Deciphering the host genetic factors conferring susceptibility to severe COVID-19 using exome sequencing.

The COVID-19 pandemic remains a significant public health concern despite the new vaccines and therapeutics. The clinical course of acute SARS-CoV-2 infection is highly variable and influenced by several factors related to the virus and the host. Numerous genetic studies, including candidate gene, exome, and genome sequencing studies, genome-wide association studies, and other omics efforts, have proposed various Mendelian and non-Mendelian associations with COVID-19 course. In this study, we conducted whole-exome sequencing on 90 unvaccinated patients from Turkey with no known comorbidities associated with severe COVID-19. Of these patients, 30 had severe, 30 had moderate, and 30 had mild/asymptomatic disease. We identified rare variants in genes associated with SARS-CoV-2 susceptibility and pathogenesis, with an emphasis on genes related to the regulation of inflammation, and discussed these in the context of the clinical course of the patients. In addition, we compared the frequencies of common variants between each group. Even though no variant remained statistically significant after correction for multiple testing, we observed that certain previously associated genes and variants showed significant associations before correction. Our study contributes to the existing literature regarding the genetic susceptibility to SARS-CoV-2. Future studies would be beneficial characterizing the host genetic properties in different populations.

Atrial electromechanical delay is impaired in patients with primary hyperparathyroidism.

INTRODUCTION: Primary hyperparathyroidism (PHPT) is an endocrine disease that poses a risk for cardiac arrhythmias. Atrial electromechanical delay (EMD) has been known as an early marker of atrial fibrillation (AF). This study aimed to evaluate the atrial EMD in PHPT. MATERIAL AND METHODS: Fifty PHPT patients (45 females, 5 males) aged 30-75 years and 38 controls (35 females, 3 males) aged 31-73 years were included in the study. Atrial EMD parameters were measured by using tissue Doppler imaging (TDI). Inter-atrial EMD was calculated as the difference between PA lateral and PA tricuspid; intra-atrial EMD was calculated as the difference between PA septum and PA tricuspid, and left-atrial EMD was calculated as the difference between PA lateral and PA septum. RESULTS: Atrial EMD parameters (PA lateral, PA septum, PA tricuspid) significantly increased in the PHPT group compared to the control group (p < 0.001, for all). Also, inter-atrial and intra-atrial EMD were higher in the PHPT group than in the control group (p < 0.001, for all). In correlation analysis, calcium was closely associated with PA lateral (r = 0.749, p < 0.001), PA septum (r = 0.735, p < 0.001), inter-atrial EMD (r = 0.807, p < 0.001), and intra-atrial EMD (r = 0.838, p < 0.001). The same correlation relationship was seen between PTH levels with PA lateral (r = 671, p < 0.001), PA septum (r = 0.660, p < 0,001), inter-atrial EMD (r = 0.674, p < 0.001), and intra-atrial EMD (r = 0.732, p < 0.001). CONCLUSIONS: Atrial EMD parameters were prolonged in PHPT. The measurement of atrial EMD parameters might be used in determining the risk of AF development in PHPT.

Chromosomal and oxidative DNA damage in non-functioning pituitary adenomas.

INTRODUCTION: Clinically non-functioning pituitary adenomas (NFPA) are common tumours of the pituitary gland and are mainly considered as benign. The primary aim of this study was to research the effects of NFPA on genome instability in patients with non-functioning pituitary adenoma by using the cytokinesis-block micronucleus cytome (CBMN-cyt) assay and 8-hydroxy- 2'-deoxyguanosine (8-OHdG) assay. The second objective of this study was to assess whether there is a relationship between age, pituitary adenoma diameters, 8-OHDG levels, CBMN site assay parameters, and tumour aggressiveness. MATERIAL AND METHODS: The study was performed on 30 patients who had been diagnosed with NFPA and were admitted to the Department of Endocrinology and Metabolism, and 20 healthy subjects of similar age and sex. RESULTS: Micronucleus (MN), nucleoplasmic bridges (NPBs), nuclear bud (NBUD) frequencies, and apoptotic and necrotic cell frequencies in patients with NFPA were found to be significantly higher than in control subjects, and plasma 8-OHdG levels in patients with NFPA were statistically significantly lower than control subjects in this study. CONCLUSIONS: It is believed that this is the first study to evaluate the aggressiveness of tumour with chromosome/oxidative DNA damage in patients with NFPA. However, further studies are needed in order to understand the cause of NFPA aggression and to evaluate these patients in terms of risk of cancer.

The significance of estrogen receptors in acromegaly: Are they useful as predictors of prognosis and therapy regimen?

OBJECTIVE: In this study, we considered to assess the presence of estrogen receptors (ER) and the expression of estrogen receptor genes (ESR) in the surgical tissue samples of acromegaly patients and the control group patients with nonfunctioning adenoma and their association with disease activity. We also aimed to determine the significance of ER positivity in acromegaly patients and to find out whether it carries a potential to be used as a predictor of prognosis and therapy regimen in the future. DESIGN: This study was conducted on a total of 67 patients over 18 years of age. The study group consisted of 34 patients with acromegaly and 33 patients with nonfunctioning pituitary adenoma. The pre- and post-operative basal pituitary hormone levels and magnetic resonance images (MRI) of all patients, as well as their remission status of all acromegaly patients were evaluated. Immunohistochemical (IHC) staining procedures for ER-α were performed on surgical tissue samples. Real-time quantitative polymerase chain reaction (RT-qPCR) method was used to determine the levels of ESR1 and ESR2 gene expressions. RESULTS: We found that IHC staining for ER-α was positive in 31.3% and 45.5% of the patients with acromegaly and nonfunctioning adenoma respectively. There was no statistically significant difference of ER-α positivity, ER-α immunoreactivity score and ESR1/ESR2 gene expression levels among the study groups (p > .05). Nevertheless, the expression of ESR1 gene was found to be 0.26 times more, and the ESR2 gene to be 0.11 times less in the acromegaly group compared to those of the nonfunctioning adenoma group. Additionally, we detected the positivity of ER-α only in acromegaly patients who were in remission. An inverse association was found between the pre-operative insulin-like growth factor-1 (IGF-1) levels and the expressions of ESR1/ESR2 gene in acromegaly patients. So these results indicated that the high ESR1 and ESR2 gene expressions in acromegaly patients are associated to the decrease of pre-operative IGF-1 values. Also an inverse association was found between the pre-operative adenoma volume and ESR1 Ct values, means that increase in ESR1 gene expression is associated to the decrease of adenoma volume. CONCLUSIONS: The current results may suggest the use of these parameters as useful prognostic markers because all ER-positive acromegaly patients were in remission and the high ESR1 and ESR2 gene expressions in acromegaly patients is associated to the decrease of pre-operative IGF-1 values. Our results need to be supported by further studies.

Five variants of the superoxide dismutase genes in Turkish women with polycystic ovary syndrome.

INTRODUCTION: Polycystic ovary syndrome (PCOS) is one of the most common endocrine-reproductive-metabolic disorders of women at reproductive age. Many investigations have revealed that reactive oxygen species (ROS) level is significantly increased in patients with PCOS compared to healthy women. OBJECT: The goal of the current study is to investigate the association between superoxide dismutase (SOD) variants and the risk of PCOS among Turkish women. METHOD AND SUBJECTS: Three hundred twelve voluntary premenopausal women (148 healthy controls and 164 patients with PCOS) 18-45 years of age were include the study. All volunteers underwent physical examination and biochemical hormones evaluation. Five selected variants in SOD1 (+35 A/C (rs2234694) and SOD2 (-102 C > T, 3'UTRT > A (rs2842980), 3'UTRA > G (rs5746136), and Ala16ValC > T (rs4880) were analysed by using polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) method. RESULT: 3'UTRA > G and Ala16ValC > T variants showed significant differences between study groups. In the additive model of rs5746136 variant having AG and GG genotype increased the PCOS risk 2-fold (OR: 1.7, 95% CI: 1.08-2.77, p = 0.003) and 5-fold (OR: 5, 95% CI: 1.7-14.2,p = 0.003) compared to AA genotype, respectively. To have a GG + AG genotype increased the PCOS risk 2-fold (OR: 2.95% Cl: 1.2-3.1, p = 0.003) compared to AA genotype in "G" dominant model. In case of the "G" recessive model, having a GG genotype increased the PCOS risk 4-fold (OR: 3.8, 95% CI: 1.3-10.4, p = 0.01) compared to AA + AG genotype. The TT genotype of rs4880 showed almost 2-fold (OR: 1.8, 95% CI: 1.12-3.0) increased PCOS risk in the "T" recessive model. CONCLUSION: It is quite likely that the variants which result in decreased function in the antioxidant defence mechanism related genes contribute to PCOS aetiology with inhibiting/reducing of ROS elimination.

Is biochemical hypoglycemia necessary during an insulin tolerance test?

Objective The insulin tolerance test (ITT) has been accepted as the gold standard test for assessing the integrity of the growth hormone (GH) - insulin-like growth factor (IGF-1) axis and the hypothalamic-pituitary-adrenal (HPA) axis. The goal of the test is to achieve clinical and biochemical hypoglycemia at a blood glucose level ≤ 40 mg/dL to effectively and correctly assess the HPA and GH-IGF-1 axes. In this study, the GH and cortisol responses of patients who achieved and failed to achieve biochemical hypoglycemia during an ITT were compared. Subjects and methods One hundred thirty-five patients with pituitary disorders were included in the study. Samples for blood glucose levels were obtained after clear symptoms of clinical hypoglycemia developed. The patients were enrolled in the hypoglycemic and nonhypoglycemic groups according to whether their plasma glucose level ≤ 40 mg/dL or > 40 mg/dL during an ITT, and the groups were compared in terms of their GH and cortisol responses. Results The mean age, body mass index and waist circumference of the two patient groups were found to be similar. The mean blood glucose level was significantly lower in the hypoglycemic group than in the nonhypoglycemic group (19.3 and 52.0 mg/dL, respectively). When the two groups were compared in terms of peak cortisol and GH responses, no statistically significant differences were found. Conclusion The data presented suggest that clinically symptomatic hypoglycemia is as effective as biochemically confirmed hypoglycemia during an ITT. Arch Endocrinol Metab. 2020;64(1):82-8.

Is biochemical hypoglycemia necessary during an insulin tolerance test?

ABSTRACT Objective The insulin tolerance test (ITT) has been accepted as the gold standard test for assessing the integrity of the growth hormone (GH) - insulin-like growth factor (IGF-1) axis and the hypothalamic-pituitary-adrenal (HPA) axis. The goal of the test is to achieve clinical and biochemical hypoglycemia at a blood glucose level ≤ 40 mg/dL to effectively and correctly assess the HPA and GH-IGF-1 axes. In this study, the GH and cortisol responses of patients who achieved and failed to achieve biochemical hypoglycemia during an ITT were compared. Subjects and methods One hundred thirty-five patients with pituitary disorders were included in the study. Samples for blood glucose levels were obtained after clear symptoms of clinical hypoglycemia developed. The patients were enrolled in the hypoglycemic and nonhypoglycemic groups according to whether their plasma glucose level ≤ 40 mg/dL or > 40 mg/dL during an ITT, and the groups were compared in terms of their GH and cortisol responses. Results The mean age, body mass index and waist circumference of the two patient groups were found to be similar. The mean blood glucose level was significantly lower in the hypoglycemic group than in the nonhypoglycemic group (19.3 and 52.0 mg/dL, respectively). When the two groups were compared in terms of peak cortisol and GH responses, no statistically significant differences were found. Conclusion The data presented suggest that clinically symptomatic hypoglycemia is as effective as biochemically confirmed hypoglycemia during an ITT. Arch Endocrinol Metab. 2020;64(1):82-8

Fear of hypoglycemia in adults with diabetes mellitus switching to treatment with IDegAsp co-formulation to examine real-world setting: an observational study (The HATICE study).

OBJECTIVES: To evaluate the clinical results of insulin degludec/aspart (IDEgAsp) therapy and its effect on the fear of hypoglycemia. METHODS: A prospective observational study has been conducted through surveys of 36 patients using insulin because of type 2 diabetes mellitus who initiated treatment with IDegAsp switching from other insulins. Patients, 18-75 years old, were recruited to the study, consecutively. Participants' age, gender, height, weight, body mass index (BMI), daily insulin dose, glycated hemoglobin (HbA1c), hypoglycemia rate, hypoglycemia fear survey (HFS) were recorded at the beginning of the study. By the end of 12th month, data was re-measured and compared with each other. RESULTS: HbA1c was declined by mean of -1.59% (95% CI -1.06 to -2.12, p<0.001). There was also a significant decrease in mean, daily insulin dose, weight and BMI values of patients via IDegAsp. While there was an increase in the amount of dipeptidyl peptidase 4-inhibitors (DPP4-i) and sodium-glucose co-transporter 2-inhibitors (SGLT2-i), there was a decrease in daily injection frequency. There was also a significant decrease in the median values of monthly hypoglycemia rate (from 2.0 to 1.0, p<0.001) and the entire HFS scores (HFS-T: from 1.09 to 0.73, p<0.001; HFS-B: from 0.83 to 0.60, p<0.001; HFS-W: from 1.33 to 0.88, p<0.001). There was a strong positive correlation between ΔHFS-B and daily injection frequency (Rho: 0.398; P: 0.016). CONCLUSIONS: IDegAsp co-formulation, combined with DPP4-i and/or SGLT2-i, can provide usefulness in terms of rates of hypoglycemia, reduced HbA1c, less injection administration, and decreased the fear of hypoglycemia in diabetics.

Differences in skin lesions of endogenous and exogenous Cushing's patients.

INTRODUCTION: Cushing's syndrome is a rare condition characterized by increased glucocorticoid levels. Dermatologically, it causes a variety of skin conditions such as atrophy, striae, acne, plethora, hypertrichosis, hirsutism, acanthosis nigricans, hyperpigmentation, alopecia, purpura and fragile skin. Although skin lesions of Cushing's syndrome have been described, exogenous and endogenous types have not been studied in detail. AIM: To determine differences in possible skin lesions depending on the cause of Cushing's syndrome. MATERIAL AND METHODS: A total of 35 patients - 16 iatrogenic Cushing's syndrome patients and 19 endogenous Cushing's syndrome patients - who were diagnosed in Erciyes University and 15 healthy individuals were included in this study. RESULTS: There was at least one skin finding in 34 (97.1%) of the patients with Cushing's syndrome and 9 (60%) in the control group (p = 0.001). Comparison regarding skin findings in patient and control groups revealed that hypertrichosis, hyperpigmentation, and fungal infections were significantly more frequent in the patient group than the control group. Hirsutism was found more frequently in the endogenous group whereas stria, hypertrichosis and fungal infections were more frequent in the exogenous group. CONCLUSIONS: Since Cushing's syndrome is a rare disease and it is often diagnosed later in life, data on the frequency of skin findings are limited and sparse in the literature. In the comparison of endogenous Cushing's and exogenous Cushing's groups, acne, hypertrichosis, and fungal infections were found more frequently in the exogenous Cushing's group and hirsutism more frequently in the endogenous Cushing's group.

Evaluation of ovarian reserve in women with overt or subclinical hypothyroidism.

INTRODUCTION: Thyroid dysfunction is among the most common autoimmune disorders in women of reproductive age. Previous studies have shown the association between autoimmune thyroid disease (AITD) and infertility. Anti-Müllerian hormone (AMH) is secreted by granulosa cells and is a useful marker for assessment of ovarian reserve. In the present study, we sought to evaluate the ovarian reserves of women with autoimmune thyroid disorder by measurement of AMH values. MATERIAL AND METHODS: This prospective study included women with newly diagnosed AITD aged between 20 and 40 years. Patients were divided into three groups: subclinical hypothyroidism (SCH, n = 21), overt hypothyroidism (OH, n = 21) and controls (CG, n = 32). Study parameters included serum free T4, free T3, thyroid-stimulating hormone, anti-thyroglobulin, anti-thyroid peroxidase antibodies, follicle-stimulating hormone, luteinizing hormone, estradiol and AMH concentrations measured in the early follicular phase. Antral follicle count (AFC) was assessed with ultrasound. Body mass index (BMI) and waist circumference of the patients were noted. RESULTS: No significant difference was found among SCH, OH and CG in regard to ovarian reserves measured by AMH values (p = 0.19) and AFC (p = 0.80). A significant negative correlation was found between AMH and BMI (r = -0.382, p = 0.001). Anti-Müllerian hormone and waist circumference (r = -0.330, p = 0.004) were also negatively correlated. CONCLUSIONS: Although AMH values were not significantly different among groups, AMH values were lower in OH and SCH patients, indicating a possible need for close monitoring of these patients.

Osteoporosis and Silent Vertebral Fractures in Nursing Home Resident Elderly Men in Turkey.

Osteoporosis is an important cause of vertebral fractures and there is an increased risk for osteoporosis in nursing home residents. Most of the men with osteoporosis and osteoporotic fractures are not diagnosed and do not receive treatment. Our study aim was to determine osteoporosis and silent vertebral fracture prevalence in male nursing home residents in Corum, Turkey. This cross-sectional study included 2 groups of patients: 71 male nursing home residents (nursing home group) with a mean age of 76.0 ± 0.8 years and 44 men living in their own homes (control group) with a mean age of 74.4 ± 0.7 years. Bone mineral densitometry was performed in all subjects, and results were evaluated according to the World Health Organization criteria. Vertebral deformity was evaluated using the spinal deformity index, and fracture risk was calculated using the Fracture Risk Assessment Tool. In all participants, serum calcium, phosphorus, 25 (OH) vitamin D, parathyroid hormone, and alkaline phosphates levels were measured and medical histories were recorded. Osteoporosis was detected in 25.3% of men residing in nursing homes and in 8.8% of men living in their own homes. Silent vertebral fracture was present in 27.8% of patients older than 65 years. Vertebral fracture rate was higher in nursing home residents (42.2%) than men living in their own homes (17.6%); 5.6% of nursing home group and 8.9% of control group patients were aware of their fractures. Our results demonstrated that male nursing home residents are at a higher risk for both osteoporosis and vertebral fractures compared to the men living in their own homes.

Is Positive Staining of Non-Functioning Pituitary Adenomas for Luteinizing Hormone Associated with a Poor Prognosis?

AIM: The aim of this study was to assess the relationships among immunohistochemical staining patterns and prognostic factors in patients with non-functioning pituitary adenoma (NFPA). MATERIAL AND METHODS: The study included 103 patients who had undergone pituitary surgery for NFPAs. The prognostic factors evaluated were initial tumor size, cavernous sinus invasion, compression of the optic chiasm, recurrence, residual tissue, reoperation, and hypopituitarism. RESULTS: Recurrence rates were higher for NFPAs with large initial tumor volume and preoperative cavernous sinus invasion. Tumor recurrence rates were higher for NPFAs positive (55.6%) than negative (10.3%) for luteinizing hormone (LH). Reoperation rate, but not recurrence rate, was higher in patients with tumors positive than negative for follicle-stimulating hormone (FSH) group. Recurrence and reoperation rates were lowest in patients with null-cell adenomas. CONCLUSION: In contrast to previous studies, we observed a higher recurrence rate in LH-positive than in LH-negative adenomas. To our knowledge, this is the first study showing an association between LH positivity and poorer prognosis; and in addition, optimal outcomes in patients with null-cell adenomas. Thus, additional studies are required to assess the relationship between LH positivity and poor prognosis in patients with NFPAs.

Relationship between gestational transient thyrotoxicosis and vitamin D.

BACKGROUND/AIM: Gestational transient thyrotoxicosis (GTT) is a transient, mild hyperthyroidism that occurs early in pregnancy and is due to human chorionic gonadotropin. There is no clear information about why only some pregnant women develop GTT. Previous papers stated that vitamin D plays a role in thyroid functions. We aimed to evaluate the relationship between vitamin D and GTT. MATERIALS AND METHODS: Fifty-three patients diagnosed with GTT at the 6th to 10th weeks of gestation were included in the study (GTT group). Thirty-five pregnant women with normal thyroid-stimulating hormone (TSH), free triiodothyronine (fT3), and free thyroxine (fT4) levels served as a control group. Vitamin D, TSH, fT3, and fT4 levels were followed during entire the pregnancy. RESULTS: TSH levels had been normalized at the 20th week of gestation in all patients with GTT (mean TSH: 0.56 ± 0.2 µIU/mL). Vitamin D levels were significantly lower in the GTT group than the controls (11.1 ± 7.7 and 16.5 ± 0.5 ng/mL, respectively; P = 0.008). CONCLUSION: Pregnant women who are diagnosed with GTT should be evaluated for possible vitamin D deficiency.

The effects of statin treatment on adrenal and sexual function and nitric oxide levels in hypercholesterolemic male patients treated with a statin.

BACKGROUND: Erectile dysfunction complaints among men treated with a statin are not uncommon. OBJECTIVES: To evaluate the effect of lowering low-density lipoprotein cholesterol (LDL-C) to target levels using varying doses of atorvastatin therapy in hypercholesterolemic male patients on adrenocortical hormones, sexual functions, and serum nitric oxide (NO) levels. METHODS: Eleven hypercholesterolemic male patients who had LDL-C levels greater than 160 mg/dL were included in the study and 11 healthy male individuals served as controls. Following basal hormone measurements, 1-and 250-mcg adrenocorticotropic hormone stimulation tests were performed in both groups, and blood sampling was performed at 0, 30, and 60 minutes for the determination of blood levels of cortisol, total testosterone (TT), free testosterone (FT), 11-deoxycortisol, and dehydroepiandrostenedione. Depending on baseline LDL-C concentrations, atorvastatin therapy was given to patients with daily doses of 5 or 10 mg and the study procedures were repeated once patients reached risk stratified goal LDL-C levels. LDL-C values after treatment were classified into 3 groups as LDL-C > 160 mg/dL, LDL-C 100 to 130 mg/dL and LDL-C < 100 mg/dL. NO levels were measured at baseline and after statin therapy. Erectile function was assessed both objectively and subjectively by using penile somatosensory evoked potential (SEP) and the International Index of Erectile Function-5 Questionnaire, respectively, at 3 different LDL-C levels. RESULTS: With regard to adrenocorticotropic hormone stimulation test (1 or 250 mcg) results, peak cortisol levels before and after statin treatment among 3 LDL-C groups and among controls did not differ significantly. However, peak TT and FT hormone levels decreased in conjunction with decreasing levels of LDL-C among the statin-treated patients, whereas dehydroepiandrostenedione and 11-11-deoxycortisol peak values did not change. N1 latency obtained during SEP, which is the first negative deflection, was prolonged with decreasing levels of LDL-C and a significant decrease in International Index of Erectile Function-5 scores were observed. When LDL-C levels of ≥ 160 mg/dl was reduced to 100 to 130 mg/dl, maximal NO elevations were noted. CONCLUSIONS: Our results suggest that decreased LDL-C levels caused by different doses of atorvastatin treatment did not associate with significant changes in adrenal hormone levels. In contrast, there was a significant relationship between attained LDL-C on statin therapy and TT and FT levels. Electrophysiologically, abnormal SEP responses obtained in the patient group with LDL-C levels below 100 indicate a negative impact on the integrity of the somatosensory pathway, which plays a role in erectile function. Reducing LDL-C with a statin was associated with both decreased testosterone levels and erectile dysfunction.

Genetic expressions of thrombophilic factors in patients with Sheehan's syndrome.

PURPOSE: The aim of this study was to evaluate the roles of factors associated with coagulation in the etiology and pathogenesis of Sheehan's syndrome (SS) which is a frequent cause of hypopituitarism in underdeveloped and developing regions of the world. METHODS: Mean prothrombin time (PT), activated partial thromboplastin time (APTT) and expression levels of genes, which included methylenetetrahydrofolate reductase (MTHFR), angiotensin I converting enzyme (ACE), coagulation factor V (FV), FVII, FVIII and FIX in 44 patients with SS were compared with 43 healthy subjects. RESULTS: The mean expression level of the ACE gene was significantly lower, while that of the FV gene was significantly higher in the patients with SS. No significant difference was found between the patients with SS and the healthy subjects in the comparisons of the remaining gene expression values, as well as in the PT and APTT values. CONCLUSION: An increased expression of the FV gene may be a contributing factor for the development of SS in some patients. Further studies are required to clarify the roles of coagulation disorders in the development of SS.

Low level of Nesfatin-1 is associated with gestational diabetes mellitus.

INTRODUCTION: Gestational diabetes mellitus (GDM) occurs in ∼10-25% of pregnancies. Nesfatin-1, plays a role in carbohydrate metabolism by inhibiting glucagon secretion, besides has a glucose-dependent insulinotropic effect. Explanation of the GDM pathogenesis is important due to preventing gestational complications. We aimed to investigate relationship between GDM and Nesfatin-1. MATERIAL AND METHODS: Seventy-nine pregnant subjects were randomly allocated to either GDM group (GDG, n = 38) or control group (CG, n = 41). For GDM diagnosis, 50 and 100 g oral glucose tolerance test (OGTT) were used. Nesfatin-1, insulin and other parameters were measured for all subjects. The homeostasis model assessment-insulin resistance (HOMA-IR) was calculated. RESULTS: Nesfatin-1 was found lower and insulin was found higher in GDG than CG. Negative correlation has been founded between Nesfatin-1 with weight, BMI, fasting glucose, serum glucose level at first hour of the 50 g OGTT and HOMA-IR. CONCLUSION: In this study, patients with GDM had lower Nesfatin-1 levels than without GDM. Therefore, when the Nesfatin-1 effects on the GDM pathogenesis is clear, it may be contributed to diagnosis and treatment of the GDM.

Distribution of RET Mutations and Evaluation of Treatment Approaches in Hereditary Medullary Thyroid Carcinoma in Turkey.

OBJECTIVE: This retrospective multicenter study, centrally conducted and supported by the Society of Endocrinology and Metabolism of Turkey, aimed to evaluate the impact of free RET proto-oncogene testing in medullary thyroid carcinoma (MTC) patients. Surgical timing, adequacy of the treatment, and frequency of prophylactic thyroidectomy (PTx) in mutation carriers were also assessed. METHODS: Genetic testing for MTC and pheochromocytoma was conducted between July 2008 and January 2012 in 512 patients. Application forms and RET mutation analyses of these patients whose blood samples were sent from various centers around Turkey were assessed retrospectively. An evaluation form was sent to the physicians of the eligible 319 patients who had confirmed sporadic MTC, familial MTC (FMTC), multiple endocrine neoplasia type 2 (MEN2), or who were mutation carriers. Physicians were asked to give information about the surgical history, latest calcitonin levels, morbidity, mortality, genetic screening, and PTx among family members. Twenty-five centers responded by filling in the forms of 192 patients. RESULTS: Among the 319 patients, RET mutation was detected in 71 (22.3%). Cys634Arg mutation was the most prevalent mutation (43.7%), followed by Val804Met in 18 patients (25.4%), and Cys634Tyr in 6 patients (8.5%). Among 192 MTC patients, the diagnosis was sporadic MTC in 146 (76.4%), FMTC in 14 (7.3%), MEN2A in 15 patients (7.9%), and MEN2B in one patient. The number of mutation carriers among 154 apparently sporadic MTC patients was 8 (5.2%). Ten patients were submitted to PTx out of twenty-four mutation carriers at a mean age of 35±19 years. CONCLUSION: Turkish people have a similar RET proto-oncogene mutation distribution when compared to other Mediterranean countries. Despite free RET gene testing, the number of the PTx in Turkey is limited and relatively late in the life span of the carriers. This is mainly due to patient and family incompliance and incomplete family counselling.

Effects of Vitamin D treatment on thyroid autoimmunity.

BACKGROUND: Vitamin D was shown to be related to autoimmune thyroid diseases (AITDs) in the previous studies. We aimed to investigate the relationship between Vitamin D and thyroid autoimmunity. MATERIALS AND METHODS: Eighty-two patients, diagnosed with AITD by the endocrinology outpatient clinic, were included in this prospective study. All of the patients had both AITD and Vitamin D deficiency, defined as serum values <20 ng/mL. They were randomly assigned into two groups. The first group included 46 patients and the second one included 36 patients. The first group was treated with Vitamin D for 1 month at 1000 IU/day. The second group served as the control group and was not treated with Vitamin D replacement. Serum thyroid-stimulating hormone, free T4 (fT4), thyroid peroxidase antibody (TPO-Ab), thyroglobulin antibody (TgAb), and Vitamin D levels were measured at the initiation of the study and again at 1 month in all patients. RESULTS: Two groups were similar with regard to age, sex, and type of thyroid disease. Whereas TPO-Ab (before; 278.3 ± 218.4 IU/ml and after; 267.9 ± 200.7 IU/ml) and TgAb (before; 331.9 ± 268.1 IU/ml and after; 275.4 ± 187.3 IU/ml) levels were significantly decreased by the Vitamin D replacement therapy in group 1 (P = 0.02, P = 0.03, respectively), the evaluated parameters in the control group did not significantly change (P = 0.869, P = 0.530, respectively). In addition, thyroid function tests did not significantly change with Vitamin D replacement in two groups. CONCLUSION: Vitamin D deficiency may contribute to the pathogenesis of AITDs. Since supplementation of the Vitamin D decreased thyroid antibody titers in this study in Vitamin D deficient subjects, in the future Vitamin D may become a part of AITDs' treatment, especially in those with Vitamin D insufficiency. Further clinical and experimental studies are required to understand the effect of Vitamin D on AITD.

The role of blood groups in the development of diabetes mellitus after gestational diabetes mellitus.

INTRODUCTION: Gestational diabetes mellitus (GDM) is a common condition that is defined as glucose intolerance of varying degree with onset or first recognition during pregnancy and it affects approximately 5% of all pregnancies all over the world. GDM is not only associated with adverse pregnancy outcomes such as macrosomia, dystocia, birth trauma, and metabolic complications in newborns, but it is also a strong predictor of transitioning to overt DM postpartum. The association of ABO blood groups with DM has been observed before in several epidemiological and genetic studies and resulted with inconsistent findings, but still there are not enough studies in the literature about the association of ABO blood groups with GDM. In this study, we aimed at investigating any possible relationship between the ABO blood group system and GDM and also the transitioning of GDM to overt DM postpartum, in Turkey. PATIENTS AND METHODS: A total of 233 patients with GDM from Kayseri Training and Research Hospital between 2002 and 2012 were included in the study. The cases that have serologically determined blood groups and Rh factor in the hospital records were included in the study, and the patients with unknown blood groups were excluded. Patients were classified according to blood groups (A, B, AB, and O) and Rh status (+/-). GDM was diagnosed based on the glucose cut-points of the International Association of the Diabetes and Pregnancy Society Groups. The distributions of blood groups of the patients with GDM were compared with the distribution of blood groups of 17,314 healthy donors who were admitted to the Turkish Red Crescent Blood Service in our city in 2012. RESULTS: There was a significant difference between the patients with GDM and control group in terms of distribution of ABO blood groups. Blood group AB was found to be higher in the patients with GDM compared to the control group (P=0.029). When the patients were compared according to the development of DM, the ratio of group O was higher than others, while the ratio of group B was lower in the group developing DM (P=0.001). There was a significant difference between the groups - GDM patients with or without DM - in terms of distribution of ABO blood groups with Rh factor and the ratio of developing DM is found to be higher in patients with +Rh factor among all the blood groups except for group B (P=0.008). CONCLUSION: In this study, we found a higher risk of GDM for the patients with blood group AB, which means that we have to be more careful on the follow-up of pregnant women with blood group AB. The patients with GDM of blood group O are under a higher risk of developing DM and also +Rh factor must be considered as another risk factor, so these patients should be closely followed postpartum by the oral glucose tolerance tests. To our knowledge, this is the first analysis that investigates the association between the ABO blood groups and transitioning to DM after GDM.

Prospective investigation of the hypothalamo-pituitary-adrenal axis in patients with tularemia.

BACKGROUND/AIM: To investigate prospectively the hypothalamo-pituitary-adrenal (HPA) axis by adrenocorticotropic hormone (ACTH) stimulation test. MATERIALS AND METHODS: Tularemia was diagnosed according to guidelines. An ACTH stimulation test (1 µg) and a dexamethasone suppression test (DST; 1 mg) were performed in patients in the acute phase of tularemia before antibiotic treatment and in the chronic phase. RESULTS: Nineteen patients (mean age: 41.0 ± 13.2 years; 57.9% female) with tularemia were enrolled in the study in 2011 and 2012. Cortisol response to ACTH stimulation test was sufficient in all patients during the acute phase. After the DST, the cortisol was not suppressed during the acute phase in only one patient. The median control time of 11 patients after acute tularemia was 13 months. During the chronic phase, cortisol response to ACTH stimulation was normal in all patients, and after DST cortisol was suppressed in all patients. The peak cortisol level after the ACTH stimulation test in the acute phase was higher than that in the chronic phase, but the difference was not statistically significant. CONCLUSION: The HPA axis of patients with tularemia was not significantly affected in the acute and chronic phases.