presence of pituitary adenoma. We investigated 161 patients with hyperprolactinemia, whose magnetic resonance imaging records of the pituitary were taken. All patients were questioned for irregular menses, infertility and examined for galactorrhea. Patients were screened for macroprolactinemia by polyethylene glycol precipitation, and a recovery of ≤40% and normal monomeric PRL level was taken as an indication of significant macroprolactinemia. Of 161 patients with hyperprolactinemia, 60 (37.26%) had macroprolactinemia. PRL levels of group II were lower than those of group I (P = 0.011), although monomeric PRL levels of group II were higher than those of group I (P = 0.0005). Of 60 macroprolactinemic patients, 16 (26.7%) had pituitary adenomas. The prevalence of pituitary adenomas was lower in group I, compared with group II (P = 0.0005). No significant differences were found between the prevalences of irregular menses and infertility of group I and II (P = 0.084, P = 0.361). Prevalence of galactorrhea in group I was lower than that in group II (P = 0.048). Prevalence of pituitary adenomas in macroprolactinemic patients is lower compared with the true hyperprolactinemic patients, but may be higher than that found in other recent studies and in the general population.

The aim was to evaluate the concentrations of lipid subfractions in relation to adipokines and metabolic parameters in adult growth hormone (GH)-deficient hypopituitary patients on conventional replacement therapy. The study included 21 GH deficient-hypopituitary patients (age: 36.0 ± 15.1 years, male/female: 7/14) on conventional replacement therapy other than GH and 20 comparable controls (age: 37.3 ± 14.0 years, male/female: 6/14). Lipid subfractions (Lipoprint system), serum adipokine (leptin, adiponectin, resistin) concentrations, body composition, a surrogate marker for insulin resistance (HOMA) and conventional lipid profile were evaluated. No statistically significant difference was found with respect to HOMA, adipokine concentrations and anthropometric parameters between patients and controls except for significantly increased waist-to-hip ratio in hypopituitary group. Total and LDL cholesterol concentrations were significantly higher in the patients. LDL particle size (268.88 ± 3.16 vs. 271.31 ± 3.11 A, P = 0.151) and small-dense LDL subfraction did not differ significantly. According to logistic regression analysis, triglyceride concentrations ≥1.69 mmol/L was the sole parameter significantly and independently predicted small (

Subclinical hypothyroidism (SH) is characterized by normal serum free T4 (FT4), free T3 (FT3) levels and increased serum thyroid-stimulating hormone (TSH) levels. Endothelial dysfunction, which is an early step of atherosclerosis, has been reported in patients with subclinical hypothyroidism. The aim of this study is to evaluate endothelial functions and the effect of L-thyroxin (L-T4) therapy on endothelial functions in SH. Twenty-seven patients with SH and 22 healthy controls were evaluated in terms of endothelial functions, using brachial artery Doppler ultrasonography. After restorating euthyroidism, measurements were repeated. Baseline and nitroglycerin induced diameter (NID) of brachial artery were similar in patients with SH and the control group. Compared to the control group, the patients with SH showed significantly reduced flow-mediated diameter (FMD). Baseline and NID values were significantly higher after LT4 therapy in SH group. FMD also significantly increased after LT4 therapy. Hypothyroidism accelerates atherogenesis through modification of atherosclerotic risk factors and direct effects on the blood vessels. In this study, we observed marked improvement in endothelial functions after L-T4 therapy in SH patients. We suggest that thyroid hormone replacement therapy may help to prevent atherosclerosis in this group of patients.

Gestational diabetes insipidus (GDI) is a rare disorder characterised by polyuria, polydypsia, and excessive thirst usually manifesting in the third trimester of pregnancy. The etiology is thought to depend on excessive vasopressinase activity, a placental enzyme that degrades arginine-vasopressin (AVP), but not 1-deamino-8-D: -arginine vasopressin (dDAVP), which is a synthetic form. This is a transient syndrome and may be associated with acute fatty liver of pregnancy and preeclampsia. The use of dDAVP in symptomatic cases has been proven as a safe method for both the mother and the fetus during the pregnancy. We report a case of recurrent gestational diabetes insipidus in successive pregnancies, which responded to dDAVP and subsided after delivery.

Thyroid cancer in ovarian teratoma is reported to be rare and experiences are limited. A 26-year-old woman had undergone bilateral cystectomy and omentectomy for bilateral cystic adnexial masses. Pathological examination showed 1.5 cm follicular variant papillary thyroid carcinoma on the basis of unilateral mature cystic teratoma. Increased CA-125 and CA19-9 levels decreased to normal reference ranges after surgery, but postoperative magnetic resonance imaging indicated multiple abdominal cystic loci. After total thyroidectomy, high dose I-131 was administered to ablate thyroid tissue. Thereafter, levothyroxine was started to achieve subclinical hyperthyroidism. No iodine uptake was detected in post-therapeutic whole body scan (WBS) other than thyroid bed. This finding supported that tumor did not show dissemination to abdomen. No uptake on the first-year evaluation with low-dose I-131 WBS suggested the complete ablation of the thyroid gland. It is recommended that thyroid carcinoma arising from ectopic thyroid tissue in a teratoma should be managed as thyroid carcinoma in thyroid. However, direct dissemination to contiguous regions in abdomen and hematogenous dissemination to distant organs should be in mind. Radical surgery including total abdominal hysterectomy, bilateral salphingo-oopherectomy, pelvic and paraaortic lymph node excision and thyroidectomy is recommended. Fertility preserving surgery may be the surgical procedure as in the present case.

To investigate short-term effects of thyroidectomy-induced hypothyroidism on leptin, adiponectin, and resistin concentrations in association with anthropometric data.Thirty premenopausal women with euthyroid nodular goiter-mean age, 44.0 ± 11.6 years; mean body mass index (BMI), 28.6 ± 5.9 kg/m2; 13 obese, 7 overweight, and 10 normal weight subjects-scheduled for total thyroidectomy were included in the study. Serum leptin, adiponectin, resistin, free triiodothyronine, free thyroxine, thyroid-stimulating hormone, glucose, insulin, and C-reactive protein concentrations, lipid profile, and anthropometric variables were determined in the euthyroid state (preoperatively) and the hypothyroid state (postoperatively, with a thyroid-stimulating hormone concentration30 mIU/L).Body weight, BMI, waist and hip circumferences, body fat mass, and serum lipid concentrations increased significantly after thyroidectomy. No significant difference was found between preoperative and postoperative serum leptin, adiponectin, and resistin concentrations. Fat tissue mass-corrected leptin, adiponectin, and resistin concentrations did not differ significantly between euthyroid and hypothyroid periods. Thyroid hormone concentrations showed no significant correlations with adipokine levels.Serum adipokine concentrations seem not to change significantly during short-term thyroidectomy-induced hypothyroidism despite significant increases in body weight, BMI, fat mass, and lipid concentrations.

ObjectiveFibroblast growth factor 23 (FGF23), a phosphatonin, inhibits renal phosphate reabsorption and suppresses 1-α hydroxylase activity. Calcitriol stimulates FGF23 synthesis in bone. We aimed to determine the effect of vitamin D replacement therapy on serum FGF23 concentrations in vitamin D-deficient women and to compare the FGF23 concentrations of vitamin D-deficient patients with healthy subjects and patients with genetically determined hypophosphatemic rachitis.Design and methodsThe study group was composed of vitamin D-deficient females (n=18, mean age 29.1±9.9 years), vitamin D-sufficient healthy females (control group;n=19, mean age 28.5±5.2 years), and patients with genetically determined hypophosphatemic rachitis (n=13, mean age 26.5±15.1 years). The groups were compared for serum FGF23, 1,25-dihydroxyvitamin D3 (1,25(OH)2D), calcium, phosphate, bone turnover markers, intact parathyroid hormone (PTH), and urinary excretion of calcium and phosphate. The vitamin D-deficient group was re-evaluated after a standard treatment regimen.ResultsSerum FGF23 concentrations were significantly lower in vitamin D-deficient patients than in vitamin D-sufficient women and hypophosphatemic rachitis group. Serum FGF23 and phosphate concentrations further decreased significantly during replacement of vitamin D (Pr=−0.469,PConclusionDecreased FGF23 concentrations, which further decline during vitamin D replacement therapy, may have favorable action on bone mineralization by counterregulatory effect on phosphate homeostasis. Lower 1,25(OH)2D concentrations at baseline and hypophosphatemia during treatment may have dominating effects on FGF23 concentrations in vitamin D deficiency, leading to decreased FGF23 concentrations at baseline and during replacement therapy.

Summary Context Data regarding serum adipocytokine and ghrelin concentrations in different stages of anorexia nervosa (AN) is conflicting. Objective Our aim is to determine serum concentrations of adiponectin (ApN), leptin and ghrelin in different stages of AN and to evaluate their relationships with study parameters. Design setting and participants Study group was composed of four subgroups: Group 1: patients with a recent diagnosis of AN (n = 19); group 2: weight recovered (10% increase in body weight compared with baseline) subgroup of group 1 during follow-up (n = 10); group 3: recovered patients with a previous history of AN but normal menstrual cycles and body weight currently (n = 10); group 4: control group (n = 10). Venous blood was obtained for measurements of biochemical/hormonal parameters, ApN, leptin and ghrelin. Body composition was determined by bioimpedance analysis. Main outcome measures Changes in adipocytokine and ghrelin concentrations and relationships with anthropometric/biochemical parameters. Results Leptin : fat mass (kg) ratio was significantly higher in group 1 patients compared with group 4 (4·3 ± 4·6 vs. 1·1 ± 0·5 µg/l kg, P