Emre Bozkirli

Subclinical Hypothyroidism Is Characterized by Increased QT Interval Dispersion among Women

Objective: Increased QT interval dispersion (QTd) is an electrocardiographic parameter shown to be associated with malignant ventricular arrhythmias and sudden death, and QT dispersion corrected for heart rate (QTc) has emerged as a potentially important predictor of cardiac death. Increased QTd has been detected to be directly related to thyroid-stimulating hormone (TSH) levels in overt hypothyroidism, however not much is known about subclinical hypothyroidism (SH). This study was conducted to investigate the QTc in SH and determine the changes following normalization of TSH levels with L-thyroxine. Subjects and Methods: Fifty-eight women with naive SH due to Hashimoto’s thyroiditis, mean age 39.37 ± 10.43 years, and 54 age-, sex- and weight-matched controls with normal TSH were included after exclusion of any factor that might interfere with cardiac conductibility. Electrocardiographic measurements were performed with a magnifier and Bazett’s formula was used to calculate QTc. The patients were separated into two groups regarding basal TSH levels (subgroup A: 5 > TSH > 10 mIU/l, n = 36; subgroup B: TSH > 10 mIU/l, n = 22). L-Thyroxine 1–2 µg/kg/day was administered to subgroup B. Results: Mean QTc interval of the study group was significantly longer than that of the control group (100 ± 30 vs. 76 ± 30 ms, p = 0.000). It was also longer in subgroup A (5 > TSH > 10 mIU/l, n = 36) and subgroup B (p = 0.001, p = 0.000, respectively). In subgroup B, following normalization of serum TSH, mean post-treatment QTc measurement was similar to that of the control group (75 ± 40 vs. 76 ± 30 ms, p > 0.05). Conclusion: We detected prolonged QTc among SH cases. Prolongation remained significant for the whole group as well as the two subgroups. The differences in QTc were corrected when TSH levels of >10 mIU/l returned to normal.

Risk Factors That can Predict Antenatal Insulin Need in Gestational Diabetes.

Background This study was undertaken to assess the association between insulin need in gestational diabetes mellitus (GDM) and clinical features and laboratory parameters. Factors that can predict insulin need are also identified. Methods Cases with GDM were included retrospectively from records. Cases which failed to achieve target blood glucose levels with medical nutrition therapy (MNT) and need insulin treatment were recorded. Risk factors which can predict antenatal insulin treatment (AIT) were identified as follows; the presence of diabetes in a first degree relative, body mass index prior to pregnancy, number of parity, history of GDM, macrosomic baby delivery (> 4,000 g), age, gestational week at time of diagnosis, body mass index during diagnosis, weight gain untill diagnosis, mean systolic and diastolic blood pressure, HbA1C level during diagnosis, and fasting plasma glucose on diagnostic oral glucose tolerance test. Presence of a statistical significance between those patient features and AIT was assessed. Independent predictors for AIT were evaluated. Results A total of 300 cases were recruited from records, 190 cases (63.3%) were followed only with MNT until delivery and 110 cases (36.7%) were initiated AIT. The association between AIT and patient factors like presence of diabetes in the pedigree, week of gestation at which GDM was diagnosed, BMI during diagnosis, HbA1C levels, and fasting plasma glucose during diagnosis was found (P = 0.03; 0.008; 0.049; 0.001 and 0.001respectively). Multivariant analysis showed that fasting plasma glucose levels during diagnosis and HbA1C levels were independent risk factors for AIT. Fasting plasma glucose values that can predict AIT were identified > 89.5 mg/dL with 72.7% sensitivity and 62.6% spesifity (P < 0.001). Positive predictive value was 73% (P < 0.001). Also, HbA1C levels that can predict AIT was found to be > 5.485% with 65.3% sensitivity and 66.7% spesifitiy(P < 0.001) with a positive predictive value 68% (P < 0.001). Conclusions Independent predictors for AIT were found as fasting plasma glucose on OGTT and HbA1c levels during diagnosis in GDM. Cases with fasting plasma glucose ≥ 89.5 mg/dL or HbA1C ≥ 5.485% should be closely followed for AIT in specified centers.

Antisynthetase syndrome with refractory lung involvement and myositis successfully treated with double filtration plasmapheresis.

Antisynthetase syndrome (ASS) is characterized by inflammatory muscle disease, pulmonary and joint involvement, and antisynthetase autoantibodies, with anti‐Jo‐1 antibody being the most common. Despite the use of immunosuppressive drugs, the prognosis of lung involvement seems poor. Herein, we report a case of refractory ASS, which maintained long‐term remission by double filtration plasmapheresis (DFPP) combined with immunosuppressive therapy. For a 65‐year‐old woman, who was diagnosed with ASS, immunosuppressive therapy was initiated and plasmapheresis (PP) was performed five times due to acute interstitial pulmonary disease and inflammatory myopathy. She remained in remission for eight months following PP. Increase in interstitial involvement was identified by lung tomography when the patient presented again with complaint of progressive increase in dyspnea and muscle pain. Although the immunosuppressive therapy was increased for the patient with elevated creatine phosphokinase (CPK) (2776 IU/mL), a rapid decrease in diffusion capacity of the lung for carbon monoxide (DLCO) was observed and the patient underwent PP. After four sessions of therapy, insufficient clinical and laboratory response was obtained (control CPK 1797 IU/mL) and because of that issue DFPP using a 2A filter was performed to the patient. There was a marked improvement in complaints of the patient, DLCO, and laboratory findings (control CPK 508 IU/mL) after three sessions of DFPP. The patient, who continued the immunosuppressive therapy after DFPP procedure, is being followed for 12 months in remission. Although our experience is limited with only one patient, DFPP seems promising as a treatment option for ASS with severe lung involvement. J. Clin. Apheresis, 28:422–425, 2013.

Impact of early versus late enteral nutrition on cell mediated immunity and its relationship with glucagon like peptide-1 in intensive care unit patients: a prospective study

IntroductionGlucagon-like peptide-1 (GLP-1) originates from the gastrointestinal system in response to the presence of nutrition in the intestinal lumen and potentiates postprandial insulin secretion. Also, it acts as an immune-modulator which has influences on cell-mediated immunity.The aim of this study was to determine the impact of early enteral nutrition versus late enteral nutrition on plasma GLP-1 levels and the relationship between GLP-1 changes and cell-mediated immunity.Materials and methodsThe study was designed as a prospective, single-blinded study and carried out in the neurology intensive care unit (ICU) of a university hospital. Twenty-four naive patients with acute thromboembolic cerebrovascular events, with National Institute of Health (NIH) stroke scores between 12 and 16, were included. Any condition interfering with GLP-1 and immunity was regarded as exclusion criterion. Two patients died, and two dropped out of the study due to complicating conditions.Patients were randomly subjected to early enteral feeding within the first 24 hours (Group 1), or late enteral feeding, beginning 48 hours after admission (Group 2) via a nasogastric tube. Calculated daily energy requirement was supplemented with parenteral nutrition, starting on the first study day for both groups. Blood samples were obtained before, and at 5, 15, 30, 60 and 120 minutes after the first enteral feeding for GLP-1 assays; this procedure was repeated on the third day. Before and 24 hours after the first enteral feeding, samples were also taken for immunological analysis. Clinical observations were recorded.Pre- and post-feeding plasma GLP-1 changes between the two groups and within groups were evaluated. Lymphocyte subgroup changes before and 24 hours after the first enteral feeding in relation to GLP-1 changes were sought as well.ResultsGroup 1 and Group 2 exhibited similar GLP-1 levels in the pre-feeding and post-feeding periods for both the first time and the third day of enteral feeding. Also, no significant change in pre-/post-feeding GLP-1 levels was observed within groups. T-helper and T-regulatory cells increased, T-cytotoxic cells decreased significantly in Group 1 (P = 0.02; P = 0.036; P = 0.0019), but remained the same in Group 2 after enteral feeding. Positive but statistically insignificant clinical effects in terms of predisposition to infections (10% vs 40%) and median time of ICU stay (10 vs 15 days) were observed in Group 1.ConclusionsDepending on our findings, we propose that early enteral feeding may cause amelioration in cell-mediated immunity via factors other than GLP-1 in ICU patients with acute thromboembolic stroke. However, the possible deleterious effects of parenteral nutrition cannot be ruled out.

Plasma fetuin-A levels are reduced in patients with hypothyroidism

OBJECTIVE To determine plasma fetuin-A levels in hypothyroid patients before and after treatment with l-thyroxine (T4) and to determine the relation between plasma fetuin-A levels with cardiovascular risk factors. DESIGN A prospective, controlled, single-blind study. METHODS Forty-four treatment-naive female patients diagnosed with hypothyroidism and 39 age- and sex-matched control subjects were enrolled. Anthropometric measurements, blood pressure, plasma TSH, fetuin-A, free T4, LDL-cholesterol, triglyceride, C-reactive protein, fibrinogen levels, and brachial artery flow-mediated dilatation were measured. All measurements were repeated after 3 months in the control group and 3 months after the attainment of euthyroidism with l-T4 replacement in the hypothyroid group. Baseline data were compared between the two groups. Posttreatment plasma fetuin-A levels of hypothyroid patients were compared with baseline levels of both groups. The relationship between plasma fetuin-A, TSH levels, and other cardiovascular risk factors was evaluated. RESULTS Plasma fetuin-A levels were ∼20% lower in hypothyroid female patients compared with the controls (P=0.0001). Fetuin-A levels increased by ∼20% in hypothyroid patients after achievement of euthyroidism (P=0.0001) and were no longer different compared with controls (P=0.38). There was a negative correlation between plasma TSH and fetuin-A levels (r=-0.79; P=0.001). There was no significant correlation between plasma fetuin-A levels and cardiovascular risk factors within or between groups. The fetuin-A levels were normalized with thyroid hormone treatment. CONCLUSION Plasma fetuin-A levels are reduced in female patients with hypothyroidism, which are restored to normal during restoration of euthyroidism. There was no relation with cardiovascular risk factors.

Assessment of tear meniscus with optical coherence tomography in thyroid-associated ophtalmopathy.

Abstract Purpose: To evaluate the tear-film meniscus with optical coherence tomography (OCT) in patients with Graves’ disease (GD). Materials and methods: Patients with GD without clinical features of thyroid-associated ophthalmopathy (TAO) (Group 1, n = 35), patients with signs of TAO (Group 2, n = 31) and healthy participants (Group 3, n = 31) were enrolled. Palpebral fissure width, Schirmer test, tear break-up time (TBUT) test and tear-film meniscus height and area obtained with Fourier-domain-OCT were analyzed. Results: TBUT test scores were 8 s (2–25) in Group 1, 8 s (2–15) in Group 2 (p = 0.380); and10 s (5–17) in Group 3 (p = 0.000 Group 1 versus 3, and 0.000 for Group 2 versus 3). Tear-film meniscus height did not significantly differ between Groups 1 and 2 (257.5 µm (86–962) and 258 µm (99–1340), respectively, p = 0.980). In Group 3, tear-film meniscus height was 316 µm (122–720) (p = 0.005 Group 1 versus 3 and 0.004 for Group 2 versus 3). Tear-film meniscus area did not significantly differ between Groups 1 and 2 (0.025 mm2 (0.004–0.250) and 0.024 mm2 (0.003–0.316), respectively, p = 0.850). In Group 3, tear-film meniscus area was 0.048 mm2 (0.006–0.75) (p = 0.000 Group 1 versus 3 and 0.000 for Group 2 versus 3). Conclusion: Tear function is significantly disturbed in GD. OCT is an effective way to assess the tearing function also in patients with GD.

Serum Immunoglobulin G4 levels are elevated in patients with Graves’ ophthalmopathy

Recent studies have shown close association between serum Immunoglobulin G4 (IgG4) levels and forms of autoimmune thyroiditis. However, there are limited data about the relationship between IgG4 and Graves’ ophthalmopathy (GO). In the present study, we aimed to determine the possible association between IgG4 and GO.

Effects of infliximab treatment in terms of cardiovascular risk and insulin resistance in ankylosing spondylitis patients

Abstract Objective. To assess the effects of infliximab treatment on insulin sensitivity and cardiovascular risk factors in patients with ankylosing spondylitis (AS). Methods. In this prospective study, 30 consecutive AS patients (23 men and 7 women) fulfilling the modified 1984 New York criteria for AS were investigated. All patients were treated with intravenous infliximab. A complete biochemical profile and assesments were obtained before and after 12 weeks of infliximab therapy. The Homoeostasis Model Assessment of Insulin Resistance Index (HOMA-IR) was used to measure insulin resistance (IR). Framingham equation was used to assess cardiovascular risk factors. Results. After 12 weeks of infliximab treatment, there was no statistically significant difference in fasting insulin, HOMA-IR, lipid parameters, body–mass index, waist circumference and waist–hip ratio, whereas fasting glucose levels (p = 0.001), triglycerides/high-density lipoprotein (HDL) ratio (p = 0.043) and total cholesterol/HDL (p = 0.041) ratio increased significantly from baseline. A significant decrease was observed for both systolic blood pressures (p < 0.001) and diastolic blood pressures (p = 0.003) in the 12th-week visit. A significant decrease was also found in terms of Framingham risk scores (p = 0.028) after treatment. Conclusions. Study results suggest that infliximab treatment may reduce cardiovascular risk and blood pressures without changing IR.

A case of inoperable malignant insulinoma with resistant hypoglycemia who experienced the most significant clinical improvement with everolimus.

Metastatic insulinomas may sometimes present with recurrent life-threatening hypoglycemia episodes. Such patients usually fail to respond to various therapeutic agents which causes constant dextrose infusion requirement. Herein, we present a resistant case of inoperable malignant insulinoma who was treated with many therapeutic agents and interventions including somatostatin analogues, Yttrium-90 radioembolization, everolimus, radiotherapy, and chemoembolization. Close blood sugar monitorization during these therapies showed the most favourable response with everolimus. Everolimus treatment resulted in rapid improvement of hypoglycemia episodes, letting us discontinue dextrose infusion and discharge the patient. However, experience with everolimus in such patients is still limited, and more precise data can be obtained with the increasing use of this agent for neuroendocrine tumours.

Serum betatrophin levels are reduced in patients with full-blown polycystic ovary syndrome

Abstract Betatrophin is defined as a new marker in glucose homeostasis and lipid metabolism. We aimed to investigate the role of serum betatrophin in full-blown polycystic ovary syndrome (PCOS) patients and 47-aged healthy women, 51 full-blown PCOS patients were included in this cross-sectional study. Betatrophin concentrations were significantly lower in PCOS group and displayed a positive correlation only with serum tryglyceride in control group (p < .05). A cutoff level (464.5 ng/L) was determined for betatrophin according to Receiver Operating Characteristic curve. Using this value, 64.7% of PCOS patients were classified as below the cutoff and in this group betatrophin was found to correlate negatively with fasting glucose, fasting insulin, and homeostasis model assessment of insulin resistance (p = .038, p = .020, and p = .014, respectively), and positively with total testosterone (p = .041). In the rest of PCOS cases (35.3%) who had betatrophin higher than cutoff, positive correlation was found with low-density lipoprotein cholesterol (p = .009). In conclusion, betatrophin levels are reduced in full-blown PCOS patients who had worse metabolic phenotype.