Socioeconomic status and the effect of prolonged pandemic confinement on anthropometric and glycaemic outcomes in adults with type 2 diabetes mellitus.

AIM: This systematic review and meta-analysis aimed to investigate the impact of COVID19 lockdown on the anthropometric and glycaemic outcomes of adults with type 2 diabetes mellitus (T2DM) and assess whether socioeconomic status (SES) was relevant to these changes. METHODS: A search of three databases was conducted. Meta-analyses using random effects models were undertaken to combine anthropometric and glycaemic measures pre- and post-confinement. Subgroup analyses according to SES were also conducted. RESULTS: This systematic review of 19 articles demonstrated that prolonged pandemic-related confinement is associated with a deterioration in both anthropometric and glycaemic outcomes among adults with T2DM. Furthermore, SES was found to be relevant to these changes. Specifically, BMI (kg/m2) showed an increase in mean difference of 0.72 (95% CI; 0.13, 1.31; p<0.05) between pre and post lockdown cohorts. High income countries displayed a greater increase in BMI compared to their lower middle-income counterparts. Regarding, fasting blood glucose (FBG), a statistically significant difference was observed in the upper middle-income group (mean difference: 5.10; 95% CI: 2.92, 7.27), and high-income group (mean difference: 6.03; 95% CI: 0.04, 12.02). There were no significant changes to weight, waist circumference, or HbA1C over the lockdown period. CONCLUSION: Our findings suggest adults with T2DM may have received less effective care over the lockdown period, particularly in high income countries. Clinics and care providers may need to adopt more intensive contact and treatment plans in the post lockdown period to prevent lasting impacts on disease progression and metabolic sequelae.

Efficacy of anti-VEGF monotherapy versus anti-VEGF therapy with subthreshold micropulse laser (SML) in the management of diabetic macular oedema (DMO): a systematic review and meta-analysis.

BACKGROUND: Intravitreal injection anti-vascular endothelial growth factor (IVI anti-VEGF) therapy serves as the primary treatment for centre involving diabetic macular oedema (DMO). Conventional laser therapy (CLT) adjunct has proven beneficial; however, it is not widely used due to significant risks of retinal scarring. Subthreshold micropulse laser (SML) therapy has, however, emerged as a comparable alternative to combination therapy, offering a distinct advantage by mitigating the risk of retinal scarring. METHODS: A search of six databases was conducted. A meta-analysis of mean differences was performed including subgroup analyses where appropriate. Primary outcome was the number of injections at 12-14 months; secondary outcomes were changes in central macular thickness (CMT) and best corrected visual acuity (BCVA) at 6-8 months and 12-14 months. RESULTS: A total of ten papers including six randomised clinical trials and four retrospective clinical studies were included in our study, capturing 563 eyes of 478 patients. Overall, the risk of bias was moderate for these studies. Significantly fewer anti-VEGF therapy injections were administered in the combination therapy versus anti-VEGF monotherapy patients at 12-14 months who had poor visual acuity (6/18 Snellen or worse) at baseline, mean difference - 2.25 (95% CI; - 3.35, - 1.15; p < 0.05). Combination therapy was not associated with significantly fewer intravitreal injections in patients with a higher visual acuity (6/15 Snellen or better) at baseline. Our analysis also showed significant improvements to both BCVA and CMT were reached at 6 - 8 month post-baseline at the 95% confidence intervals: - 1.13 (- 2.09, - 0.16) and - 4.04 (- 7.59, - 0.50). These improvements remained statistically significant at 12-14 months: - 0.94 (- 1.67, - 0.20) and - 1.92 (- 3.52, - 0.32) respectively with combination therapy. CONCLUSION: Our findings demonstrate that combination therapy (SML + IVI anti-VEGF) is associated with fewer intravitreal injections. We report a better BCVA and a reduction in CMT at 6 and 12 months from baseline with combination treatment compared to the IVI anti-VEGF monotherapy comparator. SML is a proven non-scarring cost-effective therapy for DMO that should be readily available in the medical retinal therapy as it may reduce the burden of care.

Efficacy of multidisciplinary interventions in preventing metabolic syndrome and improving body composition in prostate cancer patients treated with androgen deprivation therapy: A systematic review and meta-analysis.

BACKGROUND: Exercise is known to reduce adverse side effects of androgen-deprivation therapy (ADT) on quality of life, bone health and fatigue for prostate cancer (PCa) patients. We conducted a systematic review with meta-analysis to evaluate the effect of multidisciplinary interventions on body composition and metabolic syndrome (MetS) in ADT-treated PCa patients. METHODS: A systematic review and meta-analysis were conducted based on searches of EMBASE, MEDLINE, CENTRAL and Scopus databases from inception to March 2023. Participants included ADT-treated PCa patients who received multidisciplinary interventions including exercise, diet, nutrition, pharmacotherapy, bariatric surgery, or psychological/behavioural therapy. Primary outcomes were changes in body composition and MetS, with prostate-specific antigen (PSA) as a secondary outcome. After meta-analysis, results were reported in mean difference, 95% confidence interval and p-value, with forest plots. Additionally, we conducted subgroup analyses to compare the effect of different interventions. RESULTS: Thirty-three articles met the eligibility criteria out of 1443 articles and 28 studies were included in meta-analysis. Of 33 studies, 17 included exercise-only interventions and 10 included exercise + diet/nutrition interventions, but no studies included diet/nutrition-only interventions. All studies employed multidisciplinary approaches in developing or delivering the interventions. Most studies (85%) had low-moderate risk of bias, thus providing good evidence to this review. Overall, interventions had a positive effect on body composition measures; lean mass (LM):0.82 kg (95% CI:0.47,1.17;p < 0.00001), body fat mass (BFM):-0.68 kg (95% CI:-1.12,-0.24;p = 0.002), fat-free mass:0.75 kg (95% CI:0.14,1.37;p = 0.02) and body fat percentage (BFP):-0.99% (95% CI:-1.29,-0.68;p < 0.00001), as well as on MetS; waist circumference:-1.95 cm (95% CI:-3.10,-0.79;p = 0.0009), systolic blood pressure:-3.43 mmHg (95% CI:-6.36,-0.50;p = 0.02) and diastolic blood pressure:-2.48 mmHg (95% CI:-4.19,-0.76;p = 0.005). Subgroup-analyses showed that a combined approach including exercise + diet/nutrition was most effective in improving BFP, WC, SBP and DBP whereas exercise was more effective in improving LM and BFM. CONCLUSIONS: In ADT-treated PCa patients, multidisciplinary interventions, especially those combining exercise and diet/nutrition, can improve body composition and metabolic health.

Comparative analysis of vaginal microbiota sampling using menstrual cups and high vaginal swabs in pregnant women living with HIV-1 infection.

Background: Menstrual cups (MCs) are increasingly used to collect cervicovaginal secretions to characterise vaginal mucosal immunology, in conjunction with high vaginal swabs (HVS) for metataxonomics, particularly in HIV transmission studies. We hypothesised that both methods of collecting bacterial biomass are equivalent for 16S rRNA gene sequencing. Material and Methods: Cervicovaginal fluid (CVF) samples from 16 pregnant women with HIV-1 (PWWH) were included to represent the major vaginal bacterial community state types (CST I-V). Women underwent sampling during the second trimester by liquid amies HVS followed by a MC (Soft disc™) and samples were stored at -80°C. Bacterial cell pellets obtained from swab elution and MC (500 µL, 1 in 10 dilution) were resuspended in 120 µL PBS for DNA extraction. Bacterial 16S rRNA gene sequencing was performed using V1-V2 primers and were analysed using MOTHUR. Paired total DNA, bacterial load, amplicon read counts, diversity matrices and bacterial taxa were compared by sampling method using MicrobiomeAnalyst, SPSS and R. Results: The total DNA eluted from one aliquot of diluted CVF from an MC was similar to that of a HVS (993ng and 609ng, p=0.18); the mean bacterial loads were also comparable for both methods (MC: 8.0 log10 16S rRNA gene copies versus HVS: 7.9 log10 16S rRNA gene copies, p=0.27). The mean number of sequence reads generated from MC samples was lower than from HVS (MC: 12730; HVS:14830, p=0.05). The α-diversity metrices were similar for both techniques; MC Species Observed: 41 (range 12-96) versus HVS: 47 (range 16-96), p=0.15; MC Inverse Simpson Index: 1.98 (range 1.0-4.0) versus HVS: 0.48 (range 1.0-4.4), p=0.22). The three most abundant species observed were: Lactobacillus iners, Lactobacillus crispatus and Gardnerella vaginalis. Hierarchical clustering of relative abundance data showed that samples obtained using different techniques in an individual clustered in the same CST group. Conclusion: These data demonstrate that despite sampling slightly different areas of the lower genital tract, there was no difference in bacterial load or composition between methods. Both are suitable for characterisation of vaginal microbiota in PWWH. The MC offers advantages, including a higher volume of sample available for DNA extraction and complimentary assays.

Concentric Reversible Visual Field Loss, Nyctalopia, and Dyschromatopsia with Ezetimibe Therapy.

This is a case of ezetimibe-induced concentric field loss, dyschromatopsia, and nyctalopia in a patient with no prior history of retinal dystrophy or drug hypersensitivity. A 55-year-old Caucasian woman presents with a 1-year history of increasing concentric visual field loss, nyctalopia, photophobia, and colour vision impairment. These symptoms correlated with the commencement of ezetimibe therapy 10 mg daily for hypercholesterolaemia. She demonstrated repeatable bilateral visual field constriction on 30-2 Humphrey visual filed testing and colour vision impairment on Ishihara plates (OD: 1/17, OS: 1/17). Biochemical and radiological screening for carcinoma-associated retinopathy was unremarkable. A working diagnosis of drug-induced rod-cone dysfunction was made. Her visual symptoms and field changes completely resolved 3 months after cessation of ezetimibe therapy. This case suggests that ezetimibe is a potential cause of rod-cone dysfunction and should be considered as a differential in patients with new unexplained visual symptoms.

Determining Contemporary Barriers to Effective Multidisciplinary Team Meetings in Neurological Surgery: A Review of the Literature.

OBJECTIVE: The integration of multidisciplinary team meetings (MDTMs) for neurosurgical care has been accepted worldwide. Our objective was to review the literature for the limiting factors to MDTMs that may introduce bias to patient care. METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analysis was used to perform a literature review of MDTMs for neuro-oncology, pituitary oncology, cerebrovascular surgery, and spine surgery and spine oncology. Limiting factors to productive MDTMs and factors that introduce bias were identified, as well as determining whether MDTMs led to improved patient outcomes. RESULTS: We identified 1264 manuscripts from a PubMed and Ovid Medline search, of which 27 of 500 neuro-oncology, 4 of 279 pituitary, and 11 of 260 spine surgery articles met our inclusion criteria. Of 224 cerebrovascular manuscripts, none met the criteria. Factors for productive MDTMs included quaternary/tertiary referral centers, nonhierarchical environment, regularly scheduled meetings, concise inclusion of nonmedical factors at the same level of importance as patient clinical information, inclusion of nonclinical participants, and use of clinical guidelines and institutional protocols to provide recommendations. Our review did not identify literature that described the use of artificial intelligence to reduce bias and guide clinical care. CONCLUSIONS: The continued implementation of MDTMs in neurosurgery should be recommended but cautioned by limiting bias.

Thyrotropinoma with silent somatotroph and lactotroph adenoma during pregnancy.

Summary: Thyrotropinomas are an uncommon cause of hyperthyroidism and are exceedingly rarely identified during pregnancy, with limited evidence to guide management. Most commonly they present as macroadenomas and may cause symptoms of mass effect including headache, visual field defects and hypopituitarism. We present a case of a 35-year-old woman investigated for headaches in whom a 13 mm thyrotropinoma was found. In the lead-up to planned trans-sphenoidal surgery (TSS), she spontaneously conceived and surgery was deferred, as was pharmacotherapy, at her request. The patient was closely monitored through her pregnancy by a multi-disciplinary team and delivered without complication. Pituitary surgery was performed 6 months post-partum. Isolated secondary hypothyroidism was diagnosed postoperatively and replacement thyroxine was commenced. Histopathology showed a double lesion with predominant pituitary transcription factor-1 positive, steroidogenic factor negative plurihormonal adenoma and co-existent mixed thyroid-stimulating hormone, growth hormone, lactotroph and follicle-stimulating hormone staining with a Ki-67 of 1%. This case demonstrates a conservative approach to thyrotropinoma in pregnancy with a successful outcome. This highlights the need to consider the timing of intervention with careful consideration of risks to mother and fetus. Learning points: Thyrotropinomas are a rare cause of secondary hyperthyroidism. Patients may present with hyperthyroidism or symptoms of mass effect, including headaches or visual disturbance. Thyrotropinoma in pregnancy presents a number of pituitary-related risks including pituitary apoplexy and compression of local structures. Hyperthyroidism in pregnancy raises the risk of complications including spontaneous abortion, preeclampsia, low birthweight and premature labour. Timing of medical and surgical therapies must be carefully considered. A conservative approach requires careful monitoring in case emergent intervention is required.

Using artificial intelligence for personal protective equipment guidance for healthcare workers in the COVID-19 pandemic and beyond.

Background: Current procedures for effective personal protective equipment (PPE) usage rely on the availability of trained observers or 'buddies' who, during the COVID-19 pandemic, are not always available. The application of artificial intelligence (AI) has the potential to overcome this limitation by assisting in complex task analysis. To date, AI use for PPE protocols has not been studied. In this paper we validate the performance of an AI PPE system in a hospital setting. Methods: A clinical cohort study of 74 healthcare workers (HCW) at a 144-bed University teaching hospital. Participants were recruited to use the AI system for PPE donning and doffing. Performance was validated by the current gold standard double-buddy system across seven donning and ten doffing steps based on local infection control guidelines. Results: The AI-PPE platform was 98.9% sensitive on doffing and 85.3% sensitive on donning, when compared to remediated double buddy. On average, buddy correction of PPE was required 3.8 ± 1.5% of the time. The average time taken to don was 240 ± 51.5 seconds and doff was 241 ± 35.3 seconds. Conclusion: This study demonstrates the ability of an AI model to analyse PPE donning and doffing with real-time feedback for remediation. The AI platform can identify complex multi-task PPE donning and doffing in a single validated system. This AI system can be employed to train, audit, and thereby improve compliance whilst reducing reliance on limited HCW resources. Further studies may permit the development of this educational tool into a medical device with other industry uses for safety.

The Impact of Multidisciplinary Weight Management on Body Weight and Body Mass Composition in Women with Breast Cancer Post-Adjuvant Chemotherapy: A Retrospective Chart Review.

INTRODUCTION: Weight gain during chemotherapy for breast cancer is a well-documented adverse effect. The purpose of this study was to investigate how multidisciplinary weight management involving endocrinology, dietitian, and exercise physiology care, in a real-life healthy weight clinic (HWC) would impact body weight and mass composition in breast cancer women post-adjuvant chemotherapy compared to a cohort of non-cancer women who have been matched by age, ethnicity, smoking, and menopausal status. METHODS: Body weight (kg), BMI (kg/m2), skeletal muscle mass (SMM %), fat mass (FM %), and waist circumference (cm) were collected at baseline of the first HWC appointment, 3 months after baseline, and 6 months after baseline. A total of 32 women were included, 11 in the breast cancer cohort and 21 in the control cohort, that matched inclusion and exclusion criteria based on a retrospective chart review from 28 July 2017 to 19 July 2021. RESULTS: By 6 months, the breast cancer women had a mean weight change of -6.99 kg (SD = 3.87, p = 0.003, n = 11) and change in BMI by -2.72 kg/m2 (SD = 1.62, p = 0.004, n = 11). There was a change in SMM of 1.21% (SD = 0.73, p = 0.005, n = 11), a change in FM of -2.76% (SD = 1.33, p = 0.002, n = 11), and a change in waist circumference of -8.13 cm (SD = 4.21, p = 0.031, n = 3). By 6 months in the breast cancer cohort, there was a larger change in body weight in women who did not have MetS (-8.72 kg, SD = 2.41, n = 6) in comparison to women with MetS (-2.65 kg, SD = 3.75 kg, n = 3) (p = 0.045). CONCLUSION: Findings indicate that multidisciplinary weight management has a positive role in early-stage breast cancer survival through improving body weight and mass composition. These results can add to the development of long-term treatment plans for survivors in order to shine a light on ways to reduce risk recurrence and chronic disease mortality.

Association of clinically significant weight loss with number of patient visits and months of attendance at an Australian multidisciplinary weight management clinic.

Despite the obesity epidemic, there are relatively few multidisciplinary obesity services in Australia, and only limited data on the effectiveness of these services. The aim of this study was to evaluate the effectiveness of a university hospital-based weight management clinic-the 'Healthy Weight Clinic' in supporting patients to achieve clinically significant weight loss (≥5% reduction in body weight), weight maintenance, and changes in body composition. A retrospective review was conducted to determine weight and associated health outcomes in patients who attended an initial consultation in the first 2 years of the clinic-between March 2017 and March 2019. Follow up was at least 1 year for all patients. Patients who underwent bariatric surgery were excluded. Of 213 total patients, 172 patients attended more than one follow-up consultation for lifestyle modification. Mean weight change and percentage total weight change at last follow-up was -6.2 kg (SD 7.4) and - 6.0% (SD 6.9), respectively. For every additional clinic follow-up, there was 21.4% increased odds of achieving clinically significant weight loss, and for every additional month of follow-up, there was 10.1% increased odds of achieving clinically significant weight loss. Twenty percent of patients (34/172) maintained ≥5% of initial body weight loss for at least 1 year. Body composition measurements were also favourable, with significant changes in percentage skeletal muscle mass of +0.8% (SD 1.5) and in percentage fat mass by -1.4% (SD 3.2). Regular support in a structured holistic multidisciplinary obesity service enables patients to achieve clinically meaningful weight loss and improved skeletal muscle mass to body fat ratio, and maintain this loss for at least 1 year. Improved weight loss was associated with more patient visits and longer duration of attendance at the clinic.

Communication as a clinical skill: a challenge in the delivery of safe and effective patient care.

Communication in clinical practice has been the focus of linguistic, psychological, and sociological research for half a century, yet there is still so little emphasis on using that research to improve communication in practice. In this article, we urge for a repositioning of communication as a clinical skill, along with a stronger reliance on communication research evidence and collaboration with experts in studying and teaching these skills.

The effects of diet on weight and metabolic outcomes in patients with double diabetes: A systematic review.

With the global rise in obesity and the metabolic syndrome, double diabetes is increasingly prevalent in patients with type 1 diabetes. This review investigated the effects of diet on weight management and metabolic outcomes in patients with double diabetes. MEDLINE, CENTRAL, EMBASE, PsycINFO, CINAHL, ERIC, and Web of Science databases were searched through September 2020. Population- or individual-level dietary interventions, and observational studies investigating dietary patterns in adults with type 1 diabetes and overweight or obesity, were eligible for inclusion. The quality of studies was assessed. Four eligible studies were included in this review, comprising two randomized controlled trials, one pretest-posttest study, and one cross-sectional study. Study populations included between 10 and 1040 participants. Dietary interventions included the Mediterranean diet, low-fat diet, intermittent fasting, continuous energy restriction, and a combination of fasting and a standardized low-calorie diabetic diet (LCD). Significant weight loss was observed within groups for low-fat diet, Mediterranean diet, fasting, LCD with fasting, intermittent fasting, or continuous energy restriction, but there were no between-group differences. Weight maintenance was only achieved in interventions where fasting or intermittent fasting were present. Dietary interventions in published data failed to demonstrate effects on metabolic syndrome. Larger sample, high-quality trials conducted over longer periods are urgently required to determine the efficacy of diet for weight management and improving metabolic outcomes in individuals with double diabetes. This would provide much needed evidence-based guidance for dietary interventions, which are well known to be the cornerstone of clinical care.

Application of artificial intelligence and radiomics in pituitary neuroendocrine and sellar tumors: a quantitative and qualitative synthesis.

PURPOSE: To systematically review the literature regarding the application of machine learning (ML) of magnetic resonance imaging (MRI) radiomics in common sellar tumors. To identify future directions for application of ML in sellar tumor MRI. METHODS: PubMed, Medline, Embase, Google Scholar, Scopus, ArxIV, and bioRxiv were searched to identify relevant studies published between 2010 and September 2021. Studies were included if they specifically involved ML of MRI radiomics in the analysis of sellar masses. Risk of bias assessment was performed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) Tool. RESULTS: Fifty-eight articles were identified for review. All papers utilized retrospective data, and a quantitative systematic review was performed for thirty-one studies utilizing a public dataset which compared pituitary adenomas, meningiomas, and gliomas. One of the analyzed architectures yielded the highest classification accuracy of 0.996. The remaining twenty-seven articles were qualitatively reviewed and showed promising findings in predicting specific tumor characteristics such as tumor consistency, Ki-67 proliferative index, and post-surgical recurrence. CONCLUSION: This review highlights the potential clinical application of ML using MRI radiomic data of the sellar region in diagnosis and predicting treatment outcomes. We describe future directions for practical application in the clinical care of patients with pituitary neuroendocrine and other sellar tumors.

Vaginal Microbiota, Genital Inflammation and Extracellular Matrix Remodelling Collagenase: MMP-9 in Pregnant Women With HIV, a Potential Preterm Birth Mechanism Warranting Further Exploration.

Background: Pregnant women living with HIV infection (PWLWH) have elevated rates of preterm birth (PTB) in which HIV and cART are implicated. PWLWH also have a high prevalence of adverse vaginal microbiota, which associate with genital tract inflammation. The mechanism underlying PTB in PWLWH is unknown. We present the first data in PWLWH on genital-tract matrix-metalloproteinase-9(MMP-9), an important collagenase implicated in labour onset, and tissue inhibitor of metalloproteinases-1(TIMP-1) and explore correlations with local inflammation and vaginal bacteria. Material and Methods: Cervical vaginal fluid (CVF) collected by a soft cup and high vaginal swabs (HVS) were obtained from PWLWH and HIV uninfected pregnant women (HUPW) at three antenatal time points. Maternal characteristics, combination antiretroviral therapy (cART) exposure, and pregnancy outcome were recorded. Concentrations of MMP-9, TIMP-1 and ten cytokines were measured by immunoassays. Vaginal microbiota composition was determined through 16S rRNA amplicon sequencing. MMP-9, TIMP-1 and cytokine concentrations were compared by HIV status, cART, and prematurity and in PWLWH correlations with polymorphonuclear leucocytes, cytokines and bacterial genera were explored. Results: CVF was available for 50 PWLWH (108 samples) and 12 HUPW (20 samples) between gestation weeks 14-38. Thirty-six PWLWH conceived on cART and 14 initiated post-conception. There were five and one PTB outcomes in PWLWH and HUPW respectively. PWLWH had higher mean CVF concentrations of MMP-9 (p<0.001) and TIMP-1 (p=0.035) in the second trimester compared with HUPW with a similar trend in the third trimester. PWLWH also had higher CVF values of cytokines: IL-1ß, IL-8, IL-12 and TNF-α in both trimesters compared to HUPW (p ≤ 0.003). In PWLWH, MMP-9 positively correlated with TIMP-1 (r=0.31, p=0.002) and CVF polymorphonuclear leucocytes (r=0.57, p=0.02). Correlations were observed between MMP-9 and three cytokines: IL-1ß (r=0.61), IL-8 (r=0.57) and TNF-α (r=0.64), p<0.001, similarly for TIMP-1. Abundance of anaerobic pathobionts correlated with MMP-9: Gardnerella (r=0.44, p<0.001), Atopobium (r=0.33, p=0.005), and Prevotella genera (r=0.39, p<0.001). Conversely proportion of Lactobacillus genera negatively correlated with MMP-9 (rho=-0.46, p<0.001). MMP-9/TIMP-1 ratio increased with gestational age at sampling in PWLWH, but this was no longer significant after adjusting for confounders and no difference by prematurity was observed in this sub-study. Conclusions: Here we show strong correlations of MMP-9 to genital tract inflammation and sub-optimal bacterial genera in PWLWH indicating the ascending genital tract infection pathway may be a contributory mechanism to the high risk of PTB.

ESE audit on management of Adult Growth Hormone Deficiency in clinical practice.

Guidelines recommend adults with pituitary disease in whom GH therapy is contemplated, to be tested for GH deficiency (AGHD); however, clinical practice is not uniform. AIMS: 1) To record current practice of AGHD management throughout Europe and benchmark it against guidelines; 2) To evaluate educational status of healthcare professionals about AGHD. DESIGN: On-line survey in endocrine centres throughout Europe. PATIENTS AND METHODS: Endocrinologists voluntarily completed an electronic questionnaire regarding AGHD patients diagnosed or treated in 2017-2018. RESULTS: Twenty-eight centres from 17 European countries participated, including 2139 AGHD patients, 28% of childhood-onset GHD. Aetiology was most frequently non-functioning pituitary adenoma (26%), craniopharyngioma (13%) and genetic/congenital mid-line malformations (13%). Diagnosis of GHD was confirmed by a stimulation test in 52% (GHRH+arginine, 45%; insulin-tolerance, 42%, glucagon, 6%; GHRH alone and clonidine tests, 7%); in the remaining, ≥3 pituitary deficiencies and low serum IGF-I were diagnostic. Initial GH dose was lower in older patients, but only women <26 years were prescribed a higher dose than men; dose titration was based on normal serum IGF-I, tolerance and side-effects. In one country, AGHD treatment was not approved. Full public reimbursement was not available in four countries and only in childhood-onset GHD in another. AGHD awareness was low among non-endocrine professionals and healthcare administrators. Postgraduate AGHD curriculum training deserves being improved. CONCLUSION: Despite guideline recommendations, GH replacement in AGHD is still not available or reimbursed in all European countries. Knowledge among professionals and health administrators needs improvement to optimize care of adults with GHD.

Macrogonadotropinoma, a venous thromboembolic event and asymptomatic extensive periventricular white matter changes in a patient with Klinefelter syndrome.

Gonadotropinoma in Klinefelter syndrome (KS) is uncommon and may be a result of protracted stimulation of gonadotrophs from lack of androgen feedback. Associations of white matter changes and increased venous thromboembolic risk have been reported and need to be considered in patients with KS.

Clinical challenges of a co-secreting TSH/GH pituitary adenoma.

SUMMARY: Co-secreting thyrotropin/growth hormone (GH) pituitary adenomas are rare; their clinical presentation and long-term management are challenging. There is also a paucity of long-term data. Due to the cell of origin, these can behave as aggressive tumours. We report a case of a pituitary plurihormonal pit-1-derived macroadenoma, with overt clinical hyperthyroidism and minimal GH excess symptoms. The diagnosis was confirmed by pathology showing elevated thyroid and GH axes with failure of physiological GH suppression, elevated pituitary glycoprotein hormone alpha subunit (αGSU) and macroadenoma on imaging. Pre-operatively the patient was rendered euthyroid with carbimazole and underwent successful transphenoidal adenomectomy (TSA) with surgical cure. Histopathology displayed an elevated Ki-67 of 5.2%, necessitating long-term follow-up. LEARNING POINTS: Thyrotropinomas are rare and likely under-diagnosed due to under-recognition of secondary hyperthyroidism. Thyrotropinomas and other plurihormonal pit-1-derived adenomas are more aggressive adenomas according to WHO guidelines. Co-secretion occurs in 30% of thyrotropinomas, requiring diligent investigation and long-term follow-up of complications.