Changing presentation of acromegaly in half a century: a single-center experience.

OBJECTIVE: Investigate the changes in the characteristics of presentation, in patients with acromegaly over a period of approximately half a century. METHODS: The medical records of patients diagnosed with acromegaly between 1980 and 2023 were retrospectively reviewed. The collected data were examined to assess any changes observed over the years and a comparison was made between the characteristics of patients diagnosed in the last decade and those diagnosed in previous years. RESULTS: A total of 570 patients were included in the study, 210 (37%) patients were diagnosed in the last decade. Patients diagnosed before 2014 had longer symptom duration before diagnosis, advanced age, larger pituitary adenomas, higher incidence of cavernous sinus invasion, and higher GH and IGF-1 levels than those diagnosed last decade (p < 0.05, for all). Furthermore, the patients diagnosed before 2014 had a lower rate of surgical remission (p < 0.001), and a higher prevalence of comorbidities such as diabetes, hypertension, colon polyps, and thyroid cancer at the time of diagnosis (p < 0.05, for all). CONCLUSION: There may be a trend for earlier detection of patients with acromegaly.

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.

G-protein Coupled Estrogen Receptor Expression in Growth Hormone Secreting and Non-Functioning Adenomas.

PURPOSE: To evaluate the expression of G-protein coupled estrogen receptor (GPER1), aromatase, estrogen receptor α (ERα), estrogen receptor ß (ERß), pituitary tumor transforming gene (PTTG), and fibroblast growth factor 2 (FGF2) in GH-secreting and non-functioning adenomas (NFA). METHODS: Thirty patients with acromegaly and 27 patients with NFA were included. Gene expression was determined via quantitative reverse transcription polymerase chain reaction (QRT-PCR). Protein expression was determined via immunohistochemistry. RESULTS: There was no difference, in terms of gene expression of aromatase, ERα, PTTG, and FGF2 between the two groups (p>0.05 for all). ERß gene expression was higher and GPER1 gene expression was lower in GH-secreting adenomas than NFAs (p<0.05 for all). Aromatase and ERß protein expression was higher in GH-secreting adenomas than NFAs (p=0.01). None of the tumors expressed ERα. GPER1 expression was detected in 62.2% of the GH-secreting adenomas and 45% of NFAs. There was no difference in terms of GPER1, PTTG, FGF2 H scores between the two groups (p>0.05 for all). GPER1 gene expression was positively correlated to ERα, ERß, PTTG, and FGF2 gene expression (p<0.05 for all). There was a positive correlation between aromatase and GPER1 protein expression (r=0.31; p=0.04). CONCLUSIONS: GPER1 is expressed at both gene and protein level in a substantial portion of GH-secreting adenomas and NFAs. The finding of a positive correlation between GPER1 and ERα, ERß, PTTG, and FGF2 gene expression and aromatase and GPER1 protein expression suggests GPER1 along with aromatase and classical ERs might mediate the effects of estrogen through upregulation of PTTG and FGF2.

Bacteroidetes and Firmicutes levels in gut microbiota and effects of hosts TLR2/TLR4 gene expression levels in adult type 1 diabetes patients in Istanbul, Turkey.

AIM: The aim of this study was to determine and compare the levels of both Bacteroidetes and Firmicutes in the gut microbiota and TLR2/TLR4 gene expression in the blood of patients with type 1 diabetes mellitus (T1DM) and healthy individuals. These results may serve as a preliminary assessment to guide future research. METHOD: Between January and October 2014, stool and blood samples were collected from 53 adult T1DM patients and 53 age- and gender-matched healthy individuals. Bacteroidetes and Firmicutes levels were assessed from stool sample DNA and TLR2 and TLR4 expression levels were analyzed via qPCR using RNA from EDTA blood samples from both patients and healthy controls. RESULTS: The amounts of Bacteroidetes and Firmicutes were statistically significantly higher and lower, respectively, in the T1DM group than in the healthy control group (p < 0.001 and p < 0.001, respectively). In addition, the Firmicutes/Bacteroidetes ratios in patients with T1DM were significantly lower than in healthy controls. The TLR4 and TLR2 gene expression levels in T1DM patients were significantly upregulated and downregulated, respectively, compared to those in the control group. CONCLUSION: Our data are the first to show a relationship between T1DM and gut microbiota in our country. In addition, our results provide information about the connections between T1DM, gut microbiota, and TLR2 and TLR4 expression. We believe that Bacteroidetes and Firmicutes in the gut microbiota may play a role in the autoimmune process of T1DM and that these findings should be further investigated in the future.

The Role of Different Molecular Markers in Papillary Thyroid Cancer Patients with Acromegaly.

PURPOSE: Prevalence of papillary thyroid cancer (PTC) is increased in patients with acromegaly. We aimed to determine the protein expression of BRAF, RAS, RET, insulin like growth factor 1(IGF1), Galectine 3, CD56 in patients with PTC related acromegaly and to compare the extensity of these expressions with normal PTC patients and benign thyroid nodules. METHODS: We studied 313 patients with acromegaly followed in Cerrahpasa Medical Faculty, Endocrinology and Metabolism Clinic between 1998 and 2015. On the basis of availability of pathological specimen of thyroid tissues, thyroid samples of 13 patients from 19 with acromegaly related PTC (APTC), 20 normal PTC and 20 patients with multinodulary goiter (MNG) were histopathologically evaluated. Protein expressions were determined via immunohistochemical staining in ex-vivo tumor samples and benign nodules. RESULTS: The incidence of PTC in acromegaly patients were 6% (n=19). Among patients with PTC, APTC and MNG, all the immunohistochemical protein expressions we have studied were higher in papillary thyroid cancer groups (p<0.01, for all). Between PTC group without acromegaly and APTC, galectin 3 and IGF1 expression was significantly higher in acromegalic patients (p<0.01 for all) while RAS was predominantly higher in PTC patients without acromegaly (p<0.01). CONCLUSION: BRAF expression was not higher in PTC with acromegaly patients compared to PTC patients without acromegaly. Galectine 3 and IGF1 were expressed more intensively in APTC. These positive protein expressions may have more influence on determining malign nodules among acromegaly patients.

Sexual function in women with Cushing's Syndrome: A controlled study.

OBJECTIVE: The aim of this study is to determine the severity of female sexual dysfunction (FSD), quality of life, and depression status in female patients with Cushing's syndrome (CS). MATERIAL AND METHODS: This study included 29 sexually active women with CS and 30 healthy age and body mass index matched women. The Female Sexual Function Index (FSFI) questionnaire, Beck Depression Inventory (BDI) and Short Form Health Survey (SF-36) were filled by each participant. Plasma levels of FSH, LH, PRL, cortisol, DHEA-S, 17-hydroxyprogesterone, androstenedione, free testosterone, total testosterone and estradiol were measured. RESULTS: Female sexual dysfunction was present in 88.9% of the women with CS and 24.1% of the control group. The CS group showed a lower total FSFI score [16.6 (IQR: 5-23)] compared to the healthy women [26.8 (IQR: 25.5-30.4) (p<0.001)]. The FSFI scores in the arousal, lubrication, orgasm, pain and satisfaction domains were all lower in the women with CS (p<0.001). Both summary scores of the SF-36 were reduced in women with Cushing's syndrome compared to the control group (p=0.001). The BDI scores of patients were significantly higher than those of the control subjects (p=0.007). In patients with CS, levels of LH, estradiol, and DHEA-S04 were significantly lower while cortisol (p<0.05), and 17 hydroxyprogestrone levels were higher than control subjects (p<0.05). CONCLUSION: This study showed that majority of the women with CS had FSD. This may be related to the inhibitory effect of cortisol on sex hormones.

Renal complications of lipodystrophy: A closer look at the natural history of kidney disease.

OBJECTIVES: Lipodystrophy syndromes are a group of heterogeneous disorders characterized by adipose tissue loss. Proteinuria is a remarkable finding in previous reports. STUDY DESIGN: In this multicentre study, prospective follow-up data were collected from 103 subjects with non-HIV-associated lipodystrophy registered in the Turkish Lipodystrophy Study Group database to study renal complications in treatment naïve patients with lipodystrophy. METHODS: Main outcome measures included ascertainment of chronic kidney disease (CKD) by studying the level of proteinuria and the estimated glomerular filtration rate (eGFR). Kidney volume was measured. Percutaneous renal biopsies were performed in 9 patients. RESULTS: Seventeen of 37 patients with generalized and 29 of 66 patients with partial lipodystrophy had CKD characterized by proteinuria, of those 12 progressed to renal failure subsequently. The onset of renal complications was significantly earlier in patients with generalized lipodystrophy. Patients with CKD were older and more insulin resistant and had worse metabolic control. Increased kidney volume was associated with poor metabolic control and suppressed leptin levels. Renal biopsies revealed thickening of glomerular basal membranes, mesangial matrix abnormalities, podocyte injury, focal segmental sclerosis, ischaemic changes and tubular abnormalities at various levels. Lipid vacuoles were visualized in electron microscopy images. CONCLUSIONS: CKD is conspicuously frequent in patients with lipodystrophy which has an early onset. Renal involvement appears multifactorial. While poorly controlled diabetes caused by severe insulin resistance may drive the disease in some cases, inherent underlying genetic defects may also lead to cell autonomous mechanisms contributory to the pathogenesis of kidney disease.

Germline mutations of aryl hydrocarbon receptor-interacting protein (AIP) gene and somatostatin receptor 1-5 and AIP immunostaining in patients with sporadic acromegaly with poor versus good response to somatostatin analogues.

OBJECTIVE: To determine aryl hydrocarbon interacting protein (AIP) gene variations and AIP and somatostatin receptor (SSTR) 1-5 immunostaining in patients with apparently sporadic acromegaly with poor versus good response to somatostatin analogues (SRLs). METHODS: A total of 94 patients (66 with poor and 28 with good response to SRLs) were screened for the AIP gene variations using Sanger sequencing. Immunostaining was performed in 60 tumors. RESULTS: Several variations, albeit some with undetermined significance, were detected, especially in poor responder patients. The prevalence of AIP mutation was 2.1% in the whole group and 1.5% in patients with poor response to SRLs. AIP, SSTR2A, and SSTR2B immunostainings were decreased in patients with poor response (p < 0.05 for all), and other SSTRs did not differ between the groups (p > 0.05 for all). Patients with low AIP had decreased levels of SSTR2A and SSTR3 (p < 0.05 for all). AIP and SSTR2A immunostainings were positively correlated to the treatment response and age at diagnosis was negatively correlated (p < 0.05 for all). In poor responder patients with high SSTR2A immunostaining, SSTR2B immunostaining and preoperative tumor size were positively and negatively correlated, respectively, to SRL response (p < 0.05 for all). CONCLUSIONS: Lack of response to SRLs does not necessarily increase the risk of harboring AIP mutations. The finding of decreased AIP, SSTR2A, and SSTR2B immunostaining in patients with poor response to SRLs and decreased SSTR2A and SSTR3 level in those with low AIP immunostaining suggests a possible interaction between AIP and some SSTR subtypes that might alter SRL sensitivity.

Determinants of glucose metabolism and the role of NPY in the progression of insulin resistance in chronic migraine.

Background Chronic migraine has a well-documented association with increased insulin resistance and metabolic syndrome. The hypothalamus may play a role in the progression of insulin resistance in chronic migraine through the regulation of orexigenic peptides such as neuropeptide Y. Insulin resistance may lead to increased risk of future type 2 diabetes mellitus in patients with chronic migraine, which is more likely to occur if other pathogenetic defects of type 2 diabetes mellitus, such as impaired pancreatic ß-cell functions and defects in intestinal glucagon-like peptide-1 secretion after meals. We studied the relationship of fasting neuropeptide Y with insulin resistance, ß-cell function, and glucagon-like peptide-1 secretion in non-obese female chronic migraine patients. We also aimed to investigate glucose-stimulated insulin and glucagon-like peptide-1 secretions as early pathogenetic mechanisms responsible for the development of carbohydrate intolerance. Methods In this cross-sectional controlled study, 83 non-obese female migraine patients of reproductive age categorized as having episodic migraine or chronic migraine were included. The control group consisted of 36 healthy females. We studied glucose-stimulated insulin and glucagon-like peptide-1 secretion during a 75 g oral glucose tolerance test. We investigated the relationship of neuropeptide Y levels with insulin resistance and ß-cell insulin secretion functions. Results Fasting glucose levels were significantly higher in migraine patients. Plasma glucose and insulin levels during the oral glucose tolerance test were otherwise similar in chronic migraine, episodic migraine and controls. Patients with chronic migraine were more insulin resistant than episodic migraine or controls ( p = 0.048). Glucagon-like peptide-1 levels both at fasting and two hours after glucose intake were similar in chronic migraine, episodic migraine, and controls. Neuropeptide Y levels were higher in migraineurs. In chronic migraine, neuropeptide Y was positively correlated with fasting glucagon-like peptide-1 levels (r = 0.57, p = 0.04), but there was no correlation with insulin resistance (r = 0.49, p = 0.09) or ß-cell function (r = 0.50, p = 0.07). Discussion Non-obese premenopausal female patients with chronic migraine have higher insulin resistance, but normal ß-cell function is to compensate for the increased insulin demand during fasting and after glucose intake. Increased fasting neuropeptide Y levels in migraine may be a factor leading to increased insulin resistance by specific alterations in energy intake and activation of the sympathoadrenal system.

Clinical spectra of neuromuscular manifestations in patients with lipodystrophy: A multicenter study.

Lipodystrophy is a heterogeneous group of disorders characterized by loss of adipose tissue. Here, we report on clinical spectra of neuromuscular manifestations of Turkish patients with lipodystrophy. Seventy-four patients with lipodystrophy and 20 healthy controls were included. Peripheral sensorimotor neuropathy was a common finding (67.4%) in lipodystrophic patients with diabetes. Neuropathic foot ulcers were observed in 4 patients. Drop foot developed in 1 patient with congenital generalized lipodystrophy type 1. Muscle symptoms and hypertrophy were consistent findings in congenital generalized lipodystrophy (21/21) and familial partial lipodystrophy (25/34); on the other hand, overt myopathy with elevated creatine kinase activity was a distinctive characteristic of congenital generalized lipodystrophy type 4. Muscle biopsies revealed myopathic changes at different levels. Accumulation of triglycerides was observed which contributes to insulin resistance. All patients with congenital generalized lipodystrophy suffered from tight Achilles tendons at various levels. Scoliosis was observed in congenital generalized lipodystrophy type 4 (2/2) and familial partial lipodystrophy type 2 (2/17). Atlantoaxial instability was unique to congenital generalized lipodystrophy type 4 (2/2). Bone cysts were detected in congenital generalized lipodystrophy type 1 (7/10) and congenital generalized lipodystrophy type 2 (2/8). Our study suggests that lipodystrophies are associated with a wide spectrum of neuromuscular abnormalities.

LATE-NIGHT SALIVARY CORTISOL IS UNALTERED IN PATIENTS WITH POLYCYSTIC OVARIAN SYNDROME (PCOS), IRRESPECTIVE OF DISEASE PHENOTYPE, AND IN OBESE WOMEN, IRRESPECTIVE OF THE PRESENCE OF PCOS.

OBJECTIVE: To determine cutoff values of late-night salivary cortisol (LNSC) using an electrochemiluminescent immunoassay and investigate whether the diagnostic performance of the assay is influenced by the presence of obesity or polycystic ovary syndrome (PCOS). METHODS: A total of 124 subjects comprising 25 patients with Cushing syndrome (CS), 44 with PCOS (22 nonobese and 22 obese), 21 with constitutional obesity (CO), and 34 healthy subjects (HS) were included in the study. Two consecutive LNSC samples were collected from all participants. RESULTS: The median LNSC levels of patients with CS were significantly higher than LNSC levels of HS, patients with CO, and obese and nonobese patients with PCOS, respectively (P<.01 for all). Healthy subjects, patients with CO, and obese and nonobese patients with PCOS did not differ in terms of median LNSC levels (P>.05 for all). The cutoff values and corresponding sensitivity and specificity were similar between the groups. The comparisons of the area under curve of the first LNSC (0.963; 95% confidence interval [CI], 0.910 to 0.989), second LNSC (0.954; 95% CI, 0.898 to 0.984), and the mean of two consecutive LNSC (mLNSC) values (0.962; 95% CI, 0.909 to 0.989) did not differ significantly (P>.05 for all). A cutoff value for mLNSC of 7.45 nmol/L yielded a sensitivity of 100% and specificity of 87.5% in HS. CONCLUSION: In conclusion, LNSC is a reliable test with high diagnostic accuracy in both HS and patients with PCOS and obesity. ABBREVIATIONS: ACTH = adrenocorticotropic hormone AUC = area under the curve BMI = body mass index CO = constitutional obesity CS = Cushing syndrome E2 = estradiol ECLIA = electrochemiluminescent immunoassay FPG = fasting plasma glucose FSH = follicle-stimulating hormone HOMA-IR = homeostasis model assessment of insulin resistance HPA = hypothalamo-pituitary-adrenal HS = healthy subjects IQR = interquartile range LH = luteinizing hormone LNSC = late-night salivary cortisol LR = likelihood ratio mLNSC = mean of two consecutive LNSC samples PCOS = polycystic ovarian syndrome ROC = receiver operating characteristic UFC = urinary free cortisol WHR = waist-to-hip ratio.

Outcomes of Primary Transsphenoidal Surgery in Cushing Disease: Experience of a Tertiary Center.

BACKGROUND: To report the initial and long-term remission rates and related factors, secondary treatments, and outcomes of a series of patients with Cushing disease (CD). METHODS: We included 147 consecutive adult patients with CD who underwent primary transsphenoidal surgery (TSS) between 1998 and 2014 in this study. Eighty-two were followed up in the Cerrahpasa Medical Faculty Endocrinology and Metabolism outpatient clinic. Patients were requested to attend a long-term remission assessment; 55 could be contacted, and data for the remaining 27 patients' last visit to the outpatient clinics were reviewed for early and late remission. Six patients were excluded from the study. Magnetic resonance imaging (MRI) findings and pathologic results including mitosis, Ki-67 levels, and P53 in immunostaining of all patients were evaluated. RESULTS: Data of 82 patients with CD with an average age of 36 years [interquartile range: 29-47] were analyzed with a mean follow-up of 7.5 years [interquartile range: 5-10]. Overall initial remission rates were 72.3% after TSS. Among the 82 patients, 16 patients had Gamma Knife radiosurgery and 7 patients underwent adrenalectomy. After these additional treatments, the long-term remission rate was found as 69.7%. The highest remission rates were with microadenomas. Recurrence was most frequently seen in patients without tumor evidence on MRI. Patients with high Ki-67 levels had higher recurrence rates in long-term follow-up (P = 0.02). CONCLUSION: Life-long follow-up for patients with CD seems essential. Undetectable tumors on MRI before TSS and high Ki-67 immunopositivity were found as risk factors for tumor recurrence.

Clinical presentations, metabolic abnormalities and end-organ complications in patients with familial partial lipodystrophy.

OBJECTIVE: Familial partial lipodystrophy (FPLD) is a rare genetic disorder characterized by partial lack of subcutaneous fat. METHODS: This multicenter prospective observational study included data from 56 subjects with FPLD (18 independent Turkish families). Thirty healthy controls were enrolled for comparison. RESULTS: Pathogenic variants of the LMNA gene were determined in nine families. Of those, typical exon 8 codon 482 pathogenic variants were identified in four families. Analysis of the LMNA gene also revealed exon 1 codon 47, exon 5 codon 306, exon 6 codon 349, exon 9 codon 528, and exon 11 codon 582 pathogenic variants. Analysis of the PPARG gene revealed exon 3 p.Y151C pathogenic variant in two families and exon 7 p.H477L pathogenic variant in one family. A non-pathogenic exon 5 p.R215Q variant of the LMNB2 gene was detected in another family. Five other families harbored no mutation in any of the genes sequenced. MRI studies showed slightly different fat distribution patterns among subjects with different point mutations, though it was strikingly different in subjects with LMNA p.R349W pathogenic variant. Subjects with pathogenic variants of the PPARG gene were associated with less prominent fat loss and relatively higher levels of leptin compared to those with pathogenic variants in the LMNA gene. Various metabolic abnormalities associated with insulin resistance were detected in all subjects. End-organ complications were observed. CONCLUSION: We have identified various pathogenic variants scattered throughout the LMNA and PPARG genes in Turkish patients with FPLD. Phenotypic heterogeneity is remarkable in patients with LMNA pathogenic variants related to the site of missense mutations. FPLD, caused by pathogenic variants either in LMNA or PPARG is associated with metabolic abnormalities associated with insulin resistance that lead to increased morbidity.

Essential parameters and risk factors of the patients for diabetes care and treatment.

AIM: The aim was to explore the association between Type 2 Diabetes Mellitus [T2DM] treatment satisfactions of patients regarding their socio-economic, life-style, history medication and clinical outcome in a Turkish population SUBJECT AND METHODS: A cross-sectional study conducted from February 2016 to September 2016. Of the total 1500 diabetic patients approached, 1094 (72.9%) gave their consent. Data analysis included, sociodemographic, serum lipid profiles (LDL, HDL), calcium, uric acid, blood pressure and glycated hemoglobin (HbA1c) at baseline and after six months. The Diabetes Treatment Satisfaction Questionnaire (DTSQ) tools were used to measure the patient satisfaction. RESULTS: The mean and standard deviation of age among gender, there were significant differences between males (51.81±14.40) and females (49.76±13.99) (p=0.024). There were statistically significant differences between males and females regarding place of living (city 76% vs town 26%) p<0.001) and consanguinity (p=0.040). Almost of the patients with diabetes were overweight (males 44.5% vs females 41.8%) while more than a quarter (31.2%) males were obese. Among patients with diabetes, significantly larger proportion were treated for DM with insulin (females 28.8% vs males 22.5%) and 'insulin & oral anti diabetic drugs' (females 21.6% vs males 18.4%%; p<0.001) in comparison. Reported average sleeping haours was significantly more among males (6.5±1.1 vs. 6.1±1.2; p<0.001) than females. Males and females reported significantly greater improvements in mean values of blood glucose (-2.07 p<0.001; vs. -2.36; p=0.007), HbA1c (-1.72 p<0.001; vs. -1.47 p=0.038), potassium (+0.98 p<0.001; vs. +0.93 p<0.005); albumin (-3.38 p<0.001; vs. -3.60; p<0.001); billirubin (-0.69 p=0.049; vs. -0.98; p<0.001); uric acid (+11.9 p=0.017; vs. +14.3; p<0.001); systolic blood pressure (-3.86 p<0.001; vs. -3.2 p<0.001) and diastolic blood pressure (-3.17 p<0.001; vs. -3.2 p<0.001) in comparison to 6 months before. Multivariate stepwise regression analysis showed that the satisfaction DTSQ scores for HbA1c (p<0.001), h of sleep (p<0.001), neuropathy (p=0.007), diabetic education (p=0.014), SBP (mmHg) (p=0.021) DBP (mmHg) (p=0.028) were identified as significantly associated with higher treatment satisfaction. CONCLUSION: The study confirms a positive correlation between diabetes patient's satisfaction with care and treatment. Females DM patients compared to males had a better satisfaction score with current treatment, unacceptably low blood glucose level, flexibility in treatment and understanding of DM.

General health status and intelligence scores of children of mothers with acromegaly do not differ from those of healthy mothers.

PURPOSE: To determine the physical status and intelligence scores of children of acromegalic mothers and to compare them with those of children from mothers without acromegaly. METHODS: Six women with acromegaly who became pregnant under follow-up between 2010 and 2014 and their 16 children (group A) were assessed and compared with 16 children of healthy women (group B) and 15 children of women with prolactinoma (group C). The physical examinations of children were performed by the department of pediatric endocrinology and intelligence quotient (IQ) testing was undertaken by adult and pediatric psychiatry departments, using appropriate scales for their ages. RESULTS: Six of the 16 children (girls/boys: 7/9) were born after the diagnosis of acromegaly. Five of the 6 pregnancies occured when the patients were taking somatostatin analogs, none continued taking the drugs during pregnancy. The mean IQ of groups A, B, and C were 106.4 ± 12.5, 105.3 ± 12.5, and 103.2 ± 16.1 respectively (p > 0.05). The mean ages, birth percentiles, recent weight and height standard deviation scores were similar between groups (p > 0.05). Two siblings from group A and 1 child from group B were large for gestational age at birth. At recent follow-up, two children from group A were found tall for their age and one from group C was short for his age and was placed under the care of pediatric endocrinology clinic. CONCLUSIONS: Pregnancies in acromegaly seems to be uneventful and the general health status and IQ scores of children from women with and without acromegaly were found similar.

Multidisciplinary Approach for Acromegaly: A Single Tertiary Center's Experience.

BACKGROUND: Acromegaly is a multisystemic disease that requires a multidisciplinary approach. The aim of this study was to determine early and late remissions of patients who underwent surgery at our center and to evaluate relations between pathologic and radiologic properties of adenoma and medical and radiosurgical treatments with remissions. METHODS: The medical records of 103 patients with acromegaly who underwent endoscopic endonasal transsphenoidal surgery in Cerrahpasa Medical Faculty, Istanbul University, between 2007 and 2014 were reviewed. Clinical, biochemical, radiologic, and pathologic properties were determined. RESULTS: The total median follow-up time was 38 months [interquartile range: 24-53.5 months]. Thirty-two percent of the adenomas were microadenomas and 68% were macroadenomas The early remission rate was 51.5% and late remission was 75.2%. The sellar floor invasion was significantly lower in patients with early and late remissions (P = 0.01 and P = 0.009, respectively). The initial growth hormone (GH; P < 0.001), first-day GH (P = 0.03), 3-month GH (P = 0.001), insulin-like growth factor-1 (P = 0.004), and 6-month insulin-like growth factor-1 (P = 0.02) levels were significantly greater in patients with sellar floor invasion. The late remission rates (P = 0.004) were greter and reoperation needs (P = 0.05) were lower in patients with Ki-67 <3% than in patients with ≥3%. Seventy (68.6%) patients needed medical therapy during follow-up. CONCLUSIONS: Late remission was achieved using a multidiciplinary approach in 75.2% of 103 patients with acromegaly, and young age, male sex, high Ki-67 and mitosis indices, and cavernous sinus and sellar-floor invasion had negative effects on clinical and biochemical control of the disease.

Locally produced estrogen through aromatization might enhance tissue expression of pituitary tumor transforming gene and fibroblast growth factor 2 in growth hormone-secreting adenomas.

Aromatase, a key enzyme in local estrogen synthesis, is expressed in different pituitary tumors including growth hormone (GH)-secreting adenomas. We aimed to evaluate aromatase, estrogen receptor α (ERα), estrogen receptor ß (ERß), pituitary tumor transforming gene (PTTG), and fibroblast growth factor 2 (FGF2) expressions in GH-secreting adenomas, and investigate their correlation with clinical, pathologic, and radiologic parameters. This cross-sectional study was conducted in a tertiary center in Turkey. Protein expressions were determined via immunohistochemical staining in ex vivo tumor samples of 62 patients with acromegaly and ten normal pituitary tissues. Concordantly increased aromatase, PTTG, and FGF2 expressions were detected in the tumor samples as compared with controls (p < 0.001 for all). None of the tumors expressed ERα while ERß was detected only in mixed somatotroph adenomas. Aromatase, ERß, PTTG expressions were not significantly different between patients with and without remission (p > 0.05 for all). FGF2 expression was significantly higher in patients without postoperative and late remission (p = 0.002 and p = 0.012, respectively), with sphenoid bone invasion, optic chiasm compression, and somatostatin analog resistance (p = 0.005, p = 0.033, and p = 0.013, respectively). Aromatase, PTTG and FGF2 expressions were positively correlated with each other (r = 0,311, p = 0.008 for aromatase, FGF2; r = 0.380, p = 0.001 for aromatase, PTTG; r = 0.400, p = 0.001 for FGF2, PTTG). PTTG-mediated FGF2 upregulation is associated with more aggressive tumor features in patients with acromegaly. Also, locally produced estrogen through aromatization might have a role in this phenomenon.

Life-Threatening Hypercalcemia due to Graves' Disease and Concomitant Adrenal Failure: A Case Report and Review of the Literature.

A 47-year-old woman presented with the complaints of nausea, vomiting, and weight loss. She had a history of bilateral surrenalectomy due to Cushing's syndrome. On examination she had tachycardia and orthostatic hypotension. Laboratory examinations revealed hypercalcemia and suppressed parathyroid hormone levels. She also had thyrotoxicosis due to Graves' disease. The investigations to rule out a malignancy were negative. With steroid, zoledronic acid, and antithyroid drug treatment her symptoms were resolved and calcium level was normalized. This case highlights the importance of recognizing thyrotoxicosis and concomitant adrenal failure as a possible cause of severe hypercalcemia.