Murat Atmaca

Natural History of Congenital Generalized Lipodystrophy: A Nationwide Study From Turkey

CONTEXT Congenital generalized lipodystrophy (CGL) is a rare autosomal recessive disorder characterized by near-total lack of body fat. OBJECTIVE We aimed to study natural history and disease burden of various subtypes of CGL. DESIGN We attempted to ascertain nearly all patients with CGL in Turkey. SETTING This was a nationwide study. PATIENTS OR OTHER PARTICIPANTS Participants included 33 patients (22 families) with CGL and 30 healthy controls. MAIN OUTCOME MEASURE(S) We wanted to ascertain genotypes by sequencing of the known genes. Whole-body magnetic resonance imaging was used to investigate the extent of fat loss. Metabolic abnormalities and end-organ complications were measured on prospective follow-up. RESULTS Analysis of the AGPAT2 gene revealed four previously reported and four novel mutations (CGL1; c.144C>A, c.667_705delinsCTGCG, c.268delC, and c.316+1G>T). Analysis of the BSCL2 gene revealed four different homozygous and one compound heterozygous possible disease-causing mutations (CGL2), including four novel mutations (c.280C>T, c.631delG, c.62A>T, and c.465-468delGACT). Two homozygous PTRF mutations (c.481-482insGTGA and c.259C>T) were identified (CGL4). Patients with CGL1 had preservation of adipose tissue in the palms, soles, scalp, and orbital region, and had relatively lower serum adiponectin levels as compared to CGL2 patients. CGL4 patients had myopathy and other distinct clinical features. All patients developed various metabolic abnormalities associated with insulin resistance. Hepatic involvement was more severe in CGL2. End-organ complications were observed at young ages. Two patients died at age 62 years from cardiovascular events. CONCLUSIONS CGL patients from Turkey had both previously reported and novel mutations of the AGPAT2, BSCL2, and PTRF genes. Our study highlights the early onset of severe metabolic abnormalities and increased risk of end-organ complications in patients with CGL.

Aspirin resistance in patients with type II diabetes mellitus

Abstract Background. Diabetic patients exhibit platelet hyperreactivity, which renders them resistant to antithrombotic treatments. We aimed to investigate the prevalence and predictors of aspirin resistance in diabetic patients. Material and methods. A total of 93 diabetic and 37 non-diabetic participants were included into the study. Aspirin resistance was measured with a whole-blood desktop platelet function analyzer (PFA-100) with an epinephrine agonist. Results. Altogether 41.9% patients with DM were aspirin non-responders. Aspirin resistance was observed in 43.2% of non-diabetic patients (p = 0.89). Presence of diabetes mellitus had no effect on aspirin response (RR 0.95 (95% CI 0.44–2.05), p = 0.89) in the whole study population. Hypercholesterolemia was the only predictor of aspirin resistance in multivariate analysis in diabetic patients (RR 3.09 (95% CI 1.17–8.16), p = 0.023). Conclusion. The prevalence of aspirin resistance is comparable in diabetic and non-diabetic patients. Hypercholesterolemia is the only independent predictor of aspirin resistance in diabetic patients.

Ultrasound Elastography for Distinction Between Parathyroid Adenomas and Thyroid Nodules

The aim of this study was to detect the level of stiffness of parathyroid adenomas and to distinguish them from benign and malignant thyroid nodules using ultrasound elastography with acoustic radiation force impulse imaging.

Molecular analysis and clinical findings of Griscelli syndrome patients.

Griscelli syndrome (GS) is a rare autosomal recessive disorder associated with skin or hair hypopigmentation, hepatosplenomegaly, pancytopenia, and immunologic and central nervous system abnormalities. GS type II is caused by RAB27A mutations. We present RAB27A mutation analysis of 6 cases diagnosed as GS type II. Missense mutations (L26P and L130P) in 2 cases, deletion of 5 bases (514delCAAGC) in 2 cases, and 1 base deletion (148delA) in 2 cases were detected. This report has importance in phenotype-genotype correlation of different types of mutations including missense mutations and deletions within the RAB27A gene in GSII syndrome.

Prevalence of Autoantibodies Related to Some Autoimmune Disorders in Patients With Chronic Idiopathic Thrombocytopenic Purpura

We investigated the prevalence of antinuclear antibody (ANA), thyroid antimicrosomal (AMA) and antithyroglobulin (ATA), antigliadin (AGA) immunoglobulin G (IgG)-A, anti-endomisium (EMA) IgG-A, and tissue transglutaminase (tTG) IgG-A in 87 patients with chronic idiopathic thrombocytopenic purpura (cITP) and in 95 healthy controls. Antinuclear antibody positivity was found in 13 of 87 patients and 3 of 95 controls (P = .007). Antithyroglobulin positivity was found in 27 of patients and in 7 of the controls (P < .001). AMA positivity was found in 20 of patients and 8 of the controls (P = 0.008). Antigliadin IgG was positive in 17 patients and 1 controls (P < .001) whereas Antigliadin IgA was positive in 9 of patients and in 1 of the controls (P = .007). Anti-endomisium (IgG and IgA were not different between both groups. Tissue transglutaminase IgG was detected in 7 of patients and in 1 of the controls (P = .029). Tissue transglutaminase IgA was detected in 5 of patients and in none of the controls (P = .023). We believe that larger studies are needed to determine the long-term impact and clinical importance of these autoantibodies.

Relationship between serum DHEAS and oxidative stress levels of body mass index in healthy postmenopausal women

Objectives: Menopause is a natural step in the process of aging. Postmenopausal women have decreased levels of antioxidants and increased oxidative stress, the latter of which plays an important role in atherogenesis. The aim of the present study was to evaluate the relationship of the body mass index (BMI) with serum catalase activity, malondialdehyde (MDA), and dehydroepiandrosterone sulfate (DHEAS) levels in healthy postmenopausal women and estimate whether the MDA/DHEAS ratio is a possible marker of oxidative stress for determining cardiovascular risk in these women. Methods: We investigated serum catalase activity, MDA, and DHEAS levels, parity history, age, and BMI in 96 healthy postmenopausal women aged 50–82 years. The serum MDA levels and catalase activity were measured spectrophotometrically. The serum DHEAS levels were measured using an enzyme-linked immunosorbent assay. The ratio percentage of the serum DHEAS levels to serum MDA levels was designated as a biomarker for oxidative stress. Results: The mean BMI of the patients was 31.72 ± 6.16 kg/m2 (range = 20.5–47.94). The MDA/DHEAS ratio was significantly decreased in patients with a BMI over 30 compared to that of patients with a BMI between 25 and 30 (P = 0.025). Moreover, BMI was positively correlated with serum DHEAS levels (r = 0.285, P < 0.01) and negatively correlated with the MDA/DHEAS ratio (r = −0.241, P < 0.05) in postmenopausal women. Furthermore, BMI was observed to be a potential predictor of the MDA/DHEAS ratio based on covariance analysis (P = 0.039). Conclusions: Our results indicate that healthy, obese, postmenopausal women have a decreased MDA/DHEAS ratio. Additionally, BMI was observed to be a potential predictor of the MDA/DHEAS ratio.

Evaluation of blood neutrophil to lymphocyte and platelet to lymphocyte ratios according to plasma glucose status and serum insulin-like growth factor 1 levels in patients with acromegaly

Introduction: Cardiovascular, respiratory, and cerebrovascular diseases and malignancies are responsible for morbidity and mortality in acromegaly. Also these diseases are associated with chronic inflammation. The neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) are currently gaining interest as new markers of inflammation. Moreover, increased morbidity and mortality are positively correlated with the presence of diabetes and levels of insulin-like growth factor 1 (IGF-1) in acromegaly. The objective of the present study was to investigate the relationship between these markers and acromegaly according to plasma glucose status and serum IGF-1 levels. Materials and Methods: We retrospectively analyzed data from 61 acromegaly patients who were in a newly diagnosed period (35 male, 26 female; mean age 38.13 ± 13.98). Patients with normal plasma glucose (n = 27), impaired fasting glucose (n = 18), and diabetes mellitus (n = 16) were categorized into three different groups. NLR and PLR were compared between the study groups and were evaluated according to IGF-1 levels. Results: There were no statistically significant differences in NLR and PLR measurements among the study groups (p > 0.05). However, there were significant positive correlations between NLR and IGF-1 levels and between PLR and IGF-1 levels when all patients were evaluated (r = 0.334, p = 0.011 and r = 0.277, p = 0.035, respectively). Conclusions: This is the first report studying the relationship of NLR and PLR with glucose status and IGF-1 levels in acromegaly patients. Our study results suggest that subclinical inflammation may play a role in increased incidence of mortality and morbidity, which depends on uncontrolled IGF-1 levels in patients with acromegaly.

Glycogenic Hepatopathy in Type 1 Diabetes Mellitus.

Glycogenic hepatopathy is a rare cause of high transaminase levels in type 1 diabetes mellitus. This condition, characterized by elevated liver enzymes and hepatomegaly, is caused by irreversible and excessive accumulation of glycogen in hepatocytes. This is a case report on a 19-year-old male case, diagnosed with glycogenic hepatopathy. After the diagnosis was documented by liver biopsy, the case was put on glycemic control which led to significant decline in hepatomegaly and liver enzymes. It was emphasized that, in type 1 diabetes mellitus cases, hepatopathy should also be considered in the differential diagnoses of elevated liver enzyme and hepatomegaly.

Ocular findings in Sheehan’s syndrome

BackgroundSheehan’s syndrome (SS) is one of the most common causes of hypopituitarism. The primary effect of SS is a deficiency in production of growth hormone (GH). A number of studies have supported the association between congenital GH deficiency and ocular anomalies. However, ocular findings such as central corneal thickness (CCT), intraocular pressure (IOP), and retinal nerve fiber layer thickness (RNFLT) have not been evaluated in patients with adult GH deficiency. The objective of this study was to evaluate ocular anomalies in SS with GH deficiency under a cross-sectional design.MethodsThirty three SS patients with GH deficiency and 28 controls with no history of thyroid, adrenal, or pituitary gland diseases or surgery underwent complete hormonal and ophthalmological evaluation, including an assessment of CCTs, IOPs, and RNFLT.ResultsThe mean CCTs were significantly lower in the SS group compared with the control group (p < 0.001). There was no significant difference between patients and controls in terms of mean IOP, mean corrected IOP, and mean RNFLT (p = 0.517, p = 0.186, p = 0.965, respectively). The mean CCT was positively correlated with insulin-like growth factor 1 (IGF-1; p < 0.01) and adrenocorticotropic hormone (ACTH; p < 0.01) and negatively correlated with the corrected mean IOP (p < 0.05). In covariance analysis, IGF-1 was found to be a potential predictor of the mean CCT (p = 0.023).ConclusionsThis study is the first investigation of ocular findings in SS and adult GH deficiency. Adult GH deficiency is characterized by lower CCT values.

An Interesting Cause of Hyperandrogenemic Hirsutism

Mild clinical signs of hyperandrogenism such as hirsutism may appear during the menopausal transition as part of the normal aging process, but the development of frank virilization suggests a specific source of androgen excess. We report a case of a 68-year-old woman with signs of virilization that had started 6 months before. Clinical analyses revealed high levels of serum testosterone for a postmenopausal woman. Pelvic MRI and abdomen CT showed no evidence of ovarian and adrenal tumor. Postmenopausal hyperandrogenism can be the result of numerous etiologies ranging from normal physiologic changes to ovarian or rarely adrenal tumors. Our patient was found to have iatrogenic hyperandrogenism. This condition is rarely reported cause of virilization.