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.

Can Age at Diagnosis and Sex Improve the Performance of the American Thyroid Association Risk Stratification System for Prediction of Structural Persistent and Recurrent Disease in Patients With Differentiated Thyroid Carcinoma? A Multicenter Study.

OBJECTIVE: Although the age at diagnosis has been suggested as a major determinant of disease-specific survival in the recent TNM staging system, it is not included in the recent American Thyroid Association (ATA) guidelines to estimate the risk of recurrence. Nevertheless, the effect of sex on differentiated thyroid carcinoma (DTC) recurrence is controversial. Therefore, this multicenter study was conducted to assess whether age at diagnosis and sex can improve the performance of the ATA 3-tiered risk stratification system in patients with DTC with at least 5 years of follow-up. METHODS: In this study, the computer-recorded data of the patients diagnosed with DTC between January 1985 and January 2016 were analyzed. Only patients with proven structural persistent/recurrent disease were selected for comparisons. RESULTS: This study consisted of 1691 patients (female, 1367) with DTC. In Kaplan-Meier analysis, disease-free survival (DFS) was markedly longer in females only in the ATA low-risk category (P = .045). Nevertheless, a markedly longer DFS was observed in patients aged <45 years in the ATA low- and intermediate-risk categories (P = .004 and P = .009, respectively), whereas in patients aged <55 years, DFS was markedly longer only in the ATA low-risk category (P < .001). In the Cox proportional hazards model, ages of ≥45 and ≥55 years at diagnosis and the ATA risk stratification system were all independent predictors of persistent/recurrent disease. CONCLUSION: Applying the age cutoff of 45 years in the ATA intermediate- and low-risk categories may identify patients at a higher risk of persistence/recurrence and may improve the performance of the ATA risk stratification system, whereas sex may improve the performance of only the ATA low-risk category.

Thiol/disulfide homeostasis and its relationship with insulin resistance in patients with rosacea.

BACKGROUND: Rosacea is a chronic inflammatory cutaneous disease that can be associated with cardiometabolic disorders. Oxidative stress is included in the pathogenesis of rosacea, and thiol-disulfide homeostasis (TDH) acts as antioxidants. OBJECTIVE: To evaluate the TDH and metabolic parameters in patients with rosacea. MATERIAL AND METHODS: A total of 42 rosacea patients and 50 controls participated in this prospective study. Demographic data, clinical entities, anthropometric measurements, and laboratory findings were recorded. Additionally, TDH was measured by an automated spectrophotometric method. RESULTS: Rosacea patients had greater body mass index values (27.9 ± 5.2 kg/m² vs. 23 ± 1.4 kg/m², p < 0.001), waist-hip ratios (0.87 ± 0.1 vs. 0.77 ± 0.8, p < 0.001), and insulin resistance (3.0 ± 2.0 vs. 1.3 ± 0.5, p < 0.001) compared with controls. Disulfide levels, the disulfide/native thiol ratio (DNTR), and the disulfide/total thiol ratio (DTTR) were increased (p < 0.05) in rosacea patients. Native thiol and total thiol levels and the native/total thiol ratio (NTTR) were decreased in rosacea patients (p < 0.05). Different rosacea subtypes had no effect on oxidative stress markers. The duration of illness and insulin resistance values significantly correlated with DNTR and DTTR in the rosacea group (p < 0.05). CONCLUSION: Rosacea has a metabolic milieu with increased oxidative stress and insulin resistance.

The relationship among androgens, insulin resistance and ghrelin polymorphisms in post-adolescent male patients with severe acne vulgaris.

INTRODUCTION: Ghrelin has anti-inflammatory and immunomodulatory activities. Data about the role of ghrelin and ghrelin polymorphisms in the development of acne vulgaris in post-adolescent male patients are limited. AIM: To evaluate the role of serum androgens, insulin resistance, ghrelin and ghrelin polymorphisms in severe acne vulgaris. MATERIAL AND METHODS: Thirty-five post-adolescent male patients with a mean age of 28.0 ±5.4 years and 33 age-and BMI-matched controls were enrolled. Serum androgens, lipids, insulin sensitivity parameters and ghrelin levels were determined. The PCR method was used for GHRL polymorphisms (rs27647, rs696217 and rs34911341 genotypes). RESULTS: Patients had similar anthropometric measures to controls, except a significantly higher WHR in patients (0.92 ±0.06 vs. 0.86 ±0.08, p < 0.05). Also, FPG, HOMA-IR values, lipid profile and serum androgen levels were similar. Interestingly, patients had significantly lower ghrelin levels than controls (4.5 ±5.8 vs. 101.2 ±86.5 pg/ml, p < 0.001). The frequencies of rs696217 and rs34911341 genotypes were similar whereas the distribution of rs27647 alleles was significantly different between the groups (p < 0.05). GA and GG genotypes of GHRL rs27647 polymorphism indicated an increased risk of developing acne vulgaris (OR = 11.156, 95% CI: 2.864-43.464, OR = 5.312, 95% CI: 1.269-22.244, respectively; p < 0.05). Patients with rs27647-AA polymorphism had significantly lower GAGS scores than other groups (AA genotype 6.7 ±14.1 vs. GA genotype 24.6 ±15.7 and GG genotype 19.4 ±17.9, p < 0.001). None of the polymorphisms had a significant effect on metabolic parameters, insulin sensitivity and serum ghrelin levels. CONCLUSIONS: Decreased ghrelin levels and GA and GG genotypes of GHRL gene rs27647 polymorphism may have a role in the pathogenesis of acne vulgaris.

Adiponectin levels decrease independently of body mass index and diabetes type after the normalization of hyperglycemia

Background/aim: Acute hyperglycemia is generally a frequently encountered condition in the emergency department (ED), because it is seen as a complication of diabetes mellitus (DM). In this study, we aimed to detect the change in adiponectin levels during acute hyperglycemic states and after normalization of blood glucose with insulin treatment. Materials and methods: Forty-eight patients over the age of 18 years who were admitted to the ED with acute hyperglycemia were included in the study. Serum samples were taken from patients on admission and 6 h after the normalization of blood glucose with insulin treatment, and adiponectin levels were measured in both samples. Results: There were 21 female and 27 male patients with a median age of 58.7 ± 18 years. All patients' blood glucose levels were normalized with insulin treatment according to international recommendations. Serum adiponectin levels decreased significantly after the normalization of blood glucose in the whole group. Adiponectin levels decreased from 28.9 ± 16.5 to 12.1 ± 10.9 µg/mL (P < 0.0001) in the whole group. This decrease was independent of diabetes type and body mass index. Conclusion: Normalization of blood glucose in patients with hyperglycemia caused a decrease in adiponectin levels, independent of diabetes type and/or body weight in an acute emergency setting. Inhibited upregulation of adiponectin secretion and/or blunted suppressive effect of insulin due to hyperglycemia or exogenous insulin administration may have caused the decrease in adiponectin levels.

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.

Iatrogenic Cushing's Syndrome with Subsequent Adrenal Insufficiency in a Patient with Psoriasis Vulgaris Using Topical Steroids.

Iatrogenic Cushing's syndrome (ICS) is usually related to prolonged and/or high-dose oral or parenteral steroid use. Psoriasis vulgaris (PV) is chronic inflammatory disease and characterized by periods of attack and remission. Topical steroid (TS) is the first choice of treatment for localized and mild PV. The development of systemic side effects of the steroids is usually not observed after TS application. But the risk of developing ICS still exists. In the literature, there are a few adult cases who developed ICS and subsequent adrenal insufficiency associated with TS. In this article, a male patient with PV developing ICS and secondary adrenal insufficiency after treatment of TS for 12 years is presented.

Association between ACE and AGT polymorphism and cardiovascular risk in acromegalic patients.

PURPOSE: Whether the renin-angiotensin-aldosterone system plays a role or not in the development of cardiovascular morbidity in acromegaly patients is unknown. The aim of the study was to investigate the association between ACE (I/D) and AGT (M235T) gene polymorphisms and cardiovascular and metabolic disorders in the acromegaly. METHODS: The study included one hundred and seventeen acromegalic patients (62 F/55 M, age: 50.2 ± 12.3 years) and 106 healthy controls (92 F/14 M, age: 41.4 ± 11.3 years). PCR method was used to evaluate the prevalence of ACE and AGT genotype. RESULTS: The genotypes of ACE polymorphism in acromegalic patients were distributed as follows; 41.0% (n: 48) for DD, 44.4% (n: 52) for ID and 14.5% (n: 17) for II genotype. The control group had significantly different distribution of the ACE polymorphism [48.1% (n: 51) for DD, 25.5% (n: 27) for ID and 26.4% (n: 28) for II genotype]compared to acromegalic group. Regarding AGT polymorphism, AGT-MT genotype was seen in 88.9% of the acromegalic patients while MM and TT genotype (9.4% and 1.7%, respectively) were present in the rest. The controls had similar distribution of the AGT genotype with the acromegaly group (80.2% MT genotype, 15.1% MM genotype and 4.7% TT genotype). Due to the small number of patients with TT allele (n: 2), T carriers for AGT genotype (AGT-MT+TT) were subgrouped and compared to those with AGT-MM group. ACE-DD, ID and II groups had similar anthropometric measures, blood pressure values and baseline GH and IGF-1 levels. Significantly higher baseline GH levels were found in AGT-MM group compared to T allele carriers [40 (16-60) vs. 12 (5-36) µg/L, p < 0.05]. The compared groups in both polymorphisms had similar fasting plasma glucose levels. Patients with ACE-II genotype had significantly higher HDL-C levels compared to those with ACE-DD and ACE-ID polymorphisms (p < 0.05) whereas there was no significant difference in lipid profile between AGT-MM group and AGT-T allele carriers. Moreover, the compared groups in both polymorphisms had similar distribution of hyperlipidemia, hypertension, impaired glucose metabolism (prediabetes or type 2 diabetes mellitus) and coronary artery disease. In terms of echocardiographic parameters, systolic and diastolic function was similar among the groups in ACE and AGT genotypes. Interestingly, AGT-MM group had higher mitral inflow Apeak values than T allele carriers (0.94 ± 0.46 vs. 0.73 ± 0.20; p = 0.051). No significant difference was observed in LV mass index values in acromegalic patients among the groups in both polymorphisms. CONCLUSIONS: Both ACE (I/D) and AGT (M235T) gene polymorphisms do not seem to have a significant effect on the development of clinical properties or cardiovascular comordities of acromegalic patients.

Oxidative Stress and Periodontal Disease in Obesity.

Periodontal disease is a chronic inflammatory disease of the jaws and is more prevalent in obesity. Local and systemic oxidative stress may be an early link between periodontal disease and obesity. The primary aim of this study was to detect whether increased periodontal disease susceptibility in obese individuals is associated with local and systemic oxidative stress. Accordingly; we analyzed periodontal status and systemic (serum) and local (gingival crevicular fluid [GCF]) oxidative status markers in young obese women in comparison with age-matched lean women.Twenty obese and 20 lean women participated. Periodontal condition was determined by clinical periodontal indices including probing depth, clinical attachment level, gingival index, gingival bleeding index, and plaque index. Anthropometric, hormonal, and metabolic measurements were also performed. Blood and GCF sampling was performed at the same time after an overnight fasting. Serum and GCF total antioxidant capacity (TAOC), and total oxidant status (TOS) levels were determined, and oxidative stress index (OSI) was calculated.Clinical periodontal analyses showed higher gingival index and gingival bleeding index in the obese group (P = 0.001 for both) with no significant difference in probing depth, clinical attachment level, and plaque index between the obese and the lean women. Oxidant status analyses revealed lower GCF and serum TAOC, and higher GCF and serum OSI values in the obese women (P < 0.05 for all). GCF TOS was higher in the obese women (P < 0.05), whereas there was a nonsignificant trend for higher serum TOS in obese women (P = 0.074). GCF TAOC values showed a negative correlation with body mass index, whereas GCF OSI was positively correlated with fasting insulin and low-density lipoprotein-cholesterol levels (P < 0.05 for all). Clinical periodontal indices showed significant correlations with body mass index, insulin, and lipid levels, and also oxidant status markers.Our results suggest that young obese, otherwise healthy, women show findings of early periodontal disease (gingival inflammation) compared with age-matched healthy lean women, and that local/periodontal oxidative stress generated by obesity seems to be associated with periodontal disease.

The association between thyroid volume, L-thyroxine therapy and hepatocyte growth factor levels among patients with euthyroid and hypothyroid goitrous and non-goitrous Hashimoto's thyroiditis versus healthy subjects.

OBJECTIVE: Hashimoto's thyroiditis (HT) is the most common etiology of hypothyroidism in regions where iodine deficiency is not a concern. To date, many clinical investigations have been conducted to elucidate its pathogenesis. Several growth factors have been shown to have a role in its development. Hepatocyte growth factor (HGF) is one of the aforementioned molecules. We aimed to demonstrate whether HGF is responsible for HT and goiter development. Also, we aimed to test the hypothesis that levo-thyroxine sodium therapy will suppress HGF levels. MATERIALS AND METHODS: Sixty-one premenopausal women who were admitted to our outpatient clinic between November 2010 and September 2011 were enrolled. Three groups were determined according to their thyroid function tests (TFTs) as euthyroid Hashimoto's, control and subclinical hypothyroid Hashimoto's groups. Basal TFTs, anti-thyroid peroxidase (anti-TPO), anti-thyroglobulin (anti-tg), thyroid ultrasonography (USG) and HGF were studied and recorded. Subclinical hypothyroid HT patients received levo-thyroxine sodium replacement therapy, and were re-assessed for the same laboratory and radiologic features after a median 3.5 month follow-up. RESULTS: Basal HGF levels were not different between groups. In the subclinical hypothyroidism group, HGF levels (752.75 ± 144.91 pg/ml vs. 719.37 ± 128.05 pg/ml; p = 0.496) and thyroid volumes (12.51 ± 3.67 cc vs. 12.18 ± 4.26 cc; p = 0.7) before and after treatment did not change significantly. No correlations were found between HGF and other parameters. HGF levels were similar between subjects with nodular goiter and normal thyroid structure. CONCLUSIONS: HGF was not shown to be associated with HT and goiter development. In addition, levo-thyroxine sodium replacement therapy did not alter serum HGF levels significantly.

The clinical and cardiometabolic effects of d3-growth hormone receptor polymorphism in acromegaly.

PURPOSE: Exon 3-deleted GH receptor variant (d3-GHR) is associated with increased responsiveness to exogenous GH. The aim of this study was to determine the effect of d3-GHR polymorphism on the GH/IGF-1 relationship, clinical parameters, and comorbidity in acromegalic patients. METHODS: The study included 118 acromegalic patients (61 female and 57 male; mean age: 50.3 ± 12.2 years) and 108 healthy controls (94 female and 14 male: mean age: 41.1 ± 11.1 years). The prevalence of GHR genotypes was evaluated via PCR. RESULTS: In all, 71 (60.2%) patients had the fl/fl-GHR genotype, 40 (33.9%) were heterozygous for the fl/d3-GHR genotype, and 7 (5.9%) were homozygous for the d3/d3-GHR genotype. The prevalence of fl/fl-GHR, fl/d3-GHR, and d3/d3-GHR genotypes in the control group was 57.4, 29.6, and 13.0%, respectively-similar prevalences as in the patient group. Patients that were heterozygous and homozygous for the d3 allele were subgrouped (d3-GHR subgroup), and were compared to those with the fl/fl-GHR genotype (fl/fl-GHR subgroup). Anthropometric measures, features of pituitary adenoma, and baseline GH and IGF-1 levels were similar in both subgroups. The prevalence of coronary artery disease, hypertension, hyperlipidemia, type 2 diabetes mellitus, and multinodular goiter did not differ between patient subgroups. In total, 24 (20.3%) of the patients had cancer and the prevalence of cancer was similar in the d3-GHR (14.9%) and fl/fl-GHR (23.9%) subgroups (P = 0.23). More of the acromegalic patients that were d3 carriers had discordant GH and IGF-1 levels at baseline and post surgery, but the difference was not significant. A significant correlation between basal GH and IGF-1 levels was observed only in the patients with the fl/fl-GHR genotype (R(2) = 0.227, P < 0.001). CONCLUSION: The d3-GHR variant genotype did not have an effect on clinical features or comorbidity in acromegalic patients, but it might play a role in GH/IGF-1 level discordance in acromegaly.

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.

Assessment of cardiac autonomic functions by heart rate recovery, heart rate variability and QT dynamicity parameters in patients with acromegaly.

Cardiovascular complications are the most common causes of morbidity and mortality in acromegaly. However, there is little data regarding cardiac autonomic functions in these patients. Herein, we aimed to investigate several parameters of cardiac autonomic functions in patients with acromegaly compared to healthy subjects. We enrolled 20 newly diagnosed acromegalic patients (55% female, age:45.7 ± 12.6 years) and 32 age- and gender-matched healthy subjects. All participants underwent 24 h Holter recording. Heart rate recovery (HRR) indices were calculated by subtracting 1st, 2nd and 3rd minute heart rates from maximal heart rate. All patients underwent heart rate variability (HRV) and QT dynamicity analysis. Baseline characteristics were similar except diabetes mellitus and hypertension among groups. Mean HRR1 (29.2 ± 12.3 vs 42.6 ± 6.5, p = 0.001), HRR2 (43.5 ± 15.6 vs 61.1 ± 10.8, p = 0.001) and HRR3 (46.4 ± 16.2 vs 65.8 ± 9.8, p = 0.001) values were significantly higher in control group. HRV parameters as, SDNN [standard deviation of all NN intervals] (p = 0.001), SDANN [SD of the 5 min mean RR intervals] (p = 0.001), RMSSD [root square of successive differences in RR interval] (p = 0.001), PNN50 [proportion of differences in successive NN intervals >50 ms] (p = 0.001) and high-frequency [HF] (p = 0.001) were significantly decreased in patients with acromegaly; but low frequency [LF] (p = 0.046) and LF/HF (p = 0.001) were significantly higher in acromegaly patients. QTec (p = 0.009), QTac/RR slope (p = 0.017) and QTec/RR slope (p = 0.01) were significantly higher in patients with acromegaly. Additionally, there were significant negative correlation of disease duration with HRR2, HRR3, SDNN, PNN50, RMSSD, variability index. Our study results suggest that cardiac autonomic functions are impaired in patients with acromegaly. Further large scale studies are needed to exhibit the prognostic significance of impaired autonomic functions in patients with acromegaly.

Increased thyroid cancer risk in acromegaly.

Acromegaly increases cancer risk. We aimed to determine the prevalence and the predictors of tumors in acromegalic patients treated at our department. We retrospectively evaluated 160 acromegalic patients [79 female (mean age 52.0 ± 10.4 years) and 81 male (mean age 49.1 ± 12.4 years)] between 1990 and 2012, with a mean follow up period of 7.1 ± 5.7 years. The patients were screened with colonoscopy, mammography, thyroid and prostate ultrasonography. Malignancy was found in 34 (21.3%) patients. No significant difference was observed in the distribution of malignancy among sexes (20.3% in F vs. 22.2% in M). Thyroid cancer was the most frequent (n = 17, 10.6%) followed by the breast cancer (n = 4, 2.5%) and colorectal cancer (n = 3, 1.8%). Renal cell cancer in two patients, bladder cancer in two patients, periampullary tumor, rectal carcinoid tumor, malignant melanoma, prostate cancer, lung cancer, parotid mucoepidermoid carcinoma and malignant mesenchymal tumor in brain in one patient were detected. One patient had both thyroid and renal cell cancer. Age of patients at diagnosis of acromegaly was significantly higher in patients with cancer (45.8 ± 9.9 vs. 40.9 ± 11.3 years, p < 0.05). No significant difference was found in duration of the disease, initial GH levels and IGF-1% upper limit of normal values, the prevalence of diabetes, hypertension, coronary heart disease, hyperlipidemia and treatment modalities between the patients with/without cancer. In logistic regression analysis, older age at diagnosis was associated with malignancy risk. The risk of cancer in acromegaly especially the thyroid cancer risk seems to be more increased than known in the literature. Therefore, acromegaly patients should be screened routinely for cancer, especially for thyroid cancer due to it being up to four times higher prevalence than breast and colorectal cancer.

Vitamin D status and seasonal changes in plasma concentrations of 25-hydroxyvitamin D in office workers in Ankara, Turkey.

BACKGROUND: Lack of sun exposure is one of the primary causes of epidemic vitamin D deficiency worldwide. The aim of this study was to investigate vitamin D status and seasonal changes in summer and winter in office workers. METHODS: This study was conducted in Ankara located at 39° 52' 30" N, 32° 52' E. The study consisted of 118 premenopausal women and men aged between 21 and 52 years-old. Seasonal changes were evaluated in August and February. Fasting serum was obtained for intact parathyroid hormone (iPTH) and 25-hydroxyvitamin D (25OHD). Additional data were collected by a questionnaire that enquired about age, weight, height, wearing style, dietary calcium intake and sunlight exposure. Serum 25OHD concentration was measured using a precise HPLC assay. Low vitamin D status was defined as a 25OHD concentration less than 30 ng/mL. RESULTS: Mean serum 25OHD concentration in summer was 28.4±10.4 ng/mL and 13.8±6.6 ng/mL in winter (p<0.001). 35.6% of the subjects were vitamin D insufficient in summer and 12.7% in winter (p<0.001) while 31.5% were vitamin D deficient in summer and 83.9% in winter (p<0.001). A significant increase in iPTH levels (33.1±15.9 pg/mL vs 49.6±24.3 pg/mL, p<0.001) was observed throughout the seasonal change. No significant association was found between 25OHD levels and iPTH, body mass index, age and sun exposure index (p>0.05 for all) in both seasons. CONCLUSION: Vitamin D deficiency is very prevalent in office workers even in summer time and this should be accepted as a public health problem.

Association between novel adipocytokines adiponectin, vaspin, visfatin, and thyroid: An experimental and clinical update.

Adipose tissue secretes a variety of active biological substances, called adipocytokines, that act in an autocrine, paracrine, and endocrine manner. They have roles in appetite control, thermogenesis, and thyroid and reproductive functions. All these molecules may lead to local and generalized inflammation, mediating obesity-associated vascular disorders including hypertension, diabetes, atherosclerosis, and insulin resistance. Thyroid dysfunction is associated with changes in body weight, thermogenesis, and energy expenditure. The connections between cardiovascular risk factors such as dyslipidemia, impaired glucose tolerance, insulin resistance, atherosclerosis, and thyroid dysfunction have been reported in several studies. The adipocytokines serve as causative or protective factors in the development of these disorders in the states of thyroid dysfunction. Abnormal levels of adipocytokines (adiponectin (ADP), leptin, resistin, vaspin, and visfatin) in hypo- and hyperthyroidism have been reported with controversial results. This review aims to update the implication of novel adipokines ADP, vaspin, and visfatin in thyroid dysfunction.

Basal and meal-stimulated ghrelin, PYY, CCK levels and satiety in lean women with polycystic ovary syndrome: effect of low-dose oral contraceptive.

CONTEXT: Ghrelin is an orexigenic peptide that stimulates food intake, whereas peptide YY (PYY) and cholecystokinin (CCK) are anorexigenic gut hormones. Patients with polycystic ovary syndrome (PCOS) appear to have alterations in appetite regulation. OBJECTIVE: We aimed to determine whether fasting or meal-stimulated ghrelin, PYY, CCK, and satiety responses are different between lean PCOS patients and healthy women. We also aimed to assess the potential effect of oral contraceptive use on these hormones and satiety response. DESIGN AND SETTING: We conducted a prospective observational study in a university practice. PATIENTS: Eighteen lean PCOS patients and 18 healthy control women matched for age and body mass index underwent measurements of circulating ghrelin, PYY, CCK, and satiety index (SI) before and after a standardized mixed meal at 0, 15, 30, 45, 60, 90, 120, and 180 minutes. INTERVENTIONS: For PCOS patients who were treated with ethinyl estradiol 30 µg/drospirenone 3 mg for 3 months, measurements were repeated. MAIN OUTCOME: We measured ghrelin, PYY, and CCK levels and SI. RESULTS: At baseline, fasting ghrelin, PYY, CCK, and SI values in PCOS patients were not different from controls. Meal-stimulated PYY, CCK, and SI were also not different between the groups, whereas PCOS patients had significantly lower meal-stimulated ghrelin levels compared to controls (P = .04). Ghrelin, PYY, CCK, and SI did not show a significant change after treatment with ethinyl estradiol/drospirenone for 3 months. CONCLUSIONS: Basal and stimulated hunger and satiety hormones in lean PCOS patients are not different from lean healthy women, except for a lower meal-stimulated ghrelin response. Short-term use of a low-dose oral contraceptive does not have an effect on appetite regulation of PCOS.