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Objectives: Skin changes in acromegaly are often the first sign of the disease. The aim of this study was to describe the cutaneous findings in patients with acromegaly. In addition, a secondary aim was to investigate the possible association of these findings with remission status and concomitant endocrinopathies., Design, Patients, and Measurements: In this prospective multicenter study, 278 patients over the age of 18 years with acromegaly who were followed up in 14 different tertiary healthcare institutions were included. These patients, who were followed up by the Endocrinology Department, were then referred to a dermatologist for dermatological examination. The frequency of skin lesions was investigated by detailed dermatologic examination. Dermatological diagnosis is reached by clinical, dermatological and/or dermoscopic examination, and rarely skin punch biopsy examinations in suspicious cases. The possible association of the skin findings between remitted and nonremitted patients and with concomitant endocrinopathies were evaluated., Results: The most common skin findings in patients with acromegaly in our study were skin tags (52.5%), cherry angiomas (47.4%), seborrhoea (37%), varicose veins (33%), acneiform lesions (28.8%), hyperhidrosis (26.9%) and hypertrichosis (18.3%). Hypertrichosis was significantly more prevalent in patients nonremitted (p: .001), while xerosis cutis was significantly more prevalent in patients remitted (p: .001). The frequency of diabetes mellitus and hypothyroidism was significantly higher in patients with varicose veins and seborrhoeic keratosis than those without. Additionally, the coexistence of hypothyroidism, hyperthyroidism and galactorrhea was significantly higher in patients with Cherry angioma than in those without Cherry angioma (p-values: .024, .034 and .027, respectively). The frequency of hypogonadism in those with xerosis cutis was significantly higher than in those without (p: .035)., Conclusions: Cutaneous androgenization findings such as skin tag, seborrhoea, acne and acanthosis nigricans are common in patients with acromegaly. Clinicians should be aware that skin findings associated with insulin resistance may develop in these patients. It can be said that the remission state in acromegaly has no curative effect on cutaneous findings. Only patients in remission were less likely to have hypertrichosis. This may allow earlier review of the follow-up and treatment of acromegaly patients presenting with complaints of hypertrichosis. Additionally, it can be said that patients with skin findings such as cherry angioma may be predisposed to a second endocrinopathy, especially hypothyroidism. Including dermatology in a multidisciplinary perspective in acromegaly patient management would be beneficial to detect cutaneous findings earlier., (© 2024 John Wiley & Sons Ltd.)

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., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: The alteration of the microbiota in the mouth and gut could potentially play a role in the pathogenesis of various diseases, and conversely, these diseases may have an influence on the composition of the gut microbiota. Acromegaly disease can potentially affect physiological processes in the mouth and gut. The present study was designed to investigate the relationship between acromegaly and the oral and gut microbiota, as data on this topic are scarce., Methods: This was a multicenter, cross-sectional study. Our study included individuals diagnosed with acromegaly (who were treated and followed up, and also as an another group of patients with newly diagnosed acromegaly) and healthy participants. All three groups were assessed and compared based on age, sex, serum IGF-1, body mass index BMI as well as their stool and oral microbiota We collected demographic information from the patients, collected fecal and oral samples, performed DNA isolation followed by 16 S rRNA sequencing, and then performed bioinformatic analysis. We also analyzed the oral and fecal samples with respect to medical and surgical treatment and disease control status, specific treatments received for acromegaly, presence of comorbidities, hypopituitarism status, presence of intestinal polyps., Results: One hundred and three patients with acromegaly, 15 newly diagnosed patients with acromegaly without comorbidities and 34 healthy controls were included in the study. The Firmicutes/Bacteroidetes ratio was significantly lower in patients with acromegaly who received treatment (medical and/or surgical) than in healthy controls. In addition, a significant difference was found in the fecal and oral microbiota of patients with acromegaly with disease control compared to healthy controls. Furthermore, a significant difference was found in the fecal and oral microbiota of patients with acromegaly without disease control. Nevertheless, it was not possible to establish a clear relationship between disease control status, the presence of intestinal polyps, the presence of type 2 diabetes and the composition of the oral and gut microbiota in acromegalic patients who had received different forms of treatment., Conclusion: Patients with acromegaly show distinct gut microbiota profiles, and it is evident that factors beyond the GH/IGF-1 axis play a role in shaping the gut microbiota of individuals with acromegaly., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

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., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

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., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Introduction: Normocalcaemic hyperparathyroidism is a condition first defined in 2008, characterized by normal serum calcium and high parathormone levels. Although normocalcaemic hyperparathyroidism is considered to have a milder clinical picture compared to asymptomatic primary hyperparathyroidism, recent studies have shown that it may be associated with osteoporosis, insulin resistance, metabolic syndrome, and cardiovascular risk factors. Considering that normocalcaemic hyperparathyroidism may pose a cardiovascular risk in the setting of carotid atherosclerosis, we sought to examine the structural features of the carotid artery in patients with normocalcaemic hyperparathyroidism compared to a control group., Material and Methods: After excluding patients with hypertension, diabetes, and dyslipidaemia (other factors contributing to atherosclerosis), 37 (32 females, 5 males) patients with normocalcaemic hyperparathyroidism with a mean age of 51.2 ± 8 (min: 32, max: 66) years and 40 controls (31 females, 9 males) with a mean age of 49.3 ± 7.5 (min: 34, max: 64) years with normal serum albumin-corrected calcium and parathyroid hormone levels were included in the study. Structural features of the carotid artery including intima-media thickness (mean and maximum), lumen diameter, and the presence of plaque were assessed using B-mode ultrasound., Results: On ANCOVA analysis corrected for atherosclerotic factors (body mass index, waist circumference, fasting plasma glucose, serum cholesterol, lipid, and blood pressure), greater mean intima-media thickness was found in patients with normocalcaemic hyperparathyroidism than in controls (0.65 mm vs. 0.59 mm, respectively) (p = 0.023). Maximum carotid intima-media thickness was also greater in patients with normocalcaemic hyperparathyroidism compared to controls (0.80 mm vs. 0.75 mm, respectively) (p = 0.044). The study groups did not show a significant difference in lumen diameter and the presence of carotid plaque. In addition, a negative correlation was found between parathormone (PTH) level and lumen diameter., Conclusion: The findings of this study show that as with asymptomatic primary hyperparathyroidism, normocalcaemic hyperparathyroidism may be associated with increased cardiovascular risk by predisposing to atherosclerosis.

Purpose: Our aim was to investigate the changes in the composition of oral and gut microbiota in patients with newly diagnosed acromegaly and their relationship with IGF-1 levels., Methods: Oral and fecal samples were collected from patients with newly diagnosed acromegaly without comorbidities and from healthy controls. The composition of the microbiota was analyzed. The general characteristics, oral and stool samples of the patients and healthy control subjects were compared. The changes in microbiota composition in both habitats, their correlations and associations with IGF-1 were statistically observed using machine learning models., Results: Fifteen patients with newly diagnosed acromegaly without comorbidities and 15 healthy controls were included in the study. There was good agreement between fecal and oral microbiota in patients with acromegaly (p = 0.03). Oral microbiota diversity was significantly increased in patients with acromegaly (p < 0.01). In the fecal microbiota, the Firmicutes/Bacteroidetes ratio was lower in patients with acromegaly than in healthy controls (p = 0.011). Application of the transfer learned model to the pattern of microbiota allowed us to identify the patients with acromegaly with perfect accuracy., Conclusions: Patients with acromegaly have their own oral and gut microbiota even if they do not have acromegaly-related complications. Moreover, the excess IGF-1 levels could be correctly predicted based on the pattern of the microbiome., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

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., (Copyright © 2021 AACE. Published by Elsevier Inc. All rights reserved.)

Introduction: Although the TSH-receptor antibody (TRAb) plays a central role in the pathogenesis of Graves' disease (GD), the association between TRAb at first diagnosis and clinical and laboratory parameters is not well known. On the other hand, a minority of patients with GD may be TRAb negative, and there is a lack of adequate evidence to demonstrate the clinical and laboratory characteristics of these patients. Therefore, we aimed to investigate the association of TRAb at the initial diagnosis of GD with the clinical and laboratory parameters in a large number of patients with GD and to compare the clinical and laboratory parameters between patients with high TRAb levels and TRAb-negative patients., Material and Methods: This study included 440 patients [326 (74%) female, 114 (26%) male]. All patients were classified according to gender, age, smoking habit, and TRAb levels., Results: TRAb levels were significantly higher in male compared to female patients and in smokers compared to non-smokers. Smoking male patients had the highest TRAb levels. In regression analysis, goiter size, male gender, cigarette smoking, Graves' orbitopathy, fT3, and anti-TPO antibody levels were independently associated with high TRAb levels, while age at diagnosis and fT4 levels were not independently associated with high TRAb levels. TRAb-negative GD was diagnosed in 80 (18%) patients. TRA-negative patients had markedly less severe clinical and laboratory hyperthyroidism compared to patients with high TRAb levels. Moreover, the smoking habit was significantly lower in patients with TRAb-negative GD., Conclusions: According to our study results, TRAb levels at the initial diagnosis of GD are differently associated with clinical and laboratory parameters. Male patients and smoking patients with GD tended to have markedly higher TRAb levels and more severe clinical hyperthyroidism. Therefore, besides other contributing factors, male gender and smoking may affect TRAb levels and consequently the severity of hyperthyroidism in patients with GD. Furthermore, male gender and smoking may have a synergistic effect on TRAb levels and consequently on the severity of hyperthyroidism in patients with GD.

Objective: The frequency of Cushing's disease (CD), ACTH-independent Cushing's syndrome (CS) and autonomous cortisol secretion (ACS) in patients with obesity is not well known. Therefore, in the present study, we aimed to assess the frequency of CD, CS and ACS among the patients with obesity., Methods: This study included 813 patients (683 female, mean age 46.47±14.23 yr; mean body mass index (BMI) 37.31±6.50 kg/m 2 ). Patients with obesity were classified further to stages 1, 2, and 3, according to BMI. All patients underwent a low dose dexamethasone suppression test (LDDST). The patients with CD, CS, and ACS and patients with simple obesity were compared concerning gender, age, type-2 diabetes, hypertension (HT) and hyperlipidemia (HL)., Results: Forty-four (5.4%) out of 813 patients were diagnosed as CD, CS or ACS. CD, CS, and ACS were diagnosed in four (0.4%), two (0.2%), and 33 (4%) patients, respectively. When patients with CD, CS and ACS were compared to the patients with simple obesity, older age at diagnosis, the presence of stage-1 obesity, the presence of HT, and uncontrolled type-2 diabetes were more frequent in patients with CD, CS and ACS (p=0.001, p=0.007, p=0.004, and p=0.0026, respectively)., Conclusion: The frequency of CD, CS, and ACS is high among patients with obesity. Screening for CD, CS, and ACS in patients with stage-I obesity who are older than 50 years of age with uncontrolled type-2 diabetes and HT may be a reasonable approach., Competing Interests: Conflict of Interest: No conflict of interest was declared by the authors., (Copyright: © 2020 by Istanbul Northern Anatolian Association of Public Hospitals.)

Introduction: The outcome of medical treatment in patients with Graves' disease (GD) is generally difficult to predict. In this study, we examined the hypothesis that gender may affect the outcome of treatment with antithyroid drugs (ATDs)., Material and Methods: This is a retrospective multicentre study including 717 (514 female and 203 male) patients with the first episode of GD treated for at least 12 months. Patients were classified as relapse, poorly controlled (several episodes of hyperthyroidism followed by euthyroidism and rarely hypothyroidism, occurring after titration of ATDs), and remission., Results: During the mean follow-up time of 26.75 ± 21.25 months (between 1 and 120 months), 269 (37.5%), 176 (24.5%), and 272 (37.9%) patients experienced a relapse, a poorly controlled disease, and remained in remission, respectively. During the follow-up time, 223 (43.4%) of the female and only 49 (24%) of the male patients remained in remission. Relapse and poorly controlled disease (non-remitting GD) were more common in male compared to female patients with GD (hazard ratio 1.26, 95% CI: 1.03-1.53, p = 0.025). Graves' disease in male patients tended to relapse earlier, and male patients tended to have larger goiter sizes at diagnosis as well. The smoking habit was also significantly more frequent in males compared to female patients with GD., Conclusion: Male patients with GD have a markedly higher frequency of relapse and poorly controlled disease, as compared to female patients. Larger goiter sizes and higher frequency of smoking may contribute to the higher frequency of relapse and poorly controlled disease in male patients.

Recently, the Graves' Recurrent Events After Therapy score (GREAT) was proposed as a useful tool to predict relapse before starting antithyroid drugs (ATD) in patients with Graves' disease (GD). Therefore, we intended to assess the validity of the GREAT score in Turkish patients with GD, including patients who experienced a poorly controlled disease (multiple episodes of hyperthyroidism followed by euthyroidism or rarely hypothyroidism) during ATD dose titration. This is a retrospective multicenter study including 517 patients with the first episode of GD who were treated for at least 12 months. The patients were classified as relapse+poorly controlled disease (non-remission) and remission groups. During a median follow-up time of 35 months (12-144 months), 191 (37%) patients experienced a relapse, 136 (26.3%) a poorly controlled disease, and 190 (36.7%) remained in remission. Patients with non-remission disease tended to have significantly higher serum levels of TRAb, fT4, and fT3, and have larger goiter sizes on palpation at baseline, as compared with the remission group. Non-remission disease occurred in 12, 35, and, 53% of the patients falling into GREAT class I, II, and III, respectively (hazard ratio 2.56, 95% CI 2.02-3.51, p=0.012, and hazard ratio 3.54, 95% CI 2.12-5.91, p<0.001, for GREAT class II and III against class I, respectively). According to our study, the GREAT score is a useful tool to predict the risk of relapse as well as the occurrence of poorly controlled disease before starting treatment with ATDs., Competing Interests: The authors declare that they have no conflict of interest., (© Georg Thieme Verlag KG Stuttgart · New York.)

Objective: Previous studies have reported conflicting results regarding the mechanisms underlying the pathophysiology of pulmonary hypertension (PHT) in patients with hyperthyroidism. Therefore, in this study, we investigated the association between PHT and thyroid-stimulating hormone (TSH) receptor antibody, thyroid peroxidase antibody, thyroglobulin antibody, TSH, fT3, fT4 and dyspnea during daily activities in a large population of patients with hyperthyroidism., Methods: A total of 129 consecutive patients with hyperthyroidism, 37 with hypothyroidism and 38 euthyroid controls were enrolled in this study. The modified medical research council scale was used for the assessment of dyspnea in daily activities. All the patients and euthyroid controls underwent transthoracic echocardiography for the assessment of PHT., Results: Mild PHT was present in 35%, 36%, 13.5% and 5% of the patients with Graves׳ disease, toxic multinodular goiter, hypothyroidism and euthyroid controls, respectively. Pulmonary vascular resistance (PVR) was higher in hyperthyroid patients with PHT than in those without PHT. Moreover, a significant positive correlation was found between modified medical research council scale and pulmonary artery systolic pressure as well as PVR in patients with hyperthyroidism. No association was found between PHT and serum TSH receptor antibody, thyroid peroxidase antibody, thyroglobulin antibody, TSH, fT3 and fT4 levels., Conclusions: Mild PHT is present in a significant proportion of patients with hyperthyroidism, regardless of etiology. PVR appears to be the main cause of PHT in patients with hyperthyroidism, and neither autoimmunity nor thyroid hormones are associated with PHT in these patients. Mild dyspnea during daily activities in patients with hyperthyroidism may be related to PHT; however, severe dyspnea requires further evaluation., (Copyright © 2017 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.)

Objective: Currently, it is unclear whether pheochromocytomas can be ruled out based on low intensity on T2-weighted sequences and signal loss on out-of-phase magnetic resonance imaging (MRI) sequences. Hence, in this study, we investigated whether biochemical screening for pheochromocytoma in patients with adrenal incidentalomas (AIs) showing MRI features not suggesting pheochromocytoma would prove beneficial., Methods: We performed MRI for 300 AIs in 278 consecutive patients. All patients were screened for pheochromocytoma with plasma metanephrine and normetanephrine. Patients with high plasma levels of metanephrine and/or normetanephrine were also assessed for pheochromocytoma by urinary metanephrines., Results: Hyperintensity was detected on T2-weighted MRI sequences in 28 (9.3%) of the 300 AIs. Among these 28 incidentalomas, pheochromocytoma was diagnosed in 13 (46.4%) of the cases by histopathologic analysis. Hyperintensity on T2-weighted MRI was significantly higher in pheochromocytomas compared to the remaining AIs (P<.001). All 13 pheochromocytomas were characterized by hyperintensity on T2-weighted sequences and the absence of signal loss on out-of-phase MRI sequences. Pheochromocytoma was not detected in any of the 272 AIs that appeared hypointense or isointense on T2-weighted MRI sequences or in the 250 cases with signal loss on out-of-phase sequences., Conclusion: The results of this study suggest that AIs that appear hypointense or isointense on T2-weighted MRI sequences and those with signal loss on out-of-phase sequences may not require routine biochemical screening for pheochromocytoma. Further studies including a higher number of pheochromocytomas are required to confirm our results.

Introduction: Late-night salivary cortisol is a frequently used and easily implemented diagnostically valuable test for the diagnosis of overt Cushing's syndrome. The use of late-night salivary cortisol in the diagnosis of subclinical Cushing's syndrome is somewhat controversial. In this study, we aimed to determine the diagnostic value of late-night salivary cortisol in diagnosing subclinical Cushing's syndrome and compare it with 24-hour urinary free cortisol levels (UFC)., Material and Methods: The study consisted of 33 cases of subclinical Cushing's syndrome, 59 cases of non-functioning adrenal adenoma, and 41 control subjects. Late-night salivary cortisol and UFC were measured in all the cases. The diagnosis of subclinical Cushing's syndrome was based on combined results of 1 mg dexamethasone suppression test > 1.8 μg/dL and ACTH < 10 pg/mL., Results: Mean late-night salivary cortisol levels in subjects with subclinical Cushing's syndrome were significantly higher than in subjects with non-functioning adrenal adenoma and the control group (p < 0.001). Using a cut-off value of 0.18 μg/dL, the sensitivity and specificity of late-night salivary cortisol for diagnosing subclinical Cushing's syndrome were determined as 82% and 60%, respectively. Using a cut-off value of 137 μg/day, the sensitivity and specificity of UFC was determined as 18% and 90%, respectively., Conclusions: Because the sensitivity of late-night salivary cortisol for the diagnosis of subclinical Cushing's syndrome is limited, using it as the sole screening test for subclinical Cushing's syndrome may lead to false negative results. However, using it as an adjunct test to other tests may be beneficial in the diagnosis of subclinical Cushing's syndrome. (Endokrynol Pol 2016; 67 (5): 487-492).

Objective: To determine immunohistochemical expression of Eag1 in pituitary adenomas of patients with acromegaly and to assess the correlation between Eag1 expression with cavernous sinus invasion, tumoral Ki-67 labeling index (LI), age and gender of the patients., Methods: The paraffin embedded pituitary adenoma tissue sections of 28 patients with acromegaly who were diagnosed as monohormonal growth hormone (GH) secreting adenomas were immunostained for Eag1 using the avidin-biotin-peroxidase complex method. Eag1 immunoreactivity was scored according to the extensity of the cytoplasm and cell membrane immunoreactivity for Eag1 (score 1 = <10%, score 2 = 10-25%, score 3 = 25-50% and score 4 = >50% of the adenoma cells showed immunoreactivity for Eag1, respectively)., Results: Overall, GH secreting pituitary adenomas displayed diverse levels of Eag1 immunoreactivity, however, 64% of the adenomas displayed a strong Eag1 immunoreactivity (score 3 and 4). Five of the tumors displayed Eag1 immunoreactivity score 1, 5 displayed score 2, 10 displayed score 3 and 8 displayed score 4, respectively. No correlation was found between Eag1 immunoreactivity with cavernous sinus invasion, Ki-67 LI, age and gender of the patients., Conclusions: Our results suggest Eag1 is strongly expressed in the majority of GH secreting pituitary adenomas. However, we could not find any correlation between immunoreactivity of Eag1 with cavernous sinus invasion, Ki-67 LI, age and gender of the patients. Further studies with larger sample sizes are required to demonstrate the role of Eag1 on tumorigenesis, angiogenesis, invasion and response to the treatment in GH secreting pituitary adenomas.

Objective: The differential diagnosis of Graves disease (GD) and silent thyroiditis (ST) is important for the selection of appropriate treatment. To date, no study has compared the diagnostic utility of color Doppler ultrasonography (CDUSG), Tc-99m (technetium-99m) pertechnetate uptake, and thyroid-stimulating hormone (TSH)-receptor antibody (TRAb) for the differential diagnosis of these two conditions. In the present study, we compared the diagnostic utility of inferior thyroid artery (ITA) peak systolic and end diastolic velocities (PSV and EDV) measured by CDUSG, Tc-99m pertechnetate uptake, and TRAb for differential diagnosis of GD and ST., Methods: A total of 150 subjects with GD, 79 with ST, and 71 healthy euthyroid controls were included in the study. Diagnoses of GD and ST were made according to patient signs and symptoms, physical examination findings, the results of TRAb and Tc-99m pertechnetate uptake, and follow-up findings. All subjects underwent CDUSG for the quantitative measurement of ITA blood-flow velocities., Results: The mean ITA-PSV and EDV in patients with GD were significantly higher than in ST patients. In receiver operating characteristic analysis, the sensitivity/specificity of the 30 and 13.2 cm/s cutoff values of the mean ITA-PSV and EDV for discrimination of GD from ST were 95.3/94.9% and 89.3/88.6%, respectively. The sensitivity/specificity of the 1.0 international unit (IU)/L and 3% cutoff values of the TRAb and Tc-99m pertechnetate uptake analyses were 93.0/91.0% and 90.7/89.9%, respectively., Conclusion: The measurement of ITA-PSV by CDUSG is a useful diagnostic tool and is a complementary method to the TRAb and Tc-99m pertechnetate uptake methods for differential diagnosis of GD and ST.

Aim: To compare anterior pituitary functions between subjects with total and partial primary empty sella (PES) and to assess whether all cases with PES need endocrinological evaluation., Material and Methods: Eighty-one subjects with PES (34 total and 47 partial) were included in the study. Basal anterior pituitary and its target hormones were assessed and those with low insulin like growth factor-1 and/or low basal cortisol levels underwent insulin tolerance test (ITT)., Results: 67.4% of the subjects with total and 14.9% of those with partial PES had different degrees of hypopituitarism. However, the frequency of hypopituitarism was significantly higher in cases with total PES. The odds ratio (OR) and 95% confidence interval (CI) of secondary hypothyroidism, secondary adrenal, growth hormone and gonadotropin deficiency in subjects with total compared to those with partial PES were as follows: OR = 20.0, 95% CI 4.16 - 95.9, OR = 2.4, 95% CI 1.34 - 5.7, OR = 15.3, 95% CI 4.48 - 52.6 and OR = 10.6, 95% CI 3.37 - 33.5, respectively., Conclusion: A substantial number of subjects with PES, particularly those with total PES, have pituitary hormone deficiency, so regardless of the type of PES, all subjects must be promptly and carefully evaluated for anterior pituitary hormone deficiency.

Objective: To assess the relationship between low maternal serum 25-hydroxyvitamin D levels and gestational diabetes mellitus in Turkish pregnant women according to the severity of 25-hydroxyvitamin D deficiency and assess intact parathyroid hormone levels in women with gestational diabetes mellitus and controls with low and sufficient 25-hydroxyvitamin D levels., Methods: We analyzed serum 25-hydroxyvitamin D and intact parathyroid hormone levels in 234 women with gestational diabetes mellitus and 168 controls. To define the deficiency status, 25-hydroxyvitamin D levels were further classified into severely deficient, deficient, insufficient and sufficient groups., Results: Women with gestational diabetes mellitus had significantly lower 25-hydroxyvitamin D levels compared to controls (30.8±16.3 vs. 36.0±16.2 nmol/L). However, when subgroups of 25-hydroxyvitamin D were analyzed, gestational diabetes mellitus was significantly more common only in women with severely deficient 25-hydroxyvitamin D levels. After adjusting for covariates, only severely deficient 25-hydroxyvitamin D levels were independently associated with an increased relative risk of gestational diabetes mellitus. The relative risk of gestational diabetes mellitus in women with insufficient and deficient 25-hydroxyvitamin D levels was not statistically significant. Intact parathyroid hormone concentrations were also significantly higher in women with gestational diabetes mellitus compared to the controls (45.3±26.2 vs. 38.7±27.6 pg/ml)., Conclusions: The results obtained from this study provide novel data indicating that only severely deficient maternal serum 25-hydroxyvitamin D levels are significantly associated with an elevated relative risk of gestational diabetes mellitus, even after adjusting for established risk factors of gestational diabetes mellitus.

Aim: To determine the immunohistochemical expression of ErbB2 in adamantinomatous craniopharyngiomas (ACP) and to assess its relationship with nuclear expression of β-catenin in surgically resected human ACP tissue sections and to estimate whether these tumors could be candidates for anti-ErbB2 therapy., Material and Methods: The ErbB2 and β-catenin immunostaining was performed on paraffin embedded tissue sections of 20 ACP using avidin-biotin-peroxidase complex method. ErbB2 immunoreactivity was interpreted according to the American Society of Clinical Oncology/ College of American Pathologists criterions for breast carcinoma., Results: Foci of nuclear reactivity for β-catenin was observed in all ACP tissue specimens mainly concentrated in whorl like arrays of the epithelial cells. Two (10%) of the cases were score 3+ for ErbB2 as demonstrated by strong complete membrane staining. However, the localization of 3+ ErbB2 cells was different from those with nuclear β-catenin immunoreactivity., Conclusion: Our preliminary data demonstrate score 3+ staining for ErbB2 in 10% of ACP and different localization of 3+ ErbB2 cells and cells with nuclear β-catenin immunoreactivity. However, because of the small number of cases, further studies with larger samples should be conducted to verify and validate our preliminary data and to determine the effect of ErbB2 protein in ACP cell growth, survival and differentiation.

The objective of the current study was to determine survival and factors that affect survival in progressive systemic sclerosis (SSc) with pulmonary involvement. A total of 102 SSc patients with pulmonary involvement, diagnosed between 1994 and 2008, enrolled into the study. Pulmonary involvement was defined based on the presence of interstitial changes on high-resolution CT (HRCT). Demographical, clinical, radiological, and laboratory data of the patients were found from patient records and were used for the evaluation of survival. The mean age of the patients at diagnosis was 50 ± 12 years. In follow-up, 22 (21.5%) patients were deceased. The mean age of the patients at death was 55 ± 12 years. Seventy-eight percent of known causes of mortality were related to pulmonary complications. After any initial systemic manifestation of disease, the mean survival was 447 ± 27 months and 5, 10, 15, and 20 year survival rates were 99, 92, 83, and 72%, respectively. The mean survival after initial pulmonary manifestation was 269 ± 23 months and 5, 10 and 15 year survival rates were 91, 73 and 57%, respectively. Mean survival was 113 ± 5 months, and 5- and 10-year survival rates after the lung involvement detected with HRCT were 85 and 66%, respectively. Pulmonary artery hypertension, disease onset after the age of 40, and honeycombing on HRCT were associated with poor survival. Our data suggest that pulmonary involvement is the most important determinant factor for poor prognosis in patients with SSc. Therefore, echocardiography, pulmonary function tests, and HRCT should be performed in early stages of the disease for early diagnosis of pulmonary artery hypertension and lung involvement before irreversible vascular and interstitial changes exist.

Objective: To determine the role of peak systolic velocity, end-diastolic velocity and resistance indices of both the right and left inferior thyroid arteries measured by color-flow Doppler ultrasonography for a differential diagnosis between gestational transient thyrotoxicosis and Graves' disease during pregnancy., Methods: The right and left inferior thyroid artery-peak systolic velocity, end-diastolic velocity and resistance indices of 96 patients with thyrotoxicosis (41 with gestational transient thyrotoxicosis, 31 age-matched pregnant patients with Graves' disease and 24 age- and sex-matched non-pregnant patients with Graves' disease) and 25 age and sex-matched healthy euthyroid subjects were assessed with color-flow Doppler ultrasonography., Results: The right and left inferior thyroid artery-peak systolic and end-diastolic velocities in patients with gestational transient thyrotoxicosis were found to be significantly lower than those of pregnant patients with Graves' disease and higher than those of healthy euthyroid subjects. However, the right and left inferior thyroid artery peak systolic and end-diastolic velocities in pregnant patients with Graves' disease were significantly lower than those of non-pregnant patients with Graves' disease. The right and left inferior thyroid artery peak systolic and end-diastolic velocities were positively correlated with TSH-receptor antibody levels. We found an overlap between the inferior thyroid artery-blood flow velocities in a considerable number of patients with gestational transient thyrotoxicosis and pregnant patients with Graves' disease., Conclusions: This study suggests that the measurement of inferior thyroid artery-blood flow velocities with color-flow Doppler ultrasonography does not have sufficient sensitivity and specificity to be recommended as an initial diagnostic test for a differential diagnosis between gestational transient thyrotoxicosis and Graves' disease during pregnancy.

At present, no effective medical treatment exists for recurrent and aggressive craniopharyngiomas that are resistant to conventional therapies, including surgery and adjuvant radiotherapy. Temozolomide is an alkylating chemotherapeutic agent used routinely in the management of high grade gliomas. The response to temozolomide is suggested to be dependent on the tumoral expression of O-6 methylguanine DNA methyltransferase (MGMT). Evidence supports that low MGMT immunoexpression correlates with positive response to temozolomide. Therefore, we aimed to assess MGMT immunoexpression in adamantinomatous craniopharyngiomas, in an effort to predict the likelihood of response to temozolomide. The MGMT immunostaining was performed on 23 adamantinomatous craniofaryngiomas operated at the Sisli Etfal Training and Research Hospital and identified by histological analysis. Paraffin embedded tissue sections were immunostained for MGMT and were evaluated semi-quantitatively. Of the 23 cases evaluated, 22 (96%) demonstrated negative (<10%) and 1 (4%) demonstrated low (10%) MGMT immunoexpression. Data from this study suggest a high proportion of adamantinomatous craniopharyngiomas exhibit negative/low MGMT immunoreactivity and could be treated with temozolomide, if conventional therapy fails.

Objectives: Acute pancreatitis (AP) is a common systemic inflammatory disorder of the pancreas. The data related to the lipid changes in patients with AP were insufficient. In this study, we aimed to investigate the relation between high-density lipoprotein (HDL) and the other lipid parameters and the severity of the disease in AP cases., Methods: Seventy-five cases admitted to the Gastroenterohepatology Clinic with diagnosis of AP were included in the study. Ranson scores and Glasgow scores were used for prognosis. Lipid parameters were evaluated for the first 24 hours and after clinic and laboratory remission., Results: The causes of the disease among patients included in the study were as follows: 44 biliary origin (58.7%), 14 alcohol dependent (18.7%), 10 idiopathic (13.3%), 6 hyperlipidemic (8%), and 1 endoscopic retrograde cholangiopancreatography dependent (1.3%). Triglyceride (TG) levels of the patients included in the study measured in the first 2 days were significantly higher than TG levels measured after clinic and laboratory remission (P = 0.013). High-density lipoprotein was significantly lower in alcoholic and hypertriglyceridemic AP cases. There was a statistical correlation between HDL and Ranson (P = 0.023)., Conclusion: The low levels of HDL in AP cases during acute attack are associated with severity of the disease.

Recent publications suggest the utility of temozolomide (TMZ) in the management of aggressive pituitary adenomas and carcinomas, resistant to conventional treatments. The response to TMZ is inversely correlated with tumoral expression of O-6 methylguanine DNA methyl transferase (MGMT). Therefore, we aimed to assess MGMT immunoexpression in pure GH-secreting pituitary adenomas, in an effort to predict the likelihood of response to TMZ, and to correlate MGMT immunoexpression with Ki-67 LI and cytokeratin (CK) distribution pattern. Our material consisted of 36 GH-secreting pituitary adenomas (21 female,15 male, mean age 42.5±10.5), operated at our center between 2003 and 2010. Immunostaining for MGMT, Ki-67, and CK was performed using avidin-biotin-peroxidase complex method. Immunoreactivity for MGMT and Ki-67 was evaluated microscopically and recorded as percentages of positive nuclear immunostaining. CK distribution pattern was also evaluated microscopically and assoreted into dot-like and nondot-like pattern subtypes. MGMT immunoexpression scored as 0=none, 1=<10%, 2=<25%, 3=<50%, and 4=>50%. Staining for MGMT was <10% (score 1) in 30 (83.3%), 10-25% (score 2) in 3 (8.3%), 25-50% (score 3) in 2 (5.6%) and >50% (score 4) in 1 (2.8%) of the tumors, respectively. There was no correlation between Ki-67 LI and CK distribution pattern with MGMT immunoreactivity (P>0.05). Data from the current study suggest a large proportion of GH-secreting adenomas, including those with dot-like CK distribution pattern and high Ki-67 LI, demonstrate negative/low MGMT immunoreactivity and could be treated with TMZ, if conventional treatment fails.

Background:  Helicobacter pylori infection is a most frequent cause of chronic gastritis. H. pylori may decrease absorption of oral thyroxine by decreasing gastric acid secretion in the stomach. In this study, we aimed to investigate the change in thyroid function tests of the cases after H. pylori eradication who were not responding to high doses of thyroxine treatment before H. pylori eradication., Methods:  Hypothyroid cases who were not responding to high doses of thyroxine among the ones presented to Endocrinology and Gastroenterohepatology Clinics of Sisli Etfal Training and Research Hospital between 2009 and 2010 were included in the study. Thyroid function tests were performed two times in all cases before and after H. pylori eradication. Duodenal, antral and corporal biopsies, and jejunal aspirates and biopsies were taken during upper gastrointestinal system endoscopies performed in all patients. Cases without intestinal pathology were included in the study., Results: Serum thyrotropin (TSH), free T3, and free T4 values before H. pylori eradication were 30.5 ± 28.8 IU/mL, 2.64 ± 0.56 pg/mL, and 0.92 ± 0.32 ng/mL, respectively, and after eradication were found to be 4.2 ± 10.6 IU/mL, 3.02 ± 0.61 pg/mL, and 1.3 ± 0.34 ng/mL, respectively (p values <.001, .002, and <.001, respectively). After H. pylori eradication treatment, TSH decreased in all of the cases, factitious thyrotoxicosis developed in % 21 of these cases., Conclusion: In hypothyroid cases, H. pylori gastritis may be responsible for an inadequate response to the treatment. H. pylori eradication in the cases receiving high doses of thyroxine has a risk for thyrotoxicosis., (© 2011 Blackwell Publishing Ltd.)

We aimed to compare the prevalence of antineutrophil cytoplasmic antibody (ANCA) and its subgroups between on-treatment (with anti-thyroid drugs; propylthiouracil, methimazole) and untreated patients with hyperthyroidism in our unit. Overall 78 consecutive patients were enrolled in the study; 45 patients were on-treatment (female/male 31:14) and 33 were newly diagnosed (female/male 20:13). We have studied ANCA, perinuclear-ANCA (p-ANCA), cytoplasmic-ANCA (c-ANCA), myeloperoxidase-ANCA (mpo-ANCA), and proteinase 3-ANCA (pr3-ANCA) in sera of all the patients. The data about clinical status, laboratory tests, and physical examination and mean duration of treatment in treated group were recorded. There was no statistically significant difference between the two groups for ANCA, c-ANCA, and pr3-ANCA (P=0.13, P=0.07, and P=0.63 respectively). p-ANCA and mpo-ANCA prevalences were significantly higher in on-treatment group than in untreated group (P=0.04 and P=0.01, respectively). The mean duration of treatment was 17 months in on-treatment group. The use of antithyroid drugs (propylthiouracil, methimazole) seems to be correlated with increased prevalence of ANCA. These drugs may especially increase p-ANCA and mpo-ANCA positivity.