Landscape of congenital adrenal hyperplasia cases in adult endocrinology clinics of Türkiye-a nation-wide multicentre study.

BACKGROUND AND AIMS: Congenital adrenal hyperplasia (CAH) is a group of disorders that affect the production of steroids in the adrenal gland and are inherited in an autosomal recessive pattern. The clinical and biochemical manifestations of the disorder are diverse, ranging from varying degrees of anomalies of the external genitalia to life-threatening adrenal insufficiency. This multicenter study aimed to determine the demographics, biochemical, clinical, and genetic characteristics besides the current status of adult patients with CAH nationwide. METHODS: The medical records of 223 patients with all forms of CAH were evaluated in the study, which included 19 adult endocrinology clinics. A form inquiring about demographical, etiological, and genetic (where available) data of all forms of CAH patients was filled out and returned by the centers. RESULTS: Among 223 cases 181 (81.16%) patients had 21-hydroxylase deficiency (21OHD), 27 (12.10%) had 11-beta-hydroxylase deficiency (110HD), 13 (5.82%) had 17-hydroxylase deficiency (17OHD) and 2 (0.89%) had 3-beta-hydroxysteroid-dehydrogenase deficiency. 21OHD was the most prevalent CAH form in our national series. There were 102 (56.4%) classical and 79 (43.6%) non-classical 210HD cases in our cohort. The age of the patients was 24.9 ± 6.1 (minimum-maximum: 17-44) for classical CAH patients and 30.2 ± 11.2 (minimum-maximum: 17-67). More patients in the nonclassical CAH group were married and had children. Reconstructive genital surgery was performed in 54 (78.3%) of classical CAH females and 42 (77.8%) of them had no children. Thirty-two (50.8%) NCAH cases had homogenous and 31 (49.2%) had heterogeneous CYP21A2 gene mutations. V281L pathological variation was the most prevalent mutation, it was detected in 35 (55.6%) of 21OHD NCAH patients. CONCLUSION: Our findings are compatible with the current literature except for the higher frequency of 110HD and 17OHD, which may be attributed to unidentified genetic causes. A new classification for CAH cases rather than classical and non-classical may be helpful as the disease exhibits a large clinical and biochemical continuum. Affected cases should be informed of the possible complications they may face. The study concludes that a better understanding of the clinical characteristics of patients with CAH can improve the management of the disorder in daily practice.

Assessment of osteoprotegerin and RANKL levels and several cardiovascular risk scoring systems in acromegaly.

PURPOSE: The OPG/RANKL (osteoprotegerin/receptor activator of nuclear factor kappa-B) system, which plays a crucial role in bone metabolism, is also associated with vascular calcification. Acromegaly is characterized by excessive secretion of growth hormone and insulin-like growth factor, and studies have demonstrated an elevated risk of cardiovascular disease in individuals with acromegaly. In this study, our objective was to investigate the relationship between OPG/RANKL and various cardiovascular risk scoring systems. METHODS: We recruited 44 consecutive acromegaly patients and 41 healthy controls with a similar age and gender distribution for this study. RESULTS: While RANKL levels were significantly higher in the acromegaly group compared to the controls, OPG levels were not found to be significantly different between the two groups. Furthermore, within the acromegaly group, RANKL levels were significantly higher in patients with active acromegaly compared to those with controlled acromegaly. Osteoprotegerin levels showed a positive correlation with the Framingham risk score (FRS) in the acromegaly group. Linear regression analysis revealed an association of OPG with FRS (adjusted R2 value of 21.7%). CONCLUSION: OPG and RANKL may serve as potential markers for assessment of cardiovascular calcification and prediction of the cardiovascular risk status in acromegalic patients.

An evaluation of both serum Klotho/FGF-23 and apelin-13 for detection of diabetic nephropathy.

PURPOSE: The aim of our study is to evaluate whether serum Klotho/FGF-23 and apelin-13 can be used as new biomarkers for detection of development of nephropathy. METHODS: In this cross-sectional study, 88 type 2 diabetes mellitus (T2DM) patients and 38 healthy controls were included. The mean duration of T2DM was 11.4 ± 9.7 years. T2DM individuals were categorized into two groups as group 1 with e-GFR < 60 mL/min/1.73 m2 and group 2 with e-GFR > 60 mL/min/1.73 m2. They were also divided into two groups according to their 24 h urine albumin levels, classifying them as follows: normoalbuminuria if less than 30 mg/day and albuminuria if more than 30 mg/day. RESULTS: Mean serum Klotho levels in the T2DM group were observed to be significantly higher than in the control group. Serum apelin-13 levels were observed to be significantly lower in the T2DM group compared to the control group (p < 0.001). In the diabetic group, apelin-13 levels were positively correlated with age, waist circumference, and albuminuria while they were negatively correlated with e-GFR. Apelin-13 levels were seen to be significantly higher in group 1 (p < 0.001). CONCLUSION: Apelin-13 levels were found to be significantly higher in individuals with diabetic nephropathy than in those without diabetic nephropathy. In the diabetic group, a significant relationship was detected between apelin-13 levels and albumin excretion. Based on these findings, we consider that serum Klotho and apelin-13 levels may have a protective effect on diabetic nephropathy and can additionally be used as a biomarker to predict diabetic nephropathy.

An acromegaly case treated with clomiphene citrate: add-on treatment in primary medical therapy.

INTRODUCTION: Acromegaly is a disease with various comorbidities and hypogonadism is a common comorbidity in patients with acromegaly. Herein, we aim to present our experience with clomiphene citrate in a patient with acromegaly accompanied by hypogonadism, who declined surgery. CASE REPORT: A 40-year-old male patient with impaired fasting glucose, hyperlipidemia, and psychosis and who complained of increasing tongue growth, snoring, enlargement of the hands, spacing between the teeth, and loss of libido for the last 6 years was followed up. Acromegaly was diagnosed, with high levels of insulin-like growth factor-1 (IGF-1) and a pituitary neuroendocrine tumor measuring 11 mm; the patient had concomitant hypogonadism. Lanreotide was started as the initial primary medical treatment. Clomiphene citrate was added to the patient's treatment. The patient, whose IGF-1 level was high during follow-up, did not want to use the intramuscular testosterone esters for hypogonadism. In the third month of clomiphene citrate treatment, IGF-1 normalization was achieved and the patient's total testosterone level increased. DISCUSSION: Biochemical control is not always achieved with somatostatin receptor ligands and dopamine agonists in the treatment of acromegaly. Therefore, we support the use of clomiphene citrate (CC) as a cost-effective oral add-on treatment option in selected hypogonadal acromegaly cases.

High chitotriosidase and AGE levels in acromegaly: a case-control study.

PURPOSE: Acromegaly is associated with oxidative stress and inflammation parameters. Chitotriosidase (CHITO) is a marker of macrophage activation and plays a pivotal role in the activation of inflammatory and immunological responses. Our study aimed to determine CHITO,YKL-40, advanced glycation end product (AGE), and high-sensitivity C-reactive protein (hsCRP) levels to investigate malondialdehyde (MDA), catalase, superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) activities and to evaluate any association of these parameters with carotid intima media thickness (cIMT) in patients with controlled acromegaly. METHODS: Thirty controlled acromegaly patients and 41 age- and sex-matched control cases were studied. We obtained demographic data, hormonal and metabolic parameters, and cIMT. CHITO activity was measured with the fluorometric method of Chamoles et al. YKL-40 and hsCRP levels were measured using ELISA. AGEs were measured based on spectrofluorimetric detection. GSH-Px activity was determined by a colorimetric assay. MDA, SOD, and catalase activities were determined in hemolysis. RESULTS: Higher CHITO, AGE, and hsCRP concentrations were observed in patients with acromegaly compared to controls. SOD levels were non-significantly higher in the acromegaly group, while catalase activities were lower in patients with acromegaly. Correlation analyses of CHITO, AGEs, YKL-40, hsCRP, MDA, catalase, GSH-Px, and SOD with metabolic, anthropometric, and laboratory parameters did not demonstrate any significant correlation (p > 0.05). There was no significant difference between groups with regard to cIMT levels. CONCLUSION: This is the first study investigating CHITO and AGE levels in patients with acromegaly. Serum CHITO, AGE, and hsCRP levels in acromegalic patients were significantly increased. It may be important to evaluate CHITO, AGE, and hsCRP levels in acromegalic patients who are already under cardiometabolic surveillance due to risk of developing cardiovascular disease.

Endocrine disruptor chemicals as obesogen and diabetogen: Clinical and mechanistic evidence.

Obesity is becoming an inevitable pandemic all over the world. The World Obesity Federation predicts in the 2022 World Obesity Atlas that one billion people worldwide, including 1 in 5 women and 1 in 7 men, will be living with obesity by 2030. Moreover, the prevalence of diabetes is increasing worldwide, and diabetes is becoming more of a public health problem. Increased insulin resistance due to obesity and deficiency in insulin secretion are the two main causes of type 2 diabetes mellitus (T2DM). An exogenous chemical or mixture of chemicals that interferes with any aspect of hormone action was defined as endocrine-disrupting chemicals (EDCs). Bisphenol A (BPA), the first known EDC, was synthesized and was considered to be estrogenic. Global production of BPA has increased progressively from 5 to 8 million tons (MT) between 2010 and 2016. Furthermore, researchers estimated that the production should reach 10.2 MT by 2022. The human population is exposed to EDCs in daily life in such forms as pesticides/herbicides, industrial and household products, plastics, detergents, and personal care products. The term obesogen was used for chemicals that promote weight gain and obesity by increasing the number of adipocytes and fat storage in existing adipocytes, changing the energy balance, and finally regulating appetite and satiety. Besides the obesogenic effect, EDCs can cause T2DM through alteration in ß cell function and morphology and insulin resistance. In this review, we provide clinical and mechanistic evidence regarding EDCs as obesogen and diabetogen. However, those studies are not enough methodologically to indicate causality. In this respect, randomized clinical trials are needed to investigate the association between obesogen, diabetogen and the related metabolic clinical picture.

The Importance of DHEA-S Levels in Cushing's Syndrome; Is There a Cut-off Value in the Differential Diagnosis?

The purpose of this study was to determine possible cut-off levels of basal DHEA-S percentile rank in the differential diagnosis of patients with Cushing's syndrome (CS) with ACTH levels in the gray zone and normal DHEA-S levels. In this retrospective study including 623 pathologically confirmed CS, the DHEA-S percentile rank was calculated in 389 patients with DHEA-S levels within reference interval. The patients were classified as group 1 (n=265 Cushing's disease; CD), group 2 (n=104 adrenal CS) and group 3 (n=20 ectopic ACTH syndrome).ROC-curve analyses were used to calculate the optimal cut-off level of DHEA-S percentile rank in the reference interval in the differential diagnosis of CS, and the effectiveness of this cut-off level in the identification of the accurate etiology of CS was assessed in patients who were in gray zone according to their ACTH levels. The DHEA-S percentile rank in the reference interval were significantly lower in group 2 compared to the other two groups (p<0.001), while group 1 and group 3 had similar levels. The optimal cut-off level of DHEA-S percentile rank in the reference interval providing differential diagnosis between group 1 and group 2 was calculated as 19.5th percentile (80.8% sensitivity, 81.5% specificity) and the level demonstrated the accurate etiology in 100% of CD and 76% of adrenal CS patients who were in the gray zone. This study showed that the cut-off value of DHEA-S level less than 20% of the reference interval could be used for differential diagnosis of CD and adrenal CS with high sensitivity and specificity, and it should be taken into the initial evaluation.

Probiotic kefir consumption improves serum apolipoprotein A1 levels in metabolic syndrome patients: a randomized controlled clinical trial.

Metabolic syndrome has become a major health hazard of the modern world. Studies investigating the effects of traditional fermented foods on metabolic syndrome are limited. We hypothesized that regular kefir consumption could improve the anthropometrical measurements, glycemic control, lipid profile, blood pressure, and inflammatory status in patients with metabolic syndrome. Sixty-two participants were randomly assigned to receive either 180 mL/d probiotic kefir or unfermented milk for 12 weeks. Dietary intake, anthropometrical measurements, biochemical status, and blood pressure were assessed at baseline and the end of weeks 4, 8, and 12. Serum apolipoprotein A1 concentration increased by 3.4% in the kefir group, whereas it decreased by 2.4% in the milk group in 12 weeks (P = .03). A subgroup analysis for participants with low-density lipoprotein cholesterol (LDL-C) levels >130 mg/dL showed that serum LDL-C and apolipoprotein B concentrations (7.6% and 5.4%, respectively) significantly decreased with kefir consumption compared with the baseline values at the 12th week (P < .05), but not compared with milk consumption (P > .05). Both milk and kefir consumption was associated with lower systolic and diastolic blood pressure compared with the baseline (P < .05). The 12-weeks of kefir administration also decreased serum tumor necrosis factor-α, interleukin 6, interleukin 10, interferon-gamma, and homocysteine concentrations significantly (P < .05). In conclusion, regular dairy consumption as part of a well-balanced diet can provide favorable effects in the management of metabolic syndrome, and probiotic kefir may deserve a special interest among dairy products. This trial was registered at clinicaltrials.gov (NCT03966846).

Determining the Cardiovascular Disease Risk Factor Knowledge and Related Factors Among Adults With Type 2 Diabetes Mellitus.

In this study was to determine knowledge of cardiovascular disease (CVD) risk factors and to explore related factors among adults with type 2 diabetes mellitus (DM) who have not been diagnosed with CVD. This descriptive study was conducted with 175 adults. Data were collected individual identification form and Cardiovascular Disease Risk Factors Knowledge Level (CARRF-KL) scale. A negative correlation was found between age and CARRF-KL score. A significant difference was found between educational status and CARRF-KL score. The individuals described their health status as good, managed their condition with diet and exercise, received information from nurses, adults with DM in their family and those with no DM complications had significantly higher scores in CARRF-KL. The knowledge of an individual with DM about CVD risk factors should be assessed, CVD risks should be identified at an early stage, and individuals at risk should be subjected to screening.

Two challenging cases of pituicytoma.

INTRODUCTION: Pituicytoma is a rare tumor of the pituitary gland derived from neurohypophyseal pituicytes. CASE 1: A 58-year-old female presented with decreased vision; she was admitted to the neurosurgery department of Ege University after the detection of a pituitary macroadenoma. Magnetic resonance imaging (MRI) showed a 28 * 18 * 17-mm suprasellar mass, and laboratory tests revealed hypopituitarism. Hydrocortisone and L-thyroxine treatment were initiated, and the patient underwent resection through the endoscopic endonasal approach (EEA). The histopathological examination revealed a pituicytoma. The recurrence of tumor was detected during the 1-year follow-up, and the patient is awaiting surgery. CASE 2: A 70-year-old woman presented with visual changes; she had a past medical history of hypophyseal macroadenoma and pituicytoma resected through an EEA in 2012 and 2017, respectively. During follow-up, 2 years after the second surgery, MRI showed progression of the pituicytoma then measuring 38 × 23 × 22 mm; it had invaded the cavernous sinus and was causing hydrocephaly and panhypopituitarism. The patient underwent the third resection through the transcranial approach in order to minimize bleeding. After this surgery, the patient developed diabetes insipidus and underwent treatment with desmopressin. Histopathological examination revealed a pituicytoma. At 6-month follow-up, imaging showed a sellar suprasellar mass 37 × 22 × 24 mm invading the cavernous sinus, indicative of recurrence. In the postoperative period, the patient applied to the department of radiation oncology to have fractionated radiotherapy. DISCUSSION: Pituicytomas are known to be low-grade tumors; because of their rarity, they are a real challenge. These patients should be followed up closely.

Relationship Between Serum Agouti-Related Peptide Levels and Metabolic Syndrome in Euthymic Bipolar Patients.

INTRODUCTION: Agouti-Related Peptide (AgRP) is expressed primarily in the hypothalamic arcuate nucleus, stimulates appetite and decreases metabolism and energy expenditure. The aim of our study is to evaluate the relationship between serum Agouti-Related Peptide (AgRP) levels and metabolic syndrome in euthymic bipolar patients. METHODS: Forty euthymic bipolar patients who used only mood stabilizer for at least three months and 40 healthy volunteers as control group were included in the study. We measured fasting blood glucose levels and serum levels of AgRP, total cholesterol, triglyceride, high-density lipoprotein (HDL) and low-density lipoprotein (LDL) of all participants. The main outcome measure was the difference between patients and control groups in terms of metabolic syndrome frequency and the relationship between serum AgRP level and metabolic syndrome is also investigated. RESULTS: The metabolic syndrome was significantly more common in euthymic bipolar patients than in control group (p=0.039). Additionally, levels of blood glucose and triglyceride were significantly higher in the patient group than in the control group (p=0.006 and 0.01 respectively). Serum AgRP levels did not differ between the patient and control groups (p=0.35). Also, in euthymic bipolar patients, there was no significant difference in serum AgRP levels between patients with metabolic syndrome and those without (p=0.754). CONCLUSION: We found significantly higher frequency of metabolic syndrome in euthymic bipolar patients than in the control group. However, there was no significant difference in the levels of serum AgRP between bipolar patients with and without metabolic syndrome in either study groups.

Cardiac phenotype in familial partial lipodystrophy.

OBJECTIVES: LMNA variants have been previously associated with cardiac abnormalities independent of lipodystrophy. We aimed to assess cardiac impact of familial partial lipodystrophy (FPLD) to understand the role of laminopathy in cardiac manifestations. STUDY DESIGN: Retrospective cohort study. METHODS: Clinical data from 122 patients (age range: 13-77, 101 females) with FPLD were analysed. Mature human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) from a patient with an LMNA variant were studied as proof-of-concept for future studies. RESULTS: Subjects with LMNA variants had a higher prevalence of overall cardiac events than others. The likelihood of having an arrhythmia was significantly higher in patients with LMNA variants (OR: 3.77, 95% CI: 1.45-9.83). These patients were at higher risk for atrial fibrillation or flutter (OR: 5.78, 95% CI: 1.04-32.16). The time to the first arrhythmia was significantly shorter in the LMNA group, with a higher HR of 3.52 (95% CI: 1.34-9.27). Non-codon 482 LMNA variants were more likely to be associated with cardiac events (vs. 482 LMNA: OR: 4.74, 95% CI: 1.41-15.98 for arrhythmia; OR: 17.67, 95% CI: 2.45-127.68 for atrial fibrillation or flutter; OR: 5.71, 95% CI: 1.37-23.76 for conduction disease). LMNA mutant hiPSC-CMs showed a higher frequency of spontaneous activity and shorter action potential duration. Functional syncytia of hiPSC-CMs displayed several rhythm alterations such as early afterdepolarizations, spontaneous quiescence and spontaneous tachyarrhythmia, and significantly slower recovery in chronotropic changes induced by isoproterenol exposure. CONCLUSIONS: Our results highlight the need for vigilant cardiac monitoring in FPLD, especially in patients with LMNA variants who have an increased risk of developing cardiac arrhythmias. In addition, hiPSC-CMs can be studied to understand the basic mechanisms for the arrhythmias in patients with lipodystrophy to understand the impact of specific mutations.

Magnetic resonance spectroscopy to assess hepatic steatosis in patients with lipodystrophy.

BACKGROUND/AIMS: Lipodystrophy is a rare metabolic disorder characterized by near total or partial lack of subcutaneous adipose tissue and associated with insulin resistance. We aimed to evaluate the efficacy of magnetic resonance spectroscopy imaging (MRS) to explore the fat content of the liver in patients with lipodystrophy and to determine the relationship between the liver fat accumulation and clinical presentations of lipodystrophy. MATERIALS AND METHODS: Between July 2014 and February 2016, 34 patients with lipodystrophy were assessed by MRS for quantification of hepatic steatosis. All patients had metabolic abnormalities associated with insulin resistance. Metabolic parameters and the MRS findings were analyzed to identify potential correlations between the liver fat content and disease severity. RESULTS: The MRS fat ratios (MRS-FR) were markedly higher, indicating severe hepatic steatosis in lipodystrophy. Patients with generalized and partial lipodystrophy had comparable levels of MRS-FRs, although patients with generalized lipodystrophy were significantly younger. Patients with genetically based lipodystrophy had elevated MRS-FR compared to those with acquired lipodystrophy (p=0.042). The MRS-FR was positively correlated with liver enzyme alanine aminotransferase (p=0.028) and serum adiponectin (p=0.043). CONCLUSION: Our data suggest that MRS might be an effective, noninvasive imaging method to quantify hepatic fat content in patients with lipodystrophy. Further studies are needed to validate the technique and threshold values which would allow accurate comparison of data acquired by different machines and centers.

Effects of metformin and pioglitazone combination on apoptosis and AMPK/mTOR signaling pathway in human anaplastic thyroid cancer cells.

Anaplastic cancer constitutes 1% of thyroid cancers, and it is one of the most aggressive cancers. Treatment options are external radiation therapy and/or chemotherapy. The success rate with these treatment modalities is not satisfactory. We aimed to evaluate the effects of metformin (MET) and pioglitazone (PIO) combination on apoptosis and AMP-activated protein kinase/mammalian target of rapamycin (mTOR) signaling pathway in human anaplastic thyroid cancer cells. In this study, we evaluated the effects of MET and PIO individually and the combination of the two drugs on the cellular lines SW1736 and C643 ATC. Genes contained in the mTOR signaling pathway were examined using human mTOR Signalization RT2 Profiler PCR Array. In C643 and SW1736 cell lines, IC50 doses of MET and PIO were found out as 17.69 mM, 11.64 mM, 27.12 µM, and 23.17 µM. Also, the combination of MET and PIO was determined as an additive according to isobologram analyses. We have found the downregulation of the expression levels of oncogenic genes: AKT3, CHUK, CDC42, EIF4E, HIF1A, IKBKB, ILK, MTOR, PIK3CA, PIK3CG, PLD1, PRKCA, and RICTOR genes, in the MET and PIO combination-treated cells. In addition, expression levels of tumor suppressor genes, DDIT4, DDIT4L, EIF4EBP1, EIF4EBP2, FKBP1A, FKBP8, GSK3B, MYO1C, PTEN, ULK1, and ULK2, were found to have increased significantly. The MET + PIO combination was first applied to thyroid cancer cells, and significant reductions in the level of oncogenic genes were detected. The decreases, particularly, in AKT3, DEPTOR, EIF4E, ILK, MTOR, PIK3C, and PRKCA expressions indicate that progression can be prevented in thyroid cancer cells and these genes could be selected as therapeutic targets.

Metreleptin replacement treatment improves quality of life and psychological well-being in congenital generalized lipodystrophy.

The near total lack of subcutaneous fat in congenital generalized lipodystrophy (CGL) leads to the accumulation of fat in ectopic organs and severe insulin resistance, which are associated with serious metabolic abnormalities. Cosmetic aspects of the disease are likely to affect the quality of life (QoL) and physiological well-being in these individuals. Metreleptin, recombinant human leptin, replacement treatment has been shown to have benefits in treating the metabolic abnormalities of CGL. In a patient with CGL caused by a homozygous AGPAT2 pathogenic variant, we examined QoL and mood alterations (depression and anxiety) caused by this chronic disease. Metreleptin replacement treatment led to dramatic metabolic improvement in our patient. It was also was associated with improvements in QoL, depression and anxiety scores. We suggest that there is need for studies to document the benefit of metreleptin replacement treatment on QoL and physiological well-being in patients with CGL.

Insulin secretion-sensitivity index-2 could be a novel marker in the identification of the role of pancreatic iron deposition on beta-cell function in thalassemia major.

The purpose of this study is to evaluate the impact of insulin secretion-sensitivity index-2 (ISSI-2) in the identification of the role of pancreatic iron deposition on beta-cell function in thalassemia major. Tissue iron stores were measured with magnetic resonance imaging (MRI) in the liver (R2), pancreas (R2*), and heart (T2*). ISSI-2 was assessed as a novel oral glucose tolerance test-based measure of beta-cell function. Also, the Stumvoll index showing the insulin sensitivity and Stumvoll index estimating first and second phase insulin secretion were calculated. Fourteen of the 51 Thalassemia Major patients, aged 8-34 (mean 21.1 ± 7.2) years-old, had either an impaired glucose tolerance test (n = 9, 17.6%) or diabetes mellitus (n = 5, 9.8%)-referred to as the glucose dysregulation (GD) group. The median serum ferritin and the mean liver R2 and cardiac T2* values were not significantly different between the GD and normal glucose tolerance (NGT, n = 37) groups whereas pancreas R2* was significantly higher in the GD group compared to the NGT group (p = 0.004). Patients with GD showed significantly lower ISSI-2 index (p < 0.001) as well as the Stumvoll index and Stumvoll first and second phase indices compared to those with NGT (p < 0.001). All patients with GD displayed a pancreas R2* >50 Hz and ISSI-2 <2. In conclusion, Pancreas R2* MRI combined with ISSI-2 index may be valuable parameters to identify patients at the highest risk for developing glucose dysregulation.

Effects of Regular Kefir Consumption on Gut Microbiota in Patients with Metabolic Syndrome: A Parallel-Group, Randomized, Controlled Study.

Several health-promoting effects of kefir have been suggested, however, there is limited evidence for its potential effect on gut microbiota in metabolic syndrome This study aimed to investigate the effects of regular kefir consumption on gut microbiota composition, and their relation with the components of metabolic syndrome. In a parallel-group, randomized, controlled clinical trial setting, patients with metabolic syndrome were randomized to receive 180 mL/day kefir (n = 12) or unfermented milk (n = 10) for 12 weeks. Anthropometrical measurements, blood samples, blood pressure measurements, and fecal samples were taken at the beginning and end of the study. Fasting insulin, HOMA-IR, TNF-α, IFN-γ, and systolic and diastolic blood pressure showed a significant decrease by the intervention of kefir (p ≤ 0.05, for each). However, no significant difference was obtained between the kefir and unfermented milk groups (p > 0.05 for each). Gut microbiota analysis showed that regular kefir consumption resulted in a significant increase only in the relative abundance of Actinobacteria (p = 0.023). No significant change in the relative abundance of Bacteroidetes, Proteobacteria or Verrucomicrobia by kefir consumption was obtained. Furthermore, the changes in the relative abundance of sub-phylum bacterial populations did not differ significantly between the groups (p > 0.05, for each). Kefir supplementation had favorable effects on some of the metabolic syndrome parameters, however, further investigation is needed to understand its effect on gut microbiota composition.

Therapeutic plasma exchange in hypertriglyceridemic patients

Background/aim: High triglyceride (TG) levels are associated with increases in atherosclerotic cardiovascular disease (CVD), hepatic steatosis, and pancreatitis. Acute pancreatitis is a condition with high mortality. Therapeutic plasma exchange (TPE) in the treatment of hypertriglyceridemic pancreatitis (HTGP) is a rapid and effective treatment modality. In this study, the results of TPE were evaluated and the frequency of lipoprotein lipase (LPL) mutation in these patients was determined. Materials and methods: TPE was performed in 31 patients with HTGP at the Adult Therapeutic Apheresis Center. Results: A TG level under 500 mg/dL was achieved by applying apheresis at a median of 2 times (IQR 2­2, min 1, max 6) in the 31 cases. LPL mutation was detected in 8 (25.8%) of the 31 hypertriglyceridemia cases. When TG levels before and after TPE were evaluated, the mean TG level before TPE was significantly higher (3132 ± 1472 mg/dL) than the mean TG level afterwards (948 ± 465 mg/dL, P < 0.001). This result represented a decrease of 69.7% TG after TPE. Conclusion: TPE is a safe, fast, and effective treatment modality in experienced centers.

A Distinct Clinical Phenotype in Two Siblings with X-linked Adrenoleukodystrophy.

OBJECTIVES: X-linked adrenoleukodystrophy(X-ALD) is a rare X-linked recessive metabolic disorder. The mutations in the ATP Binding Cassette Subfamily D Member 1 (ABCD1) gene account for the underlying molecular mechanism. Herein, we present two siblings with X-ALD due to a missense, presumably identical, ABCD1 mutation, who had extremely distinct clinical phenotypes. MATERIAL AND METHODS: Patient 1 (6y/o) was admitted with primary adrenal insufficiency (PAI). His VLCFA analysis and cranial MRI suggested the diagnosis of X-ALD with no cranial involvement. Although the PAI was successfully managed using hydrocortisone replacement therapy, during follow-up he was admitted with the complaints of perception impairment, seizures, loss of vision and deafness suggesting cranial involvement which was not able to be recovered despite intensive supportive therapies; in the end patient died. Patient 2 (21y/o) had mild symptoms of PAI with no organ manifestation. He was undertaken to a molecular genetics analysis for ABCD1 gene due to history of his brother. His VLCFA analysis revealed mildly elevated C26, C22 and C26/C22 ratio suggesting ALD diagnosis. However, his cranial imaging and other results were within normal limits. CONCLUSION: Two siblings with X-ALD due to presumably an identical, missense ABCD1 mutation and distinct clinical phenotype have confirmed the lack of phenotype-genotype correlation and proved the essential role of molecular genetics analysis in the early diagnosis. It is crucial to follow up for the development of cranial involvement and decide a bone marrow transplantation which is the only option that can prevent the progression of the disease, thus extend the lifespan.