Machine Learning May Be An Alternative To BIPSS In The Differential Diagnosis Of ACTH-Dependent Cushing's Syndrome.

OBJECTIVE: This study aimed to develop machine learning (ML) algorithms for the differential diagnosis of adrenocorticotropic hormone (ACTH)-dependent Cushing's syndrome (CS) based on biochemical and radiological features. METHODS: Logistic regression algorithms were used for ML, and the area under the receiver operating characteristics curve (AUROC) was used to measure performance. We used Shapley Contributed Comments (SHAP) values, which help explain the results of the ML models to identify the meaning of each feature and facilitate interpretation. RESULTS: A total of 106 patients, 80 with Cushing's disease (CD) and 26 with ectopic ACTH syndrome (EAS), were enrolled in the study. The ML task was created to classify patients with ACTH-dependent CS into CD and EAS. The average AUROC value obtained in the cross-validation of the logistic regression model created for the classification task was 0.850. The diagnostic accuracy of the algorithm was 86%. The SHAP values indicated that the most important determinants for the model were the 2-day 2-mg dexamethasone suppression test, the > 50% suppression in the 8-mg high-dose dexamethasone test, late-night salivary cortisol, and the diameter of the pituitary adenoma. We have also made our algorithm available to all clinicians via a user-friendly interface. CONCLUSION: ML algorithms have the potential to serve as an alternative decision support tool to invasive procedures in the differential diagnosis of ACTH-dependent CS.

The Effect of Metformin Treatment on Disease Control in Patients with Acromegaly.

BACKGROUND: The increase in portal insulin levels has been shown to upregulate growth hormone receptor expression in the liver, leading to increased insulin-like growth hormone- 1 levels. Metformin inhibits hepatic gluconeogenesis and reduces fasting insulin. OBJECTIVE: We evaluated the effect of metformin treatment in patients with acromegaly on growth hormone, insulin-like growth hormone-1, and pituitary adenoma size. METHODS: Patients who were followed up with the diagnosis of acromegaly in Istanbul University- Cerrahpasa, Cerrahpasa Medical Faculty were evaluated. The patients were divided into three groups after pituitary adenectomy as those who received somatostatin receptor ligand and metformin treatment (group A), somatostatin receptor ligand treatment only (group B), and those who received metformin treatment only (group C). Groups A and B were compared with each other, and patients in group C were compared among themselves. RESULTS: While the median insulin-like growth factor-1 level decreased to 170 ng/ml in Group A after the treatment, the median insulin-like growth factor-1 level decreased to 229 ng/ml in Group B, and a statistically significant difference was found between the two groups (p =0.020). There was no significant difference in post-treatment growth hormone levels and residual adenoma sizes between groups A and B (p >0.005). In group C, there was no significant difference in growth hormone values pre-and post-metformin treatment (p =0.078); however, the median insulin-like growth factor-1 level decreased from 205 ng/ml to 168 ng/ml during metformin treatment and was found to be statistically significant (p =0.027). CONCLUSION: Due to the effect of metformin treatment on insulin-like growth factor-1 values in patients with acromegaly, it can be used in disease control, as well as diabetes treatment.

Is There A Connection Between Primary Hypophysitis and Celiac Disease?

AIM: To investigate the autoimmune and genetic relationship between primary hypophysitis (PH) and celiac disease (CD). METHODS: The study was retrospective and patients with PH followed in our clinic between 2007 and 2022 were evaluated. Clinical, endocrinologic, pathologic, and radiologic findings and treatment modalities were assessed. Patients diagnosed with CD in the Gastroenterology outpatient clinic in 2020-2022 were included in the study as a control group. Information such as sociodemographic data, year of diagnosis, human leukocyte antigen (HLA) DQ2/8 information, CD-specific antibody levels, pathologic results of duodenal biopsy, treatment received, follow-up status, additional diseases, hormone use, and surgical history was obtained from patient records at PH.In patients diagnosed with PH, a duodenal biopsy was obtained, and the tissue was examined for CD by experienced pathologists. Anti-pituitary antibody (APA) and anti-arginine-vasopressin (AAVP) antibody levels of individuals with PH and CD were measured. RESULTS: The study included 19 patients with lymphocytic hypophysitis, 30 celiac patients, and 30 healthy controls. When patients diagnosed with lymphocytic hypophysitis were examined by duodenal biopsy, no evidence of CD was found in the pathologic findings. The detection rate of HLA-DQ2/8 was 80% in celiac patients and 42% in PH (p=0.044). (APA and AAVP antibodies associated with PH were tested in two separate groups of patients and in the control group. APA and anti-arginine vasopressin (AAVP) levels in PH, CD and healthy controls, respectively M [IQR]: 542 [178-607];164 [125-243]; 82 [74-107] ng/dL (p=0.001), 174 [52-218]; 60 [47-82]; 59 [48-76] ng/dL (p=0.008) were detected. The presence of an HLA-DQ2/8 haplotype correlates with posterior hypophysitis and panhypophysitis (r=0.598, p=0.04 and r=0.657, p=0.02, respectively). CONCLUSION: Although patients with PH were found to have significant levels of HLA-DQ2/8, no CD was found in the tissue. Higher levels of pituitary antibodies were detected in celiac patients compared with healthy controls, but no hypophysitis clinic was observed at follow-up. Although these findings suggest that the two diseases may share a common genetic and autoimmune basis, the development of the disease may be partially explained by exposure to environmental factors.

The Association between Serum 25-Hydroxyvitamin D3 Levels and Pro-Inflammatory Markers in New-Onset Type 2 Diabetes Mellitus and Prediabetes.

In this study, we aimed to reveal the pro-inflammatory effects of serum 25-hydroxyvitamin D3 (Vit D) deficiency and insufficiency in new-onset type 2 diabetes mellitus (T2DM) and prediabetes. We recruited 84 prediabetes patients, 94 new-onset T2DM patients and 113 healthy participants. We measured the levels of C-reactive protein (CRP), fibrinogen, ferritin, interleukin-1ß (IL-1ß), interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-α (TNF-α), nuclear factor kappa-B (NF-κB) and mitogen-activated protein kinase (MAPK) in the serum of the participants. ANOVA Bonferroni and Kruskal-Wallis Dunn tests were used to compare the inflammation markers and vitamin D levels between the groups. Based on covariance analysis with age, gender and BMI, the Vit D levels of the T2DM group were significantly lower (p < 0.003). Pro-inflammatory markers and CRP were significantly higher in prediabetic and diabetic subjects. In the prediabetes group, IL-1ß, IL-6, IL-8, TNF-α and MAPK were significantly higher in those with Vit D insufficiency and deficiency groups. In the T2DM group, IL-1ß, IL-6, IL-8, TNF-α, NF-κB, MAPK and CRP were significantly higher in those with Vit D insufficiency and deficiency. Our study emphasizes the pro-inflammatory effects of Vit D deficiency and insufficiency in new-onset type 2 diabetes mellitus and prediabetes.

The effect of radioiodine therapy on blood cell count in patients with differentiated thyroid cancer.

PURPOSE: This study aimed to investigate the long-term effects of radioiodine treatment (RAI) on blood cell counts in patients with differentiated thyroid cancer (DTC) and to describe the characteristics of patients at high risk for blood cell count abnormalities. METHODS: The study included patients with DTC who underwent RAI treatment between 2007 and 2017. Patients with regular complete blood counts for at least 5 years were included, while those with diseases or treatments that could influence blood count parameters were excluded. Blood cell count abnormalities were defined according to the Common Terminology Criteria for Adverse Events version 5.0, and factors influencing these abnormalities were examined. RESULTS: A total of 225 patients were analyzed. The mean age at diagnosis was 45.8 ± 13.9 years, and 76.5% of patients were female. In the first year after RAI, leukocyte, neutrophil, and lymphocyte counts were significantly reduced compared with baseline values. The leukocyte and neutrophil counts returned to baseline values by the third year, while the decrease in lymphocytes continued until the fifth year. Blood cell count abnormalities developed in 16 patients (7.1%) within the first year after RAI. Risk factors for blood cell count abnormalities within the first year after RAI included male sex, older age, T4, N1, and M1 disease, as well as higher RAI doses. In logistic regression analysis, only RAI dose remained independently associated with blood cell count abnormalities. CONCLUSION: These results suggest an association between RAI dose and blood cell count abnormalities, characterized by mild lymphopenia, and indicate that the risk of mild lymphopenia persists over time. Careful consideration should be given when planning high-dose RAI for patients at a high risk of blood cell count abnormalities, such as males with metastatic disease and of advanced age.

The Combination of Dopamine Agonist Treatment and Surgery May Be the Best Option in Challenging Prolactinoma Cases: A Single-Centre Experience.

OBJECTIVE: To investigate the initial and long-term remission rates, factors related to remission, secondary treatments, and outcomes for patients with prolactinoma who underwent endoscopic transsphenoidal surgery (ETSS). METHODS: The medical files of the 45 prolactinoma patients who underwent ETSS between 2015 and 2022 were retrospectively reviewed. Relevant demographic and clinical data were obtained. RESULTS: Twenty-one (46.7%) patients were female. The median age of patients at ETSS was 35 (interquartile range, 22.5-50) years. The median clinical follow-up of patients was 28 (interquartile range 12-44) months. The initial surgical remission rate was 60%. Recurrence was detected in 7 patients (25.9%). Postoperative dopamine agonists were used in 25 patients, radiosurgery in 2, and second ETSS in 4 patients. After these secondary treatments, the long-term biochemical remission rate was 91.1%. The factors associated with failure in surgical remission are: male gender, older age, higher tumor size, advanced Knosp and Hardy stage, and elevated prolactin level at diagnosis. A prolactin level of <19 ng/mL in the first postoperative week predicted surgical remission with a sensitivity of 77.8% and a specificity of 70.6% in patients who received preoperative dopamine agonist treatment. CONCLUSIONS: In macro adenomas and/or giant adenomas with cavernous sinus invasion, and significant suprasellar extension, which constitutes the difficult part of prolactinoma treatment, neither surgery nor medical treatment alone may be effective enough. Both treatment modalities should be carried out together by a team of neurosurgery and endocrinology in the management of these patients.

Does the Association of Hashimoto's Thyroiditis with Differentiated Thyroid Cancer Really Have a Protective Role?

The study is an investigation of aggressive tumor features, prognosis, and disease-specific mortality rates of differentiated thyroid cancer (DTC) in the presence of concomitant Hashimoto's Thyroiditis (HT). The data of patients with DTC followed in our tertiary care center between 2000-2022 were analyzed. Variables such as patient age, gender, preoperative serum autoantibody levels, tumor characteristics, and treatment modalities were obtained from medical records. The diagnosis of HT was based either on the presence of a positive result in the pathological examination and/or on antibody positivity. A total of 637 patients [mean±SD age, 44.9±13.5 years; 485 women [76.1%)] were included in the analysis. The overall prevalence of coexistent HT was 22.9% (n=146). The disease-specific mortality associated with DTC was 2.9%. DTC patients with HT compared to those without; have more positive lymphovascular invasion (p<0.001), and lymph node metastases (p<0.001). According to the Kaplan-Meier curves, disease-specific survival rates among DTC patients without HT were significantly higher than patients with HT (log-rank p=0.002). The disease-specific mortality rate was 4.79% in DTC patients with HT, it was 1.43% in those without HT. Hashimoto thyroiditis was not associated with a 10-year recurrence-free survival (p=0.059). Differentiated thyroid cancers with concomitant HT are associated with some aggressive tumor features (such as lymphovascular invasion and nodal metastasis) and lower survival. In staging systems based on tumor risk factors, it may be useful to evaluate the presence of concomitant HT as a prognostic factor.

Visceral Adiposity Index as an Indicator of Cardiometabolic Risk in Patients with Congenital Adrenal Hyperplasia.

Aim: To evaluate the cardiometabolic risk in patients with CAH (21 (OH) enzyme deficiency) on the basis of the visceral adiposity index (VAI), which indicates dysfunction of the visceral adipose tissue (VAT). Materials and Methods: A total of 41 patients and 38 body mass index (BMI), age, and gender-matched healthy controls (HC) were included. The patients' and HCs' age, gender, waist circumference (WC), BMI information and total cholesterol (TC), high-density lipoprotein (HDL), triglyceride (TG) values, smoking, and medication history were obtained from medical charts. Weight, height, WC, and blood pressure levels were measured. Patients' and HCs' BMI, Framingham risk scores (FRS), VAI and Ferriman-Gallwey scores were calculated. The patients' and HCs' age, gender TC, HDL, and TG, androstenedione, dehydroepiandrosterone sulfate (DHEASO4), 17 hydroxyprogesterone (17(OH)P) values, smoking, and medication history were obtained from medical charts. Body fat and muscle mass levels were measured with Tanita T 6360. Results: Gender distribution, mean age, and BMI of patients with CAH were 34/7, 30 ± 8, 27 ± 5.4; HC subjects 30/8, 30 ± 6, 27 ± 3.8 (P = 0.9, 0.6, 0.9, respectively). The VAI values of patients with a diagnosis of CAH 3.7 (2.3-6.9) were found to be significantly higher than those of HC patients 2.5 (1.8-3.9; P = 0.02). The mean glucocorticoid doses of the patients were 17 ± 9 mg/day. The glucocorticoid dose level was determined as independent risk factor on the FRS (P = 0.03, ß = 0.04) and VAI (P = 0.018, ß = 0.17). Conclusion: Glucocorticoid dose optimization should be done more carefully to improve metabolic and cardiovascular outcomes in CAH patients.

A Genetic Assessment of Dopamine Agonist-Induced Impulse Control Disorder in Patients With Prolactinoma.

CONTEXT: Dopamine agonist (DA)-induced impulse control disorder (ICD) represents a group of behavioral disorders that are increasingly recognized in patients with prolactinoma. OBJECTIVE: We aimed to examine the genetic component of the underlying mechanism of DA-induced ICD. METHODS: Patients with prolactinoma receiving dopamine agonist (cabergoline) treatment were included in the study. These patients were divided into 2 groups: patients who developed ICD due to DA and patients who did not. Patients were evaluated for polymorphisms of the DRD1, DRD3, COMT, DDC, GRIN2B, TPH2, OPRK1, OPRM1, SLC6A4, SLC6A3, HTR2A genes. RESULTS: Of the 72 patients with prolactinoma using cabergoline, 20 were diagnosed with ICD. When patients with and without ICD were compared according to genotype frequencies, OPRK1/rs702764, DRD3/rs6280, HTR2A/rs6313, SLC6A4/rs7224199, GRIN2B/rs7301328, TPH2/rs7305115, COMT/rs4680, DRD1/rs4532 polymorphisms significantly increased in patients with DA-induced ICD. CONCLUSION: Our results show that multiple neurotransmission systems affect DA-induced ICD in patients with prolactinoma.

Effect of metformin on thyroid cancer risk in patients with acromegaly: A preliminary observational study.

PURPOSE: To evaluate the role of metformin on thyroid cancer risk in patients with acromegaly. METHODS: Medical charts of 534 patients with acromegaly that were followed-up between 1983 and 2019 were reviewed. Patients with follow-up duration at least 6 months were included. Cohort entry was defined as first visit date. The date of each case's thyroid cancer diagnosis was defined as index date. Patients were followed until the index date, death, or last visit date, whichever came first. Nested case-control study design was selected to evaluate the association between metformin and the thyroid cancer risk in patients with acromegaly. RESULTS: 291 patients with acromegaly were included into final analysis. The mean age at acromegaly diagnosis was 42.3 ± 1.3 years. The median follow-up duration was 76 [34-132] months. Among 291 patients, 13 patients (4.5%) had thyroid cancer. Thirty-one percent (n = 92) of the patients used metformin for 6 months or longer. One standard deviation (SD) increase in average growth hormone increased the odds of having thyroid cancer by 1.164 folds (p = 0.017). One SD increase of the average insulin-like growth factor 1 to upper limit of normal ratio increased the odds of having thyroid cancer by 1.201 folds (p = 0.004). If a patient used metformin for at least 6 months, the odds to have thyroid cancer was decreased, multiplied by 0.62 with a 95% confidence interval of [0.47, 0.83] (p = 0.0013). The risk of thyroid cancer decreased with increasing duration of metformin use. CONCLUSION: Metformin may decrease the thyroid cancer risk in patients with acromegaly.

Machine learning as a clinical decision support tool for patients with acromegaly.

OBJECTIVE: To develop machine learning (ML) models that predict postoperative remission, remission at last visit, and resistance to somatostatin receptor ligands (SRL) in patients with acromegaly and to determine the clinical features associated with the prognosis. METHODS: We studied outcomes using the area under the receiver operating characteristics (AUROC) values, which were reported as the performance metric. To determine the importance of each feature and easy interpretation, Shapley Additive explanations (SHAP) values, which help explain the outputs of ML models, are used. RESULTS: One-hundred fifty-two patients with acromegaly were included in the final analysis. The mean AUROC values resulting from 100 independent replications were 0.728 for postoperative 3 months remission status classification, 0.879 for remission at last visit classification, and 0.753 for SRL resistance status classification. Extreme gradient boosting model demonstrated that preoperative growth hormone (GH) level, age at operation, and preoperative tumor size were the most important predictors for early remission; resistance to SRL and preoperative tumor size represented the most important predictors of remission at last visit, and postoperative 3-month insulin-like growth factor 1 (IGF1) and GH levels (random and nadir) together with the sparsely granulated somatotroph adenoma subtype served as the most important predictors of SRL resistance. CONCLUSIONS: ML models may serve as valuable tools in the prediction of remission and SRL resistance.

Discrimination between non-functioning pituitary adenomas and hypophysitis using machine learning methods based on magnetic resonance imaging­derived texture features.

PURPOSE: Hypophysitis is a heterogeneous condition that includes inflammation of the pituitary gland and infundibulum, and it can cause symptoms related to mass effects and hormonal deficiencies. We aimed to evaluate the potential role of machine learning methods in differentiating hypophysitis from non-functioning pituitary adenomas. METHODS: The radiomic parameters obtained from T1A-C images were used. Among the radiomic parameters, parameters capable of distinguishing between hypophysitis and non-functioning pituitary adenomas were selected. In order to avoid the effects of confounding factors and to improve the performance of the classifiers, parameters with high correlation with each other were eliminated. Machine learning algorithms were performed with the combination of gray-level run-length matrix-low gray level run emphasis, gray-level co-occurrence matrix-correlation, and gray-level co-occurrence entropy. RESULTS: A total of 34 patients were included, 17 of whom had hypophysitis and 17 had non-functioning pituitary adenomas. Among the 38 radiomics parameters obtained from post-contrast T1-weighted images, 10 tissue features that could differentiate the lesions were selected. Machine learning algorithms were performed using three selected parameters; gray level run length matrix-low gray level run emphasis, gray-level co-occurrence matrix-correlation, and gray level co-occurrence entropy. Error matrices were calculated by using the machine learning algorithm and it was seen that support vector machines showed the best performance in distinguishing the two lesion types. CONCLUSIONS: Our analysis reported that support vector machines showed the best performance in distinguishing hypophysitis from non-functioning pituitary adenomas, emphasizing the importance of machine learning in differentiating the two lesions.

Effects of SGLT2 inhibitors on patients with diabetic kidney disease: A preliminary study on the basis of podocyturia.

BACKGROUND: The aim of this study was to investigate the effects of sodium glucose cotransporter 2 inhibitors (SGLT2i) on the glomerulus through the evaluation of podocyturia in patients with diabetic kidney disease (DKD). METHODS: The study population was composed of 40 male patients with type 2 diabetes mellitus; 22 of them received SGLT2i (SGLT2i group), and the others who did not were the control. The DKD-related parameters of patients were monitored before SGLT2i initiation, and then in the third and sixth month of the follow-up period. Patients' demographic, clinical, laboratory, and follow-up data were obtained from medical charts. Microalbuminuria was measured in 24-h urine. The number of podocytes in the urine was determined by immunocytochemical staining of two different markers, namely podocalyxin (podx) and synaptopodin (synpo). Concentrations of urine stromal cell-derived factor 1a and vascular endothelial growth factor cytokines were quantified with an enzyme-linked immunosorbent assay kit. RESULTS: At the end of the follow-up period, decreases in glycosylated hemoglobin, glucose, systolic and diastolic blood pressure, uric acid level, and microalbuminuria, and improvement in body mass index level and weight loss were significant for the SGLT2i group. On the other hand, there was no significant difference in terms of these parameters in the control group. The excretion of synaptopodin-positive (synpo+ ) and podocalyxin-positive (podx+ ) cells was significantly reduced at the end of the follow-up period for the SGLT2i group, while there was no significant change for the control. CONCLUSIONS: At the end of the follow-up period, male patients receiving SGLT2i had better DKD-related parameters and podocyturia levels compared to baseline and the control group. Our data support the notion that SGLT2i might have structural benefits for glomerular health.

Fibroblast Growth Factor Receptor-4 Expression in Pituitary Adenomas is Associated with Aggressive Tumor Features.

PURPOSE: To investigate the relationship of Fibroblast Growth Factor Receptor-4 (FGFR-4) expression with radiologic, pathologic, and clinical parameters in pituitary adenomas. METHODS: Among 307 patients who underwent pituitary surgery for a pituitary adenoma between 2000 and 2015, we included 161 patients (53 gonadotroph, 26 corticotroph, 25 null cell, 22 lactotroph, 13 somatotroph, 8 adenomas with unusual combination, 7 Pit-1 positive adenomas, and 7 lactosomatotroph) based on availability of pathology specimens. Patients' radiologic, pathologic, and clinical parameters were determined. FGFR-4 immunostaining was evaluated using a semi-quantitative histologic score (H-score). RESULTS: The mean follow-up period was 61 (IQR=32-84) months. The median H-scores for FGFR-4 were higher in patients without remission, those with residual lesion, and T2-hyperintense adenoma (p<0.05). Ki-67 level was higher in patients without remission compared to those in remission (p<0.05). The mean Ki-67 levels did not differ between patients with and without residual lesion or T2-hyperintense tumor (p>0.05). There was no significant difference (p>0.05) when the H-score and Ki-67 levels were assessed in terms of sex, sellar-dural invasion, Knosp and a grading system for superior, inferior, parasellar, anterior and posterior tumor extension Classification, tumor function or presence of poor subtype. Adenomas with Ki-67 expression ≥3% had higher FGFR4 expression levels than those with <3% expression (p=0.002). There was a weak positive correlation between H-score and Ki-67 (p=0.011; r=0.201). CONCLUSIONS: Higher levels of FGFR-4 in pituitary adenomas could be use a marker for more aggressive tumor behavior.

Can "VAI" Better Indicate Metabolic Syndrome Compared with Other Metabolic Syndrome-Related Parameters in Patients with Thyroid Nodules? A Study from Turkey.

Background: To investigate the relationship between visceral adiposity index (VAI) and other metabolic syndrome (MetS)-related parameters, and thyroid nodules. Methods: This single-center, prospective, case-control study included 67 patients with thyroid nodules and 48 healthy volunteers with similar age, sex, and body mass index (BMI). Biochemical parameters were obtained from medical charts. Anthropometric measurements and total body composition analysis were performed to calculate VAI and other MetS parameters. The parenchymal structure was evaluated according to VESINC (Volume, Echogenicity, Sonographic texture, Infiltration of pseudonodular Nodules, Cysts) system on thyroid ultrasound and nodule characteristics were also detected. MetS was defined according to International Diabetes Federation criteria. Results: We examined a total of 67 patients with thyroid nodule and 48 healthy volunteers. Sixty-one (91%) were female in the patient group; and 43 (90%) were female in the control group. The mean age was 48.5 ± 11.6 years in the patient group; 47.2 ± 9.5 years in the control. The median VAI was significantly higher in the patient group than the control group [4.1 interquartile range (IQR: 2.6-5.9) vs. 3 (IQR: 2-4.3), P = 0.024]. There was a positive correlation between VAI and BMI, waist/hip ratio (WHpR), waist/height ratio (WHtR), and homeostasis of model assessment of insulin resistance (HOMA-IR). On the other hand, there was no significant correlation between VAI and thyroid function tests and autoantibodies and thyroid volume. Conclusions: In conclusion, we demonstrated that MetS was more common in patients with thyroid nodules. Although VAI and HOMA-IR levels were significantly different between the two groups, we found no significant difference in terms of waist circumference, WHpR, and WHtR. This might suggest that VAI compared with these parameters, better predicts the risk of MetS in patients with thyroid nodules.

Primary hypophysitis: Experience of a Single Tertiary Center.

PURPOSE: The authors review the clinical outcomes of patients with primary hypophysitis (PH). METHODS: Patients with PH who were followed up between 2007 and 2018 at our clinic were evaluated. Clinical, endocrinologic, pathologic, radiologic findings and treatment modalities were assessed. RESULTS: Seventeen patients with PH were assessed. The median follow-up was 24 (range, 6-84) months. Histologic confirmation was available in 8 patients (6 lymphocytic hypophysitis, 1 lymphocytic-granulomatous hypophysitis, 1 xanthomatous hypophysitis). None of the cases were diagnosed after pregnancy. Two patients had an autoimmune disease. The most commonly seen symptom was headache. The most common anterior pituitary deficiencies were hypocortisolemia and hypothyroidism. The radiologic findings of the patients at the time of diagnosis revealed various results including space-occupying lesion (41.2%), loss of posterior hypophysis bright spot (47.1%), pituitary stalk thickening (41.2%), uniform contrast enhancement (17.6%), partially empty sella (11.8%), optic chiasm compression (11.8%). The most frequent initial treatment modality was observation. Ten patients who were followed up conservatively had no endocrinologic deterioration; additional treatment was not needed in 8 of these 10 patients. The second most frequent initial treatment modality was pituitary surgery. Five patients received steroid treatment. We found serious adverse effects during steroid treatment in 3 of 5 (60%) patients; unilateral avascular necrosis of the femoral head (n=2), diabetes mellitus(n=1). CONCLUSION: Correctly diagnosing PH and giving appropriate treatment is challenging. It is unclear whether active treatment with steroids improves clinical outcomes. The serious adverse effects of steroids are also taken into account. Observation, surgery and/or radiotherapy can be appropriate treatment modalities for selected patients.

SNPs of miR-23b, miR-107 and HMGA2 and their Relations with the Response to Medical Treatment in Acromegaly Patients.

INTRODUCTION: Acromegaly is a chronic disease of increased growth hormone (GH) secretion and elevated insulin-like growth factor-I (IGF-I) levels induced by a pituitary adenoma. HMGA2 (high mobility group A2) and AIP (aryl hydrocarbon receptor-interacting protein) expression levels are related to GH-secreting adenomas, and also a response to Somatostatin Analogs (SSAs). We studied SNPs in miR-107 and miR-23b that related with AIP and HMGA2 genes respectively and control their expression, and also SNP in the 3'UTR of HMGA2 gene. Our aim was to investigate genotype distributions of the studied SNPs, as well as the possible relationship between disease and/or response to SSAs treatment in patients with acromegaly. MATERIAL AND METHODS: Genotypes were determined by qRT-PCR method from DNA materials obtained blood samples of acromegaly patients (141) and healthy individuals (99). The genotype distributions of patients and healthy groups, as well as the relationship between the clinical data of the disease and genotypes were statistically compared. RESULTS: In acromegaly patients with T-allele, p53 expression (p=0.049) was significantly higher. In patients with CT+TT genotype and T-allele who were responder to SSA-treatment Ki-67 index (respectively p=0.019, p=0.020 respectively) was higher. We did not observe the genotypes for miR-23b and miR-107 polymorphisms in the patients and control group of Turkish population. CONCLUSION: The genetic variations of the miRNAs genes related with HMGA2 and AIP genes were not seen in our study. Although there is no relationship between HMGA2-rs1351394 polymorphism and acromegaly disease, T allele was associated with some clinical features related to adenoma in patients with acromegaly.

The effect of somatostatin analogs and acromegaly on the upper gastrointestinal system.

PURPOSE: To evaluate the effects of somatostatin analogs and disease activity status on the upper gastrointestinal system in patients with acromegaly. METHODS: One hundred eighty-one patients with acromegaly were retrospectively assessed. The demographic, biochemical, pathologic, and radiologic data of the patients were evaluated. The upper gastrointestinal endoscopies and endoscopic biopsies were investigated. We divided patients into four groups according to the use of somatostatin analogs, and into two groups according to disease activity. We compared the data of patients between groups A, B, C, and D, and controlled/uncontrolled groups separately. RESULTS: Before and in the peri-endoscopic period, 67 and 27 patients were being treated with octreotide long-acting release (LAR) (group A) and lanreotide autogel (group B), respectively. Twenty-one patients used somatostatin analogs, but they were stopped for various reasons before upper gastrointestinal endoscopy (group C), and 66 patients did not use a somatostatin analog (group D). In the peri-endoscopic period, 103 (60%) patients were responsive to medical and/or surgical treatment and 67 (40%) patients were non-responsive. The rate of gastritis was higher in group A than in groups B and D. The incidence of duodenitis and gastric ulcer was much higher in group D. The rate of gastritis was higher in the controlled group compared to the uncontrolled group. CONCLUSION: The study showed that octreotide LAR treatment could be a risk factor in addition to known factors for the development of gastritis in patients with acromegaly.

Efficacy and Safety of Stereotactic Radiotherapy in Cushing's Disease: A Single Center Experience.

OBJECTIVE: To determine the efficacy and safety of stereotactic radiotherapy (RT) in patients with Cushing's disease (CD). METHODS: The study included 38 patients [31 patients who received gamma knife radiosurgery (GKS) and 7 patients who received cyberknife hypofractionated RT (HFRT)] with CD. Hormonal remission was considered if the patient had suppressed cortisol levels after low dose dexamethasone, normal 24-hour urinary free cortisol (UFC), and lack or regression of clinical features. RESULTS: Biochemical control after RT was observed in 52.6% of the patients with CD and median time to hormonal remission was 15 months. Tumor size control was obtained in all of the patients. There was no significant relationship between remission rate and laboratory, radiological and pathological variables except for preoperative UFC. Remission rate was higher in patients with lower preoperative UFC. Time to remission increased in parallel to postoperative cortisol and 1mg DST level. Although medical therapy before RT did not affect the rate of- and time to remission, medical therapy after RT prolonged the time to hormonal remission. CONCLUSION: In this current single center experience, postoperative cortisol and 1mg DST levels were found as the determinants of time to remission. Although medical therapy before RT did not affect the rate of- and time to remission, medical therapy after RT prolonged the time to biochemical control . This latter finding might suggest a radioprotective effect of cortisol lowering medication use on peri-RT period.

Effectiveness of Cabergoline Treatment in Patients with Acromegaly Uncontrolled with SSAs: Experience of a Single Tertiary Center.

PURPOSE: To evaluate the effectiveness of cabergoline and the parameters affecting cabergoline response as add-on treatment to somatostatin analaogues (SSA) in patients with acromegaly uncontrolled with SSAs. MATERIAL AND METHOD: One hundred and twenty-nine acromegalic patients uncontrolled with SSA who had cabergoline added to their treatment were included in this retrospective study. Patients were divided into the SSAs + cabergoline-responsive (group 1) and non-responsive groups (group 2), and biochemical, pathologic, and radiologic parameters were assessed. RESULTS: IGF-1 normalization was achieved in 75 of 129 patients (58%) when cabergoline was added to the SSA treatment. Female patients were significantly higher in group 1 compared to group 2 (p=0.006). Group 1 had significantly smaller pre- and post-cabergoline tumor size (p=0.011, p=0.007 respectively), lower levels of IGF-1 in pre-and post-operative period (p=0.040, p=0.001), and lower levels of IGF-1 in pre- and post-cabergoline treatment (p<0.001). Cavernous invasion on sellar magnetic resonance imaging, dural invasion in pathologic examination were not significantly different between the groups. Sellar invasion in pathologic examination was significantly higher in group 1 (p=0.011). No significant difference was found in proliferation indices between two groups. The presence of fibrous bodies was significantly lower in group 1 (p=0.010). CONCLUSION: Cabergoline can be added to the treatment of acromegalic patients uncontrolled with SSAs due to its ease of use and low economic cost, especially in patients with acromegaly who have small adenomas and no fibrous bodies.