Anti-Mullerian Hormone Levels Increase After Bariatric Surgery in Obese Female Patients With and Without Polycystic Ovary Syndrome.

This study was aimed to investigate the effect of weight loss by bariatric surgery on the level of anti-Mullerian hormone (AMH) in morbidly obese female patients with or without polycystic ovary syndrome (PCOS). This prospective study includes 70 females, obese, and fertile patients of reproductive age. All patients were evaluated to determine the changes in weight, body mass index (BMI), serum AMH, and other biochemical parameters at the end of six months. The mean levels of the preop and postop AMH were 1.66±0.87 ng/ml and 5.99±1.39 ng/ml in the PCOS group; 1.35±0.76 ng/ml and 6.23±1.47 ng/ml in the non-PCOS group, respectively. The postop AMH levels were significantly higher than the preop levels for both groups (p<0.001). There were significant differences in the level of glucose, low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglyceride, total cholesterol, hemoglobin A1c, HOMA-IR, insulin between preop and postop 6th month. A negative correlation was found between postop AMH and body weight in all patients (r=-0.337, p=0.031). Postop AMH levels were negatively correlated with postop BMI levels in the non-PCOS patient group (r=-0.408, p=0.043). No significant difference was observed between the PCOS and non-PCOS groups in terms of all the parameters examined. In conclusion, our study suggests that the significantly increased AMH levels by losing weight with bariatric surgery in patients with morbid obesity with and without PCOS may indicate the improvement of fertilization potential. It could be considered when evaluating fertility in patients with morbid obesity.

The assessment of total antioxidant capacity and superoxide dismutase levels, and the possible role of manganese superoxide dismutase polymorphism in acromegaly.

Oxidative status is attributed to endothelial dysfunction and might be one of the key mechanisms of endothelial dysfunction in acromegaly. In this study, we aimed to investigate the effect of acromegaly on superoxide dismutase (SOD) and total antioxidant capacity (TAC) levels, and the possible influence of human manganese superoxide dismutase (MnSOD) polymorphism on these levels. 51 acromegaly patients and 57 age and sex matched healthy subjects were recruited to the study in Bezmialem Vakif University Hospital between 2011 and 2014. The median SOD and TAC levels were 42.7 (33-60) pg/mL and 1,313.7 (155-1,902) µM in acromegaly; and 46.3 (38-95) pg/mL and 1,607.3 (195-1,981) µM in healthy subjects (p < 0.001, p < 0.001). SOD levels were decreased in controlled and uncontrolled patients compared to healthy subjects (p = 0.05 and p = 0.002, respectively). Controlled and uncontrolled acromegaly displayed significantly decreased levels of TAC compared to healthy subjects (p < 0.05 and p < 0.001, respectively). SOD levels were not associated with MnSOD polymorphisms in acromegaly. In conclusion, this study showed that acromegaly was associated with decreased levels of SOD and TAC, and controlling the disease activity could not adequately improve these levels.

Rapid improvement in visual loss with cabergoline treatment in a giant prolactinoma case: 5 years survey.

Giant prolactinoma is a rare subset of macroadenomas. Limited studies demonstrated which therapy could be successfully used in the first-line therapy of giant prolactinoma. We presented a case with a 54 × 40 × 40 mm pituitary adenoma and optic chiasmatic compression with left sphenoid sinus invasion. The tumor caused a loss of visual field of the right side. Cabergoline treatment was started with dose of 1.5 mg/week. Fifteen days later, the clinical visual acuity examination showed a significant improvement in the patient with visual field defect. After the five years follow-up magnetic resonance imagining showed reduction of the adenoma size (17 × 12 mm) was significant. Our findings suggest that, cabergoline can be used as a first-line therapy in giant prolactinomas because tumoral shrinkage without a surgical procedure and rapid improvement in visual field defect is achieved with this medical treatment.

Esophagus motility in overt hypothyroidism.

PURPOSE: Gastrointestinal tract is one of the most affected systems in hypothyroidism. Despite decreased esophageal emptying, prolonged esophageal and gastric transit time have been indicated in previous reports, the mechanism of thyroid hormones activity and antibodies on the esophagus motility is not yet fully understood. This study was conducted to evaluate the esophagus motility by manometry in hypothyroid patients. METHODS: The study enrolled with 28 overt, newly diagnosed hypothyroid patients and 29 age- and sex-matched healthy controls. Twenty-one females and 7 males with overt hypothyroidism and 22 females and 7 males with healthy control subjects were recruited to study. Esophageal manometry was performed using MMS (Medical Measurement Systems bv. The Netherlands) Solar GI-Air-Charged Intelligent Gastrointestinal Conventional Manometry. RESULTS: The lower esophageal sphincter pressure (LESP) was 19.5 ± 6.5 mmHg in hypothyroid patients and 17.48 ± 4.65 mmHg in controls, and there was no significant difference (p = 0.18). Percentage of relaxation was 61.5 and 80.9 %, and it was significantly lower in hypothyroid patients than controls (p < 0.001). Additionally, duration of relaxation was found 3.85 ± 2.3 and 5.5 ± 2.28 s in patients and controls, respectively (p = 0.009). In patient group, LESP was positively correlated with fT3 (p = 0.033), and the duration of the contraction was negatively correlated with fT4 (p = 0.044). CONCLUSION: In this study, we observed that hypothyroid state can affect esophagus motility via shortened duration of relaxation and reduced percentage of relaxation even if in patients without any gastrointestinal symptoms. Further studies are needed to clarify the effect of thyroid hormones on esophagus motility.

Polycystic ovary syndrome is associated with P-wave prolongation and increased P-wave dispersion.

BACKGROUND: The polycystic ovary syndrome (PCOS) is associated with various cardiac manifestations including cardiac arrhythmias. P-wave dispersion (Pdis) is an appealing marker for predicting the risk of developing atrial arrhythmias. The purpose of this study was to evaluate P-wave durations and Pdis in patients with PCOS. METHODS: Forty adult patients with PCOS and 46 age- and sex-matched healthy individuals were included in this study. P-wave maximum duration (Pmax) and P-wave minimum duration (Pmin) were calculated on the 12-lead electrocardiogram, and the difference between the Pmax and the Pmin was defined as Pdis. All individuals also underwent transthoracic echocardiographic evaluation. RESULTS: Pmax and Pdis were significantly higher in patients with PCOS compared with controls (p = 0.007, p < 0.001, respectively). There was no difference in Pmin duration between both the groups (p = 0.2). Waist-to-hip ratio, insulin and homeostasis model assessment of insulin resistance (HOMA-IR) were higher in the PCOS group. Early mitral inflow deceleration time (DT) (p < 0.001) and isovolumetric relaxation time (p = 0.003) were longer in PCOS group. Waist-to-hip ratio, DT, E/A ratio and diastolic blood pressure correlated with Pdis. CONCLUSIONS: Patients with PCOS have prolonged Pmax and Pdis. The increase in those parameters may be an indicator for identification of patients at increased risk of atrial fibrillation.

Effect of stressful life events on the initiation of graves' disease.

OBJECTIVE: The aim of this study was to investigate the relationship between stressful life events (LESs) and its effect on the initiation of Graves' disease (GD) and toxic nodular goitre (TNG). PATIENTS AND METHOD: Forty-five patients with GD, 24 patients with TNG and 36 healthy control (CG) were included to the study. Graves and TNG patients had diagnosed within the last 12 months, with clinical and biochemical confirmation in Endocrinology Metabolism Outpatient Clinic of Cerrahpasa Medical School. The Holmes-Rahe Stress Scale and the Life Experience Survey (LES) was the psychological evaluation instrument used in this study. RESULTS: There was no significant difference according to Holmes-Rahe scale (Graves & TNG P = 0.329, Graves & Control P = 0.115, TNG and control P = 0.571). According to LES scale when negative event number, positive event number, neutral events and their effects are considered, between Graves and TNG groups no statistically difference was observed (P = 0.139, P = 0.083, P = 0.167, P = 0.162, P = 0.861). The number and impact of negative SLEs were significantly higher in GD compared to CG (P = 0.015, P < 0.001). CONCLUSION: According to LES scale GD patients has significant difference with respect to CG when negative event number and impact are considered.

Brain Diffusion Tensor Imaging Findings in Hashimoto's Thyroiditis.

BACKGROUND AND PURPOSE: Hashimoto's thyroiditis (HT) is a type of autoimmune thyroid disease. Diffusion tensor imaging (DTI) can evaluate microstructural brain involvement in various diseases. We aimed to investigate whether there were any DTI differences in patients with HT, and the relationship between DTI values and disease duration time and thyroid peroxidase antibodies (TPOAb) levels. METHODS: We prospectively included 36 patients with HT (mean age 41.6 ± 13.8 years, range 18-64 years) and 18 age and sex-matched healthy control subjects (mean age 41.6 ± 13.1 years, range 18-63 years). All patients were euthyroid at the time of imaging. Fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) values of 15 distinct neuroanatomical locations were measured and compared. RESULTS: FA values of the patients with HT were lower in cingulum, globus pallidus (GP), cerebellar white matter (CWM) than the control (P = .019, .002, and <.001, respectively). MD values of the CWM in patients were higher than the control (P = .008). AD values of patients with HT were lower in the cingulum, posterior limbs of the internal capsule, GP, and putamen (P = .038, .038, .030, and .045, respectively). RD values of cingulum and CWM in HT were higher than controls (P <.001 and P = .011, respectively). There was a negative relationship between the FA values of PLIC and a positive relationship between the MD values of the corona radiata and TPOAb levels were detected. CONCLUSIONS: The current DTI study presented microstructural changes in the neurocognitive-related areas that may be related to accompanying neurological findings in HT.

Genetic Variation in NFKB1 Gene Influences Liver Enzyme Levels in Morbidly Obese Women.

BACKGROUND: Morbid obesity (MO), characterized by low-grade inflammation, is associated with increased C-reactive protein (CRP). NF-KB is a candidate factor for inflammatory responses in inflammatory diseases such as obesity. The objective of our study was to investigate the relationship between NFKB1 gene variations and the risk of MO in the context of the high/normal level of liver enzymes such as Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), gamma-glutamyl transpeptidase (GGT), and alkaline phosphatase (ALP). METHODS: We analyzed the distribution of NFKB1 -94 ins/del ATTG (rs28362491) polymorphism using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP)and liver enzymes serum levels using ELISA in 182 MO patients with CRP level ≥20 mg/L and 200 healthy controls in a female Turkish population. RESULTS: We found that having ins/ins genotype of rs28362491 is a risk factor in both high level and normal level liver enzymes of ALT (P = 0.0335, P = 0.0134), AST (P = 0.0285, P = 0.0113) and ALP (P = 0.0079, P = 0.0363) whereas having ins/ins genotype of rs28362491 is a risk factor in only high-level liver enzyme of GGT (P = 0.0003). CONCLUSION: Our results suggest that ins/ins genotype of SNP rs28362491 is linked to MO with high-level ALT, AST, ALP, and GGT.

The Role of p16 and MDM2 Gene Polymorphisms in Prolactinoma: MDM2 Gene Polymorphisms May Be Associated with Tumor Shrinkage.

AIM: Prolactinomas are thought to arise from clonal expansion of a single mutated cell which is subjected to growth stimuli of several permissive factors, although the pathogenetic mechanisms underlying tumorigenesis remain unclear. The present study aimed to investigate the role of p16 (540C→G and 580C→T) and mouse double minute 2 (MDM2) (SNP309T→G) gene polymorphisms in tumorigenesis and characteristics of prolactinoma. PATIENTS AND METHODS: A total of 74 patients with prolactinoma and 100 age- and gender-matched healthy individuals were enrolled in the study. Serum prolactin levels were measured by enzyme-linked immunosorbent assay (ELISA). p16 and MDM2 polymorphisms were determined by polymerase chain reaction-restriction fragment polymorphism and agarose gel electrophoresis. RESULTS: p16 540C→G genotype distribution was found to be: CC: 66.2%, CG: 28.4%, GG: 5.4%; p16 580C→T genotype distribution was found to be: CC: 82.4%, CT: 17.6%, TT: 0% and MDM2 genotype distribution was found to be: TT: 31.1%, TG: 47.3%, GG: 21.6% in patients with prolactinoma. Tumor diameter before treatment was correlated with prolactin levels before treatment and percentage of prolactin decrease with treatment (r=0.719, p<0.001, p=0.034 r=0.256, respectively). The number of patients with tumor size decrease of more than 50% in those with homozygous genotype (TT+GG) of MDM2 SNP309T→G was significantly higher than in heterozygous genotype (TG) carriers (odds ratio(OR)=0.18, 95% confidence interval(CI)=0.06-0.58; p=0.003). CONCLUSION: This study showed that p16 and MDM2 polymorphisms do not play a decisive role in tumorigenesis, but some genotypes of these polymorphisms might be associated with follow-up characteristics of prolactinoma.

Comparison of Pulse Rate Variability and Heart Rate Variability for Hypoglycemia Syndrome.

BACKGROUND: Heart rate variability (HRV) is a signal obtained from RR intervals of electrocardiography (ECG) signals to evaluate the balance between the sympathetic nervous system and the parasympathetic nervous system; not only HRV but also pulse rate variability (PRV) extracted from finger pulse plethysmography (PPG) can reflect irregularities that may occur in heart rate and control procedures. OBJECTIVES: The purpose of this study is to compare the HRV and PRV during hypoglycemia in order to evaluate the features that computed from PRV that can be used in detection of hypoglycemia. METHODS: To this end, PRV and HRV of 10 patients who required testing with insulin-induced hypoglycemia (IIHT) in Clinics of Endocrinology and Metabolism Diseases of Bezm-i Alem University (Istanbul, Turkey), were obtained. The recordings were done at three stages: prior to IIHT, during the IIHT, and after the IIHT. We used Bland-Altman analysis for comparing the parameters and to evaluate the correlation between HRV and PRV if exists. RESULTS: Significant correlation (r > 0.90, p < 0.05) and close agreement were found between HRV and PRV for mean intervals, the root-mean square of the difference of successive intervals, standard deviation of successive intervals and the ratio of the low-to-high frequency power. CONCLUSIONS: In conclusion, all the features computed from PRV and HRV have close agreement and correlation according to Bland-Altman analyses' results and features computed from PRV can be used in detection of hypoglycemia.

The use of complementary medicine in patients with diabetes.

OBJECTIVE: Diabetes mellitus (DM) is a growing health problem with serious complications. The chronic and progressive nature of the disease often leads patients to use complementary and integrative medicine. The present study aimed to investigate the frequency of use of alternative medicine by patients with DM and the products used. METHODS: Between September 2014 and May 2015, 301 patients with DM were selected from Bezmialem Foundation University Hospital Diabetes Clinic to participate in the study. RESULTS: The results of the study indicate that 81 (26.9%) patients had tried alternative medicine, and 50 (16.6%) patients continued to use some form of alternative medicine product. A total of 43 (14.3%) patients used such products every day and 24 (8%) patients had used alternative medicine products for up to 6 months. Glycated hemoglobin (HbA1c) levels were significantly decreased in patients using alternative medicine products compared to the remainder of patients in the study (p=0.017). No other significant difference was found between the two groups. It was observed that among patients using alternative medicine products, only 10 (12%) had informed their physicians. CONCLUSION: This study indicated that patients with diabetes are very likely to use alternative medicine products. Additional studies are needed to further determine the efficacy of these products. Patients as well as health providers must be educated about complementary medicine and alternative products.

Acromegaly can be associated with impairment of LES relaxation in the oesophagus.

INTRODUCTION: Although prolonged small intestine and colonic transit time has been demonstrated in acromegaly patients, the influence of acromegaly on oesophagus motility and the pathological mechanisms involved are still not clarified. We aimed to investigate manometric measurements to ascertain whether oesophagus motility is affected in active acromegaly patients. MATERIAL AND METHODS: The study was performed in an institutional referral centre at a tertiary care hospital. Twenty-three acromegaly patients (mean age 43.2 ± 13.2 years) and 25 sex- and age-matched healthy control subjects (mean age 48.6 ± 7.9 years) were recruited to a case-control study. Oesophageal manometry was performed using MMS (Medical Measurement Systems, Netherlands) Solar GI - Air Charged Intelligent Gastrointestinal Conventional Manometry. RESULTS: In manometric measurements the lower oesophageal sphincter pressure was 18 ± 7 mmHg in acromegaly patients and 15.6 ± 4.4 mm Hg in controls, and there was no significant difference (p = 0.17). The percentage of relaxation was 64.8% and 81.8%, respectively, and it was significantly lower in acromegaly patients than in controls (p < 0.001). Additionally, the duration of relaxation was found to be 4 ± 1.9 seconds and 5 ± 1.7 seconds in patients and controls, respectively (p = 0.049). CONCLUSIONS: Our study has demonstrated a significant reduction in the percentage and duration of lower oesophageal sphincter relaxation in oesophagus motility even in acromegaly patients without any gastrointestinal symptoms. Further clinical and pathophysiological studies are required to clarify the underlying mechanisms of gastrointestinal motility disorders in acromegaly.

Investigation of the vitamin D receptor polymorphisms in acromegaly patients.

OBJECTIVE: The genetic structural alterations in the majority of somatotroph adenomas are not clarified and the search for novel candidate genes is still a challenge. We aimed to investigate possible associations between vitamin D receptor (VDR) polymorphisms and acromegaly. DESIGN, PATIENTS, AND METHODS: 52 acromegaly patients (mean age 45.7 ± 1.9 years) and 83 controls (mean age 43.1 ± 2.6 years) were recruited to the study. VDR polymorphism was determined by polymerase chain reaction-based restriction fragment length polymorphism methods. RESULTS: The distribution of VDR genotypes showed a significant difference in the frequencies of VDR FokI genotypes between patients and controls (P = 0.034). VDR FokI ff genotype was significantly decreased in acromegaly patients (P = 0.035) and carriers of FokI Ff genotype had a 1.5-fold increased risk for acromegaly (OR: 1.5, 95% CI: 1.07-2.1; P = 0.020). IGF1 levels after treatment were significantly higher in patients carrying the Ff genotype compared to carrying ff genotype (P = 0.0049). 25(OH)D3 levels were significantly lower in acromegaly patients (P < 0.001). CONCLUSIONS: Our study suggests that VDR FokI genotypes might affect the development of acromegaly and VDR polymorphisms may play a role in the course of acromegaly as a consequence of altering hormonal status.

Real-life safety and efficacy of vildagliptin as add-on to metformin in patients with type 2 diabetes in Turkey--GALATA study.

OBJECTIVE: To evaluate tolerability/safety and the efficacy of the combination of vildagliptin plus metformin in a real-life population of patients with type 2 diabetes mellitus (T2DM). RESEARCH DESIGN AND METHODS: This multicenter, single-arm, 6 month, observational, prospective cohort study was conducted at 39 centers across Turkey. T2DM patients on vildagliptin and metformin for ≤4 weeks were enrolled regardless of their previous antidiabetic therapy. MAIN OUTCOME MEASURES: Efficacy was evaluated by measuring hemoglobin A1c (HbA1c) levels. Tolerability/safety parameters evaluated included hypoglycemic events, gastrointestinal events, peripheral edema and weight gain. RESULTS: This study enrolled 665 patients with a mean ± standard deviation (SD) age of 55.1 ± 10.2 years and female predominance (n = 394, 59.2%). Safety was assessed in all enrolled patients. Hypoglycemia was reported in 10 (1.5%) patients (95% confidence interval = 0.8-2.7%). Efficacy was assessed in 289 (43.5%) patients treated for 6 ± 1 months; these patients showed a mean decrease in HbA1c of 0.8% from baseline value of 7.8% (p < 0.001). The percentages of patients who achieved HbA1c targets of ≤6.5% and ≤7.0% were significantly increased, from 10.7% to 33.6% and from 22.1% to 52.6%, respectively (p < 0.001 each). The decrease in HbA1c was independent of baseline HbA1c (≤8% vs. 8-10% vs. ≥10%), age (≤65 vs. >65 years) and body mass index (<30 vs. ≥30 kg/m(2)) (p < 0.001 each). In total, 136 adverse events (AEs) were observed in 71 (10.7%) patients; 10 (1.5%) patients experienced hypoglycemia and gastrointestinal AEs were most commonly reported (n = 29, 4.4%). CONCLUSIONS: In a 'real-life' setting, the vildagliptin and metformin combination was associated with significant improvements in reaching target HbA1c levels, even in elderly and obese patients with T2DM. Moreover, vildagliptin and metformin demonstrated a good overall tolerability/safety profile.

Does DRD2 polymorphism influence the clinical characteristics of prolactinoma?

OBJECTIVES: Genetic alterations explaining the clinical variability of prolactinomas still could not be clarified and dopamine D2 receptor (DRD2) polymorphism is a putative candidate for the variable response to dopaminergic treatment. The present study was conducted to investigate the influence of DRD2 TaqI A polymorphism on initial and follow-up characteristics of prolactinoma. PATIENTS AND METHODS: Seventy-two patients with prolactinoma and 98 age and gender matched control subjects were recruited to the case-control study. Serum prolactin levels were assessed by enzyme-linked immunosorbent assay and DRD2 polymorphism was determined by polymerase chain reaction and restriction length polymorphism analysis. RESULTS: Decrease of prolactin levels and the tumor shrinkage after cabergoline treatment were 93.9±5.9% and 58.3±33.1% in microadenomas and 96.1±6.1% and 51.7±29.3 in macroadenomas (P=0.02 and P>0.05, respectively). We observed no significant difference for DRD2 genotypes and the alleles between the patients and healthy group (P>0.05). Prolactin levels before treatment were correlated with tumor diameter before and after treatment and the percentage of prolactin decrease with treatment (P<0.001 r=0.58, P<0.001 r=0.40 and P<0.001 r=0.47, respectively). Tumor diameter before the treatment was also correlated with the tumor diameter after the treatment (P<0.001 r=0.64) and the percentage of prolactin decrease (P=0.01 r=0.30). However, no significant association was found between characteristics of prolactinoma and DRD2 genotypes and alleles (P>0.05). CONCLUSION: This study revealed that DRD2 TaqI A receptor polymorphism was not associated with the development of prolactinoma and its clinical characteristics. Future studies are needed to clarify the clinical implications of genetic alterations in prolactinoma.

Polymorphism of the NFKB1 affects the serum inflammatory levels of IL-6 in Hashimoto thyroiditis in a Turkish population.

Hashimoto thyroiditis (HT) is a chronic inflammatory autoimmune disease of thyroid gland affected by interaction of multiple genes and various cytokines. Variants in the genes coding for the NFKB and IKB proteins can be potentially involved in the development of the inflammatory diseases. NFKB, a key transcription factor of the regulation of immune responses, is interesting candidate for association studies about autoimmune disorder. The aim of the present study was to investigate the relationship between NFKB1 and NFKBIA (NFKB1 inhibitor gene) polymorphisms, and the risk of HT in a Turkish Population in the context of IL-6 serum levels which may contribute to susceptibility to the disease. We analyzed the distribution of NFKB1-94ins/del ATTG and NFKBIA 3'UTR A→G polymorphisms using PCR-RFLP method and IL-6 serum levels using ELISA method in 120 HT patients and 190 healthy controls in Turkish population. Although, there was no statistical significant difference in distribution of the genotypes and alleles of NFKB1-94ins/del ATTG or NFKBIA 3'UTR A→G polymorphisms in patients and control subjects as single, ins/ins/GG combined genotype had protective effect on the disease when compared to ins/ins/AG combined genotype as combined genotypes of both polymorphisms. In addition to this finding, IL-6 serum levels in HT patients with del/del genotype were significantly higher than in patients with del/ins genotype (p<0.001). According to the combined genotype analysis of NFKB1-94ins/del ATTG and NFKBIA 3'UTR A→G polymorphisms, IL-6 levels were also higher in patients with del/del genotype when at least one G allele existing (p=0.007). Therefore, our findings suggest that the functional promoter NFKB1-94ins/del ATTG polymorphism was significantly associated with population HT disease through acting by directly modulating IL-6 serum levels.

Association of PARP-1, NF-κB, NF-κBIA and IL-6, IL-1ß and TNF-α with Graves Disease and Graves Ophthalmopathy.

BACKGROUND: Graves Disease (GD) is an autoimmune disorder affected by an interaction of multiple genes such as Nuclear Factor-κB (NF-κB), Nuclear Factor-κB Inhibitor (NF-κBIA), Poly (ADP-ribose) polymerase-1 (PARP-1) and cytokines like Interleukin-1ß (IL-1ß), Interleukin-6 (IL-6) and Tumor Necrosis Factor-α (TNF-α) and mostly accompanied by an ocular disorder, Graves Ophthalmopathy (GO). We hypothesize that there is a relationship between GD, GO, polymorphisms of inflammatory related genes and their association with cytokines, which may play important roles in autoimmune and inflammatory processes. SUBJECTS AND METHODS: To confirm our hypothesis, we studied the polymorphisms and cytokine levels of 120 patients with GD and GO using PCR-RFLP and ELISA methods, respectively. RESULTS: We found that patients with GG genotype and carriers of G allele of PARP-1 G1672A polymorphism are at risk in the group having GD (p=0.0007) while having GA genotype may be protective against the disease. PARP-1 C410T polymorphism was found to be associated with GO by increasing the risk by 1.7 times (p=0.004). Another risk factor for development of GO was the polymorphism of del/ins of NFkB1 gene (p=0.032) that increases the risk by 39%. Levels of cytokines were also elevated in patients with GD, but no association was found between levels of cytokines and the development of GO as there was no change in levels of cytokines. CONCLUSIONS: We suggest that, PARP-1 and NFkB1 gene polymorphisms may be risk factors for developing Graves Disease and Ophthalmopathy.

Association of three SNPs in the PARP-1 gene with Hashimoto's thyroiditis.

Poly(ADP-ribose) polymerase-1 (PARP-1) has a vital role in the progression of the inflammatory response, and its inhibition confers protection in various models of inflammatory disorders. Therefore, we investigated the effect of promoter and exon variations of the PARP-1 gene on the risk for the inflammatory disease Hashimoto's thyroiditis (HT). This case-control association study was comprised of 141 HT patients and 150 controls from a group of women in a Turkish population. Two polymorphisms in the promoter region of the PARP-1 gene, rs2793378 and rs7527192, were analyzed using the PCR-RFLP method. In addition, single nucleotide polymorphism (SNP) rs1136410, which is located at codon 762, was analyzed using bidirectional sequencing. The combined genotype and haplotype analyses of these polymorphisms were performed using SPSS 18 and Haploview 4.2. The results were statistically analyzed by calculating the odds ratios and 95% confidence interval using Pearson's χ (2)-test and Fisher's exact test (two-sided). Although we had a number of significant results, the associations became nonsignificant following a Bonferroni correction for multiple comparisons. Nonetheless, a protective factor against HT was still observed for the heterozygous genotype (TC) of SNP rs1136410 (P=0.001), even following Bonferroni correction, and according to the rs2793378-rs7527192 combined analysis, the occurrence of the TT/GA combined genotype was significantly higher in the controls (P=0.007). These results prove that the heterozygosity of SNP rs1136410 provides a protective effect against HT disease in a group of women in a Turkish population.

Does hormonal control obviate positive airway pressure therapy in acromegaly with sleep-disordered breathing?

INTRODUCTION: Acromegaly is a disease in which uncontrolled release of growth hormone occurs after closure of epiphyseal plates, causing changes in the body that can lead to sleep disordered breathing (SDB). No definite guidelines regarding the treatment of SDB in acromegaly are available. In this study, we aimed to investigate the prevalence of SDB in acromegaly and whether hormonal control alters the necessity of positive airway pressure (PAP) therapy in acromegaly patients with SDB. METHODS: Forty-two acromegaly patients were included in the study and divided into two groups according to disease status, i.e., active or well controlled. All patients underwent polysomnography. Fourteen patients with active acromegaly were diagnosed with SDB and were evaluated for PAP therapy with polysomnography both before and 6 months after disease control was achieved. RESULTS: Sleep-disorder breathing was diagnosed in 22 of 42 patients, 7 of 20 patients with controlled-disease and 15 of 20 patients with active diseases. There were significant reductions in respiratory disturbance index (RDI), apnea index, desaturation index, central apnea number, and rapid eye movement-phase RDI at the control polysomnography. Initially, PAP therapy was indicated in 12 of 14 patients and PAP therapy indication held in 11 patients after acromegaly control was achieved. CONCLUSION: Our study revealed that over half of patients with acromegaly had SDB. Furthermore, SDB severity decreases with acromegaly treatment; however, this decrease does not change the indication for PAP therapy; therefore, PAP therapy should not be delayed in acromegalic SDB patients.

Electrocardiographic and echocardiographic evidence of myocardial impairment in patients with overt hypothyroidism.

OBJECTIVE: Our aim was to evaluate cardiac function and myocardial contractility in patients with overt hypothyroidism using two-dimensional speckle tracking echocardiography (2D-STE) strain imaging and real-time three-dimensional echocardiography (RT3DE) and compare the changes at one month after starting the treatment. We also compared the P wave dispersion (Pdis) in patients with and without hypothyroidism. SUBJECTS AND METHODS: Forty-one patients with overt hypothyroidism and forty age- and body mass index-matched healthy subjects underwent conventional echocardiography, RT3DE and 2D-STE for assessment of resting LV function. Electrocardiography (ECG) recordings were obtained and the P wave parameters were calculated. Measurements of RT3DE volumes and ejection fraction (EF) were performed. Global longitudinal strain (GLS) was calculated from 3 standard apical views using 2D-STE. RESULTS: Patients with overt hypothyroidism had significantly longer isovolumic contraction time (P<0.001), deceleration time (P<0.001) and isovolumic relaxation time (P<0.001). On RT3DE evaluation, none of the patients in both groups had LV systolic dysfunction with comparable LVEF and LV volumes. However, speckle tracking analysis showed that GLS was significantly reduced in the overt hypothyroidism group compared to control group (P<0.001). At one month follow-up after the treatment, GLS significantly improved in overt hypothyroidism group (P<0.001). Patients in the overt hypothyroidism group had increased Pdis compared to control group (P=0.02). CONCLUSIONS: Overt hypothyroidism may be related to impairment of LV longitudinal myocardial function, and 2D-STE is useful for the detection of early impairment. Successful treatment of overt hypothyroidism has a beneficial effect on cardiac functions. In addition, overt hypothyroidism has increased risk for atrial arrhythmias due to high Pdis value.