Changes in olfactory function and olfactory bulb after treatment for acromegaly.

PURPOSE: This study aimed to investigate the olfactory functions of the acromegaly patients and to discuss the possible causes of olfactory dysfunction in acromegaly patients. METHODS: A case-control study was carried out in a tertiary referral center. 52 patients with acromegaly (Acromegaly group) and 52 healthy individuals (Control group) were included in the study. All acromegaly patients included in the study were in the late postoperative period. The Connecticut Chemosensory Clinical Research Center (CCCRC) test was carried out and olfactory bulb (OB) volumes were measured in both of the groups. RESULTS: There was a significant difference between the mean CCCRC total scores of the acromegaly and control groups (p = .000). The mean of right and left OB volumes in the acromegaly group was significantly higher than the control group (p = .004) CONCLUSION: In this study, we found that acromegaly patients are likely to experience olfactory dysfunction. It is important to examine these patients' olfactory functions at the time of diagnosis and clinic follow-up. CLINICAL TRIAL NUMBER: NCT04138537.

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.

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.

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.

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.

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.

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.

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.

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.