Fatma Ela Keskin

Clinical presentations, metabolic abnormalities and end-organ complications in patients with familial partial lipodystrophy

OBJECTIVE Familial partial lipodystrophy (FPLD) is a rare genetic disorder characterized by partial lack of subcutaneous fat. METHODS This multicenter prospective observational study included data from 56 subjects with FPLD (18 independent Turkish families). Thirty healthy controls were enrolled for comparison. RESULTS Pathogenic variants of the LMNA gene were determined in nine families. Of those, typical exon 8 codon 482 pathogenic variants were identified in four families. Analysis of the LMNA gene also revealed exon 1 codon 47, exon 5 codon 306, exon 6 codon 349, exon 9 codon 528, and exon 11 codon 582 pathogenic variants. Analysis of the PPARG gene revealed exon 3 p.Y151C pathogenic variant in two families and exon 7 p.H477L pathogenic variant in one family. A non-pathogenic exon 5 p.R215Q variant of the LMNB2 gene was detected in another family. Five other families harbored no mutation in any of the genes sequenced. MRI studies showed slightly different fat distribution patterns among subjects with different point mutations, though it was strikingly different in subjects with LMNA p.R349W pathogenic variant. Subjects with pathogenic variants of the PPARG gene were associated with less prominent fat loss and relatively higher levels of leptin compared to those with pathogenic variants in the LMNA gene. Various metabolic abnormalities associated with insulin resistance were detected in all subjects. End-organ complications were observed. CONCLUSION We have identified various pathogenic variants scattered throughout the LMNA and PPARG genes in Turkish patients with FPLD. Phenotypic heterogeneity is remarkable in patients with LMNA pathogenic variants related to the site of missense mutations. FPLD, caused by pathogenic variants either in LMNA or PPARG is associated with metabolic abnormalities associated with insulin resistance that lead to increased morbidity.

Evaluation of cognitive functions in gestational diabetes mellitus.

OBJECTIVE To evaluate the association between cognitive functions and metabolic status in cases with gestational diabetes mellitus (GDM). METHODS In this study 44 patients with GDM and 45 normal pregnant were included. Depression was evaluated with Becks depression inventory (BDI). Cognitive functions were evaluated with Montreal cognitive assessment (MOCA), paced auditory serial addition test (PASAT), spatial recall test (SRT), symbol digit modalities (SDMT), and word list generation (WLG). RESULTS The mean gestational age, educational level and account of previous birth of the subjects in the study were not statistically different between the groups. The mean scores of BDI of the 2 groups were not statistically different. MOCA score and SDMT was significantly decreased in GDM in comparison to NP (p=0.005, p=0.04 respectively). Also, SDMT score was inversely correlated with number of pregnancies, postprandial blood glucose and HbA1c.The scores of PASAT, SRT, SPART and WLG were statistically similar between the groups. CONCLUSIONS Our findings may be a clue for early onset of impairment in cognitive functions in cases with new onset diabetes during pregnancy.

Sexual function in women with Cushing’s Syndrome: A controlled study

OBJECTIVE The aim of this study is to determine the severity of female sexual dysfunction (FSD), quality of life, and depression status in female patients with Cushings syndrome (CS). MATERIAL AND METHODS This study included 29 sexually active women with CS and 30 healthy age and body mass index matched women. The Female Sexual Function Index (FSFI) questionnaire, Beck Depression Inventory (BDI) and Short Form Health Survey (SF-36) were filled by each participant. Plasma levels of FSH, LH, PRL, cortisol, DHEA-S, 17-hydroxyprogesterone, androstenedione, free testosterone, total testosterone and estradiol were measured. RESULTS Female sexual dysfunction was present in 88.9% of the women with CS and 24.1% of the control group. The CS group showed a lower total FSFI score [16.6 (IQR: 5-23)] compared to the healthy women [26.8 (IQR: 25.5-30.4) (p<0.001)]. The FSFI scores in the arousal, lubrication, orgasm, pain and satisfaction domains were all lower in the women with CS (p<0.001). Both summary scores of the SF-36 were reduced in women with Cushings syndrome compared to the control group (p=0.001). The BDI scores of patients were significantly higher than those of the control subjects (p=0.007). In patients with CS, levels of LH, estradiol, and DHEA-S04 were significantly lower while cortisol (p<0.05), and 17 hydroxyprogestrone levels were higher than control subjects (p<0.05). CONCLUSION This study showed that majority of the women with CS had FSD. This may be related to the inhibitory effect of cortisol on sex hormones.

Germline mutations of aryl hydrocarbon receptor-interacting protein (AIP) gene and somatostatin receptor 1–5 and AIP immunostaining in patients with sporadic acromegaly with poor versus good response to somatostatin analogues

ObjectiveTo determine aryl hydrocarbon interacting protein (AIP) gene variations and AIP and somatostatin receptor (SSTR) 1–5 immunostaining in patients with apparently sporadic acromegaly with poor versus good response to somatostatin analogues (SRLs).MethodsA total of 94 patients (66 with poor and 28 with good response to SRLs) were screened for the AIP gene variations using Sanger sequencing. Immunostaining was performed in 60 tumors.ResultsSeveral variations, albeit some with undetermined significance, were detected, especially in poor responder patients. The prevalence of AIP mutation was 2.1% in the whole group and 1.5% in patients with poor response to SRLs. AIP, SSTR2A, and SSTR2B immunostainings were decreased in patients with poor response (p < 0.05 for all), and other SSTRs did not differ between the groups (p > 0.05 for all). Patients with low AIP had decreased levels of SSTR2A and SSTR3 (p < 0.05 for all). AIP and SSTR2A immunostainings were positively correlated to the treatment response and age at diagnosis was negatively correlated (p < 0.05 for all). In poor responder patients with high SSTR2A immunostaining, SSTR2B immunostaining and preoperative tumor size were positively and negatively correlated, respectively, to SRL response (p < 0.05 for all).ConclusionsLack of response to SRLs does not necessarily increase the risk of harboring AIP mutations. The finding of decreased AIP, SSTR2A, and SSTR2B immunostaining in patients with poor response to SRLs and decreased SSTR2A and SSTR3 level in those with low AIP immunostaining suggests a possible interaction between AIP and some SSTR subtypes that might alter SRL sensitivity.

The Role of Different Molecular Markers in Papillary Thyroid Cancer Patients with Acromegaly

PURPOSE Prevalence of papillary thyroid cancer (PTC) is increased in patients with acromegaly. We aimed to determine the protein expression of BRAF, RAS, RET, insulin like growth factor 1(IGF1), Galectine 3, CD56 in patients with PTC related acromegaly and to compare the extensity of these expressions with normal PTC patients and benign thyroid nodules. METHODS We studied 313 patients with acromegaly followed in Cerrahpasa Medical Faculty, Endocrinology and Metabolism Clinic between 1998 and 2015. On the basis of availability of pathological specimen of thyroid tissues, thyroid samples of 13 patients from 19 with acromegaly related PTC (APTC), 20 normal PTC and 20 patients with multinodulary goiter (MNG) were histopathologically evaluated. Protein expressions were determined via immunohistochemical staining in ex-vivo tumor samples and benign nodules. RESULTS The incidence of PTC in acromegaly patients were 6% (n=19). Among patients with PTC, APTC and MNG, all the immunohistochemical protein expressions we have studied were higher in papillary thyroid cancer groups (p<0.01, for all). Between PTC group without acromegaly and APTC, galectin 3 and IGF1 expression was significantly higher in acromegalic patients (p<0.01 for all) while RAS was predominantly higher in PTC patients without acromegaly (p<0.01). CONCLUSION BRAF expression was not higher in PTC with acromegaly patients compared to PTC patients without acromegaly. Galectine 3 and IGF1 were expressed more intensively in APTC. These positive protein expressions may have more influence on determining malign nodules among acromegaly patients.

Renal complications of lipodystrophy: A closer look at the natural history of kidney disease

Lipodystrophy syndromes are a group of heterogeneous disorders characterized by adipose tissue loss. Proteinuria is a remarkable finding in previous reports.

Determinants of glucose metabolism and the role of NPY in the progression of insulin resistance in chronic migraine

Background Chronic migraine has a well-documented association with increased insulin resistance and metabolic syndrome. The hypothalamus may play a role in the progression of insulin resistance in chronic migraine through the regulation of orexigenic peptides such as neuropeptide Y. Insulin resistance may lead to increased risk of future type 2 diabetes mellitus in patients with chronic migraine, which is more likely to occur if other pathogenetic defects of type 2 diabetes mellitus, such as impaired pancreatic β-cell functions and defects in intestinal glucagon-like peptide-1 secretion after meals. We studied the relationship of fasting neuropeptide Y with insulin resistance, β-cell function, and glucagon-like peptide-1 secretion in non-obese female chronic migraine patients. We also aimed to investigate glucose-stimulated insulin and glucagon-like peptide-1 secretions as early pathogenetic mechanisms responsible for the development of carbohydrate intolerance. Methods In this cross-sectional controlled study, 83 non-obese female migraine patients of reproductive age categorized as having episodic migraine or chronic migraine were included. The control group consisted of 36 healthy females. We studied glucose-stimulated insulin and glucagon-like peptide-1 secretion during a 75 g oral glucose tolerance test. We investigated the relationship of neuropeptide Y levels with insulin resistance and β-cell insulin secretion functions. Results Fasting glucose levels were significantly higher in migraine patients. Plasma glucose and insulin levels during the oral glucose tolerance test were otherwise similar in chronic migraine, episodic migraine and controls. Patients with chronic migraine were more insulin resistant than episodic migraine or controls (p = 0.048). Glucagon-like peptide-1 levels both at fasting and two hours after glucose intake were similar in chronic migraine, episodic migraine, and controls. Neuropeptide Y levels were higher in migraineurs. In chronic migraine, neuropeptide Y was positively correlated with fasting glucagon-like peptide-1 levels (r = 0.57, p = 0.04), but there was no correlation with insulin resistance (r = 0.49, p = 0.09) or β-cell function (r = 0.50, p = 0.07). Discussion Non-obese premenopausal female patients with chronic migraine have higher insulin resistance, but normal β-cell function is to compensate for the increased insulin demand during fasting and after glucose intake. Increased fasting neuropeptide Y levels in migraine may be a factor leading to increased insulin resistance by specific alterations in energy intake and activation of the sympathoadrenal system.

Mucosal gastric calcinosis in a hypocalcaemic patient

1Department of Internal Medicine, Cerrahpaşa Medical Faculty, Istanbul University, Istanbul, Turkey 2Department of Gastroenterology, Cerrahpasa Medical Faculty, Istanbul University, Istanbul, Turkey 3Department of Pathology, Cerrahpasa Medical Faculty, Istanbul University, Istanbul, Turkey 4Department of Internal Medicine Endocrinology, Cerrahpaşa Medical Faculty, Istanbul University, Istanbul, Turkey

LATE-NIGHT SALIVARY CORTISOL IS UNALTERED IN PATIENTS WITH POLYCYSTIC OVARIAN SYNDROME (PCOS), IRRESPECTIVE OF DISEASE PHENOTYPE, AND IN OBESE WOMEN, IRRESPECTIVE OF THE PRESENCE OF PCOS

OBJECTIVE To determine cutoff values of late-night salivary cortisol (LNSC) using an electrochemiluminescent immunoassay and investigate whether the diagnostic performance of the assay is influenced by the presence of obesity or polycystic ovary syndrome (PCOS). METHODS A total of 124 subjects comprising 25 patients with Cushing syndrome (CS), 44 with PCOS (22 nonobese and 22 obese), 21 with constitutional obesity (CO), and 34 healthy subjects (HS) were included in the study. Two consecutive LNSC samples were collected from all participants. RESULTS The median LNSC levels of patients with CS were significantly higher than LNSC levels of HS, patients with CO, and obese and nonobese patients with PCOS, respectively (P<.01 for all). Healthy subjects, patients with CO, and obese and nonobese patients with PCOS did not differ in terms of median LNSC levels (P>.05 for all). The cutoff values and corresponding sensitivity and specificity were similar between the groups. The comparisons of the area under curve of the first LNSC (0.963; 95% confidence interval [CI], 0.910 to 0.989), second LNSC (0.954; 95% CI, 0.898 to 0.984), and the mean of two consecutive LNSC (mLNSC) values (0.962; 95% CI, 0.909 to 0.989) did not differ significantly (P>.05 for all). A cutoff value for mLNSC of 7.45 nmol/L yielded a sensitivity of 100% and specificity of 87.5% in HS. CONCLUSION In conclusion, LNSC is a reliable test with high diagnostic accuracy in both HS and patients with PCOS and obesity. ABBREVIATIONS ACTH = adrenocorticotropic hormone AUC = area under the curve BMI = body mass index CO = constitutional obesity CS = Cushing syndrome E2 = estradiol ECLIA = electrochemiluminescent immunoassay FPG = fasting plasma glucose FSH = follicle-stimulating hormone HOMA-IR = homeostasis model assessment of insulin resistance HPA = hypothalamo-pituitary-adrenal HS = healthy subjects IQR = interquartile range LH = luteinizing hormone LNSC = late-night salivary cortisol LR = likelihood ratio mLNSC = mean of two consecutive LNSC samples PCOS = polycystic ovarian syndrome ROC = receiver operating characteristic UFC = urinary free cortisol WHR = waist-to-hip ratio.