New Anthropometric Measurements: Relationship to Thyroid Functions in Euthyroid Obese Subjects.

Introduction Body mass index (BMI) is unable to make a distinction between muscle mass and fat mass. Therefore, new anthropometric measurements, such as a body shape index (ABSI), body round index (BRI), and body adiposity index (BAI), have been formulated in recent years. Many studies have reported a correlation between BMI and thyroid function. In this study, we aimed to investigate the relationship between the above-mentioned new anthropometric measurements and thyroid functions in euthyroid obese subjects. Methods We included 675 euthyroid (TSH ≥ 0.4 and < 4.5 mIU/l) individuals from the obesity outpatient clinic, aged between 18 and 65 years old, with BMI ≥ 30. Thyroid-stimulating hormone (TSH), free T4 (fT4) and free T3 (fT3), anthropometric measurements (weight, height, and waist circumference), and bioelectric impedance analyses [percent body fat (PBF) and fat-free mass (FFM)] of individuals were measured and recorded. ABSI, BRI, and BAI were calculated with the data from these measurements. Anthropometric measurements were compared to thyroid function tests. Results Eighty percent of the subjects were female. The mean age and BMI were 38 ± 17 years and 38 ± 6 kg/m2, respectively. TSH was found to be negatively correlated with ABSI (p = 0.006) and positively correlated with BAI (p < 0.001), but a statistically significant relationship with BRI (p = 0.193) was not determined. Free T4 was not associated with any of the anthropometric measurements.While fT3 was determined to be positively correlated with ABSI (p = 0.008) and negatively correlated with PBF and BAI (p = 0.001, p = 0.002, respectively), no statistically significant relationship with fT3 and BRI was determined. Conclusion TSH is positively correlated with measurements of adiposity such as BMI, PBF, BAI while indexes in which abdominal obesity increases, such as waist circumference (WC), waist-hip ratio (WHR), and ABSI, are correlated with fT3 levels.

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.

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.

Biochemical and pathologic factors affecting technetium-99m-methoxyisobutylisonitrile imaging results in patients with primary hyperparathyroidism.

OBJECTIVE: Technetium 99 m methoxyisobutylisonitrile (Tc-99m MIBI) scintigraphy represents the most commonly utilized imaging modality for the detection of the diseased gland in patients with primary hyperparathyroidism (PHPT). In this study, we aimed to identify potential biological factors with an impact on MIBI sensitivity. METHODS: A total of 147 patients with surgically confirmed parathyroid adenomas were assessed retrospectively. Data including medical history, biochemical and hormonal measurements, cervical US, Tc-99m MIBI scans as well as pathology reports were retrieved and recorded. RESULTS: Of the 147 patients, there were a total of 77, 39, and 31 cases with a positive, negative, and suspicious parathyroid adenoma on Tc-99m MIBI scan, respectively. Serum calcium (Ca), parathyroid hormone (PTH) and 25 (OH) D levels were comparable among MIBI positive and negative patients [Ca: 11.5 ± 0.9 vs 11.3 ± 0.9 mg/dL (P = 0.42); PTH: 216 (146-347) vs 194 (140-317) pg/mL (P = 0.45); 25(OH)D: 8.4 (5.7-18.2) vs 10.0 (4.7-23.3) ng/mL (P = 0.64), respectively]. P-glycoprotein (P-gp) staining was negative in both groups. Also, pathological examination of tissue preparations revealed no difference in terms of the volume of the adenomas, incidence of cystic adenomas, cell-type dominance (oxyphilic cell), percent fat, and Ki-67 ratio in MIBI positive and negative groups. The rate of hyalinization was 13% in MIBI positive and 28% in MIBI negative subjects, the difference being statistically significant (P = 0.04). CONCLUSION: Presence of hyalinization in parathyroid adenomas was found to be negatively correlated with MIBI scan results.

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.

Correlation of BRAF mutation and SUVmax levels in thyroid cancer patients incidentally detected in 18F-fluorodeoxyglucose positron emission tomography.

The prognostic importance of 18F-fluorodeoxyglucose avidity in primary thyroid tumor and molecular basis responsible for its mechanism has not yet been well characterized. In this study, we aimed to evaluate the correlation between the maximum standardized uptake levels and B-type Raf kinase mutation positivity in incidentally detected papillary thyroid cancer patients during 18F-fluorodeoxyglucose positron emission tomography examination. We retrospectively evaluated 6873 18F-fluorodeoxyglucose-positron emission tomography scans of consecutive subjects from a database search for tumor staging in 2014 at our hospital Nuclear Medicine Center. In total, 135 patients had focal 18F-fluorodeoxyglucose uptake in the thyroid. Of these, 76 patients had fine-needle aspiration biopsy. 18F-fluorodeoxyglucose-maximum standardized uptake of the positron emission tomography-detected nodules was recorded. B-type Raf kinase (V600E) mutation and p53 protein expression were evaluated in papillary thyroid cancer patients. The incidence of thyroid incidentaloma in 18F-fluorodeoxyglucose-maximum standardized uptake scans was 2 % (135/6873). Of the 76 patients evaluated, 41 % (n = 31) were diagnosed papillary thyroid cancer. B-type Raf kinase mutation was positive in 51 % (17/30) of the papillary thyroid cancer patients. Maximum standardized uptake levels of the nodules (≥1 cm) were significantly higher in B-type Raf kinase-mutated papillary thyroid cancer patients than in non-mutated patients [16.6 (10.4-27.9) vs. 9.7 (6.8-11.1); P = 0.007]. Correlation analysis revealed that maximum standardized uptake was significantly associated with B-type Raf kinase mutation positivity (r = 0.519; P = 0.005). Logistic regression analysis showed an association between maximum standardized uptake and B-type Raf kinase mutation positivity even after adjustment for age and gender (P = 0.01). B-type Raf kinase mutation is closely related to 18F-fluorodeoxyglucose-positron emission tomography maximum standardized uptake levels in patients with incidentally detected papillary thyroid cancer.

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.

Evaluation of acute and chronic MRI features of sacroiliitis in asymptomatic primary hyperparathyroid patients.

Asymptomatic primary hyperparathyroidism (PHPT) is characterized with autonomous overproduction of parathyroid hormone without signs or symptoms associated with hyperparathyroidism. Before symptoms become obvious, PHPT may affect structures like sacroiliac joints, which consist of bone. So, in the asymptomatic PHPT patients, structural and inflammatory changes in sacroiliac joints may lead to confusion during diagnosis workup of axial spondyloarthropathy. In this study, we evaluated active and chronic sacroiliac magnetic resonance imaging (MRI) changes relevant to sacroiliitis in the patients with asymptomatic PHPT and interpreted bone marrow edema within the scope of Assessment of SpondyloArthritis International Society-Outcome Measures in Rheumatology Clinical Trials (ASAS-OMERACT) criteria. Forty-nine patients with asymptomatic PHPT, 26 patients with newly diagnosed axial spondyloarthropathy (SpA), and 37 healthy controls were enrolled. All subjects were evaluated by sacroiliac MRI for four active (bone marrow edema, enthesitis, capsulitis, and synovitis) and four chronic (subchondral sclerosis, subchondral/periarticular erosions, periarticular fat deposition, and bony bridges/ankylosis) lesions relevant to sacroiliitis. Bone marrow edema compatible with ASAS-OMERACT active sacroiliitis criteria in sacroiliac MRI was fulfilled by 16.3 % (8/49) of the asymptomatic PHPT patients which was similar with controls but statistically lower than axial SpA. Moreover, asymptomatic PHPT patients and controls were similar for other chronic or active MRI findings. Also, we detected lower frequency of all other MRI findings, except enthesis, in asymptomatic PHPT patients according to axial SpA. Acute inflammatory including bone marrow edema fulfilling ASAS-OMERACT active sacroiliitis criteria and chronic structural sacroiliac lesions relevant to sacroiliitis in MRI were detected in asymptomatic PHPT similar frequency with controls but as expected, lower than axial SpA. But, these findings could not be attributed to excessive secretion of parathyroid hormone.

Voice characteristics associated with polycystic ovary syndrome.

OBJECTIVES/HYPOTHESIS: To test the assumption that voice is changed in polycystic ovary syndrome (PCOS) and identify changes that occur. STUDY DESIGN: Cross-sectional pilot study. METHODS: Thirty patients with PCOS and a control group of 22 age-matched and body mass index-matched healthy women were included. Demographic data, anthropometric measurement, serum androgens, and Voice Handicap Index-10 were determined. Transnasal fiberoptic laryngoscopy and rigid stroboscopy were performed. Supraglottic hyperfunction was assessed during fiberoptic laryngoscopy. Presence of supraglottic hyperfunction was interpreted as abnormal muscle tension pattern. Glottal closure configuration and vibratory wave characteristics were evaluated via stroboscopy. Acoustic analysis was performed with the Dr. Speech software program version 4 (Tiger DRS Inc., Seattle, WA). RESULTS: Voice complaints and acoustic parameters were similar between groups, whereas serum androgens were significantly higher in patients (P < 0.001). Laryngeal examination detected pathology in 17 (56.7%) patients and two (9.1%) controls (P < 0.001). Fiberoptic examination determined supraglottic hyperfunction in 11 patients but in only two controls (P = 0.023). In stroboscopy, incomplete glottal closure configuration and impaired vocal fold vibration were present in 10 and 11 patients, respectively, whereas only one control had glottal closure abnormality and none of the controls had abnormal vibration (P = 0.028 and P = 0.001, respectively). CONCLUSION: Abnormal muscle tension patterns and impaired vocal fold vibration are frequent among patients with PCOS; but they are not accompanied by increased vocal symptoms or deteriorated acoustic voice parameters. This may be important for professional voice users or in extensive or extraordinary voice use demands in patients with PCOS. LEVEL OF EVIDENCE: 3b. Laryngoscope, 126:2067-2072, 2016.

Relationship Between Parathormone and Obesity-Linked Disorders.

BACKGROUND: In this study, we aimed to investigate whether high parathormone (PTH) levels in obese patients contribute to the metabolic complications of obesity. METHODS: A total of 400 obese subjects aged 18-65 years were included. Anthropometric bioelectrical bioimpedance measures, blood tests, and 75 gram oral glucose tolerance test results were evaluated. RESULTS: Of the 400 obese subjects, 335 were female. The mean age was 39 ± 10 years. The median body mass index was 36 (interquartile range 34-41). Subjects were divided into quartiles according to blood PTH levels. Groups included quartile 1 [n = 100, median PTH; 42 (range 36-45)], quartile 2 [n = 100, median PTH; 55 (51-59)], quartile 3 [n = 100, median PTH; 73 (68-78)], and quartile 4 [n = 100, median PTH; 99 (89-125)]. Quartiles were evaluated with a generalized linear model adjusted for age, sex, and season of recruitment. Systolic and diastolic blood pressure, fasting glucose, homeostatic model assessment-estimated insulin resistance, insulin sensitivity index, triglyceride level, and high-density lipoprotein cholesterol (HDL-C) were not different among quartiles. PTH and 25 hydroxyvitamin D (25(OH)D) were not associated with higher odds of prevalent metabolic syndrome in obese subjects (odds ratio, OR, 0.99 [95% confidence interval, CI, 0.981.00], P = 0.38 and 0.99 95% CI 0.96-1.01], P = 0.46, respectively). Decreased 25(OH)D levels were significantly correlated with higher odds of low HDL-C (OR 0.96 [95% CI 0.93-0.99], P = 0.04). CONCLUSIONS: PTH does not contribute to the occurrence of metabolic components of obesity, but there is a positive correlation between 25(OH)D and HDL-C.

Arg25Pro (c.915G>C) polymorphism of transforming growth factor ß1 gene suggests an association with increased risk for Hashimoto's thyroiditis.

BACKGROUND: The etiopathogenesis of Hashimoto's thyroiditis (HT) - has not been clearly elucidated although the role of chronic inflammation, endothelial dysfunction, and imbalance between pro- and anti-inflammatory cytokines has been established. Transforming growth factor ß1 (TGFß1) is required to maintain immune homeostasis, and is implicated in lymphocyte infiltration, production of autoantibodies and thyrocyte destruction seen in patients with HT. AIM: The aim of the present study was to investigate the possible association of Leu10Pro (c.869T>C) and Arg25Pro (c.915G>C) single nucleotide polymorphisms (SNPs) of TGFß1 gene with the occurrence of HT. METHODS: We analyzed the genotype and allele frequencies of polymorphisms at codon 10 and 25 in 178 patients who had been diagnosed as having HT and 197 healthy controls using PCR-restriction fragment length polymorphism (RFLP). RESULTS: There was no notable risk for HT afflicted by Leu10Pro (c.869T>C) polymorphism of TGFß1 gene. However, there was a significant increase of Arg25Pro (c.915G>C) C allele frequency in patients with HT compared with healthy controls (p=0.003, OR=1.87, 95% CI=1.23-2.84). Moreover, heterozygous (CG) subjects had a 2.53-fold increased risk for developing HT with respect to wild (GG) homozygotes (p<0.001, 95% CI=1.57-4.05). TSH levels in CG heterozygous patients were increased in comparison with wild homozygotes (p=0.006). CONCLUSION: This study indicates that the Arg25Pro (c.915G>C) polymorphism of TGFß1 gene may be related to increased risk for HT.

A case of Madelung's disease accompanied by Klinefelter's syndrome.

UNLABELLED: Madelung's disease is a rare fat metabolism disorder characterised by benign multiple symmetric, encapsulated lipomatosis. The exact cause of the disease is unknown; it may be associated with chronic alcoholism and mutations in mitochondrial DNA (A8344G), but there have been cases without these factors reported in the literature. A 29-year-old man with a 6-year history of diabetes mellitus was admitted to our hospital for poorly regulated diabetes and decreased libido. He was not an alcohol consumer. His family history was unremarkable. Physical examination revealed that he had a eunuchoid body shape. There was a symmetric excess fat accumulation in his submandibular, deltoid, nuchal, suprapubic and inguinal areas. He was diagnosed with Madelung's disease, and imaging studies supported the diagnosis. Hormonal evaluation revealed a hypergonadotropic hypogonadism. Karyotype analysis revealed a 47,XXY mutation. Genetic research showed no mitochondrial DNA mutation. Metabolic disorders, such as diabetes mellitus, hyperlipidaemia, hyperuricaemia and liver disease, endocrine gland diseases, such as hypothyroidism, and neurological diseases, such as polyneuropathy and cognitive disorders, may accompany Madelung's disease. The present study represents the first reported case of Madelung's disease accompanied by Klinefelter's syndrome. LEARNING POINTS: Madelung's disease is a rare fat metabolism disorder characterised by benign multiple symmetric and encapsulated lipid accumulation.The exact cause of the disease is unknown.Metabolic disorders, such as diabetes mellitus, hyperlipidaemia, hyperuricaemia and liver disease, endocrine gland diseases, such as hypothyroidism, and neurological diseases, such as polyneuropathy and cognitive disorders, may accompany Madelung's disease.

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.

The evaluation of endothelin 1 (EDN1) and endothelin receptor type A (EDNRA) gene polymorphisms in Hashimoto's thyroiditis.

PURPOSE: Endothelin1 (EDN1) is well established marker of inflammation. The functions of EDN1 are mediated mainly by endothelin receptors type A (EDNRA). The etiopathogenesis of Hashimoto's thyroiditis (HT) remains still elusive although the role of chronic inflammation and subsequent endothelial dysfunction has been established. This study examined firstly the possible association of EDN1 (G5665Tand T-1370G) and EDNRA (C+70G and G-231A) single nucleotide polymorphisms (SNPs) with the occurrence of HT, and evaluates the relationship between genotypes and clinical/laboratory manifestation of HT. MATERIALS AND METHODS: We analyzed genotype and allele distributions of above mentioned polymorphisms in 163 patients with HT and 181 healthy controls by real-time PCR combined with melting curve analysis. RESULTS: No significant associations between HT and variant alleles of EDN1 5665 and -1370, as well as EDNRA +70 and -231 SNPs were found. Haplotype analysis demonstrated that there was a strong (D'=0.76, r(2)=0.487) and weak (D'=0.403, r(2)=0.086) linkage disequilibrium (LD) between EDN1 -1370 and 5665, and between EDNRA -231 and +70 SNPs, respectively. However, haplotype frequencies in patients were similar to those in controls. In addition, it was observed that the EDNRA +70 G allele had protective effect against early (at age before 40 years) disease onset of HT (OR: 0.51, 95% CI=0.32-0.79, p=0.003). CONCLUSION: Although no significant associations between susceptibility to HT with EDN1 5665 and -1370, as well as with EDNRA+70 and -231 SNPs were found, EDNRA +70 polymorphism was related with decreased risk for early onset HT.

Arg25Pro (c.915G>C) polymorphism of transforming growth factor ß1 gene increases the risk of developing Graves' disease.

BACKGROUND: Graves' disease (GD) arises due to complex interactions between genetic and environmental factors. Transforming growth factor ß1 (TGFß1) is required to maintain immune homeostasis, and is implicated in lymphocyte infiltration, thyroid follicular cell hyperplasia, and production of autoantibody in the thyroid gland of patients with GD. AIM: The aim of the present study was to investigate the possible association of Leu10Pro (c.869T>C) and Arg25Pro (c.915G>C) single nucleotide polymorphisms (SNPs) of TGFß1 gene with the occurrence of GD. METHODS: We analyzed the genotype and allele frequencies of these SNPs in 171 patients with GD and 197 healthy controls using PCR-restriction fragment length polymorphism (RFLP). RESULTS: The distribution of Leu10Pro (c.869T>C) genotype and allele frequencies in the control and GD groups were not significantly different. However, there was a significant increase of Arg25Pro (c.915G>C) C allele frequency in patients with GD compared with healthy controls (p<0.0001, OR=4.77, 95% CI=3.32-7.03). In addition, C allele carrying subjects (CG+CC) had 5.31-fold increased risk for developing GD according to GG homozygotes (p<0.0001, 95% CI=3.43-8.44). No association between polymorphisms and GD phenotypes was observed. CONCLUSION: This study indicates that the Arg25Pro (c.915G>C) polymorphism of TGFß1 gene may be related to occurrence of GD.

Polymorphisms of endothelin 1 (G5665T and T-1370G) and endothelin receptor type A (C+70G and G-231A) in Graves' disease.

PURPOSE: Endothelin 1 (EDN1) is a strong angiogenic and mitogenic factor, playing a key role in hypervascularization, thyroid follicle cell hyperplasia, and lymphocyte infiltration in the thyroid gland of patients with Graves' disease (GD). EDN1 induces angiogenesis and mitogenesis via endothelin receptor type A (EDNRA). This study examined the possible association of EDN1 (G5665T and T-1370G) and EDNRA (C+70G and G-231A) single nucleotide polymorphisms (SNPs) with the occurrence of GD, and evaluates the relationship between genotypes and clinical/laboratory manifestations of GD. MATERIALS AND METHODS: We analyzed genotype and allele distributions of EDN1 and EDNRA polymorphisms in 165 patients with GD and 181 healthy controls by real-time PCR combined with melting curve analysis. RESULTS: No significant associations between GD and variant alleles of the studied polymorphisms were observed. However, the anti-thyroid peroxidase (anti-TPO) and anti-thyroglobulin (anti-TG) levels in EDN1 G5665T GG genotype were higher than those in T allele carriers (GT+TT) (p=0.001 and p=0.026, respectively). In addition, anti-TPO levels in EDN1 T-1370G wild-type homozygous patients were found to be higher than in mutant gene carrying patients (GT+GG) (p=0.006). The presence of EDNRA+70G allele was associated with 3.37-fold increased risk for development of ophthalmopathy in GD patients (p=0.009). CONCLUSION: Although there were no associations between EDN1 (G5665T and T-1370G) and EDNRA (C+70G and G-231A) SNPs and susceptibility to GD, EDN1 G5665T and T-1370G polymorphisms were related to alterations of autoantibody production and EDNRA C+70G polymorphism is related with increased risk for ophthalmopathy in GD patients.

ICAM1 K469E and E-selectin S128R polymorphisms could predispose to increased autoantibody production and TSH suppression in Graves' disease.

The etiopathogenesis of Graves' disease (GD) has not been clearly elucidated although the role of chronical inflammation and endothelial dysfunction has been established. Adhesion molecules such as intercellular adhesion molecule 1 (ICAM1), vascular cell adhesion molecule 1 (VCAM1), and E-selectin are secreted from vascular endothelium and promote accumulation of leukocytes in damaged endothelial areas. This study examined the possible association of ICAM1 (G241R and K469E), VCAM1 (T-1591C and T-833C), and E-selectin (S128R) single nucleotide polymorphisms (SNPs) with the occurrence of GD. ICAM1 (G241R and K469E), VCAM1 (T-1591C and T-833C), and E-selectin (S128R) SNPs in DNA from peripheral blood leukocytes of 171 patients with GD and 259 healthy controls were investigated by real-time PCR combined with melting curve analysis using fluorescence-labeled hybridization probes. We did not find significant differences in the distributions of studied polymorphisms, nor in the haplotype frequencies between patients with GD and healthy control. However, the anti-TPO levels in E-selectin 128R allele carrying subjects (SR + RR) were higher than S128S genotype (p < 0.05). In addition, the decline of TSH levels was more prominent in ICAM1 469 E carrying subjects (KE + EE) in comparison with wild homozygotes (p < 0.05). Although there is not association between ICAM1 (G241R and K469E), VCAM1 (T-1591C and T-833C), and E-selectin (S128R) SNPs and susceptibility to GD, higher anti-TPO in E-selectin 128 SR + RR, and lower TSH in ICAM1 469 KE + EE subjects suspect that these genotypes are prone to increased antithyroid autoantibody production with more accentuated TSH suppression in GD. Further studies with a larger cohort, analyzing other polymorphisms in ICAM, VCAM1 and E-selectin genes are necessary to support our observations.

G241R and K469E polymorphisms of intercellular adhesion molecule 1 (ICAM-1) could predispose to Hashimoto thyroiditis.

This study examined firstly the possible association of G241R and K469E single nucleotide polymorphisms (SNPs) of ICAM-1 gene with the occurrence of Hashimoto thyroiditis (HT). G241R and K469E SNPs in DNA from peripheral blood leukocytes of 190 HT and 247 healthy controls were investigated by real-time PCR combined with melting curve analysis using fluorescence-labeled hybridization probes. There was a significant increase of ICAM-1 241R allele frequency in patients with HT compared with healthy controls (P = 0.04, OR = 1.84, 95 % CI = 1.00-3.37). Regarding ICAM-1 K469E polymorphism, patients homozygous for E allele had 1.73-fold increased risk for developing HT according to KK homozygotes (P = 0.04, 95 % CI = 1.00-3.01). The 469E allele frequency was higher in HT patients according to controls, however the difference was at borderline significance (P = 0.05, OR = 1.30, 95 % CI = 1.00-1.70). No associations between polymorphisms and HT phenotypes were observed. We suggest that the G241R and K469E SNPs of ICAM-1 gene may be related to occurrence of HT. However, more studies with larger sample size including other loci of the ICAM-1 gene are necessary to support our findings before any definite statement can be made about the relationship between HT and ICAM-1 polymorphism.