Once-Weekly Insulin Icodec With Dosing Guide App Versus Once-Daily Basal Insulin Analogues in Insulin-Naive Type 2 Diabetes (ONWARDS 5) : A Randomized Trial.

BACKGROUND: Inadequate dose titration and poor adherence to basal insulin can lead to suboptimal glycemic control in persons with type 2 diabetes (T2D). Once-weekly insulin icodec (icodec) is a basal insulin analogue that is in development and is aimed at reducing treatment burden. OBJECTIVE: To compare the effectiveness and safety of icodec titrated with a dosing guide app (icodec with app) versus once-daily basal insulin analogues (OD analogues) dosed per standard practice. DESIGN: 52-week, randomized, open-label, parallel-group, phase 3a trial with real-world elements. (ClinicalTrials.gov: NCT04760626). SETTING: 176 sites in 7 countries. PARTICIPANTS: 1085 insulin-naive adults with T2D. INTERVENTION: Icodec with app or OD analogue (insulin degludec, insulin glargine U100, or insulin glargine U300). MEASUREMENTS: The primary outcome was change in glycated hemoglobin (HbA1c) level from baseline to week 52. Secondary outcomes included patient-reported outcomes (Treatment Related Impact Measure for Diabetes [TRIM-D] compliance domain score and change in Diabetes Treatment Satisfaction Questionnaire [DTSQ] total treatment satisfaction score). RESULTS: The estimated mean change in HbA1c level from baseline to week 52 was greater with icodec with app than with OD analogues, with noninferiority (P < 0.001) and superiority (P = 0.009) confirmed in prespecified hierarchical testing (estimated treatment difference [ETD], -0.38 percentage points [95% CI, -0.66 to -0.09 percentage points]). At week 52, patient-reported outcomes were more favorable with icodec with app than with OD analogues (ETDs, 3.04 [CI, 1.28 to 4.81] for TRIM-D and 0.78 [CI, 0.10 to 1.47] for DTSQ). Rates of clinically significant or severe hypoglycemia were low and similar with both treatments. LIMITATION: Inability to differentiate the effects of icodec and the dosing guide app. CONCLUSION: Compared with OD analogues, icodec with app showed superior HbA1c reduction and improved treatment satisfaction and compliance with similarly low hypoglycemia rates. PRIMARY FUNDING SOURCE: Novo Nordisk A/S.

Capillary microarchitectural changes are independent of disease activity in acromegaly.

OBJECTIVE: Although atherosclerosis-related macrovascular complications are well known in acromegaly, studies on endothelial function and arteriolar level are contradictory. In order to test the hypothesis, microvascular changes associated with macrovascular changes in acromegaly, we aimed to evaluate microvascular changes in nailfold capillaries and carotid intima-media thickness (CIMT) in patients with acromegaly. DESIGN: In this cross-sectional observation study, of total 70 patients with acromegaly [ten (14.3 %) were active acromegaly (AA), 60 (85.7 %) were controlled acromegaly (CA)] and 74 healthy controls were enrolled. Microvascular structure was evaluated using the nailfold video capillaroscopy, and CIMT was measured using ultrasonography. RESULTS: The median number of capillaries was less [10 no./mm (min-max: 5-16) vs. 11 no./mm (min-max: 9-15); p = 0.001] in the acromegaly group than in the controls. Capillaries below 6-8 per/mm was more common in the acromegaly patients [six (8.6 %) vs. one (1.4 %); p = 0.046]. All capillaroscopic parameters were similar among the patients with CA or AA. CIMT levels were higher in the acromegaly group than in the control group [0.60 mm (0.43-0.86) vs. 0.38 mm (0.27-0.59); p < 0.001], and AA patients had higher CIMT than CA patients (p = 0.037). None of the clinical or laboratory parameters including growth hormone and IGF-1 were related to capillaroscopic parameters or CIMT. CONCLUSION: Decreased capillary number was the major capillaroscopic finding in acromegaly and there was no significant difference between active and controlled cases, but CIMT was found to be higher in the active group. Increased CIMT levels in acromegaly were not associated with capillary changes. Large-scale, prospective studies are needed to make a definite conclusion about the effect of the disease activity on nailfold capillaries and its association with macrovascular changes.

Assesment of attainment of recommended TSH levels and levothyroxine compliance in differentiated thyroid cancer patients.

OBJECTIVE: Thyroid-stimulating hormone (TSH) suppression treatment can induce signs and symptoms of hyperthyroidism and hypothyroidism due to inappropriate treatment or poor compliance to the treatment. The current study aimed to investigate TSH levels, frequency of being on target TSH, adherence to levothyroxine (LT4) suppression treatment in differentiated thyroid cancer (DTC) patients after surgery in a multicentric setting. DESIGN AND PATIENTS: This multicentric cross-sectional study was conducted at 21 medical centres from 12 cities in Turkey. DTC patients followed at least one year in the same center included in the study. Clinical data, serum TSH, free thyroxine (FT4), thyroglobulin (Tg) and anti-Tg levels were recorded during the most recent visit. Body mass index, systolic and diastolic blood pressures, pulse rate were measured. LT4 doses were recorded and doses per kilogram of bodyweight were calculated. Pill ingestion habits recorded and adherence to the therapy were evaluated using the Morisky Medication Adherence Scale and categorized as good, moderate or poor compliant based on their scores. Risk stratification forpredicting the disease persistance and/or reccurence was assessed using the American Joint Committee on Cancer-7th edition thyroid cancer staging calculator. TSH serum concentrations were classified as severe suppression (TSH < 0.01 mU/L), moderate suppression (TSH: 0.01-0.1 mU/L), mild suppression (TSHL 0.1-0.5 mU/L), euthyroid (TSH: 0.5-4 mU/L) and hypothyroid (TSH > 4 mU/L). TSH levels can also be classified as on being on target, under the target, or beyond over the target, according to the American Thyroid Association recommendations. RESULTS: A group of 1125 patients (F/M: 941/184, 50.7 ± 11.7 years) were included in the study. The mean LT4 daily dosage was 132.4 ± 39.6 mcg/day. TSH levels showed severe suppression in 99 (%8.8) patients, moderate suppression in 277 (%24.6) patients and mild suppression in 315 (%28) patients and euthyroid range in 332 (%29.5) patients and hypothyroid range in 97 (8.6%). TSH levels were in target in 29.2% of the patients 20.4% of the patients were undertreated, 50.4% overtreated. The daily LT4 dose and LT4 dose/kg were significantly higher in the severe suppression group (p < .001, p < .001). According to the Morisky scale, 564 patients (50.1%) were good compliant, 368 patients (32.7%) were moderate compliant, and 193 patients (17.1%) were noncompliant. Patients with poor compliance need a higher dose of LT4 compared to the good compliance group (p < .001). TSH levels of patients with good compliance were 0.67 ± 1.96 mU/L and TSH with poor compliance was 2.74 ± 7.47 mU/L (p < .001). TSH levels were similar in patients on fixed and alternating dosages. CONCLUSION: In 29.2% of the DTC patients, serum TSH levels were at target levels. Remaining of the study group have TSH levels under or over treatment range, exposing the patient to medication side effects. Majorty of the study group 82.8% have good or moderate adherence to LT4 therapy. Reaching TSH targets requires simplified and applicable guidelines and following the guideline recommendations.

Capillary microarchitectural changes in Cushing's syndrome.

PURPOSE: Macrovascular alterations are prominent in Cushing's syndrome (CS). Microvascular abnormalities are yet to be established. This cross-sectional observational study aimed to evaluate microvascular changes in nailfold capillaries and their association with disease status and carotid intima-media thickness (CIMT) as a marker of atherosclerosis. METHODS: A total of 70 patients with CS [46 (65.7%) ACTH-dependent pituitary adenoma and 24 (34.3%) adrenocortical adenomas] and 100 healthy controls were enrolled. The microvascular structure was evaluated using nailfold video-capillaroscopy (NVC). RESULTS: The median number of capillaries was less [10 mm (IQR: 2, min-max:7-14) vs. 11 mm (IQR: 2, min-max:9-19) (p < 0.001)], the median limb diameter and capillary width were wider in the CS group than in the controls (p = 0.016 and p = 0.002, respectively). Microhemorrhages within limited areas were more frequent in the CS group than in the controls (p = 0.046). Observed capillary changes were similar among the patients with CS with remission or active disease. CIMT levels were higher in the CS group than in the controls and similar in subjects with active disease and remission. Univariate logistic regression analyses revealed that the number of capillaries and capillary widths were associated with body mass index (BMI), the presence of type 2 diabetes mellitus, HbA1c, and CIMT. CONCLUSION: Morphologic alterations present similarly in nailfold capillaries in subjects with CS regardless of disease status, resembling changes in chronic atherosclerotic diseases. Microvascular changes in nailfold capillaries measured using NVC can be used as a marker in the assessment of cardiovascular risk in patients with CS.

Identifying Clinical Characteristics of Hypoparathyroidism in Turkey: HIPOPARATURK-NET Study.

Hypoparathyroidism is an orphan disease with ill-defined epidemiology that is subject to geographic variability. We conducted this study to assess the demographics, etiologic distribution, treatment patterns and complication frequency of patients with chronic hypoparathyroidism in Turkey. This is a retrospective, cross-sectional database study, with collaboration of 30 endocrinology centers located in 20 cities across seven geographical regions of Turkey. A total of 830 adults (mean age 49.6 ± 13.5 years; female 81.2%) with hypoparathyroidism (mean duration 9.7 ± 9.0 years) were included in the final analysis. Hypoparathyroidism was predominantly surgery-induced (n = 686, 82.6%). The insulting surgeries was carried out mostly due to benign causes in postsurgical group (SG) (n = 504, 73.5%) while patients in nonsurgical group (NSG) was most frequently classified as idiopathic (n = 103, 71.5%). The treatment was highly dependent on calcium salts (n = 771, 92.9%), calcitriol (n = 786, 94.7%) and to a lower extent cholecalciferol use (n = 635, 76.5%) while the rate of parathyroid hormone (n = 2, 0.2%) use was low. Serum calcium levels were most frequently kept in the normal range (sCa 8.5-10.5 mg/dL, n = 383, 46.1%) which might be higher than desired for this patient group. NSG had a lower mean plasma PTH concentration (6.42 ± 5.53 vs. 9.09 ± 7.08 ng/l, p < 0.0001), higher daily intake of elementary calcium (2038 ± 1214 vs. 1846 ± 1355 mg/day, p = 0.0193) and calcitriol (0.78 ± 0.39 vs. 0.69 ± 0.38 mcg/day, p = 0.0057), a higher rate of chronic renal disease (9.7% vs. 3.6%, p = 0.0017), epilepsy (6.3% vs. 1.6%, p = 0.0009), intracranial calcifications (11.8% vs. 7.3%, p < 0.0001) and cataracts (22.2% vs. 13.7%, p = 0.0096) compared to SG. In conclusion, postsurgical hypoparathyroidism is the dominant etiology of hypoparathyroidism in Turkey while the nonsurgical patients have a higher disease burden with greater need for medications and increased risk of complications than the postsurgical patients.

Does concomitant prolactin measurement increase the accuracy of inferior petrosal sinus sampling?

INTRODUCTION: Prolactin (PRL) measurement during inferior petrosal sinus sampling (IPSS) can be helpful to improve the accuracy. We aimed to evaluate the effect of measuring PRL levels as a predictor for the accuracy of IPSS and evaluate its impact on the lateralization of adenomas. METHODS: In this retrospective cohort study, we reviewed 51 patients who had undergone IPSS for the investigation of ACTH-dependent hypercortisolism. RESULTS: Forty-nine patients had proven Cushing's disease (CD), one had EAS, and the remaining one patient had adrenal adenoma. Forty-seven patients had an above 2 ACTH IPS/P ratio at baseline, and all the post-corticotropin-releasing hormone (CRH) ACTH IPS/P ratios of patients with proven CD were above 3. In these two patients whose ACTH IPS/P ratio at baseline was below 2, PRL IPS/P ratios were above 1.8 in only the dominant side, which was considered secondary to a prolactin intersinus gradient due to the biological effects of the tumor. PRL-adjusted ACTH IPS/P ratios were > 1.3 in all patients with proven CD; it was 0.7 in the patient with EAS. Surgically confirmed positive lateralization was observed in 55.1% of patients with the ACTH gradient, but when PRL-adjusted ACTH IPS/IPS ratios were used in addition to the ACTH gradient, the ratio increased to 67.3%. CONCLUSION: Although PRL-adjusted ACTH IPS/P ratios can be helpful to improve the accuracy of results during IPSS procedures, a prolactin intersinus gradient towards the ACTH-dominant side in patients with CD may invalidate PRL as an indicator of pituitary venous outflow.

Skin autofluorescence Is associated With low bone mineral density in type 2 diabetic patients.

Although the risk of bone fracture is increased in type 2 diabetes (T2DM), bone mineral density (BMD) is increased rather than decreased. Accumulation of advanced glycation end products (AGEs) adversely influences the fracture resistance of bone in T2DM. We hypothesized that SAF is also associated with BMD levels in type 2 diabetic patients and aimed to evaluate the association of SAF with BMD and the presence of osteoporosis. This cross-sectional case-control study included 237 patients with T2DM (F/M: 133/104, 56.2±11.9 yrs) and 100 age- and sex-matched controls (F/M: 70/30, 54.8±8.8 yrs). Skin autofluorescence, a validated non-invasive measure of tissue AGEs, is used to detect the accumulation of AGEs in skin collagen using AGE Reader (DiagnOptics B.V., Groningen, The Netherlands). In addition, BMD was measured with DEXA (Lunar DPX-L). Patients with T2DM had higher SAF values compared to control group (2.21±0.53 AU vs. 1.79±0.33 AU, p < 0.001). Male subjects had higher SAF compared to women (2.34±0.53 AU vs. 2.11±0.50 AU, p < 0.001). Subjects with below -2.5 femoral neck or lumbar T scores had higher SAF measurements compared to subjects with normal T scores (2.46±0.53 AU vs. 2.18±0.52 AU, p = 0.006). Femoral neck BMD was lower in subjects with T2DM (0.946±0.345 g/cm2 vs. 1.005±0.298 g/cm2, p = 0.002). There was a negative correlation between SAF and femoral neck BMD (r=-0.24, p < 0.001), femoral neck T scores (r=-0.24, p < 0.001), L1-4 BMD (r=-0.10, p = 0.005), L1-4 T score (r=-0.16, p=0.001) and a positive correlation between SAF and age (r=0.44, p < 0.001), body mass index (r:0.16, p = 0.002) and HbA1c (r=0.37, p < 0.001). Accumulation of skin AGEs was increased, and BMD levels were decreased in diabetic patients. A negative association between SAF and BMD was detected, indicating a relationship between higher AGE accumulation and low BMD and osteoporosis in diabetic patients. Long-term prospective studies are needed to identify the practical use of SAF measurement in diabetic bone disease.

Clinical predictors of incipient vertebral fractures and bone mineral density in kidney transplant patients.

PURPOSE: Kidney transplant recipients are prone to metabolic bone diseases and consequent fractures. This study aimed to evaluate the incidence of incipient vertebral fractures, osteopenia, osteoporosis, and the clinical factors associated with incipient vertebral fractures in a group of kidney transplant patients. METHODS: Two hundred sixty-four patients (F/M 124/140, 45.3 ± 13 years) who had undergone kidney transplantation in tertiary care centers were included. Vertebral fractures were assessed semiquantitatively using conventional thoracolumbar lateral radiography in 202 of the patients. RESULTS: Vertebral fractures were observed in 56.4% (n = 114) of the study group. The frequency of osteoporosis was 20.0% (53 of 264 patients), and osteopenia was 35.6% (94 of 264 patients). Bone mineral density (BMD) levels were in the normal range in 40.3% (n = 46) of the subjects with vertebral fractures. It was in the osteoporotic range in 20.1% (n = 23) and the osteopenic range in 40.3% (n = 46). Vertebral fractures were associated with age, duration of hemodialysis, BMI, and femoral neck Z score (R2 37.8%, p = 0.027). CONCLUSION: As incipient vertebral fractures can be observed in patients with normal BMD levels in kidney transplant recipients, conventional X-ray screening for vertebral fractures may be beneficial for a proper therapy decision of metabolic bone disease in kidney transplant recipients.

Morbid obesity leads to increased skin autofluorescence independent of metabolic syndrome components.

BACKGROUND: Obesity, diabetes mellitus, and metabolic syndrome (MetS) are associated with increased accumulated skin advanced glycation end products. We aimed to evaluate the association of MetS components with skin autofluorescence (SAF) in patients with morbid obesity. METHODS: Eight hundred and one patients with morbid obesity and 94 age-matched controls with normal body mass index (BMI) and normal glucose metabolism were included. Advanced glycation end products (AGEs) were measured using SAF in the forearm, with an AGE reader. RESULTS: The prevalence of MetS in patients with morbid obesity was 65.5% (n = 525). Type 2 diabetes mellitus (type 2 DM) and hypertension were present in 40.9% (n = 328) and 43.7% (n = 357). Patients with morbid obesity and those with MetS had higher SAF measurements compared with the control group, 1.85 ± 0.44 arbitrary unit (AU) and 1.86 ± 0.43 AU vs. 1.72 ± 0.30 AU, respectively (p = 0.016). There was no difference in SAF levels between patients with and without MetS. SAF measurements of patients without MetS were not statistically different from the control group (p = 0.076). Patients with five MetS criteria had higher SAF measurements compared with patients with fewer MetS components (p = 0.019). There was no difference in SAF levels between patients with type 2 DM, impaired glucose metabolism, and patients with normal glucose metabolism (p = 0.513). DISCUSSION: Although MetS and type 2 DM are known as factors related to increased SAF levels, obesity can cause elevated SAF measurements in different ways independent of concomitant comorbid diseases. Larger studies with longer follow-ups are needed to enlighten the underlying mechanism.

Is there an increased cardiovascular risk in patients with prolactinoma? A challenging question.

PURPOSE: Epicardial adipose tissue thickness (EATT) is considered to be a surrogate for visceral fat and a novel cardiovascular risk indicator. Hyperprolactinemia has been shown to be associated with increased cardiovascular risk. The aim was to evaluate the association between EATT, carotid intima media thickness (CIMT), and cardiac functions in patients with prolactinoma. METHODS: Patients with the diagnosis of prolactinoma were included. The control group consisted of healthy age matched individuals with normal prolactin levels. Prolactin, fasting blood glucose (FBG), insulin, hemoglobin A1c (HbA1c), alanine aminotransferase (ALT), total cholesterol, triglycerides, and high (HDL) and low density lipoprotein (LDL) cholesterol were measured. EATT, CIMT, cardiac systolic, and diastolic functions were determined using echocardiography. RESULTS: We evaluated 67 patients with prolactinoma (aged 40.7 ± 11.9 years, F/M: 51/16) and 57 controls (aged 42.5 ± 7.4 years, F/M: 36/21). Of the 67 patients, 24 had normal prolactin levels. FBG level was higher in prolactinoma patients than in controls. Patients and controls had similar HbA1c, HOMA-IR, ALT, total, HDL, LDL cholesterol, and triglycerides levels, and similar cardiac systolic and diastolic functions. Prolactinoma patients had greater EATT (3.0 ± 0.5 mm vs. 2.6 ± 0.4 mm, p < 0.001) and CIMT (0.57 ± 0.08 mm vs. 0.52 ± 0.04 mm, p = 0.03) than controls. EATT was correlated with body mass index, FBG, HbA1c, and triglyceride levels. CONCLUSIONS: EATT and CIMT were greater in patients with prolactinoma, although they had normal cardiac systolic and diastolic functions.

Determinants of remission in a case series of medullary thyroid carcinoma

Background/aim: We aimed to present the clinical results of patients with medullary carcinoma under follow-up in our center and to determine parameters affecting remission and lymph node metastases. Material and methods: A retrospective analysis was performed of the medical records of 27 patients with MTC who were followed up between 2004 and 2020. Results: The mean age at diagnosis was 47.7 ± 14 years. The mean follow-up was 7.29 ± 4.9 years. Metastatic neck lymphadenopathy was detected in eight (29.6%) patients; none had distant metastasis at the time of diagnosis. The median tumor diameter was 1.50 (range: 0.4­6) cm. The median postoperative calcitonin level was 3.3 (range, 0.5­871) ng/L. Relapse occurred in 2 (range, 1­14) years after the first surgery in three (11.1%) patients. In the last visit, 7 (25.9%) patients had a structural incomplete response, and three (11.1%) patients had a biochemical incomplete response. Seventeen (59.3%) patients were in remission, no patients died of MTC or any other cause. Elevated postoperative calcitonin level was a significant prognostic parameter for remission (p = 0.12) and lymph node metastasis (p < 0.001). Conclusion: Elevated postoperative calcitonin level and perithyroid soft tissue invasion were significant prognostic parameters for remission and lymph node metastasis. Postoperative calcitonin level and calcitonin doubling time should be considered for prognostic and survival risk assessments.

Practical use of insulin degludec/insulin aspart in a multinational setting: beyond the guidelines.

Insulin degludec/insulin aspart (IDegAsp) is a fixed-ratio co-formulation of insulin degludec, which provides long-lasting basal insulin coverage, and insulin aspart, which targets postprandial glycaemia. This review provides expert opinion on the practical clinical use of IDegAsp, including: dose timings relative to meals, when and how to intensify treatment from once-daily (OD) to twice-daily (BID) dose adjustments, and use in special populations (including hospitalized patients). IDegAsp could be considered as one among the choices for initiating insulin treatment, preferential to starting on basal insulin alone, particularly for people with severe hyperglycaemia and/or when postprandial hyperglycaemia is a major concern. The recommended starting dose of IDegAsp is 10 units with the most carbohydrate-rich meal(s), followed by individualized dose adjustments. Insulin doses should be titrated once weekly in two-unit steps, guided by individualized fasting plasma glucose targets and based on patient goals, preferences and hypoglycaemia risk. Options for intensification from IDegAsp OD are discussed, which should be guided by HbA1c, prandial glucose levels, meal patterns and patient preferences. Recommendations for switching to IDegAsp from basal insulin, premixed insulins OD/BID, and basal-plus/basal-bolus regimens are discussed. IDegAsp can be co-administered with other antihyperglycaemic drugs; however, sulphonylureas frequently need to be discontinued or the dose reduced, and the IDegAsp dose may need to be decreased when sodium-glucose co-transporter-2 inhibitors or glucagon-like peptide-1 receptor agonists are added. Considerations around the initiation or continuation of IDegAsp in hospitalized individuals are discussed, as well as in those undergoing medical procedures.

The role of serum E-selectin level and E-selectin gene S128R polymorphism on the enlargement of renal cyst in patients with polycystic kidney disease: Genetic background of renal cyst growth
.

BACKGROUND: To determine the role of E-selectin gene S128R polymorphism on the enlargement of renal cysts in patients with polycystic kidney disease (PKD). MATERIALS AND METHODS: 76 PKD patients with no comorbidity were enrolled in the study. Serum E-selectin levels were analyzed by enzyme-linked immunoabsorbent assay (ELISA). E-selectin gene S128R (561 A>C, rs: 5361) polymorphism was examined by polymerase chain reaction restriction fragment length (PCR-RFLP). Magnetic resonance imaging was performed at baseline evaluation and at the end of the 1st year to determine cyst enlargement and total kidney volume (TKV). RESULTS: No significant difference was identified between AA genotype and AC or CC variants of E-selectin gene S128R polymorphism in terms of age, disease duration, baseline cyst volume, cyst volume at the 12th month, baseline dominant cyst volume, and dominant cyst volume at the 12th month. In contrast, a significant difference was determined between the groups with regard to the change of TKV (2.9 ± 13.4 vs. 5.2 ± 16.3 mm3; respectively, p = 0.01). In the correlation analysis, the serum E-selectin level was significantly correlated to glucose, alanine transaminase, creatinine, calcium, phosphorus, total protein, albumin, and end diastolic volume (p = 0.0001, p = 0.001, p = 0.03, p = 0.021, p = 0.023, p = 0.002, p = 0.003, and p = 0.047, respectively). Multivariate logistic regression analysis demonstrated a 1.32-fold higher risk of cyst enlargement in patients with CC polymorphism when compared to AA genotype (p = 0.052), but not between AA and AC genotypes or CC and AC genotypes. CONCLUSION: PKD patients with CC variants of the E-selectin gene S128R polymorphism are at greater risk of cyst enlargement. The results of the present study should be confirmed with further studies with large sample size and longer duration of follow-up.

Preoperative plasmapheresis experience in Graves' disease patients with anti-thyroid drug-induced hepatotoxicity.

Hepatotoxicity is a rare but serious side effect of antithyroid drug (ATI) therapy in Graves' disease patients. Cessation of ATI drug is needed in most of the patients if liver enzymes highly elevated or in case of agranulocytosis. Permanent therapy, surgery or radioactive iodine ablation are the treatment choices to ensure euthyroidism in active Graves' disease patients. Therapeutic plasma exchange (TPE) can be an option to ensure euthyroidism, especially in patients scheduled for urgent surgery. In the present study, we present consecutive five cases of methimazole related severe hepatotoxicity that underwent TPE before thyroid surgery. The median number of apheresis sessions was 3 (range: 2-5). Free triiodothyronine (FT3) 65-83 %, free thyroxine (FT4) 22-66 %, thyrotropin receptor antibodies (TRAB) 55-96 % decreases were observed. All patients underwent total thyroidectomy. TPE is an effective method to reduce serum FT3, FT4, TRAB levels in the short term to provide better thyroid hormone status before urgent surgery in ATI induced toxic hepatitis patients.

Effects of vitamin D supplementation on insulin sensitivity and androgen levels in vitamin-D-deficient polycystic ovary syndrome patients.

AIM: The aim of this study was to identify the effects of vitamin D supplementation on insulin sensitivity and androgen levels in vitamin-D-deficient polycystic ovary syndrome (PCOS) patients. METHODS: Sixty-seven vitamin-D-deficient (25-hydroxyvitamin D [25(OH)D] levels below 20 ng/mL) PCOS patients and 54 vitamin-D-deficient non-PCOS volunteer subjects matched for age and body mass index were enrolled to this prospective study. All participants were given 50 000 IU/week cholecalciferol orally for 8 weeks and 1500 IU/day for 4 weeks. Insulin sensitivity was calculated with the Matsuda insulin sensitivity index (ISI) based on an oral glucose tolerance test. Matsuda ISI, gonadal hormones (estrogen, testosterone, androstenedione), and 25(OH)D levels were studied before and at the end of the 12th week of vitamin D load. RESULTS: After vitamin D supplementation, serum androstenedione levels had decreased significantly (P = 0.007) and Matsuda ISI values had increased significantly (P = 0.001) in the PCOS group but no significant changes were seen in those parameters in controls. We observed positive correlations between 25(OH)D levels and Matsuda ISI (r = 0.307; P < 0.01), and negative correlations between 25(OH)D levels and total testosterone (r = -0.306; P < 0.01) and androstenedione (r = -0.275; P < 0.01) levels in the PCOS group. CONCLUSION: Vitamin D supplementation increased insulin sensitivity and decreased androgen levels in vitamin-D-deficient women with PCOS but did not have any effect in vitamin-D-deficient non-PCOS women. These results may indicate the possible role of vitamin D in the complex pathogenesis of PCOS.

Determinants of low bone mineral density in premenopausal polycystic ovary syndrome patients.

OBJECTIVE: The aim of this study was to evaluate the bone mineral density (BMD) values and to determine the associations between BMD and insulin sensitivity, hyperandrogenemia, body mass index (BMI), and sex hormones in premenopausal polycystic ovary syndrome (PCOS) patients. METHODS: A hundred and three women with PCOS and sixty age- and BMI-matched healthy control women were enrolled to this cross-sectional study. Serum androgen and estradiol (E2) levels were measured. Homeostasis model assessment of insulin resistance (HOMA-IR) and MATSUDA insulin sensitivity index (ISI) were calculated. BMD was measured with a dual X-ray absorptiometer. RESULTS: Lumbar BMD (LBMD) and femoral neck BMD (FnBMD) values were significantly lower in PCOS group than controls [(p < 0.01) and (p < 0.01)]. In PCOS group, hyperandrogenemic women had higher LBMD and FnBMD values than normoandrogenemic PCOS patients [(p < 0.01) and (p < 0.01)]. In PCOS group, LBMD was significantly correlated with HOMA-IR (r = 0.617; p < 0.01), MATSUDA ISI (r = -0.665; p < 0.01), serum E2 (r = 0.488; p < 0.01), total testosterone (r = 0.436; p < 0.01), and androstenedione (r = 0.337; p < 0.01) levels. Similar correlations observed for FnBMD. CONCLUSIONS: Despite the positive effects of hyperandrogenemia and hyperinsulinemia, PCOS patients have lower bone mineral density due to hypoestrogenism. Insulin resistance, BMI, estrogen, and androgen levels are the determinants of BMD in PCOS.

Does cardiovascular risk vary according to the criteria for a diagnosis of polycystic ovary syndrome?

AIM: The risk of cardiovascular disease is higher in women with polycystic ovary syndrome (PCOS) compared to healthy individuals. Chronic inflammation, insulin resistance, hyperandrogenemia, hyperlipidemia and increased oxidative stress are known to have a role in the formation of atherosclerosis and cardiovascular disease. The aim of our study was to evaluate if cardiovascular risk varied according to different PCOS criteria, using carotid intima-media thickness (CIMT), which is an important marker of major cardiovascular events in the later stages of life. METHODS: The study group included 52 women aged 18-35 diagnosed with PCOS, and the control group comprised 45 age-matched healthy women. Body mass index, CIMT, fasting serum glucose and insulin levels and hormonal and lipid profiles were compared between the groups. RESULTS: There was no significant difference in CIMT levels between the groups. The CIMT levels in the PCOS group did not differ whether hyperandrogenism, polycystic ovary-like appearance on ultrasound or oligo/anovulation status were present or not. Furthermore, when all cases were divided into subgroups according to BMI values, the CIMT values were similar between the groups. CONCLUSION: Because PCOS and atherosclerosis both have a complex nature, it is likely that the evaluation of CIMT alone may not be sufficient to determine endothelial dysfunction in a reproductive age group.

Vitamin D Levels in Takayasu's Arteritis and a Review of the Literature on Vasculitides.

OBJECTIVE: Takayasu's arteritis (TAK) is a chronic, large-vessel vasculitis. Vitamin D, as a steroidal hormone, has recently been shown to have immunoregulatory and immunosuppressive effects. Low vitamin D levels are demonstrated in various autoimmune disorders. The aim of this study is to investigate vitamin D levels in patients with TAK. A comprehensive review of vitamin D levels in systemic vasculitides (SVs) is also performed. METHODS: The study included 36 patients with TAK, 28 patients with Behçet's disease (BD) as disease control and 30 sex-matched healthy controls. Plasma 25-hydroxy vitamin D (25(OH) vit D) levels were measured with high-performance liquid chromatography. "Deficiency" was defined as 25(OH) vit D levels below 25 nmol/l and "insufficiency" as below 50 nmol/l. RESULTS: Plasma 25(OH) vit D levels were significantly lower in TAK patients (16.93 ± 10.62 nmol/l) than healthy controls (64.63 ± 21.82 nmol/l). Vitamin D level in BD patients (38.8 ± 20.9 nmol/l) is lower than healthy controls but higher than TAK patients. The frequency of vitamin D deficiency was 83.3% in patients with TAK compared to 3.3% in healthy controls. Plasma 25(OH) vit D levels were same between clinically active and inactive patients. In literature review, very few studies were found to investigate vitamin D in SVs. CONCLUSION: We observed a high prevalence of vitamin D deficiency in patients with TAK. As various immune effects of vitamin D on mononuclear cells and arterial endothelium is shown, vitamin D deficiency can be a predisposing factor for immune activation in SV. We therefore suggest monitorization and replacement of vitamin D status in all TAK and other SV patients.

The Economic Impact of Obesity in Turkey: A Micro-Costing Analysis.

Background: Turkey currently has the highest obesity prevalence among its European counterparts. 32% and 61% of the population live with obesity and overweight, respectively. Overweight and obesity are linked to non-communicable diseases that incur incremental health and economic costs. The significant public health concern warrants an assessment of the cost of obesity. Methods: A micro-costing approach from the public payer perspective was conducted to estimate direct healthcare costs associated with ten obesity-related comorbidities (ORCs) in Turkey. Clinical practice guidelines and a systematic literature review informed ORCs and the respective cost categories. This was subsequently validated by a steering committee comprising seven experts. Seventy public sector physicians were surveyed to estimate healthcare resource use. Unit costs were derived from Social Security Institute's Healthcare Implementation Communique. Cost items were summed to determine the annual cost per patient per ORC, which was validated by the steering committee. Medical inflation was considered in a scenario analysis that varied resource unit costs. Results: Chronic kidney disease, heart failure and type 2 diabetes are the costliest ORCs, incurring an annual cost of 28,600 TRY, 16,639 TRY and 11,993 TRY, respectively. Individuals in Turkey with any ORC triggered direct healthcare costs ranging 1857-28,600 TRY annually. Costs were driven by tertiary care resources arising from treatment-related adverse events, disease complications and inpatient procedures. In the scenario analysis, medical resource unit costs were inflated by 18.7% and 39.4%, triggering an average increase in cost across all ORCs of 1998 TRY and 4210 TRY, respectively. Conclusion: Our findings confirm that obesity and its complications result in significant financial burden to the public healthcare system. By quantifying the burden of obesity across a comprehensive spectrum of ORCs, our study aims to support the economic case for investing in appropriate obesity interventions.

Comparison of staging and recurrence predictors in patients with differentiated thyroid cancer between the 7th and 8th editions of the American Joint Committee on Cancer staging systems.

BACKGROUND: The predictive value of American Joint Committee on Cancer (AJCC) 8 for recurrence in differentiated thyroid cancer (DTC) is not known. We aimed to compare AJCC 7 and 8 regarding the differences in staging and recurrence predictors in DTC. METHODS: Demographic, clinical (duration of disease and follow-up, the extent of surgery), laboratory (TSH, fT4, thyroglobulin, and antithyroglobulin), pathological (type of thyroid cancer, localization, multifocality, diameter, extrathyroidal extension [ETE], and lymph node [LN] metastasis), and imaging findings (sonography, and whole-body scan), and follow-up features (metastases, recurrence and/or persistence, and RAI need) were retrospectively analyzed in adult patients with DTC followed-up for at least six months. Staging was determined in accordance with AJCC 7 and AJCC 8, prediction of recurrence and persistence by ATA risk stratification, and death risk by AMES systems. The alterations in staging and recurrence predictors were analyzed. RESULTS: A majority of study patients (N.=524) were female (N.=424) and diagnosed with papillary cancer (N.=511), the median age at diagnosis was 44. 97.89% (N.=93) of stage 2-4 patients (N.=95) in AJCC 7 were down-staged in AJCC 8. We down-staged 41 patients of 45-55 years of age into stage 1 in AJCC 8 independent of LN status. A percentage of 26.71% of patients (N.=140) did have persistence, 9.54% (N.=50) persistence at the last follow-up, and 9.54% (N.=50) had recurrence. According to AJCC 8, T4 and AMES high risk were predictors for recurrence (hazard ratio: 3.053, P=0.023; hazard ratio:2.465, and P=0.005; respectively). Both AJCC 7 and 8 were associated with recurrence (P=0.008 and P<0.001, respectively). Stage 4 in AJCC 7, and stages 3 and 4 in AJCC 8 better predicted the probability of recurrence. CONCLUSIONS: Our findings suggest that AJCC 8 better predicted the recurrence in DTC than AJCC 7. In AJCC 8, T4 tumor, AMES high risk, stages 3 and 4 predicted recurrence. The vast majority of patients with stages 2-4 in AJCC 7 were down-staged in AJCC 8.