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.

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.

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.

Effect of endothelial dysfunction on the pathogenesis of urolithiasis in patients with metabolic syndrome.

OBJECTIVE: The aim of the present prospective clinical study was to investigate the possible effect of endothelial dysfunction in urolithiasis. METHODS: The study included 92 patients older than 18 years. The patients were divided into 4 groups with 23 patients each as group 1: metabolic sydrome (MetS) (-) stone disease (SD) (-), group 2: MetS (-) SD (+), group 3: MetS (+) SD (-) and group 4: MetS (+) SD (+). C-reactive protein, homocysteine, uric acid, and creatinine levels were evaluated between the groups. Endothelial (dys)function was evaluated based on the brachial artery flow-mediated dilation (FMD) measurement. RESULTS: The mean age was 41.9 ± 10.2 (range, 18-62) years. Mean FMD value was 15.9 ± 18.2% (range, 24.0-68.5%). A strong significant difference was found between group 1 and 2 (p < .001); group 1 and 3 (p < .001) and group 1 and 4 (p < .001) with regard to FMD. CONCLUSION: These results suggest that endothelial dysfunction plays an important role in the pathogenesis of urolithiasis in patients with MetS.

Does Primary Hyperparathyroidism Have an Association with Thyroid Papillary Cancer? A Retrospective Cohort Study.

BACKGROUND: To investigate the relationship between primary hyperparathyroidism (pHPT) and papillary thyroid cancer (PTC). METHODS: The perioperative findings of 275 patients with pHPT who underwent surgery between January 2014 and December 2017 were retrospectively reviewed. Thirty-one patients were diagnosed with pHPT and PTC concurrently. Pathology results and demographic findings of these patients were compared with 186 patients who underwent thyroidectomy and diagnosed with PTC at the same time interval. RESULTS: The co-occurrence of pHPT and PTC was 11.3% (31/275). The median ages of the pHPT, pHPT + PTC, and PTC groups were 55, 57, and 50 years old, respectively (p < 0.001). The diameter of tumor was smaller in the pHPT + PTC group [median 7 mm (range 0.5-25 mm) vs. 15 mm (range 1-100 mm)], with higher rates of microcarcinomas (p < 0.001), than the patients in the PTC group. Examination of tumor morphology showed higher rates of tumor capsule invasion and multicentricity in the pHPT + PTC group than those in the isolated PTC group (p = 0.02, p = 0.04, respectively). CONCLUSION: The pHPT + PTC group had significantly smaller tumor diameter than the PTC group. This result may support the idea that pHPT leads to overdiagnosis of PTC. However, observation of high rates of tumor capsule invasion and multicentricity in the pHPT + PTC group may suggest an associative etiology with more aggressive PTC.

Dehydroepiandrosterone sulfate/free androgen index ratio predicts a favorable metabolic profile in patients with polycystic ovary syndrome.

Potential effect of hyperandrogenemia on metabolic disturbances in polycystic ovary syndrome (PCOS) has always been a matter of interest. We analyzed the records of 125 patients with PCOS and 54 age-matched healthy women. All participants underwent biochemical and hormonal assessment and a 75 g oral glucose tolerance test was performed. PCOS and control groups were comparable in terms of age. Dehydroepiandrosterone sulfate/free androgen index (DHEAS/FAI) ratio was negatively correlated with body mass index (BMI) (p < .001), fasting glucose (p = .02), area under the curve (AUC) of glucose (p = .03), AUC of insulin (p = .001), homeostasis model assessment-estimated insulin resistance (HOMA-IR) (p < .001), and triglycerides (TG) (p = .009), and positively correlated with insulin sensitivity index (ISI) (p < .001) and high-density lipoprotein cholesterol (HDL-C) (p < .001) among PCOS patients. In logistic regression analysis, higher DHEAS/FAI ratio levels were associated with lower risk of low HDL-C [RR(95%CI); 0.97(0.95-0.98); p < .001] as well as atherogenic dyslipidemia (TG/HDL-C) [RR(95%CI); 0.97(0.94-0.99); p = .035] even after adjustment for BMI in the PCOS group. Androgens, DHEAS and FAI act differently on metabolic parameters. Our results demonstrate that high DHEA-S/FAI ratio levels are associated with a more favorable metabolic profile.

Thyroid volumes and serum VEGF levels in dyslipidemic patients: effects of statin treatment

Background/aim: Defective vascularization may be important in thyroid nodular disease. In this study, we aimed to investigate serum vascular endothelial growth factor (VEGF) levels in dyslipidemic patients with thyroid nodules, as well as the effects of statin therapy Materials and methods: The study included 37 dyslipidemic patients with thyroid nodules and 32 dyslipidemic patients without thyroid nodules. Anthropometry, serum VEGF levels, biochemical parameters, thyroid-stimulating hormone (TSH), free triiodothyronine (fT3) and free thyroxine (fT4) levels, and thyroid sonography were determined before and after 6 months of statin therapy. Results: Patients with and without thyroid nodules had similar metabolic parameters. Serum VEGF levels did not differ between the groups. In patients with nodules, VEGF levels remained unchanged (P = 0.931) after statin therapy. However, serum VEGF levels were lowered by statin treatment in patients without nodules (P = 0.030). Statin therapy resulted in a decrease in the dominant thyroid nodule volume. The changes in thyroid volume and dominant thyroid nodule volume were not correlated with changes in VEGF, body mass index, total cholesterol, low-density lipoprotein cholesterol, or homeostatic model assessment of insulin resistance (HOMA-IR). Conclusion: Although statin treatment decreases serum VEGF levels in dyslipidemic patients without thyroid nodules, it has no lowering effect on serum VEGF levels in patients with thyroid nodules. The decrease in thyroid nodule volume with statin treatment was associated with neither metabolic parameters nor serum VEGF levels.

PERCUTANEOUS ETHANOL INJECTION FOR BENIGN CYSTIC AND MIXED THYROID NODULES.

OBJECTIVE: We aimed to determine the effect of percutaneous ethanol injection (PEI) on volume of cystic and mixed thyroid nodules, thyroid function tests (TFTs), antibody titers, and cytologic changes for 1 year. METHODS: Fifty-five nodules from 53 patients with cystic and mixed properties treated with PEI were included. Nodule volumes, TFTs, and thyroid autoantibodies were analyzed at baseline, 6 months, and 12 months. Fine-needle aspiration biopsy (FNAB) was performed to PEI-treated nodules in the 12th month. Thyroid nodules were classified into three groups by structural properties (purely cystic, predominantly cystic, predominantly solid). RESULTS: PEI caused a volume reduction of 80.7% at 6 months and 82.1% at 12 months, without any serious complications. PEI was repeated 1.4 ± 0.4 times with a mean total ethanol amount of 3.6 ± 3.1 mL. Volume reduction in the purely cystic nodules in the 6th and 12th months after PEI was greater than the volume reductions in predominantly cystic and predominantly solid nodules. We found that smaller nodules had greater volume reductions after PEI in the 12th month. During the study, patients remained euthyroid. Antithyroglobulin levels were decreased at 12 months. None of the FNAB results were compatible with a malignant or suspicious for malignancy cytology at the 12th month. CONCLUSION: PEI is an effective means of treatment for benign cystic and mixed thyroid nodules, without any serious side effects. We can also assume that PEI is not a trigger for autoimmunity and malignancy development over the short term. ABBREVIATIONS: anti-TG = anti-thyroglobulin; anti-TPO = anti-thyroperoxidase; AUS = atypia of unknown significance; CV = coefficient of variation; FNAB = fine-needle aspiration biopsy; fT3 = free triiodothyronine; fT4 = free thyroxine; PEI = percutaneous ethanol injection; TFT = thyroid function test; TSH = thyroid-stimulating hormone; US = ultrasonography.

Suppressed Adiponectin Levels and Increased Adiponectin Response to Oral Glucose Load in Lean Women with Severe Acne Normalizes after Isotretinoin Treatment.

BACKGROUND/AIM: Isotretinoin, the drug of choice for severe acne, might be associated with a decrease in insulin sensitivity. Adiponectin is an adipose tissue-derived protein that increases insulin sensitivity. In this study, we aimed to investigate adiponectin levels in postadolescent severe acne and the effect of isotretinoin on adiponectin levels. METHODS: Participants included 18 female patients with severe acne and 18 healthy women matched for age and body mass index (BMI). Acne patients completed a 6-month isotretinoin treatment. Anthropometric measurements, serum adiponectin, lipids, fasting glucose, fasting insulin, and homeostatic model assessment for insulin resistance (HOMA-IR) were determined, and a standard 2-h oral glucose tolerance test (OGTT) was performed in healthy women once and in patients with acne before and after treatment. RESULTS: At baseline, patients with acne had significantly lower serum adiponectin levels than controls. Isotretinoin treatment resulted in a significant increase in weight, BMI, and triglyceride and adiponectin levels. Glucose metabolism markers in patients with acne and controls were similar at baseline and did not change after treatment. Baseline OGTT in acne patients revealed an increased adiponectin response at 2 h, which was not present in healthy controls. Remarkably, this OGTT-induced adiponectin increment in acne patients was diminished after isotretinoin treatment. CONCLUSION: Adiponectin levels are differently regulated in women with severe acne and healthy controls in that circulating basal levels in patients are suppressed and show an increase in response to oral glucose load. Suppression of baseline adiponectin ameliorates after 6 months of isotretinoin treatment, reaching levels similar to those of healthy controls.

THE RESULTS OF PARATHYROID HORMONE ASSAY IN PARATHYROID ASPIRATES IN PRE-OPERATIVE LOCALIZATION OF PARATHYROID ADENOMAS FOR FOCUSED PARATHYROIDECTOMY IN PATIENTS WITH NEGATIVE OR SUSPICIOUS TECHNETIUM-99M-SESTAMIBI SCANS.

OBJECTIVE: This study aimed to evaluate the results of parathyroid hormone (PTH) assay in parathyroid aspirates to determine uniglandular disease by an endocrinologist-performed ultrasound (US) in patients with discordant or negative technetium-sestamibi scans and to evaluate whether this procedure increases the number of focused parathyroidectomies (FPs). METHODS: We analyzed the data of 65 patients who underwent an endocrinologist-performed US-guided parathyroid fine-needle aspiration (FNA) with PTH wash-out, retrospectively. The results of PTH wash-out procedure and the reports of parathyroid surgery and pathology were reviewed. RESULTS: Of 65 patients, 54 had positive PTH wash-out results. The median serum PTH level of patients with positive and negative PTH wash-out results was 143 (25 and 75% interquartile range [IQR], 114 to 197) versus 154 (IQR, 115 to 255) pg/mL (P = .45), and the median PTH in FNA was 3,533 (IQR, 1,481 to 3,534) versus 6.0 (IQR, 1 to 6) pg/mL (P<.001), respectively. Forty-five patients underwent surgery. Of the operated patients, 42 had positive PTH wash-out results and had successful FP. Four patients with redo surgery had positive PTH wash-out results and were successfully re-operated with FP. Of 11 patients with negative PTH wash-out results, 3 had bilateral neck exploration (BNE) surgery and 2 patients were successfully operated, while surgery was unsuccessful in 1 patient, despite BNE. CONCLUSION: Our study results suggest that endocrinologist-performed US and parathyroid FNA with PTH wash-out increases the number and success of FPs. In particular, patients with redo surgery may benefit from this procedure. ABBREVIATIONS: 4D-CT = four-dimensional computed tomography BNE = bilateral neck exploration FNA = fine-needle aspiration FNAB = fine-needle aspiration biopsy FP = focused parathyroidectomy IQR = 25 and 75% inter-quartile range PHPT = primary hyperparathyroidism PPV = positive predictive value PTH = parathyroid hormone 99mTc = technetium US = ultrasound.

High circulating levels of sICAM-1 and sVCAM-1 in the patients with Hashimoto's thyroiditis.

OBJECTIVE: To investigate whether soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1) levels are increased in euthyroid patients with Hashimoto's thyroiditis (HT) and whether they are associated with thyroid autoimmunity and metabolic parameters. DESIGN: Cross-sectional. SUBJECTS AND METHODS: In total, 80 euthyroid patients with HT and 80 age- and body mass index (BMI)-matched control participants were included. Serum sICAM-1, sVCAM-1, free triiodothyronine (fT3), free thyroxine (fT4), thyroid-stimulating hormone (TSH), thyroid peroxidase antibody (anti-TPO), thyroglobulin antibody (anti-TG), fasting blood glucose (FBG), insulin, and lipid levels and homeostasis model assessment for insulin resistance (HOMA-IR) were assessed in all participants. RESULTS: The patients with HT had significantly higher levels of sICAM-1 and sVCAM-1 than controls (both p < 0.001). The difference was sustained after adjustment for TSH and levothyroxine use. Regression analysis demonstrated that sICAM-1 was related to anti-TPO (p < 0.001), and sVCAM-1 was related to both anti-TPO and-TG (p < 0.001 and p = 0.03, respectively); this relationship was sustained after adjustment for age and BMI. Although FBG and HOMA-IR were higher in the HT group, logistic regression analysis revealed that there was no effect of anti-TPO, anti-TG, sICAM-1, sVCAM-1, and C-reactive protein (CRP) on the occurrence of high FBG and high HOMA-IR. CONCLUSION: sICAM-1 and sVCAM-1 levels were significantly elevated in the patients with euthyroid HT and correlated closely with thyroid autoimmunity. However, soluble adhesion molecules had no relation with glucose metabolism parameters in the HT patients.

Effects of thyrotrophin, thyroid hormones and thyroid antibodies on metabolic parameters in a euthyroid population with obesity.

OBJECTIVE: To investigate whether thyroid function in the euthyroid range and thyroid autoimmunity status would affect metabolic measures in individuals with obesity. DESIGN: Cross-sectional. PATIENTS: We retrospectively evaluated 5300 consecutive obese (BMI ≥30 kg/m(2) ) subjects attending the Obesity Outpatient Clinic. Subjects with overt or subclinical thyroid disease, diabetes mellitus, chronic disease or using any medication were excluded. After exclusion, 1275 euthyroid [TSH values >0·4 and <4·5 µIU/ml, free triiodothyronine (FT3), free thyroxine (FT4) in the normal reference range] obese subjects (aged 18-65 years) were eligible for the study. MEASUREMENTS: The physical and biochemical records of the subjects at first admission to the obesity outpatient clinic were examined. RESULTS: Eighty-three per cent (n = 1063) of the study population were women. Antithyroid peroxidase (anti-TPO) positivity was 14%, and antithyroglobulin (anti-TG) positivity was 15%. TSH was 1·8 µIU/ml (1·3-2·4) in antibody-negative subjects and 2·1 µIU/ml (1·4-2·9) in antibody-positive subjects. Neither TSH nor thyroid antibody positivity was associated with insulin resistance (IR) and atherogenic dyslipidaemia after adjustment for confounders. FT3 was positively associated with IR (P < 0·001) and atherogenic dyslipidaemia (P = 0·03); however, this association lost its significance after adjustment for age, gender and BMI. FT4 was negatively associated with IR and this association remained even after adjustment for confounders (P < 0·001). CONCLUSION: TSH and thyroid antibody positivity were not related with metabolic measures. Low-normal FT4 had an inverse association with HOMA-IR even after adjustment for confounders.

Normocalcemic hyperparathyroidism and insulin resistance.

OBJECTIVE: To determine whether insulin resistance (IR) accompanies normocalcemic primary hyperparathyroidism (NCPHP). METHODS: Twenty-five patients with NCPHP and 25 age-, sex-, and body mass index (BMI)-matched controls were included the study. Patients were diagnosed NCPHP if their serum calcium (Ca) concentrations and ionized serum Ca levels were in the normal range but parathyroid hormone (PTH) levels were inappropriately and persistently high. Subjects with 25-hydroxyvitamin D (25[OH]D) levels ≥20 ng/dL were included in the study. The upper limit of PTH was calculated using a nomogram for each subject. Patients and controls underwent a standard 75-gram oral glucose tolerance test (OGTT). IR was assessed by the homeostasis model assessment (HOMA-IR) and insulin sensitivity index (ISogtt). RESULTS: There were no differences between the demographic features of patients with NCPHP and the control group. IR frequency was not different between groups (P = .14). HOMA-IR was higher and ISogtt was lower in patients with NCPHP than the control group, but the differences were not significant (P = .17 and P = .22, respectively). We did not find any correlation between PTH and glucose metabolism markers (HOMA-IR, ISogtt, glycated hemoglobin [HbA1c], and BMI) in either of the groups. CONCLUSION: The results of this study indicate that IR is not more common in patients with NCPHP, and PTH is not related to ISogtt or HOMA-IR.

Color Doppler analysis of uterine, spiral, and intraovarian artery blood flow before and after treatment with cabergoline in hyperprolactinemic patients.

Prolactin (PRL) may have stimulatory effects on vascular resistance. We aimed to analyze uterine, spiral, and intraovarian artery blood flow by Doppler ultrasonography in hyperprolactinemic patients prior to and after treatment with cabergoline. The study was conducted in Sisli Etfal Training and Research Hospital gynecology outpatient clinic between 1 March 2010 and 30 September 2011. Twenty-four women with symptomatic hyperprolactinemia in reproduction age were included in the study. All hyperprolactinemic patients were studied prior to and following the suppression of circulating PRL levels by cabergoline. Patients were examined by standard B-mod and color transvaginal ultrasonography. Pulsality index (PI), resistance index (RI), and systolic/diastolic ratio (S/D) were recorded. The median PRL value was 86 (62-120) ng/ml before treatment and 4.0 (2.5-6.4) ng/ml after the treatment (p < 0.001). We found a significant association among PRL, uterine, spiral, and intraovarian artery RI with linear regression analysis (p < 0.001 for all three arteries). Uterine, spiral, and intraovarian artery PI (p = 0.021, p < 0.001, and p < 0.001, respectively) and RI (p = 0.001, p < 0.001, and p < 0.001, respectively) significantly decreased after cabergoline treatment. In conclusion, this is a pilot study which shows for the first time that PRL increases the uterine, endometrial, and intraovarian vascular resistance and cabergoline reverses this effect.

Fasting and post-prandial glucagon like peptide 1 and oral contraception in polycystic ovary syndrome.

OBJECTIVE: We aimed to investigate whether fasting and meal regulated glucagon like peptide 1 (GLP-1) secretion are altered in patients with polycystic ovary syndrome (PCOS) compared to healty women and whether oral contraceptive use influence GLP-1 secretion dynamics in the syndrome. DESIGN: Prospective observational study. PATIENTS: Fourteen lean normal glucose tolerant patients with PCOS and 11 age- and body mass index (BMI)-matched healthy women. MEASUREMENTS: Glucagon like peptide 1, glucose and insulin levels were measured during a standardized meal tolerance test and area under the curves (AUCs) were calculated. Whereas healthy controls were assessed at baseline, all tests were repeated in women with PCOS after treatment with ethinyl estradiol 30 µg/drospirenone 3 mg (EE/DRSP) for 3 months. RESULTS: Both fasting and post-meal levels of GLP-1 were significantly reduced in women with PCOS compared to controls (P = 0·022 and P = 0·028, respectively). AUC for GLP-1 was also lower in PCOS (P = 0·012). Glucose and insulin measurements did not show a significant change between the groups. In the PCOS group, GLP-1, glucose and insulin levels did not show any change after 3 months of EE/DRSP use. CONCLUSION: GLP-1 levels both at fasting and in response to a meal are blunted in lean women with PCOS compared to healthy women. Short term oral contraception do not alter GLP-1 secretion in PCOS. Disturbance in incretin secretion dynamics might contribute to the risk of impaired glucose tolerance and type 2 diabetes in PCOS.

Impaired aortic elastic properties in patients with adult-onset hypogonadism.

BACKGROUND: Recent studies have shown a strong relationship between testosterone levels and vasomotor actions. The aim of this study is to compare the elastic properties of the aorta in male patients with hypogonadism and eugonadal healthy control subjects. METHOD: A total of 22 male with hypogonadism (mean age: 35.2 ± 9.5 years, mean disease duration: 5.3 ± 1.8 years) and 25 age-, sex- and weight-matched eugonadal healthy subjects (mean age: 34.5 ± 8.2 years) were enrolled in the study. Aortic stiffness (ß) index, aortic strain (AoS) and aortic distensibility (AoD) were calculated from the aortic diameters measured by transthoracic echocardiography and blood pressure obtained by sphygmomanometer. RESULTS: The routinely performed echocardiographic parameters were similar between patient and control groups. There were significant differences between the control and patient groups in ß index (1.75 ± 0.44 vs 2.68 ± 1.72, p < 0.001), AoS (18.52 ± 6.44 vs 12.35 ± 3.88%, p < 0.001) and AoD (7.56 ± 2.86 vs 3.96 ± 1.24, 10(-6) cm(2)/dyn, p < 0.001). There were statistically significant positive correlations between the serum total testosterone level and AoD (r = 0.539, p < 0.001) and AoS (r = 0.372, p = 0.036); moreover, there was a negative correlation between the serum total testosterone level and ß index (r = - 0.462, p = 0.001). In multivariate analysis, serum total testosterone level was significantly related with AoD, AoS and ß index (respectively, RR = 2.88, p = 0.004; RR = 3.45, p = 0.001; RR = 2.64, p = 0.01). CONCLUSION: The study results showed that aortic elasticity was impaired in patients with hypogonadism. We also have demonstrated a statistically significant correlation between aortic elastic properties and the serum total testosterone level.

Voice characteristics of acromegaly.

Acromegaly's effect on voice is still indefinite. We aimed to define acoustic characteristics of patients with acromegaly. Cross-sectional case-control study was designed. Thirty-seven patients with acromegaly and 30 age- and sex-matched healthy controls were included. Fundamental frequency (F0) and measurements related to frequency, amplitude, noise and tremor of the obtained voice sample were analyzed using Multi-Dimensional Voice Program. Absolute jitter (Jita) and jitter percent (Jitt), shimmer in decibel and shimmer percent, noise to harmonic ratio and soft phonation index, fundamental frequency tremor frequency and frequency tremor intensity index represented the parameters related to frequency, amplitude, noise and tremor of the voice sample, respectively. Patients with acromegaly, especially the uncontrolled patients, exhibited significant differences in frequency perturbation measurements. Jitt of all patients and Jita of uncontrolled patients were significantly higher than that of control group (p = 0.044 and p = 0.043, respectively). Jitter which is a measure of frequency perturbation can be assumed as an indicator of hoarse and deepened voice. Jita of all patients and Jitt of uncontrolled patients were elevated, but not reaching a statistical significance. Controlled and active patients had similar analysis of acoustic parameters. In the correlation analysis, shimmer and IGF-1 (insulin like growth factor 1) was found to be positively correlated in all patients with acromegaly and in female patients. When the p value is adjusted according to Bonferroni correction regarding the use of ten parameters for acoustic analysis (so adjusted p is <0.005), all the statistically significant findings become insignificant. Considering the parameters test different properties of voice, it is reasonable to pay attention to the findings. Patients with acromegaly have increased frequency perturbations measures, but this increase is non-significant according to Bonferroni correction. This may be perceptually sensed as hoarse voice. Amplitude perturbations within the voice of the patients with acromegaly are positively correlated with IGF-1 levels, this correlation is also non-significant according to Bonferroni correction.

Functional and structural evaluation of hearing in acromegaly.

CONTEXT: The impact of acromegaly on the auditory system remains unknown. OBJECTIVE: This study aimed to examine audiological symptoms and the structure and function of the auditory system in patients with acromegaly. DESIGN/SETTING AND PATIENTS: The study included 44 patients with acromegaly. Pure tone audiometry, speech audiometry, tympanometry, otoacoustic emissions testing, computerized tomography of the temporal bone and magnetic resonance imaging of the ear were performed in all patients. The study also included 36 age- and sex-matched healthy controls. The patients with acromegaly were divided into three subgroups, as follows: controlled disease (n=13); partially controlled disease (n=16); uncontrolled disease (n = 15). RESULTS: In all, 43% of the patients with acromegaly had hearing loss, and 20% had had an episode of otitis in at least one ear. Median pure tone average (PTA) in the patients with acromegaly was 12.5 dB (range: 2-72 dB), vs 8.3 dB (range: 0-20 dB) in the control group (P < 0.001). PTA did not differ significantly between the three patient subgroups. Audiometric tests showed various degrees of hearing loss in at least one ear in 21 patients (48%). Conductive, sensorineural and mixed type hearing loss in at least one ear was noted in 9%, 30% and 18% of the patients, respectively. Auditory imaging showed that 50% of the patients had temporomandibular joint degeneration (TMJD). CONCLUSIONS: Hearing loss is quite common in patients with acromegaly. Contrary to common belief, in this study, conductive hearing loss did not occur more frequently than other types. Based on PTA findings in the controls and patients with acromegaly, acromegaly caused hearing loss, but the level of disease activity had no effect on hearing. Middle ear pressure problems might be caused by increased perilymph because of growth hormone (GH)-related volume overload.

Pigment epithelium-derived factor increases in type 2 diabetes after treatment with metformin.

OBJECTIVE: Pigment epithelium-derived factor (PEDF) has anti-angiogenic, immunomodulatory and anti-inflammatory properties. In addition to the significant role it plays in reducing diabetic complications, PEDF is now used in the treatment of certain cancers. It possibly plays a role in insulin resistance cases, too. However, whether metformin treatment has any significant effects on PEDF levels is not known. In this study, we investigated the regulation of PEDF in type 2 diabetes in relation to fat mass and insulin resistance before and after the use of metformin for treatment. DESIGN: Prospective cohort study. SUBJECTS: Thirty-six patients with newly diagnosed type 2 diabetes and 33 healthy individuals. MEASUREMENTS: Baseline weight, waist circumference (WC), fasting (FPG) and postprandial (PPPG) glucose, insulin, HbA1c, HOMA, PEDF and total/truncal fat mass were determined both in the diabetic and control subjects. Procedures were repeated in the diabetic group after a 6-month metformin treatment. RESULTS: Baseline FPG, PPPG, HbA1c, HOMA, weight, WC and truncal fat mass were higher in patients with diabetes whereas PEDF levels were found to be comparable with the controls. We completed the study with 31 of the 36 patients with diabetes we had selected for the study. We observed a decrease in the weight, WC, FPG, PPPG, HOMA, total and truncal fat mass of the patients while there was a significant rise in the PEDF levels (P = 0·002) after the metformin treatment. On the other hand, no significant correlation was observed between the change in PEDF levels and the clinical and laboratory findings. CONCLUSION: Our study is the first to identify a metformin-related increase in PEDF levels in diabetes. The increase observed in PEDF levels after the metformin treatment does not seem to be related to the changes in insulin resistance, fat mass or glycemic control. Hence, our results suggest that further investigation is necessary to determine the direct effects of metformin on PEDF gene and protein expression in vitro.

The role of vascular endothelial growth factor in the development of papillary thyroid carcinoma in patients with lymphocytic thyroiditis.

BACKGROUND: Vascular endothelial growth factor (VEGF) plays a pivotal role in the pathogenesis of autoimmune chronic inflammatory conditions and papillary thyroid carcinoma (PTC). We hypothesized that, as VEGF expression is increased both in PTC and in lymphocytic thyroiditis (LT), it may stimulate the development of PTC in patients with LT. To evaluate this, we examined both tumor and adjacent non-tumoral tissues of PTC patients with and without LT. METHODS: A total of 50 patients with PTC (52.50±7.41 years) and 17 patients with nodular goiter (NG) (50.47±10.38 years) were included in the study. According to the presence of LT, patients with PTC were further divided into two groups. Immunohistochemical analyses of VEGF were conducted in all patients and for PTC patients, both tumor tissue and adjacent non-tumoral tissue were evaluated. RESULTS: The scores for intensity of staining and percentage of labeled thyrocytes for VEGF were found to be significantly higher in the PTC patients than in the NG patients (p<0.001, p<0.001, respectively). The tumor tissue revealed similar scores for PTC patients with LT and without LT. However, the scores in adjacent non-tumoral tissue were higher in PTC patients with LT than in patients without LT (p=0.004, p=0.01, respectively). CONCLUSIONS: To the best of our knowledge, our results are the first to demonstrate that the expression of VEGF in adjacent non-tumoral tissue were higher in PTC patients with LT than in those without, which shows a possible role of VEGF expression in the progression of PTC in the presence of LT.