Use of levothyroxine for euthyroid, thyroid antibody positive women with infertility: Analyses of aggregate data from a survey of European thyroid specialists (Treatment of Hypothyroidism in Europe by Specialists: An International Survey).

OBJECTIVES: The use of levothyroxine (LT4) treatment aiming to improve fertility in euthyroid women with positive thyroid peroxidase antibodies (TPOAb) is not supported by the available evidence. The aim of the study was to document the use of LT4 by European thyroid specialists in such patients. DESIGN: The data presented derive from Treatment of Hypothyroidism in Europe by Specialists, an International Survey (THESIS), a questionnaire conducted between 2019 and 2021 to document the management of hypothyroidism by European thyroid specialists. Here, we report the aggregate results on the use of LT4 in infertile, euthyroid women with positive TPOAb. RESULTS: A total of 2316/5406 (42.8%) respondents stated that LT4 may be indicated in TPOAb positive euthyroid women with infertility. The proportion of those replying positively to this question varied widely across different countries (median 39.4, range 22.9%-83.7%). In multivariate analyses males (OR: 0.8; CI: 0.7-0.9) and respondents >60 years (OR: 0.7; 0.6-0.8) were the least inclined to consider LT4 for this indication. Conversely, respondents managing many thyroid patients ("weekly" [OR: 1.4; CI: 1.0-1.9], "daily" [OR: 1.8; CI: 1.3-2.4]) and practicing in Eastern Europe (OR: 1.5; CI: 1.3-1.9) were most likely to consider LT4. CONCLUSIONS: A remarkably high number of respondents surveyed between 2019 and 2021, would consider LT4 treatment in TPOAb positive euthyroid women with infertility. This view varied widely across countries and correlated with sex, age and workload, potentially influencing patient management. These results raise concerns about potential risks of overtreatment.

Glucose control during pregnancy in patients with type 1 diabetes correlates with fetal hemodynamics: a prospective longitudinal study.

BACKGROUND: Maternal diabetes adversely affects fetal cardiovascular system development. Previous studies have reported that the fetuses of mothers with diabetes exhibit both structural and functional changes; nevertheless, prior studies have not examined the association between glucose control and fetal cardiac morphology and performance. Thus, the objective was to determine the association between fetal cardiac morphology and function and maternal glucose control in type 1 diabetes and to compare the differences in measured cardiac parameters between the fetuses of mothers with diabetes and healthy controls. METHODS: In this prospective, longitudinal case-control study - including 62 pregnant women with type 1 diabetes mellitus and 30 healthy pregnant women - fetal cardiac assessment using B-mode, M-mode, and spectral pulsed-wave Doppler was performed in the second and third trimesters. In women with T1DM, glycated hemoglobin and data obtained from glucose sensors - including the percentage of time in, below, and above the range (TIR, TBR, and TAR, respectively), and coefficient of variation (CV) - were analyzed across three time periods: the last menstrual period to 13 (V1), 14-22 (V2), and 23-32 weeks (V3) of gestation. Fetal cardiac indices were compared between groups, and the correlation between glucose control and fetal cardiac indices was assessed. RESULTS: At 28-32 weeks, the fetuses of women with T1DM exhibited increased left ventricular end-diastolic length, relative interventricular septum thickness, right ventricular cardiac output, and pulmonary valve peak systolic velocity compared with healthy controls. At 18-22 weeks, pulmonary and aortic valve diameters, left and right ventricular stroke volumes, and left cardiac output inversely correlated with the CV and glycated hemoglobin levels at V1 and V2. Furthermore, at 28-32 weeks, pulmonary and aortic valve diameters, left ventricular stroke volume, cardiac output, and right/left atrioventricular valve ratio inversely correlated with the TBR at V1, V2, and V3. Moreover, diastolic functional parameters correlated with the TAR and glycated hemoglobin levels, particularly after the first trimester. CONCLUSION: In women with T1DM, maternal hyperglycemia during pregnancy correlates with fetal diastolic function, whereas glucose variability and hypoglycemia inversely correlate with fetal left ventricular systolic function in the second and third trimesters.

Patients' Persistent Symptoms, Clinician Demographics, and Geo-Economic Factors Are Associated with Choice of Therapy for Hypothyroidism by European Thyroid Specialists: The "THESIS" Collaboration.

Background: Hypothyroidism is common, however, aspects of its treatment remain controversial. Our survey aimed at documenting treatment choices of European thyroid specialists and exploring how patients' persistent symptoms, clinician demographics, and geo-economic factors relate to treatment choices. Methods: Seventeen thousand two hundred forty-seven thyroid specialists from 28 countries were invited to participate in an online questionnaire survey. The survey included respondent demographic data and treatment choices for hypothyroid patients with persistent symptoms. Geo-economic data for each country were included in the analyses. Results: The response rate was 32.9% (6058 respondents out of 17,247 invitees). Levothyroxine (LT4) was the initial treatment preferred by the majority (98.3%). Persistent symptoms despite normal serum thyrotropin (TSH) while receiving LT4 treatment were reported to affect up to 10.0% of patients by 75.4% of respondents, while 28.4% reported an increasing such trend in the past 5 years. The principal explanations offered for patients' persistent symptoms were psychosocial factors (77.1%), comorbidities (69.2%), and unrealistic patient expectations (61.0%). Combination treatment with LT4+liothyronine (LT3) was chosen by 40.0% of respondents for patients who complained of persistent symptoms despite a normal TSH. This option was selected more frequently by female thyroid specialists, with high-volume practice, working in countries with high gross national income per capita. Conclusions: The perception of patients' dissatisfaction reported by physicians seems lower than that described by hypothyroid patients in previous surveys. LT4+LT3 treatment is used frequently by thyroid specialists in Europe for persistent hypothyroid-like symptoms even if they generally attribute such symptoms to nonendocrine causes and despite the evidence of nonsuperiority of the combined over the LT4 therapy. Pressure by dissatisfied patients on their physicians for LT3-containing treatments is a likely explanation. The association of the therapeutic choices with the clinician demographic characteristics and geo-economic factors in Europe is a novel information and requires further investigation.

High prevalence of venous thrombotic events in Cushing's syndrome: data from ERCUSYN and details in relation to surgery.

OBJECTIVE: The aim of this study was to evaluate the prevalence of venous thromboembolism (VTE) in patients included in the European Registry on Cushing's syndrome (ERCUSYN), compare their clinical characteristics with those who did not develop VTE and identify risk factors for VTE. DESIGN: A retrospective observational cohort study. METHODS: Data extraction from the registry was taken on February, 7, 2022. At the time there were 2174 patients diagnosed with Cushing's syndrome (CS) and 95 VTEs were reported in the database. RESULTS: Of 95 VTE events 70 (74%) were in pituitary-dependent CS patients, 12 (12.5%) in adrenal-dependant CS, 10 (10.5%) in ectopic CS, and 3 (3%) in CS due to other causes. Sex, 24-hour urinary free cortisol (UFC) value at diagnosis, as well as the number of operations remained statistically significant predictors of VTE. Of patients who were treated with at least one surgery, 12 (13%) VTE occurred before and 80 (87%) after the surgery. Nearly half of these VTEs occurred within six months since the operation (36; 45%). Over half of the centers that reported VTE did not routinely anticoagulate CS patients. Anticoagulation schemes varied widely. CONCLUSION: Patients with CS have an elevated risk of developing VTE for an extended period of time. From ERCUSYN cohort patients have higher risk for VTE if they need multiple surgeries to treat CS, are males and have high UFC values at the diagnosis of CS. Since there is no agreement on thromboprohpylaxis, a protocol for VTE prevention that is widely adopted appears to be necessary for patients with CS.

Characteristics of specialists treating hypothyroid patients: the "THESIS" collaborative.

Introduction: Thyroid specialists influence how hypothyroid patients are treated, including patients managed in primary care. Given that physician characteristics influence patient care, this study aimed to explore thyroid specialist profiles and associations with geo-economic factors. Methods: Thyroid specialists from 28 countries were invited to respond to a questionnaire, Treatment of Hypothyroidism in Europe by Specialists: an International Survey (THESIS). Geographic regions were defined according to the United Nations Statistics Division. The national economic status was estimated using World Bank data on the gross national income per capita (GNI per capita). Results: 5,695 valid responses were received (response rate 33·0%). The mean age was 49 years, and 65·0% were female. The proportion of female respondents was lowest in Northern (45·6%) and highest in Eastern Europe (77·2%) (p <0·001). Respondent work volume, university affiliation and private practice differed significantly between countries (p<0·001). Age and GNI per capita were correlated inversely with the proportion of female respondents (p<0·01). GNI per capita was inversely related to the proportion of respondents working exclusively in private practice (p<0·011) and the proportion of respondents who treated >100 patients annually (p<0·01). Discussion: THESIS has demonstrated differences in characteristics of thyroid specialists at national and regional levels, strongly associated with GNI per capita. Hypothyroid patients in middle-income countries are more likely to encounter female thyroid specialists working in private practice, with a high workload, compared to high-income countries. Whether these differences influence the quality of care and patient satisfaction is unknown, but merits further study.

Severe Cushing's syndrome from an ectopic adrenocorticotropic hormone-secreting neuroendocrine tumour treated by osilodrostat.

Summary: Severe Cushing's syndrome from an ectopic adrenocorticotropic hormone-producing tumour is rare but often demands rapid diagnostics and treatment of hypercortisolism with its comorbidities. Pharmacotherapy of hypercortisolism by ketoconazole, metyrapone and osilodrostat is currently available. If unsuccessful or insufficient a bilateral adrenalectomy is an option. We present a 28-year-old female with severe Cushing's syndrome caused by a bronchial metastatic neuroendocrine tumour (NET). Hypercortisolism was efficiently treated by osilodrostat with block-replace and then titration regimen. A once-daily dose was finally used with normalised cortisol levels. Androgen levels measured by liquid chromatography-mass spectrometry were slightly elevated during the treatment but without any symptoms. A simple once-daily use of osilodrostat with titration regimen led to normalised cortisol levels in a severe Cushing's syndrome patient with an uncurable bronchial NET. Transient hypocortisolism during treatment appeared but was easily treated by hydrocortisone. Learning points: Cushing's syndrome from an ectopic adrenocorticotropic hormone-producing tumour is rare. Cortisol upregulation is often severe and rapid, though clinical signs are not always fully pronounced. Rapid treatment is a key for preventing and reducing complications such as fractures, thromboembolism, bleeding, hyperglycaemia, and arterial hypertension. The novel potent steroidogenesis inhibitor osilodrostat can be used as first-line treatment for reducing hypercortisolism.

The way to data: opinions and recommendations for the provision of health data for secondary use.

Healthcare data held by state-run organisations is a valuable intangible asset for society. Its use should be a priority for its administrators and the state. A completely paternalistic approach by administrators and the state is undesirable, however much it aims to protect the privacy rights of persons registered in databases. In line with European policies and the global trend, these measures should not outweigh the social benefit that arises from the analysis of these data if the technical possibilities exist to sufficiently protect the privacy rights of individuals. Czech society is having an intense discussion on the topic, but according to the authors, it is insufficiently based on facts and lacks clearly articulated opinions of the expert public. The aim of this article is to fill these gaps. Data anonymization techniques provide a solution to protect individuals' privacy rights while preserving the scientific value of the data. The risk of identifying individuals in anonymised data sets is scalable and can be minimised depending on the type and content of the data and its use by the specific applicant. Finding the optimal form and scope of deidentified data requires competence and knowledge on the part of both the applicant and the administrator. It is in the interest of the applicant, the administrator, as well as the protected persons in the databases that both parties show willingness and have the ability and expertise to communicate during the application and its processing.

Pediatric Cushing's disease: Case reports and retrospective review.

BACKGROUND: We report four pediatric subjects with Cushing's disease (CD) diagnosed in the Czech Republic. We focus on initial symptoms of Cushing's syndrome (CS) which can lead to early diagnosis, on typical symptoms of CS in children, their age and sex distribution, the mean length of symptoms prior to diagnosis, indication for examination, post-cure growth, sexual development and pituitary function in our four CD patients after transsphenoidal pituitary surgery (TSS). We describe the diagnostic process leading to confirmation of CD and we emphasize the biochemical and radiological diagnostic difficulties. CONCLUSIONS: Pediatric CD has a number of features distinct from adult CD. Our retrospective analysis confirmed the presence of growth retardation and change in facial appearance with development of moon face as the first symptoms of CS. According to our observation, growth retardation is prior to development of moon face. The other typical symptoms frequently seen in pediatric patients are pseudo-precocious puberty in both sexes, hirsutism in pubertal girls due to excessive adrenal androgen secretion and pubertal delay. A corticotropin-releasing hormone (CRH) test and especially bilateral inferior petrosal sinus sampling for ACTH (BIPSS) contribute to confirming the diagnosis of CD and excluding ectopic ACTH syndrome in children with unvisible adenoma on pituitary magnetic resonance imaging (MRI).

Establishing the Optimal Time for Induction of Labor in Women with Diet-Controlled Gestational Diabetes Mellitus: A Single-Center Observational Study.

To determine the optimal week for labor induction in women with diet-controlled gestational diabetes mellitus by comparing differences in perinatal and neonatal outcomes of labor induction to expectant management at different gestational weeks. Methods: This was a retrospective analysis of a prospectively recruited cohort of 797 singleton pregnancies complicated by diet-controlled gestational diabetes mellitus that were diagnosed, treated, and delivered after 37 weeks in a tertiary, university-affiliated perinatal center between January 2016 and December 2021. Results: The incidence of neonatal complications was highest when delivery occurred at 37 weeks, whereas fetal macrosomia occurred mostly at 41 weeks (20.7%); the frequency of large for gestational age infants did not differ between the groups. Conversely, the best neonatal outcomes were observed at 40 weeks due to the lowest number of neonates requiring phototherapy for neonatal jaundice (1.7%) and the smallest proportion of neonates experiencing composite adverse neonatal outcomes defined as neonatal hypoglycemia, phototherapy, clavicle fracture, or umbilical artery pH < 7.15 (10.4%). Compared with expectant management, the risk for neonatal hypoglycemia was increased for induction at 39 weeks (adjusted odds ratio 12.29, 95% confidence interval 1.35−111.75, p = 0.026) and that for fetal macrosomia was decreased for induction at 40 weeks (adjusted odds ratio 0.11, 95% confidence interval 0.01−0.92, p = 0.041), after adjusting for maternal pre-pregnancy body mass index, nulliparity, and mean pregnancy A1c. Conclusions: The lowest rate of neonatal complications was observed at 40 weeks. Labor induction at 40 weeks prevented fetal macrosomia.

Association between gestational diabetes mellitus and bioavailability of insulin-like growth factors and role of their binding proteins.

OBJECTIVE: Insulin-like growth factors (IGFs) are involved in regulating growth and metabolism and increase insulin sensitivity, improve glucose metabolism, and are potentially related to gestational diabetes mellitus (GDM) and its complications for mothers and fetuses. DESIGN: This study aimed to assess serum levels and cord blood levels of IGF system components in pregnant women with (39 participants) and without GDM (22 participants). Blood samples were obtained at 28-32 and 36-38 weeks of gestation and 6-12 months after delivery. Cord blood samples were obtained during delivery. Results between both groups as well as between single visits were statistically compared. RESULTS: Both IGF1 and IGF2 maternal serum levels did not differ between the GDM and non-GDM groups. However, levels of IGF-binding proteins (IGFBPs) were different. IGFBP4 levels were decreased during pregnancy and after delivery in women with GDM, while IGFBP7 levels were increased during pregnancy in women with GDM. Cord blood IGFBP3 and IGFBP7 levels were increased (p < 0.001 for IGFBP3, p = 0.003 for IGFBP7), while IGFBP4 levels were decreased (p < 0.001) in the GDM group compared with the non-GDM group. CONCLUSIONS: Although IGF levels did not differ, changes in their function level could still persist possibly because of the effects of the binding proteins, especially their promoting or inhibitory effects on IGFs. These results should be considered in interpretation of IGF levels.

Pituitary incidentaloma.

Pituitary incidentaloma are being accidentally found during imaging procedures in approximately 10% of normal population. Facing pituitary incidentalomas endocrinologists have to decide about further management based on the assessment of hormonal activity, aetiology, size, and possible compressive symptoms. Treatment of choice for prolactinomas is medical therapy. Surgical treatment is a treatment of choice for other hormonally active tumours and in case of complications as defects of visual field, pituitary apoplexy with compressive symptoms, ophthalmoplegia respectively. Tumour not indicated for surgical treatment are followed-up by imaging techniques and in indicated cases also by endocrinological or visual field evaluation.

Use of thyroid hormones in hypothyroid and euthyroid patients: a 2020 THESIS questionnaire survey of members of the Czech Society of Endocrinology.

BACKGROUND: Inconsistencies in the management of hypothyroidism have been reported among endocrinologists in different European countries. Aim of this study was to explore Czech endocrinologists' use of thyroid hormones in hypothyroid and euthyroid patients. METHODS: We used a web-based survey containing 32 questions regarding the use of thyroid hormones. Four-hundred thirty-two members of the Czech Society of Endocrinology received an e-mail invitation to participate in the survey. RESULTS: We received and analysed 157 responses (112 females and 45 males) from the 432 members (36.3%). According to 99.4% of the respondents, levothyroxine (LT4) is the primary drug of choice for the treatment of hypothyroidism. Liothyronine (LT3) was used in clinical practice by 29.9% of responders. According to 90.5% of respondents, thyroid hormones may be indicated in biochemically euthyroid patients. Female physicians prescribe thyroid hormones in euthyroid infertile women with high antibody levels more frequently than male physicians (P = 0.003). Most Czech endocrinologists (76.4%) consider combined therapy with LT4 and LT3 in various clinical scenarios, but only 1 of 29 hypothyroid physicians (3.5%) would recommend it to their patients, and only 4 out of 128 respondents (3.1%) would consider LT3 or desiccated thyroid for themselves, if diagnosed with hypothyroidism. CONCLUSION: LT4 is the primary thyroid hormone used in the Czech Republic for treatment of hypothyroidism. At variance with thyroid guideline recommendations, Czech endocrinologists are quite liberal when prescribing thyroid hormones to euthyroid patients and in the use of LT4/LT3 combination treatment for hypothyroid patients with persisting symptoms.

Tumor induced osteomalacia - A long way toward correct diagnosis and management.

Tumor-induced osteomalacia (TIO) is an uncommon type of osteomalacia associated with phosphaturic mesenchymal tumors (PMTs). Due to nonspecific symptoms, the diagnosis and appropriate management of the disease is often delayed for many years. Involvement of spine with TIO associated tumors is exceedingly rare. We present a 53-year-old woman with a 10-year history of bone pain, muscle weakness and multiple bone fractures that markedly impaired her quality of life. Biochemical evaluation revealed hypophosphatemia due to renal phosphate wasting and elevated plasma fibroblast growth factor 23 (FGF-23) concentration indicating PMT. It was found using 68Ga DOTA TOC PET/CT scan in the vertebral body L2. The patient underwent surgical resection of the tumor. Postoperatively, there was a significant decrease in phosphaturia, normalization of serum phosphate, 1.25 dihydroxyvitamin D and plasma FGF23 concentration. Thereafter the patient's condition markedly improved concerning her motility and basic daily activities. This case report demonstrates the first known case of TIO in the Slovakia and points to a long way from onset of symptoms toward correct diagnosis and successful surgical management.

Pregnancy of women with type 1 diabetes mellitus - the effect of preconception care on perinatal results. Ten years of experience.

INTRODUCTION: Despite the ever-improving medical care, pregnancies of women with type 1 diabetes mellitus (T1DM) are at increased risk of complications for both mother and child. Optimal compensation of diabetes before and during pregnancy is an essential protective factor reducing the risk of congenital malformations, pregnancy loss, and other complications. The pregnancy of women with T1DM should be planned, ideally at a time of optimal diabetes compensation. Target glycated hemoglobin (HbA1c) values until the range of 42-48 mmol/mol should be achieved at least three months before pregnancy. Our work aimed to evaluate the perinatal results of pregnancies in women with T1DM and the eff ect of preconception counseling and adequate T1DM compensation before pregnancy on perinatal outcomes. METHODS AND RESULTS: Retrospective analysis of pregnancy and perinatal outcomes of women with T1DM were followed up at the Department of Gynecology and Obstetrics, General University Hospital in Prague and First Faculty of Medicine, Charles University between 2008 to 2018. A total of 221 women with T1DM were included in the analysis. Adequate (HbA1c  48 mmol/mol at least 3 months before conception) and inadequate diabetes compensation at the beginning of the pregnancy had 59 (26.7%) and 162 (72.3%) women, respectively. Pregnancies of women with adequate diabetes compensation were more often planned (55.9 vs. 24.7%; P  95th percentile; 22.0 vs. 35.8%; P = 0.027). CONCLUSION: The pregnancy of women with T1DM is burdened by a number of perinatal and neonatal complications. In the study group, most women with T1DM became pregnant unintentionally at a time of inadequate diabetes compensation. Women who achieved adequate diabetes compensation before pregnancy had a lower incidence of perinatal complications. Therefore, it is advised that women with T1DM should plan their pregnancy, attend preconception and antenatal care, and give birth in perinatal centers, which provide coordinated care from diabetologists, gynecologists, obstetricians, and neonatologists.

Predictive and prognostic significance of tumour subtype, SSTR1-5 and e-cadherin expression in a well-defined cohort of patients with acromegaly.

In somatotroph pituitary tumours, somatostatin analogue (SSA) therapy outcomes vary throughout the studies. We performed an analysis of cohort of patients with acromegaly from the Czech registry to identify new prognostic and predictive factors. Clinical data of patients were collected, and complex immunohistochemical assessment of tumour samples was performed (SSTR1-5, dopamine D2 receptor, E-cadherin, AIP). The study included 110 patients. In 31, SSA treatment outcome was evaluated. Sparsely granulated tumours (SGST) differed from the other subtypes in expression of SSTR2A, SSTR3, SSTR5 and E-cadherin and occurred more often in young. No other clinical differences were observed. Trouillas grading system showed association with age, tumour size and SSTR2A expression. Factors significantly associated with SSA treatment outcome included age, IGF1 levels, tumour size and expression of E-cadherin and SSTR2A. In the group of SGST, poor SSA response was observed in younger patients with larger tumours, lower levels of SSTR2A and higher Ki67. We observed no relationship with expression of other proteins including AIP. No predictive value of E-cadherin was observed when tumour subtype was considered. Multiple additional factors apart from SSTR2A expression can predict treatment outcome in patients with acromegaly.

The possible role of endocrine dysfunction of adipose tissue in gestational diabetes mellitus.

Gestational diabetes mellitus (GDM) is diabetes that is first diagnosed in the second or third trimester of pregnancy in patients who did not have a history of diabetes before pregnancy. Consequences of GDM include increased risk of macrosomia and birth complications in the infant and an increased risk of maternal type 2 diabetes mellitus (T2DM) after pregnancy. There is also a longer-term risk of obesity, T2DM, and cardiovascular diseases in the child. GDM is the result of impaired glucose tolerance due to pancreatic ß-cell dysfunction on a background of insulin resistance that physiologically increases during pregnancy. The strongest clinical predictors of GDM are overweight and obesity. The fact that women with GDM are more likely to be overweight or obese suggests that adipose tissue dysfunction may be involved in the pathogenesis of GDM, similarly to T2DM. Adipose tissue is not only involved in energy storage but also functions as an active endocrine organ secreting adipokines (specific hormones and cytokines) with the ability to alter insulin sensitivity. Recent evidence points to a crucial role of numerous adipokines produced by fat in the development of GDM. The following text summarizes the current knowledge about a possible role of selected adipokines in the development of GDM.

Subclinical Inflammation and Adipose Tissue Lymphocytes in Pregnant Females With Gestational Diabetes Mellitus.

CONTEXT: Gestational diabetes mellitus (GDM) is accompanied by subclinical inflammation; however, little is known about local inflammation in adipose tissue and placenta. OBJECTIVE: To analyze systemic and local subclinical inflammation and adipose tissue lymphocyte content and phenotype in pregnant women with and without GDM. DESIGN: Observational study. SETTINGS: Academic hospital. PATIENTS: Twenty-one pregnant women with GDM (GDM group), 16 pregnant women without GDM (non-GDM group) and 15 nonpregnant control women (N group). INTERVENTIONS: Serum samples taken at 28 to 32 (visit 1 [V1]) and 36 to 38 (V2) gestational weeks and 6 to 12 months after delivery (V3) in the GDM and non-GDM group and before elective gynecological surgery in the N group. Subcutaneous (SAT) and visceral adipose tissue (VAT) obtained during cesarean delivery or surgery. MAIN OUTCOME MEASURES: Serum levels and adipose tissue expression of proinflammatory cytokines, adipose tissue lymphocyte content and phenotype (for a subset of GDM and non-GDM subjects). RESULTS: Accented proinflammatory state in GDM was documented by increased circulating tumor necrosis factor-α (TNF-α) levels. In both groups of pregnant females total lymphocytes were higher in VAT compared to SAT. In GDM subjects B cells and NKT cells were higher in SAT compared to VAT and T helper cells were increased relative to SAT of non-GDM group, while no intercompartmental adipose tissue differences were seen in non-GDM women. CONCLUSIONS: Pregnant females had higher total lymphocyte count in VAT relative to SAT regardless of GDM. In addition to increased systemic subclinical inflammation, GDM was associated with significant differences in lymphocyte composition between subcutaneous and visceral adipose tissue depots.

Early versus late Gamma Knife radiosurgery for Cushing's disease after prior resection: results of an international, multicenter study.

OBJECTIVE: The optimal time to perform stereotactic radiosurgery after incomplete resection of adrenocorticotropic hormone (ACTH)-producing pituitary adenoma in patients with Cushing's disease (CD) remains unclear. In patients with persistent CD after resection of ACTH-producing pituitary adenoma, the authors evaluated the association of the interval between resection and Gamma Knife radiosurgery (GKRS) with outcomes. METHODS: Pooled data from 10 institutions participating in the International Radiosurgery Research Foundation were used in this study. RESULTS: Data from 255 patients with a mean follow-up of 65.59 ± 49.01 months (mean ± SD) were analyzed. Seventy-seven patients (30%) underwent GKRS within 3 months; 46 (18%) from 4 to 6 months; 34 (13%) from 7 to 12 months; and 98 (38%) at > 12 months after the resection. Actuarial endocrine remission rates were higher in patients who underwent GKRS ≤ 3 months than when treatment was > 3 months after the resection (78% and 65%, respectively; p = 0.017). Endocrine remission rates were lower in patients who underwent GKRS at > 12 months versus ≤ 12 months after the resection (57% vs 76%, respectively; p = 0.006). In multivariate Cox regression analyses adjusted for clinical and treatment characteristics, early GKRS was associated with increased probability of endocrine remission (hazard ratio [HR] 1.518, 95% CI 1.039-2.218; p = 0.031), whereas late GKRS (HR 0.641, 95% CI 0.448-0.919; p = 0.015) was associated with reduced probability of endocrine remission. The incidence of some degree of new pituitary deficiency (p = 0.922), new visual deficits (p = 0.740), and other cranial nerve deficits (p = 0.610) was not significantly related to time from resection to GKRS. CONCLUSIONS: Early GKRS is associated with an improved endocrine remission rate, whereas later GKRS is associated with a lower rate of endocrine remission after pituitary adenoma resection. Early GKRS should be considered for patients with CD after incomplete pituitary adenoma resection.

A Consensus on the Diagnosis and Treatment of Acromegaly Comorbidities: An Update.

OBJECTIVE: The aim of the Acromegaly Consensus Group was to revise and update the consensus on diagnosis and treatment of acromegaly comorbidities last published in 2013. PARTICIPANTS: The Consensus Group, convened by 11 Steering Committee members, consisted of 45 experts in the medical and surgical management of acromegaly. The authors received no corporate funding or remuneration. EVIDENCE: This evidence-based consensus was developed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to describe both the strength of recommendations and the quality of evidence following critical discussion of the current literature on the diagnosis and treatment of acromegaly comorbidities. CONSENSUS PROCESS: Acromegaly Consensus Group participants conducted comprehensive literature searches for English-language papers on selected topics, reviewed brief presentations on each topic, and discussed current practice and recommendations in breakout groups. Consensus recommendations were developed based on all presentations and discussions. Members of the Scientific Committee graded the quality of the supporting evidence and the consensus recommendations using the GRADE system. CONCLUSIONS: Evidence-based approach consensus recommendations address important clinical issues regarding multidisciplinary management of acromegaly-related cardiovascular, endocrine, metabolic, and oncologic comorbidities, sleep apnea, and bone and joint disorders and their sequelae, as well as their effects on quality of life and mortality.

The relationship of mitochondrial dysfunction and the development of insulin resistance in Cushing's syndrome.

PURPOSE: Cushing's syndrome is characterized by metabolic disturbances including insulin resistance. Mitochondrial dysfunction is one pathogenic factor in the development of insulin resistance in patients with obesity. We explored whether mitochondrial dysfunction correlates with insulin resistance and other metabolic complications. PATIENTS AND METHODS: We investigated the changes of mRNA expression of genes encoding selected subunits of oxidative phosphorylation system (OXPHOS), pyruvate dehydrogenase (PDH) and citrate synthase (CS) in subcutaneous adipose tissue (SCAT) and peripheral monocytes (PM) and mitochondrial enzyme activity in platelets of 24 patients with active Cushing's syndrome and in 9 of them after successful treatment and 22 healthy control subjects. RESULTS: Patients with active Cushing's syndrome had significantly increased body mass index (BMI), homeostasis model assessment of insulin resistance (HOMA-IR) and serum lipids relative to the control group. The expression of all investigated genes for selected mitochondrial proteins was decreased in SCAT in patients with active Cushing's syndrome and remained decreased after successful treatment. The expression of most tested genes in SCAT correlated inversely with BMI and HOMA-IR. The expression of genes encoding selected OXPHOS subunits and CS was increased in PM in patients with active Cushing's syndrome with a tendency to decrease toward normal levels after cure. Patients with active Cushing's syndrome showed increased enzyme activity of complex I (NQR) in platelets. CONCLUSION: Mitochondrial function in SCAT in patients with Cushing's syndrome is impaired and only slightly affected by its treatment which may reflect ongoing metabolic disturbances even after successful treatment of Cushing's syndrome.