Muzaffer Ilhan

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.

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

Abstract 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.

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.

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.

Evaluation of the Patients with Hyperprolactinemia

The frequency of hyperprolactinemia may vary according to the population studied. Various studies in the general population have reported the prevalence of 0.4%–17% (3). As expected, it is higher in endocrinology or gynecology outpatient clinics. The incidence of hyperprolactinemia can be as high as 9% in amenorrhoeic women, 25% in women with galactorrhea, 16%–30% in women with infertility, and 70% in women with both amenorrhea and galactorrhea (2, 4, 5). ABSTRACT Hyperprolactinemia is characterized by the elevation of prolactin levels in circulation. It is the most common disorder of the hypothalamic–pituitary axis. Proper evaluation of the etiology in these patients is extremely important for the accurate follow-up and treatment. This review study aimed to discuss differential diagnoses and key points in patients with hyperprolactinemia.

Parathyroid Carcinoma Case Report: Rapid Control of Refractory Hypercalcemia with Denosumab

Parathyroid carcinoma is a very rarely seen endocrine tumor which courses with severe hypercalcemia. Fluid replacement, diuretic therapy, bisphosphonates and calcimimetic agents are the main steps of the treatment in the control of lifethreatening hypercalcemia. There is limited information about the use of denosumab in recurrent and refractory hypercalcemia associated with parathyroid carcinoma. In this case report, we discussed the use of denosumab and other treatment approaches for a 44-year-old male patient diagnosed with parathyroid carcinoma who had a history of recurrent kidney stones, and evaluated with resistant and recurrent hypercalcemia. Normocalcemia could not be achieved during the follow-up after parathyroidectomy in the patient but rapid reduction of calcium was observed after the injection of denosumab. Denosumab may be considered as an alternative treatment agent with rapid efficiency in patients with severe hypercalcemia and parathyroid carcinoma.

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.

Effects of Weight Loss with Bariatric Surgery on Platelet Count and Volume

Obesity is a chronic, metabolic disease associated with increased risk of cardiovascular disease and characterized by increased mortality and morbidity (1). Coronary artery disease is the leading cause of obesity-related cardiovascular diseases, and platelet activation and aggregation are important pathophysiological mechanisms in the development of cardiovascular disease (2, 3). Although the mean platelet volume (MPV) and number is an important determinant for platelet activation, it has been found to be associated with cardiovascular diseases such as myocardial infarction, stroke and preeclampsia (4-6). Higher MPV in obese patients in comparison to healthy population is considered to be one of the mechanisms that explain the increase in cardiovascular risk in obese patients (7). However, there are a limited number of studies on the effect of weight loss on platelet count and especially on MPV in obese patients. Previous studies have indicated that weight loss through diet and exercise may be associated with MPV (8).

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.