Disease-free survival and the prognostic factors affecting disease-free survival in patients with medullary thyroid carcinoma: a multicenter cohort study.

PURPOSE: Despite several factors that may have been associated with poor disease-free survival (DFS) in patients with medullary thyroid carcinoma (MTC), only a few studies have evaluated the prognostic factors affecting DFS in MTC patients. Therefore, this study evaluated the prognostic factors affecting DFS, in a large number of patients with MTC. METHODS: Patients treated for MTC were retrospectively analyzed. Patients were stratified as having persistent/recurrent disease and no evidence of disease (NOD) at the last follow-up. The factors affecting DFS after the initial therapy and during the follow-up period were investigated. RESULTS: This study comprised 257 patients [females 160 (62.3%), hereditary disease 48 (18.7%), with a mean follow-up time of 66.8 ± 48.5 months]. Persistent/recurrent disease and NOD were observed in 131 (51%) and 126 (49%) patients, respectively. In multivariate analysis, age > 55 (HR: 1.65, p = 0.033), distant metastasis (HR: 2.41, p = 0.035), CTN doubling time (HR: 2.7, p = 0.031), and stage III vs. stage II disease (HR 3.02, p = 0.048) were independent predictors of persistent/recurrent disease. Although 9 (8%) patients with an excellent response after the initial therapy experienced a structural recurrence, the absence of an excellent response was the strongest predictor of persistent/recurrent disease (HR: 5.74, p < 0.001). CONCLUSIONS: The absence of an excellent response after initial therapy is the strongest predictor of a worse DFS. However, a significant proportion of patients who achieve an excellent response could experience a structural recurrence. Therefore, careful follow-up of patients, including those achieving an excellent response is essential.

The impact of microscopic extrathyroidal extension on the clinical outcome of classic subtype papillary thyroid microcarcinoma: a multicenter study.

OBJECTIVES: Despite the presumed overdiagnosis of papillary thyroid microcarcinoma (PTMC) which has resulted in a new trend toward less-extensive surgery and a preference for active surveillance, the impact of microscopic extrathyroidal extension (mETE) on the clinical outcomes of PTMC is still controversial. This study assessed the impact of mETE on the clinical outcomes of patients with classic subtype PTMC. METHODS: The data of consecutive patients who underwent thyroidectomy and were histopathologically diagnosed as classic subtype PTMC were analyzed. Cox's proportional hazards model was used to assess the impact of contributing variables on persistent/recurrent disease. Disease-free survival was estimated using the Kaplan-Meier method. RESULTS: This study included 1013 patients (84% females), with a mean follow-up period of 62.5 ± 35.3 months. Patients with mETE had a significantly higher rate of locoregional persistent/recurrent disease than patients without mETE (9.8% vs 2.1%, p < 0.001). The disease-free survival rate was significantly lower in patients with mETE than in those without (90.2% vs 97%, Log-Rank p < 0.001). Furthermore, mETE and neck lymph node involvement were independent predictors of persistent/recurrent disease in multivariate analysis (HR: 2.43, 95% CI:1.02-5.81, p = 0.043; HR: 4.38, 95% CI: 1.7-11.2, p = 0.002, respectively). CONCLUSIONS: In patients with the classic subtype of PTMC, mETE is an independent predictor of persistent/recurrent disease and is associated with a lower DFS rate. However, neck lymph node involvement is the strongest predictor of persistent/recurrent disease. Therefore, PTMCs with mETE and neck lymph node involvement are at a higher risk of persistent/recurrent disease than individuals lacking both characteristics.

Do Histologically Aggressive Subtypes of Papillary Thyroid Microcarcinoma have Worse Clinical Outcome than Non-Aggressive Papillary Thyroid Microcarcinoma Subtypes? A Multicenter Cohort Study.

Histologically aggressive micropapillary thyroid carcinomas (PTMC) subtypes are thought to be associated with an aggressive clinical course. However, evidence for unfavorable clinical outcomes in patients with aggressive PTMC subtypes is not clear. In this study, we intended to determine the difference in clinical outcomes between patients with aggressive and non-aggressive PTMC subtypes. In this multicenter cohort study, the computer-recorded clinical and histopathological data of patients who underwent thyroid surgery between January 2000 - January 2021 in 9 referral centers and were diagnosed as PTMC were analyzed. A total of 1585 patients [female 1340 (84.5%), male 245 (15.5%), mean age 47.9±11.63 years), with a mean follow-up time of 66.55±37.16 months], were included in the study. Ninety-eight cases were diagnosed as aggressive and 1487 as non-aggressive subtypes. Persistent/recurrent disease was observed in 33 (33.7% )and 41 (2.8%) patients with aggressive and non-aggressive subtypes (p<0.001). Diseases-free survival rates were markedly lower in patients with aggressive than in those with non-aggressive PTMC subtypes (66.3 vs. 94.8%, log-rank p<0.001). Moreover, in multivariate analysis, aggressive histology was an independent predictor of persistent/recurrent disease, after controlling for other contributing factors (HR 5.78, 95% CI 3.32-10, p<0.001). Patients with aggressive PTMC subtypes had higher rates of incomplete biochemical and structural response than patients with non-aggressive subtypes as well (p<0.001). Aggressive PTMC subtypes share many characteristics with histologically identical tumors>1 cm in size. Therefore, the histopathological subtype of PTMC should be taken into consideration to tailor a personalized management plan.

Effects of Treatment Adherence on Quality of Life in Hypoparathyroid Patients.

OBJECTIVES: This study aimed to evaluate the current situation of hypoparathyroid patients and to investigate the relationship between treatment adherence and quality of life. STUDY DESIGN: Prospective, multicentre study. METHODS: Adult patients presenting with the diagnosis of hypoparathyroidism to 20 different endocrinology clinics were included. They were receiving conventional therapies for hypoparathyroidism, using calcium, active vitamin D, and magnesium. We collected data on demographic features, disease- and treatment-related information, and results of routine laboratory tests, treatment adherence, and presence of complications. Beck Depression Inventory, Beck Anxiety Inventory, and Short Form-36 quality of life assessments were administered. RESULTS: Among the 300 patients studied, 60.7% were adherent to their treatment, and 34.1% had complications. Anxiety and depression scores were significantly higher in non-adherent versus treatment-adherent patients (p<0.001 and p=0.001, respectively). Most of the domains of quality-of-life scores were also significantly lower in non-adherent patients. Both anxiety and depression scores showed significant, negative correlations with serum calcium and magnesium concentrations (r=-0.336, p<0.001 and r=-0.258, p<0.001, respectively). CONCLUSIONS: Nearly 40% of the patients were non-adherent to conventional treatment for hypoparathyroidism, and such patients had higher anxiety and depression scores and poorer quality of life scores. Conventional treatment might not be sufficient to meet the needs of patients with hypoparathyroidism. In addition to seeking new therapeutic options, factors influencing quality of life should also be investigated and strategies to improve treatment adherence should be developed.

Comparison of echocardiographic findings in patients with nonfunctioning adrenal incidentalomas.

Adrenal incidentalomas (AIs) are usually discovered incidentally after imaging unrelated to adrenal glands. We aimed to evaluate standard risk factors for systemic atherosclerosis and echocardiographic changes in patients with nonfunctioning AIs and compare them with normal subjects. We evaluated 70 patients diagnosed with AIs and 51 healthy controls. Mean levels were determined for HbA1c, LDL, uric acid, fasting plasma insulin, HOMA, and neutrophil-to-lymphocyte ratio (NLR), and these values were found to be significantly higher in the patients than the controls. The mean left atrial diameter, interventricular septum thickness, posterior wall thickness, left ventricular mass, E-wave deceleration time, isovolumetric relaxation time, and the median ratio of the early transmittal flow velocity to the early diastolic tissue velocity (E/Em) were higher in patients with AIs compared to controls. The mitral annular early diastolic velocity was lower in patients with AIs. The mean aortic diastolic diameter, stiffness index (SI), and aortic strain were higher, and aortic distensibility was lower in the patients. The mean right ventricular diameter, right atrial major-axis diameter, and right atrial minor-axis diameter were statistically higher in the patient group than the controls. A negative correlation was found between the NLR and aortic strain and aortic distensibility, while a positive correction was found between the NLR and SI. We found altered left ventricular (LV) and right ventricular (RV) echocardiographic findings in patients with AIs without known cardiovascular disease. Aortic stiffness was also increased. These changes may be related to an increase in cardiovascular risk factors in AI patients.

A case of mediastinitis accompanied with hyperosmolar nonketotic coma.

Mediastinitis is a serious infection involving mediastinal spaces after cervical infections spread along the facial planes. A late diagnosis of mediastinitis may result in death. Here we present a diabetic patient suffered from mediastinit accompanied with hyperosmolar nonketotic coma. A 61 years old male patient with type 2 diabetes was admitted to our hospital, with complaint of generalized worsening and fever. A diagnosis of nonketotic hyperosmolar coma was done and proper treatment started immediately. Neck tomography revealed abscess formation in the upper mediastinum. The needle aspirat culture failed to show bacterial growth. After five days of antibiotic treatment the patient's symptoms resolved. The abscess formation and pleural effusion almost disappeared on control tomography. No similar case presentation was seen in the current literature. Apart from this case, mediastinit should be keep in mind when a patient suffered from dysphagia, fever and cervical swelling.

Autoimmune Fibrotic Adverse Reactions in One-Year Treatment with Cabergoline for Women with Prolactinoma.

AIM: Cabergoline is related to an elevated risk of fibrotic adverse reactions including cardiac valvular and pleuropulmonary fibrosis. We investigated pulmonary and cardiac valve fibrosis and immunological markers before and after 3 and 12 months of treatment with cabergoline in women with prolactinoma. MATERIAL-METHODS: The study included thirty-two women with newly diagnosed prolactinoma and 28 healthy women. CAB cumulative dose was 7.8±5.5 mg after 3-month therapy, and 31±22 mg after 12-month follow-up. The risk of autoimmune adverse fibrotic reactions related to CAB treatment including cardiac valvulopathy and pulmonary fibrosis were assessed by a transthoracic echocardiography and pulmonary function tests, respectively. Immunological markers including Antistreptolysin O, Rheumatoid factor, Immunglobuline E, Antinuchlear antibody were also evaluated. RESULTS: Before the start of CAB therapy, the total prevalence of trace grade of mitral, aortic, pulmonic, and tricuspid valve regurgitations were found as 34%, 3%, 6.3%, and 39 % respectively in women with prolactinoma. After improving of prolactin levels with CAB treatment, no change was found in the prevalence of the all valve regurgitations. There was no deterioration in pulmonary function tests. Rheumatoid factor was found higher in newly diagnosed women with prolactinoma than in healthy women (p=0.01), and this was improved by CAB therapy (p=0.005). CONCLUSION: The prospective study indicated that sufficient cabergoline doses for a period of one year treatment of prolactinoma were not found to be related to fibrotic adverse reactions including cardiac valvular and pulmonary fibrosis or increased levels of immunological marker, apart from rheumatoid factor. For the first time Rf was found higher in newly diagnosed women with prolactinoma and was improved after cabergoline therapy.

Distribution of RET Mutations and Evaluation of Treatment Approaches in Hereditary Medullary Thyroid Carcinoma in Turkey.

OBJECTIVE: This retrospective multicenter study, centrally conducted and supported by the Society of Endocrinology and Metabolism of Turkey, aimed to evaluate the impact of free RET proto-oncogene testing in medullary thyroid carcinoma (MTC) patients. Surgical timing, adequacy of the treatment, and frequency of prophylactic thyroidectomy (PTx) in mutation carriers were also assessed. METHODS: Genetic testing for MTC and pheochromocytoma was conducted between July 2008 and January 2012 in 512 patients. Application forms and RET mutation analyses of these patients whose blood samples were sent from various centers around Turkey were assessed retrospectively. An evaluation form was sent to the physicians of the eligible 319 patients who had confirmed sporadic MTC, familial MTC (FMTC), multiple endocrine neoplasia type 2 (MEN2), or who were mutation carriers. Physicians were asked to give information about the surgical history, latest calcitonin levels, morbidity, mortality, genetic screening, and PTx among family members. Twenty-five centers responded by filling in the forms of 192 patients. RESULTS: Among the 319 patients, RET mutation was detected in 71 (22.3%). Cys634Arg mutation was the most prevalent mutation (43.7%), followed by Val804Met in 18 patients (25.4%), and Cys634Tyr in 6 patients (8.5%). Among 192 MTC patients, the diagnosis was sporadic MTC in 146 (76.4%), FMTC in 14 (7.3%), MEN2A in 15 patients (7.9%), and MEN2B in one patient. The number of mutation carriers among 154 apparently sporadic MTC patients was 8 (5.2%). Ten patients were submitted to PTx out of twenty-four mutation carriers at a mean age of 35±19 years. CONCLUSION: Turkish people have a similar RET proto-oncogene mutation distribution when compared to other Mediterranean countries. Despite free RET gene testing, the number of the PTx in Turkey is limited and relatively late in the life span of the carriers. This is mainly due to patient and family incompliance and incomplete family counselling.

Changes in the before and after thyroxine treatment levels of adipose tissue, leptin, and resistin in subclinical hypothyroid patients.

BACKGROUND: Subclinical hypothyroidism (SH) occurs when serum thyroid stimulating hormone (TSH) concentrations are raised and serum thyroid hormone concentrations are normal. The effect of SH on the proinflammatory adipose cytokine releasing visceral adipose tissue (VAT) is not clear. The aim of this study is to identify the difference between the pre and posttreatment levels of VAT, leptin, and resistin in SH patients. METHODS: There were 51 SH patients and 43 age- and gender-matched healthy subjects included in the study. Thyroid functions, biochemical tests, leptin, resistin, and visceral and subcutaneous fat measurements were made. The measurements were repeated in the SH group in the third month following L-thyroxin treatment. RESULTS: Initially, high sensitivity C-reactive protein, carotid artery intima-media thickness (mm), leptin, and resistin levels were significantly higher in the SH group compared to the controls, while the other parameters were similar. While no correlation was observed between TSH levels and adipokines, a positive correlation was detected between waist circumference and leptin levels (r = 0.549, p < 0.01). Visceral adipose tissue was positively correlated to age, waist circumference, and leptin levels, but negatively correlated to free thyroxin (T4) levels (r = 0.419, p = 0.009; r = 0.794, p < 0.01; r = 0.515, p < 0.01 and r = - 0.416, p = 0.009, respectively). A significant decrease was observed in VAT volume, leptin, and resistin levels of SH patients following levothyroxine treatment. Conclusion The reduced VAT volume, leptin, and resistin levels in SH patients following treatment may support the idea that TSH affects adipose tissue functions.

Evaluation of atherosclerosis after cessation of cabergoline therapy in patients with prolactinoma.

OBJECTIVE: The aim of the study was to determine whether atherosclerotic risk markers exist at the moment and after withdrawal of cabergoline (CAB) therapy in patients who had taken a suitable dose of CAB therapy for a suitable period of time before cessation of CAB. METHODS: This study was designed as prospective cross-sectional. Out of a total of 115 patients with prolactinoma, 42 non-obese women with microprolactinoma, who met the Pituitary Society criteria (2006) for the withdrawal of long-term CAB therapy, and 30 healthy patients participated in our study. The number of patients excluded from the study were as follows: 34 patients with tumor shrinkage of less than 50%; 10 who received DA treatments for less than 2 years; 9 who were treated with bromocriptine; and 20 who had diabetes mellitus, hypertension, hyperlipidemia, obesity, renal disease, coronary arterial disease, or were tobacco smokers. The patients were evaluated for anthropometric, metabolic, and inflammatory parameters at the time of cessation of CAB therapy and at the 3rd and 12th months after the withdrawal of CAB therapy. Endothelial dysfunction was determined by flow-mediated dilation (FMD) of the brachial artery and carotid intima media thickness (IMT), which were assessed by high resolution ultrasonography (USG) by the same practitioner. RESULTS: At the moment of cessation of CAB therapy, the FMD percentage in patients with prolactinoma was worse than that in healthy controls (p=0.0029). After the withdrawal of CAB treatment, fibrinogen (p=0.036), mean platelet volume (MPV) (p<0.001), carotid IMT (p=0.041), and high-density lipoprotein cholesterol (HDL C) (p=0.048) were worse in the relapse patients than those in the remission patients. Furthermore, only MPV values were found to be significantly related to a relapse of hyperprolactinemia among all atherosclerotic risk markers [area under the curve: 0.830 (95% CI 0.685-0.974) (p<0.001)]. CONCLUSION: Unfavorable cardiovascular risk profiles are a problem for patients with prolactinoma during cessation and after CAB withdrawal.

Normocalcemic hyperparathyroidism is associated with complications similar to those of hypercalcemic hyperparathyroidism.

Normocalcemic primary hyperparathyroidism (NC-PHPT) is a variant of hyperparathyroidism, characterized by normal serum calcium levels, high parathyroid hormone (PTH) and normal 25-OH vitamin D status. The present study aimed to compare complications related to hyperparathyroidism in patients with NC-PHPT and hypercalcemic PHPT (HC-PHPT). We retrospectively evaluated the records of 307 PHPT patients between January 2010 and March 2013. We excluded patients with impaired renal function and liver failure. All patients underwent a biochemical and hormonal examination including serum glucose, albumin, total calcium, phosphorus, creatinine, lipoproteins, PTH and 25-OH vitamin D. Nephrolithiasis and bone mineral density were documented based on a review of the medical records. The study population consisted of 36 (12 %) males and 271 (88 %) females with a mean age of 53.3 ± 9.5 years (29-70 years). Twenty-three of the patients were diagnosed with NC-PHPT (group 1) and 284 were diagnosed with HC-PHPT (group 2). There were no significant differences in terms of age, gender, prevalence of hypertension, low bone mineral density and kidney stones between the groups. The mean thyroid-stimulating hormone (TSH) and low-density lipoprotein (LDL) levels were significantly higher in group 1 than in group 2. Our study found that patients with NC-PHPT have similar several complications as patients with HC-PHPT. NC-PHPT patients have higher TSH levels despite being within the normal range, and higher LDL-C levels than patients with HC-PHPT. However, this relationship needs to be clarified in future studies with larger cohorts.

Irisin levels in the progression of diabetes in sedentary women.

CONTEXT: The recently discovered peptide irisin has been hypothesized to be a regulator of body metabolism. However, studies ended up with controversial results. In the present study, we aimed to investigate irisin levels in sedentary women at different stages of prediabetes. DESIGN, SETTING, AND SUBJECTS: We performed a cross-sectional analysis of circulating levels of irisin in 263 females similar for age and body mass index (BMI) and the groups included 52 normal glucose tolerance (NGT), 60 isolated impaired fasting glucose (IFG), 36 isolated impaired glucose tolerance (IGT), 65 both IFG and IGT and 50 type 2 diabetic patients. All patients were exercising less than 150 min/week. RESULTS: Plasma irisin levels were significantly lower in IFG+IGT (2.86 ± 0.6 µg/mL, p: 0.019) and T2DM (2.83 ± 0,5 µg/mL, p: 0.005) patients compared to NGT (3.16 ± 0.3 µg/mL) patients. After age adjustment there was a negative correlation between irisin and BMI (r: -0.141; p: 0.031), postprandial glucose (PPG) (r: -0.142; p: 0.030), low density lipoprotein-cholesterol (LDL-C) (r: -0.138; p: 0.035) and triglyceride (TG) (r: -0.214; p: 0.001) and a positive correlation between irisin and high density lipoprotein-cholesterol (HDL-C) (r:.142; p: 0.030). After adjustment for age and BMI; PPG (r: -0. 137; p: 0.037), LDL-C (r: -0. 143; p: 0.029) and TG (r: -0.203; p: 0.002) were considered to correlate with irisin levels. Subgroup analysis revealed that TG levels were correlated with irisin levels in IFG (r: -0.347; p: 0.014) and IGT (r: -0.397; p: 0.030) patients. CONCLUSION: In our cohort of sedentary women, irisin levels were lower in patients with IFG+IGT and with diabetes than in patients with NGT. There is no correlation between irisin levels and BMI. Irisin is a myokine decreasing gradually with the progression of glucose intolerance and T2DM and is not correlated with BMI in sedentary women.

High prevalence of Hashimoto's thyroiditis in patients with polycystic ovary syndrome: does the imbalance between estradiol and progesterone play a role?

OBJECTIVE: Some similar factors, such as genetic susceptibility and subinflammation/autoimmunity, contribute to development of both polycystic ovary syndrome (PCOS) and Hashimoto's thyroiditis (HT), suggesting a potential pathogenic link between the two common disorders. In this study, we investigated the relationship between PCOS and HT, considering the possible effect of PCOS-related hormonal and metabolic factors on thyroid autoimmunity. METHODS: Eighty-six reproductive-age women diagnosed with PCOS according to Rotterdam criteria and 60 age-BMI matched control women were included in the study. All subjects had thyroid function tests, thyroid peroxidase anti-body (anti-TPO), thyroglobulin anti-body (anti-Tg), LH, FSH, estradiol, progesterone, androgens, fasting glucose, insulin, lipid, homeostasis model assessment insulin resistance (HOMA-IR) levels, thyroid and pelvic ultrasounds. RESULTS: TSH, anti-TPO (p = 0.017), anti-Tg (p = 0.014), LH, DHEAS, testosterone, and HOMA-IR levels were significantly higher and progesterone were lower in PCOS women than in controls. Free T4, free T3, FSH, estradiol levels and thyroid volume were similar between the two groups. A higher percentage of PCOS patients had elevated TSH (26.7 and 5%; p = 0.001), anti-TPO (26.7 and 6.6%; p = 0.002), and anti-Tg (16.2 and 5%; p = 0.039). HT was more common in PCOS patients compared to controls (22.1 and 5%; p = 0.004). Estradiol (p = 0.003) were higher in anti-TPO positive PCOS women than anti-TPO negative ones. Anti-TPO was correlated positively with estradiol, estradiol/progesterone ratio, and TSH. CONCLUSIONS: This study demonstrated a higher prevalence of HT, elevated TSH, anti-TPO, and anti-Tg levels in PCOS patients. Increased estrogen and estrogen/progesterone ratio seem to be directly involved in high anti-TPO levels in PCOS patients.

Should insulin resistance be screened in lean hirsute women?

The role of insulin resistance (IR) is well-documented in obese women with polycystic ovary syndrome (PCOS). Controversies exist concerning the presence of IR in idiopathic hirsutism (IH) or if it is a manifestation of high body mass index (BMI). We aimed to investigate the presence/absence of IR in lean hirsute women. One-hundred fifty-one lean women with hirsutism [96 PCOS (group 1) and 55 IH (group 2)] and 58 age-and BMI-matched healthy controls (group 3) were recruited in the study (mean age 25.21 ± 6.1 versus 26.26 ± 4.6years; BMI 21.79 ± 1.7 versus 22.02 ± 2.2 kg/m(2), respectively). Significantly higher insulin and HOMA-IR, and significantly lower fasting glucose insulin ratio (FGIR), quantitative insulin sensitivity check index (QUICKI), reciprocal insulin, and Raynaud index were detected in groups 1 and 2 than in group 3 (p < 0.05). These IR indices were similar between groups 1 and 2. The number of patients with IR (HOMA-IR > 2, FGIR < 7.2, or QUICKI < 0.357) was significantly higher in groups 1 and 2 than in group 3, but was similar between groups 1 and 2. A higher frequency of IR occurs in lean hirsute women regardless of they having PCOS or IH. IR may contribute to aetiopathogenesis of IH, or may cause some metabolic abnormalities in these patients.

Higher body mass index and larger waist circumference may be predictors of thyroid carcinoma in patients with Hürthle-cell lesion/neoplasm fine-needle aspiration diagnosis.

OBJECTIVE: High body mass index (BMI) has been found to be associated with raised thyroid cancer risk, particularly in women. We examined the associations for BMI and waist circumference (WC) with thyroid cancer risk among women with Hürthle-cell lesion/neoplasm (HLN) on fine-needle aspiration biopsy (FNAB) with the hypothesis that BMI and WC could guide the management of these challenging indeterminate lesions. METHODS: This cross-sectional study included 224 women with HLN who underwent thyroidectomy. In all patients, TSH and thyroid auto-antibodies were evaluated, and thyroid nodule features were recorded. Patients were grouped according to BMI (<30 or ≥30 kg/m(2)) and WC (<88 or ≥88 cm). Relationships of thyroid cancer with BMI and WC were assessed using logistic regression analysis. RESULTS: Mean weight, BMI (31·26 ± 5·1 vs 26·47 ± 5·9, P < 0·001), WC (98·23 ± 7·6 vs 86·18 ± 11, P = 0·001), and proportion of patients with high BMI (≥30 kg/m(2)) (65·9 vs 33·8%, P < 0·001) or large WC (≥88 cm) (84·1 vs 47·9%, P < 0·001) were significantly higher in malignant group compared to benign group. In regression analysis, BMI and WC significantly associated with existence of malignancy. Malignancy risk was 3·819-fold higher (95% CI: 2·068-7·054) in BMI≥30 kg/m(2) group compared to BMI<30 kg/m(2), which was independent of TSH and age. Large WC was also associated with increased risk (OR = 5·593, 95% CI: 2·736-11·434). Baseline tumour characteristics were similar according to BMI and WC groups. CONCLUSIONS: A great BMI and large WC were associated with higher thyroid cancer risk in patients with FNAB diagnosis of HLN. Further studies are needed to use BMI or WC in the management of patients with HLN.

Effect of androgen replacement therapy on atherosclerotic risk markers in young-to-middle-aged men with idiopathic hypogonadotropic hypogonadism.

OBJECTIVE: Idiopathic hypogonadotropic hypogonadism is a rare disorder. This study evaluated the effect of androgen replacement therapy on atherosclerotic risk markers in young-to-middle-aged men with this disorder. DESIGN AND METHODS: Forty-three male patients aged 30 (range: 24-39 years) who were newly diagnosed with idiopathic hypogonadotropic hypogonadism and 20 age-, sex- and weight-matched controls (range: 26-39 years) were included in the study. Androgen replacement therapy was given according to the Algorithm of Testosterone Therapy in Adult Men with Androgen Deficiency Syndromes (2010; Journal of Clinical Endocrinology and Metabolism, 95, 2536). The patients were assessed at a pretreatment visit and 3 and 6 months after the treatment. Inflammatory markers and lipid parameters were evaluated. Endothelial function was assessed with brachial flow-mediated dilation of a brachial artery and high-resolution ultrasonography of the carotid intima-media thickness. RESULTS: The carotid intima-media thickness (P < 0·001) was higher and the brachial flow-mediated diameter (P = 0·002) was lower in patients with idiopathic hypogonadotropic hypogonadism compared to the control subjects at the pretreatment visit. There was a negative correlation between the total testosterone level and carotid intima-media thickness (r = -0·556, P = <0·001). The carotid intima-media thickness and per cent flow-mediated diameter were significantly improved in the patient group 6 months after the androgen replacement therapy (P = 0·002 and 0·026, respectively). CONCLUSIONS: This study indicated that low total testosterone levels can be considered a significant marker of atherosclerosis in patients with idiopathic hypogonadotropic hypogonadism and that androgen replacement therapy significantly reduces atherosclerotic risk markers in these patients after 6 months.

Visceral fat measurement by ultrasound as a non-invasive method - can it be useful in evaluating subclinical atherosclerosis in male patients with hypopituitarism and growth hormone deficiency?

INTRODUCTION: Growth hormone (GH) deficiency, either isolated or combined with other pituitary hormone deficiencies, is associated with increased mortality and abnormal body composition, particularly visceral adiposity. We aimed to investigate the effects of GH deficiency with or without sex steroid deficiencies on ultrasonographic visceral fat (VF) and cardiovascular risk markers in patients with hypopituitarism on conventional hormone replacement therapy. MATERIAL AND METHODS: Forty hypopituitarism patients (24 women, 16 men; mean age 48 ± 16.1 years) with GH deficiency and 15 age- and sex-matched healthy controls were included in this cross-sectional study. The patients were stable on conventional hormone replacement but they were not on GH therapy. Patients who had sex steroid replacement were classified as Group 1 (n = 19), and patients who did not use sex steroids were classified as Group 2 (n = 21). Anthropometric measurements were performed. VF in three regions, subcutaneous fat, and carotid intima-media thickness (CIMT) were measured. VF volume was calculated by using a formula. RESULTS: Visceral fat volume and mean CIMT were significantly higher in patients than healthy controls (p = 0.001 and 0.019 respectively). Homocysteine and hs-CRP were higher in patients (p < 0.05). In males, VF volume and VF thickness measured between abdominal muscle and splenic vein were significantly correlated with CIMT (r = 0.54, p = 0.047 and r = 0.66, p = 0.010 respectively). Furthermore, there was a strong positive correlation between VF thickness in pararenal region and homocysteine (r = 0.74, p = 0.001) in males. CONCLUSIONS: VF volume evaluated by ultrasound can be accepted as a cause of subclinical atherosclerosis in GH deficient hypopituitary patients, particularly males.

Non-functioning adrenal incidentalomas are associated with higher hypertension prevalence and higher risk of atherosclerosis.

INTRODUCTION: Adrenal incidentalomas (AIs) have been associated with an increased incidence of several cardiovascular risk factors. The aim of this study was to investigate plasma adiponectin, leptin, resistin, homocysteine, high sensitive C-reactive protein levels, and carotid intima media thickness (CIMT) in patients with non-functioning AI (NFAI). MATERIALS AND METHODS: This study included data from 28 patients with NFAI (Group 1) and 41 controls (Group 2). Of the patients, 50 were female and 19 were male, and the mean age was 46.7 (range 37-65) years. RESULTS: There were no significant differences between Group 1 and 2 in terms of age, sex, or BMI. Hypertension prevalence was significantly higher in the NFAI group than in the control group (p = 0.01). Both groups had similar lipid, blood glucose, homocysteine, uric acid, high-sensitivity CRP levels. Adiponectin, leptin, and resistin levels were similar in both groups. CIMTs were significantly higher in the NFAI group. CONCLUSION: There is increasing evidence that several cardiometabolic risk factors occur with higher prevalence in non-functioning adrenal incidentaloma patients compared to age-matched healthy subjects. In our study, hypertension prevalence and CIMT were higher in the NFAI group. Serum adipokine levels were similar for both groups.

Association of mean platelet volume with androgens and insulin resistance in nonobese patients with polycystic ovary syndrome.

BACKGROUND: Mean platelet volume (MPV) is generally accepted as a new marker of cardiovascular disease risk in several studies. OBJECTIVES: This study aimed to determine the association of MPV with androgen hormones and insulin resistance (IR) in nonobese patients with polycystic ovary syndrome (PCOS). PATIENTS AND METHODS: A total of 136 patients with newly diagnosed reproductive-age PCOS (regarding the criteria of new PCOS phenotypes, based on the Rotterdam criteria) who were nonobese with the mean age of 25 years (25.39 ± 5.51) and mean body mass index (BMI) of 21 kg/m(2) (22.07 ± 2.13) were included. In addition, 59 healthy subjects with mean age of 26 years (22.07 ± 2.13) and mean BMI of 22 kg/m(2) (21.52 ± 3.84) were recruited as control. Total blood count (including MPV), total testosterone, free testosterone, dehydroepiandrosterone-sulfate (DHEAS), and androstenedione levels were recorded. IR was calculated from blood chemistry measurements of fasting insulin and glucose according to updated homeostasis model assessment. RESULTS: No differences were observed in mean MPV values between patients and control group (9.02 fL (8.5-10.1) and 8.9 fL (7.7-9.1), respectively; P = 0.777). MPV values were similar among nonobese patients with and without IR and control subjects (P > 0.05). We detected significantly lower values of MPV in patients with hyperandrogenemia in comparison to patients with normal androgen levels (8.7 and 9.5 fL, P = 0.012). There was a negative correlation between total testosterone, DHEAS, and MPV (P = 0.016, r = -0.229; and P = 0.006, r = -0.261, respectively). Multiple logistic regression analyses confirmed the independence of these associations. CONCLUSIONS: Our study revealed that nonobese women with and without PCOS have similar MPV values. While IR does not have any effect on MPV, elevated androgen levels are associated with a low MPV in nonobese patients with PCOS.