Metabolic syndrome and Visceral Adiposity Index in non-functional adrenal adenomas

ABSTRACT Objective: We aimed to identify metabolic dysfunction in non-functioning adrenal adenomas (NFAAs) and Visceral Adiposity Index (VAI) predictability in the practical estimation of metabolic syndrome (MetS) in NFAAs. Subjects and methods: 134 NFAA patients and 68 control subjects matched for age, sex, and body mass index (BMI) were included in the study. After physical, biochemical, and endocrine evaluation, IDF and NCEP ATP III criteria were used to determine MetS. HOMA-IR and VAI were calculated for both study group subjects. Results: MetS was significantly higher in the NFAA patients. The incidence of MetS by IDF and NCEP criteria was 52.9%,48.5% in the NFAI and 32.3%,30.8% in the control group (p < 0.01, p = 0.02). The risk of MetS was increased in NFAA (75.6 vs. 24.4%, p = 0.017, OR = 1.34, 95% CI = 1.06-1.68). Glucose, HOMA IR, hypertension, and VAI were significantly increased in NFAA patients. The risk of MetS was independently associated with high VAI (79.2 vs. 20.8%, p = 0.001, OR = 2.22; 95% CI = 1.70-2.91). Conclusion: MetS, insulin resistance, and VAI are more prevalant in NFAA patients than in healthy individuals. VAI can be used with high specificity to estimate MetS in NFAA patients.

Metabolic syndrome and Visceral Adiposity Index in non-functional adrenal adenomas.

Objective: We aimed to identify metabolic dysfunction in non-functioning adrenal adenomas (NFAAs) and Visceral Adiposity Index (VAI) predictability in the practical estimation of metabolic syndrome (MetS) in NFAAs. Subjects and methods: 134 NFAA patients and 68 control subjects matched for age, sex, and body mass index (BMI) were included in the study. After physical, biochemical, and endocrine evaluation, IDF and NCEP ATP III criteria were used to determine MetS. HOMA-IR and VAI were calculated for both study group subjects. Results: MetS was significantly higher in the NFAA patients. The incidence of MetS by IDF and NCEP criteria was 52.9%,48.5% in the NFAI and 32.3%,30.8% in the control group (p < 0.01, p = 0.02). The risk of MetS was increased in NFAA (75.6 vs. 24.4%, p = 0.017, OR = 1.34, 95% CI = 1.06-1.68). Glucose, HOMA IR, hypertension, and VAI were significantly increased in NFAA patients. The risk of MetS was independently associated with high VAI (79.2 vs. 20.8%, p = 0.001, OR = 2.22; 95% CI = 1.70-2.91). Conclusion: MetS, insulin resistance, and VAI are more prevalant in NFAA patients than in healthy individuals. VAI can be used with high specificity to estimate MetS in NFAA patients.

Optical coherence tomography angiography characteristics of the retinal and optic disc morphology in prolactinoma.

PURPOSE: To investigate changes in the retinal and optic disc (OD) morphology in prolactinoma patients without optical chiasmal compression and/or visual field defects using optical coherence tomography angiography (OCTA). METHODS: In this cross-sectional imaging study, 16 consecutive prolactinoma patients (group 1, 32 eyes) and 15 age- and gender-matched healthy subjects (group 2, 30 eyes) underwent a thorough neuro-ophthalmological examination, which included testing for the presence of any intracranial compressive lesion that could cause optic neuropathy. Retinal morphological parameters, outer retinal and choriocapillaris flow areas, as well as OD vessel density (VD) and retinal nerve fiber layer (RNFL) thickness in for quadrants were then measured using OCTA. RESULTS: Mean age (p = 0.537) and gender (p = 0.385) of participants in groups 1 and 2 did not differ significantly. The mean BCVA for both groups was 0.00 ± 0.00 logMAR. Microadenomas made up the majority of prolactinomas (87.1 %). All retinal morphological parameters in deep capillary plexus (excluding foveal VD) differed significantly between groups 1 and 2 (whole: p < 0.001, parafoveal: p = 0.021, and perifoveal: p < 0.001). Peripapillary RNFL thickness in temporal (p < 0.001), nasal (p = 0.010), and inferior (p = 0.007) quadrants also differed significantly between the two groups. Foveal deep (r = -0.304, p = 0.035) and choriocapillaris flow (r = -0.511, p = 0.008) were negatively correlated with tumor size at diagnosis. CONCLUSIONS: Significant microvascular morphological changes, particularly in the deep retinal layer, as well as in the peripapillary RNFL thickness, were observed in prolactinoma patients. OCTA appears to be capable of detecting non-manifest circumpapillary and even intra-retinal microvascular changes even when there are no obvious signs of prolactinoma-related ocular complications caused by chiasmal compression.

Circulating sTweak is associated with visceral adiposity and severity in patients with obstructive sleep apnea syndrome.

Hypoxia is linked to an inflammatory imbalance in obstructive sleep apnea syndrome (OSAS). Circulating soluble tumor necrosis factor (TNF)-like weak inducer of apoptosis (sTWEAK) is a cytokine that regulates inflammation and insulin resistance in adipose tissue. This study first investigated sTWEAK concentrations in patients OSAS and evaluated associations between sTWEAK concentrations and visceral adiposity, metabolic dysfunction, and hypoxia observed in OSAS. Forty age, sex, and body mass index-matched patients with simple habitual snoring (HSS) and 70 patients with OSAS were included. Patients were divided according to OSAS severity: mild-moderate (apnea-hypopnea index, AHI 5-30 events/h) and severe (AHI ≥ 30 events/h). Anthropometric data, glucose metabolism, visceral fat (VF) ratio, and sTWEAK levels were compared. sTWEAK levels were higher in the OSAS group than in the HSS group (931.23 ± 136.48 vs. 735.22 ± 102.84 ng/L, p = 0.001). sTWEAK levels were higher in severe OSAS than in mild-moderate OSAS (1031.83 ± 146.69 vs. 891.01 ± 110.01 ng/L, p = 0.002. When we evaluated the sTWEAK value and AHI, VF ratio, total cholesterol, blood pressure, homeostasis model of assessment-insulin resistance, and high-sensitivity C-reactive protein using multiple regression analysis, a significant correlation was found between sTWEAK levels and AHI (p < 0.001). It was found that sTWEAK levels were not correlated with glucose metabolism and VF ratio. Increased circulating sTWEAK levels were associated with the severity of OSAS. High sTWEAK levels were correlated with increased AHI. sTWEAK concentrations are linked to severe OSAS.

Clinical evaluation of pituitary insufficiency in adult population

Background/aim: This retrospective study aimed to investigate the clinical profile of pituitary insufficiency (PI) in adult population. Materials and methods: One hundred and fifty patients who were diagnosed as having PI between 2012 and 2018 (53.3% female, mean age 48.13 ± 15.83 years) were retrospectively analyzed. Results: Age at diagnosis was higher in females as compared with males (51.13 ± 15.95 vs. 44.70 ± 15.08 years, P = 0.012). The most frequent presenting signs were headache (29.4%) and visual disturbance (19.6%) in general. Females frequently presented with headache (33.3%), whereas males presented with sexual dysfunction (34.4%). The most frequent cause of PI was nonfunctional pituitary adenoma (28.8%) in general population. A frequent cause of PI was Sheehan's syndrome (33.8%) among females and nonfunctional pituitary adenoma (38.6%) among males. Pituitary macroadenoma (75.8%) was frequent in pituitary tumors with PI. 55.3 % of the patients had 4 pituitary hormones deficiencies and 26.0% of patients had 3 pituitary hormones deficiencies. Gonadotropin deficiency was the leading pituitary hormone deficiency. The frequency of posttraumatic PI was 4.7% in the general population. Conclusion: Nonfunctional pituitary adenoma was the most common cause of PI among males and Sheehan's syndrome was a major etiologic factor in females. Sheehan's syndrome remains an important health problem in Turkey although obstetric care has improved. Posttraumatic PI should be considered in the differential diagnosis of idiopathic PI.

Melanocortin 3 receptor gene polymorphism is associated with polycystic ovary syndrome in Turkish population.

Polycystic ovary syndrome (PCOS) is a frequent complex disorder with an ill-defined etiology. Genetic factors seem rather effective at the occurrence of the disease, however, the evidence of established various studies results are unsatisfied. We aimed to make a contribution to the genetic baseline of the disease by investigating melanocortin 3 receptor gene polymorphism in affected patients. 101 PCOS patients and 162 age-matched healthy volunteered control subjects recruited to the study. PCOS patients classified according to their BMI class and insulin resistance situation. Anthropometric measurements, physical examination results, laboratory findings, and hormone levels were recorded for each participant and analysis of two SNPs on the MC3R gene; rs3746619 and rs3827103 were performed. Although no significant difference was observed in rs3827103 polymorphism between PCOS patients and controls; rs3746619 polymorphism was determined associated with PCOS in the heritage of dominant (AA + AC) and co-dominant (AA) genotypes. Two polymorphisms did not found related to obesity and insulin resistance in PCOS subgroups analysis. MC3R gene rs 3746619 polymorphism was found associated with PCOS in the Turkish population and may make a contribution to the genetic baseline of the disease.

Factors associated with glomerular filtration rate variation in primary hyperparathyroidism after parathyroidectomy

Background/aim: Prolonged hypercalcemia impairs renal function, and a reduced glomerular filtration rate (GFR) is typical in advanced primary hyperparathyroidism (PHPT). There are scarce data related to predictors of renal impairment in patients with PHPT. Hence, we aimed to evaluate changes in kidney function in PHPT patients after parathyroidectomy (PTX) and identify factors associated with GFR variation in these patients. Materials and methods: One hundred and twenty-five patients with PHPT who underwent surgery between 2012 and 2014 were enrolled in the study. Patients were divided into two groups according to GFR values: patients whose GFR was lower than 60 mL/min/1.73 m2 and higher than 60 mL/min/1.73 m2. Demographic and laboratory parameters were compared before and 6 months after parathyroidectomy. Results: Prevalence of antihypertensive drug users and patients with renal cysts and parathormone (PTH) and alkaline phosphatase levels were higher in patients with GFR of ≥60 than in GFR of <60 mL/min/1.73 m2 (P < 0.05). Systolic BP, uric acid, and magnesium were decreased in patients with GFR of ≥60, but GFR did not change in the two groups after parathyroidectomy. After parathyroidectomy, calcium and PTH decreased but 25(OH)D3 and phosphorus increased in the two groups. In multiple regression analysis, age, calcium, and baseline GFR were independent predictors of GFR variation. Parathyroid adenoma volume and urinary calcium were not independent predictors of GFR change. Conclusion: Olderage, higher preoperative calcium, and GFR were factors associated with GFR increase in PHPT patients after parathyroidectomy. Further renal impairment was prevented by parathyroidectomy in PHPT patients

The effect of disease activity on thyroid nodules in patients with acromegaly.

Nodular thyroid disease is a very common disorder in patients with acromegaly. Insulin-like growth factor-1 (IGF-1) is a thyroid growth factor, and there is a correlation between IGF-1 levels and thyroid volume (TV) in patients with acromegaly. There is no study investigating the impact of somatostatin analog (SSA) treatment on thyroid nodule volume in patients with acromegaly. We aimed to assess thyroid nodule volume change with SSA treatment in patients with persistent acromegaly. We retrospectively analyzed data from 108 consecutive patients with acromegaly who were followed up by our clinic after undergoing surgery between 2002 and 2014. Patients who were cured after surgery were excluded. We only selected 43 patients (21 males, 22 females, mean age 52.8 ± 11.9 years) who did not meet the criteria of remission postoperatively, who were treated with SSA for at least six months and had normal thyroid function. Patients were divided into three groups (well-controlled, controlled, and active) according to their IGF-1 and growth hormone (GH) levels. All patients underwent an evaluation of TV and total thyroid nodule volume (TTNV) by ultrasound. TTNV decreased significantly in patients with well-controlled acromegaly (0.44 [0.75] to 0.23 [0.73], p < 0.001). TTNV did not change in controlled patients (0.18 [1.28] to 0.13 [1.54], p = 0.959); however TTNV increased in patients with active acromegaly (0.77 [1.46] to 1.03 [1.88], p = 0.028). Successful medical treatment of patients with active acromegaly decreases thyroid nodule volume. Sustained exposure to IGF-1 may cause an increase in thyroid nodule volume in patients with acromegaly.

VDR gene FokI polymorphism as a poor prognostic factor for papillary thyroid cancer.

This is the first study to investigate the effect of vitamin D receptor ( VDR) gene single-nucleotide polymorphisms on the clinicopathologic features of papillary thyroid cancer in Turkey. A total of 165 patients with papillary thyroid cancer and 172 controls were included in this case-control study. VDR gene single-nucleotide polymorphisms FokI (rs2228570), BsmI (rs1544410), ApaI (rs7975232), and TaqI (rs731236) were evaluated using reverse-transcription polymerase chain reaction. VDR gene polymorphisms BsmI, ApaI, and TaqI did not differ between the papillary thyroid cancer group and control group (p > 0.05, each). BsmI, ApaI, and TaqI were not associated with papillary thyroid cancer risk. The VDR gene FokI CT/TT genotype was associated with an increased papillary thyroid cancer risk (CT vs CC: odds ratio = 1.71, 95% confidence interval = 1.15-2.76, p = 0.028; TT vs CC: odds ratio = 2.44, 95% confidence interval = 1.29-4.62, p = 0.005; CT/TT vs CC: odds ratio = 1.88, 95% confidence interval = 1.20-2.96, p = 0.006; CT/CC vs TT: odds ratio = 1.80, 95% confidence interval = 1.05-3.20, p = 0.041). VDR gene polymorphisms were not in linkage disequilibrium. The FokI TT genotype was associated with having T3 and T4, stage III/IV, extra-thyroidal invasion. The FokI CT/TT or TT genotype was associated with developing N1 status, multifocality, tumor size ≥10 mm, and treatment with radioiodine therapy. Persistence/recurrence did not differ between the FokI genotypes. Carriers of the FokI T allele were at an increased risk of more advanced tumor-node-metastasis stage, greater tumor size, multifocality, and extra-thyroidal invasion of papillary thyroid cancer compared with the CC genotype. VDR gene FokI T allele and TT genotype correlated with aggressiveness of papillary thyroid cancer; thus, FokI could be useful as a poor prognostic factor to assess the high risk of papillary thyroid cancer.

Heart-type fatty acid binding protein levels in elderly diabetics without known cardiovascular disease.

BACKGROUND: Cardiovascular disease (CVD) is reported to be higher in elderly diabetics. Serum heart-type fatty acid binding protein (H-FABP) is a serum marker of myocardial ischemia. We aimed to investigate the association between serum H-FABP level and conventional cardiovascular risk factors, inflammatory markers and subclinical atherosclerosis in elderly diabetics without overt CVD. PATIENTS AND METHODS: A total of 50 elderly diabetic patients without overt CVD and 30 age-, sex- and body mass index (BMI)-matched healthy controls were enrolled. Anthropometric and biochemical parameters, serum H-FABP, high-sensitivity C-reactive protein (hs-CRP), fibrinogen and carotid intima-media thickness (CIMT) were measured. Logistic regression analyses (adjustments for age, sex, hypertension, smoking, diabetes, BMI, blood pressure, lipid, blood glucose, hemoglobin A1c, hs-CRP and fibrinogen) were performed to evaluate the association between H-FABP and cardiovascular risk factors and atherosclerosis indices. RESULTS: Serum fibrinogen (421.50±85.52 mg/dL vs 319.17±30.77 mg/dL, p=0.023), CIMT (0.70±0.12 mm vs 0.59±0.06 mm, p<0.001) and hs-CRP (5.72±4.50 mg/dL vs 1.60±0.72 mg/dL, p<0.001) were significantly higher in diabetic patients than controls. The mean serum H-FABP level did not differ between groups (1571.79±604.60 ng/mL vs 1500.25±463.35 ng/mL, p=0.905). H-FABP was positively correlated with fibrinogen (r2=0.473, p<0.001), hs-CRP (r2=0.323, p=0.003) and CIMT (r2=0.467, p<0.001). After full adjustments, the serum H-FABP level was independently associated with an increase in the fibrinogen level (odds ratio [OR] =4.21, 95% confidence level [CI] =1.49-11.90). CONCLUSION: Serum H-FABP was similar in the elderly diabetic patients without known CVD when compared with the nondiabetic control group. H-FABP does not possess a high diagnostic value as a cardiovascular marker when used alone; however, it may add supplementary information in patients with a high fibrinogen level.

Is fibroblast growth factor 23 a new cardiovascular risk marker in gestational diabetes?

ABSTRACT Objective This study was designed to compare the serum levels of fibroblast growth factor 23 (FGF23) among patients with gestational diabetes mellitus (GDM) and healthy pregnant women, and to evaluate the association between hormonal and metabolic parameters. Subjects and methods A total of 82 pregnant women were consecutively enrolled in the study. Of these, 46 were diagnosed as having GDM; the remaining 36 healthy pregnant women served as controls in a cross-sectional study design. The womens' ages ranged from 22 to 38 years and gestational ages, from 24 to 28 weeks. Serum samples were analyzed for FGF23 levels using an enzyme-linked immunosorbent assay. Results Serum FGF23 levels were increased in patients with GDM compared with controls (median, 65.3 for patients with GDM vs. 36.6 ng/mL for healthy controls; p = 0.019). Mean fasting glucose (105.6 ± 7.4 vs. 70.2 ± 7.2 mg/dL, p < 0.001), HbA1c (5.6 ± 0.5 vs. 4.9 ± 0.5%, p < 0.001), insulin (median, 11.1 vs. 8.7 µIU/mL, p = 0.006) and HOMA-IR (3.0 (1.8) vs 1.4 (0.6), p < 0.001) levels were significantly higher in patients with GDM than in controls. Serum FGF23 level was positively correlated with body mass index (r2 = 0.346, p < 0.05), FPG (r2 = 0.264, p < 0.05), insulin (r2 = 0.388, p < 0.05), HOMA-IR (r2 = 0.384, p < 0.05). Conclusion Serum FGF23 levels were higher in women with GDM compared with controls. The present findings suggest that FGF23 could be a useful marker of cardiovascular disease in GDM.

Screening for celiac disease in poorly controlled type 2 diabetes mellitus: worth it or not?

BACKGROUND: Recent studies have demonstrated that immune factors might have a role in the pathophysiology of insulin resistance and type 2 diabetes mellitus (T2DM). Inappropriate glycemic control in patients with T2DM is an important risk factor for the occurrence of diabetes complications. The prevalence of celiac disease (CD) is high in type 1 diabetes mellitus however, there are scarce data about its prevalence in T2DM. Our aim was to investigate the prevalence of celiac disease among insulin-using type 2 diabetes patients with inappropriate glycemic control. METHODS: IgA tissue transglutaminase antibodies (tTGA IgA) test was performed as a screening test. A total of 135 patients with T2DM whose control of glycemia is inappropriate (HbAlc value >7%) in spite of using insulin treatment for at least 3-months (only insulin or insulin with oral antidiabetic drugs) and 115 healthy controls were enrolled in the study. Upper gastrointestinal endoscopy with duodenal biopsy was performed to all patients with raised tTGA IgA or selective lgA deficiency. RESULTS: Gender, age, body mass index (BMI) and tTGA IgA, kreatinin, calcium, LDL-cholesterol (LDL-C), total cholesterol, 25-OH vitamin D3 levels were similar between groups. Systolic and diastolic blood pressure, waist circumference, fasting plasma glucose, postprandial plasma glucose, urea, sodium, HbA1c, LDL-C, triglyceride, vitamin B12 levels were significantly higher in DM group (p < 0.0001). BMI, high-sensitive CRP, microalbuminuria, and AST, ALT, potassium, phosphorus levels were significantly higher in the T2DM group (p < 0.05). HDL-cholesterol and parathormone levels were significantly lower in the T2DM group (p < 0.05). Two of the 135 patients with T2DM were diagnosed with CD (1.45%). CONCLUSIONS: The prevalence of celiac disease among patients with type 2 diabetes, with poor glycemic control despite insulin therapy, is slightly higher than the actual CD prevalence in general population. Type 2 diabetic patients with inappropriate control of glycemia in spite of insulin treatment might be additionally tested for Celiac disease especially if they have low C-peptide levels.

PENTRAXIN 3 AS A NEW CARDIOVASCULAR MARKER IN ADRENAL ADENOMAS.

OBJECTIVE: Pentraxin 3 (PTX3) is an acute-phase glycoprotein, which is increased in patients with cardiovascular disease (CVD) and considered as a predictor of CVD in the general population. Both functional and nonfunctional adrenal tumors are associated with a higher risk of cardiovascular events and mortality. We aimed to investigate plasma PTX3 levels in patients with functioning and nonfunctioning adrenal tumors and determine its relationship with cardiovascular risk factors. METHODS: Twenty-one patients with functional adrenal tumors (11 pheochromocytomas, 9 Cushing syndrome, and 1 primary hyperaldosteronism), 28 patients with nonfunctional adrenal incidentalomas, and 40 healthy controls were enrolled in the study. Serum PTX3 levels were measured using a human PTX3 enzyme-linked immunosorbent assay. RESULTS: PTX3 concentrations were significantly higher in the adrenal tumor group compared with the control group (3,001.64 ± 374.64 pg/mL vs. 1,173.59 ± 168.89 pg/mL; P<.001). PTX3 concentrations were positively correlated with carotid intima media thickness (CIMT) (r2, 0.464; P<.001), high-sensitivity C-reactive protein (hsCRP) (r2, 0.551; P<.001), diastolic blood pressure (r2, 0.334; P = .003), systolic blood pressure (r2, 0.312; P = .006), and urinary metanephrine concentrations (r2, 0.320; P = .041). Serum PTX3 concentrations in patients with functional adrenal tumors and comorbidities including hypertension, diabetes mellitus, or CVD were higher than in those without comorbidities (3,654.54 ± 447 pg/mL vs. 1,026.96 ± 447.97 pg/mL; P = .008). CONCLUSION: We found that serum PTX3 concentrations increased in both functional and nonfunctional adrenal tumors. PTX3 levels were correlated with cardiovascular risk factors such as CIMT, hsCRP, and blood pressure. ABBREVIATIONS: BMI = body mass index; CIMT = carotid intima-media thickness; CRP = C-reactive protein; CT = computed tomography; CVD = cardiovascular disease; FGF2 = fibroblast growth factor 2; hsCRP = high-sensitivity C-reactive protein; PA = primary hyperaldosteronism; PTX3 = pentraxin 3.