The clinical presentation of acromegaly reflects systemic effects of chronic growth hormone (GH) and insulin-like growth factor 1 (IGF-I) excess. Diagnostic delay frequently ranges from 6 to 10 years. While classical manifestations such as acral enlargement and facial coarsening are diagnostically important, many patients initially develop nonspecific symptoms, including sleep apnea, carpal tunnel syndrome, arthralgia, and metabolic disturbances. The lack of symptom/comorbidity specificity highlights the need for improved screening strategies, particularly for patients without overt acral changes. Comorbidity cluster analyses, potentially supported by artificial intelligence, may facilitate earlier identification, prompting biochemical confirmation of the diagnosis. Biochemical evaluation has benefited from advances in hormone assay harmonization and the establishment of robust age-adjusted reference ranges. Serum IGF-I is the preferred initial screening test due to its stability and reflection of integrated GH secretion. However, interpretation of assay values should consider age, sex, assay variability, and confounding conditions such as diabetes, liver or renal disease, obesity, pregnancy, and estrogen exposure. For discordant biochemical and clinical findings, it is recommended to repeat IGF-I and to measure GH during an oral glucose tolerance test (OGTT). Although random GH levels are often elevated and correlate with somatotroph adenoma size, GH suppression during OGTT is the gold-standard confirmatory test, especially in patients with borderline results. The use of ultrasensitive GH assays has lowered the recommended nadir GH cut-off threshold to ∼0.4 µg/L, with assay-specific considerations. Advances in high-resolution MRI and PET/MRI, alongside AI-driven facial recognition, electronic medical record analysis, and radiomics, offer promising avenues for earlier and more accurate diagnosis of acromegaly.
Obstructive sleep apnea syndrome (OSAS) is a highly prevalent condition, particularly among at-risk populations such as patients with obesity, diabetes, or chronic respiratory disease. There is a growing need for simplified, automated diagnostic approaches that can be implemented outside specialized sleep laboratories. We conducted a prospective, interventional study in two hospital centers in Alsace (France), comparing an automated mandibular movement analysis device (Sunrise®) with standard ventilatory polygraphy (VP). Agreement between the two methods for determining the apnea-hypopnea index (AHI) was assessed using Bland-Altman analysis. Thirty-seven patients were enrolled, from whom 29 pairs of recordings (78%) were suitable for analysis. Seven Sunrise® failures and one ventilatory polygraphy failure, were due mainly to sensor malfunctions or connectivity issues. In comparison with VP, Sunrise® tended to overestimate AHI, with a mean difference of +4.76 events/h. The limits of agreement ranged from -15.4 to +24.9 events/h, indicating moderate variability between the methods. The Sunrise® device demonstrates feasibility for use in non-expert clinical settings and shows reasonable agreement with ventilatory polygraphy, supporting its potential as a simplified screening tool for OSAS. However, these results should be interpreted cautiously, especially for high AHI, and technical limitations must be addressed in future "real world" studies.
Patients with primary bilateral macronodular adrenal hyperplasia, recently reclassified as bilateral macronodular adrenal disease (BMAD), have bilateral benign large adrenocortical nodules and variable cortisol excess. BMAD is considered a rare cause of overt Cushing's syndrome but a more frequent cause of bilateral adrenal incidentalomas. Initially considered a sporadic disease, the bilateral nature of the adrenal nodules and familial aggregation suggested a genetic origin. Indeed, genomic studies have improved our understanding of BMAD pathogenesis and identified several genetic events responsible for BMAD. As rare syndromic presentations were described, non-syndromic etiologies were also identified, suggesting distinct molecular backgrounds among BMAD cases. Firstly, germline heterozygous inactivating mutations of the ARMC5 gene, discovered in 2013, are now known to account for around 20-25% of sporadic cases and most familial cases. A second molecular group was later identified, characterized by germline heterozygous pathogenic variants and loss of heterozygosity of the lysine demethylase 1A gene (KDM1A, or LSD1) in familial and sporadic GIP-dependent BMAD, representing less than 5% of BMAD cases. Similarly to ARMC5, the stepwise inactivation of KDM1A, an epigenetic regulator gene, supports a tumor suppressor model of tumorigenesis. The latter, more heterogeneous, molecular group remains globally unelucidated, with the exception of reports of pathogenic variants in genes involved in the PKA and cAMP signaling pathways. In all cases, genetic counseling should be offered to identify affected members and to screen for BMAD.
Diabetes increases the risk of disability, and vice versa. Disability, defined as a limitation in bodily function, can compromise diabetes management and lead to chronic glycemic imbalance. Training healthcare professionals and providing patients with appropriate assistive devices can reduce the impact of disability on diabetes management. More regular diabetes screening is also warranted in patients with disabilities due to their increased risk of chronic diseases. In Switzerland, it is crucial to develop adapted therapeutic education materials to ensure equitable access to medical information for patients with disabilities. Le diabète sucré augmente le risque de handicap, et inversement. Le handicap, défini comme une limitation des fonctions du corps, peut compromettre la prise en charge du diabète et conduire à un déséquilibre glycémique chronique. La formation des équipes médicales et soignantes, associée à la mise en place de moyens auxiliaires adaptés, permet de limiter l’impact d’un handicap sur la gestion du diabète. Un dépistage plus régulier du diabète est également indiqué chez les personnes en situation de handicap, compte tenu du risque accru de maladies chroniques dans cette population. En Suisse, le développement de supports d’éducation thérapeutique adaptés est crucial afin de garantir un accès équitable à l’information médicale pour les personnes en situation de handicap.
Primary aldosteronism (PA) is a common yet still underdiagnosed cause of secondary hypertension (HTN). We report two cases illustrating the variability of its clinical presentation: one revealed by left ventricular hypertrophy, the other by refractory hypertension. These observations highlight the importance of a structured diagnostic approach to determine the PA subtype and tailor management accordingly. Early diagnosis improves blood pressure control, corrects electrolyte disturbances, and prevents aldosterone-related visceral complications. These findings also support the need for more systematic screening of this common yet often overlooked condition. L’hyperaldostéronisme primaire (HAP) est une cause fréquente, mais sous-diagnostiquée, d’hypertension artérielle (HTA) secondaire. Nous rapportons deux cas illustrant la variabilité de sa présentation clinique : l’un révélé par une hypertrophie ventriculaire gauche, l’autre par une HTA réfractaire. Ces observations rappellent l’importance d’une démarche diagnostique structurée afin de préciser le sous-type d’HAP et d’adapter la prise en charge. Un diagnostic précoce permet d’améliorer le contrôle tensionnel, de corriger les anomalies hydro-électrolytiques et de prévenir les complications viscérales liées à l’excès d’aldostérone. Ces observations soulignent ainsi la nécessité d’un dépistage plus systématique de cette pathologie fréquente, mais insuffisamment diagnostiquée.
Adrenocortical tumors (ACTs) are rare pediatric malignancies, typically presenting with signs of virilization or hypercortisolism. However, nonclassical presentations may delay diagnosis and complicate management. Our study aimed to illustrate the diagnostic and therapeutic challenges posed by atypical forms of pediatric ACTs through a series of five diverse clinical cases. We report five cases of pediatric ACTs with unusual features: bilateral tumors, acute stroke due to hypertensive crisis, incidental discovery after trauma, misleading hormonal workup, or gradual onset of premature pubarche, and hemorrhagic lesion. In two cases, the diagnosis was delayed due to initial absence of endocrine evaluation. One patient experienced tumor rupture following biopsy, leading to metastasis and death despite intensive treatment. Histopathological scoring (Wieneke score) was heterogeneous and did not always correlate with outcome. Two patients had underlying cancer predisposition syndromes (Li-Fraumeni and Beckwith-Wiedemann). This case series highlights the wide phenotypic variability of pediatric ACTs, which may mimic benign or unrelated conditions. Early recognition, systematic hormonal evaluation, and avoidance of biopsy are critical for improving prognosis. Multidisciplinary management is essential, and genetic screening should be systematically considered, even in the absence of suggestive personal or familial history.
Rare differences of sex development (DSD) encompass all medical situations in which chromosomal sex, gonadal development, or external genitalia are atypical. Genetic investigations of these medical conditions, often diagnosed in the neonatal period, have evolved considerably over the past 20 years. Excluding congenital adrenal hyperplasia, whose diagnosis is clinical and hormonal, a genetic diagnosis is done in 2026 in only approximately 35% of DSD children with 46, XY and 46, XX DSD outside CAH, using next-generation sequencing (NGS) or genome analysis. In 2021, for the first time, a legal framework organizing the care of children with a variation in genital development (VGD), sometimes referred to as "intersex children" or "children with differences in sex development" (DSD), was introduced in France (article L. 2131-6 of the Code of Public Health). The law requires national multidisciplinary case review for any DSD children, except life-saving treatment, and put genetics at the center of the framework. Posterior/proximal hypospadias may, if clinically isolated and with a normal hormonal and genetic profile, fall outside this new framework. Children with 46, XY hypospadias, carrying a pathogenic variant fall within the scope of the law. This subtle distinction, lacking scientific support, makes family care pathways difficult to understand and therefore more distressing.
The primary objective of this study was to assess the contribution of fetal echocardiography in a population of women with pre-gestational diabetes to the detection of severe fetal heart disease. The secondary objective was to analyse the prevalence of heart disease according to periconceptional HbA1c levels. Observational, single-centre, retrospective study conducted over ten years (2014-2024), including all pregnancies complicated by pre-gestational diabetes monitored in a type III maternity unit. The type of diabetes, periconceptional HbA1c, ultrasound data and perinatal outcomes were collected. Severe congenital heart disease was confirmed postnatally and defined by the need for neonatal surgical intervention. A total of 331 women corresponding to 428 pregnancies were included. All underwent fetal echocardiography by a paediatric cardiologist. The overall prevalence of congenital heart disease was 4.4% (19/428), including 1.5% of severe forms (6/428). All severe heart defects were detected during screening ultrasound. 6.9% of women with a periconceptional HbA1c ≥ 10% had severe heart disease. Systematic fetal echocardiography by a paediatric cardiologist does not appear to offer any additional benefit for the sensitivity of primary screening for severe diabetes-related heart disease. Echocardiography should be reserved for the precise characterisation of heart disease if it is detected during screening and diagnostic ultrasound and/or in cases of uncontrolled diabetes.
Anorexia nervosa (AN) is a serious illness in which more than half of all deaths are due to malnutrition. Critically low energy and protein intake are known causes of massive weight loss, whereas micronutrient deficiencies due to a low-calorie food pattern remain poorly characterized in children with AN. Micronutrient deficiencies in AN, such as selenium deficiency, are known to increase anxiety and the risk of suicide. Two large studies in adults highlighted frequent selenium and copper deficiencies; this information is lacking in children. The present study aimed to provide a comprehensive description of the micronutrient status in pediatric AN and evaluate whether deficiencies differ according to AN subtype (restricting, R, binge-eating/purging, BP). A retrospective, single-center, descriptive study was conducted in a cohort of children with AN who were evaluated at a specialist eating disorders center from 2016 to 2022. The sample comprised 349 patients (mean age 14.7 ± 1.8 years); 91.4% had AN-R, 8.6% BP. Mean weight loss was 18.2% ± 10.7%, and initial BMI was 16.7 ± 1.1 kg/m2 according to the International Obesity Task Force. At least one micronutrient deficiency was found in 90% of patients; 51.3% experienced multiple deficiencies. The most common were selenium (23.5%), copper (18.4%), and vitamin A (29.1%). The prevalence of deficiencies was similar between AN-R and AN-BP, except for potassium and calcium which were significantly lower in AN-BP. Micronutrients deficiencies are frequent in pediatric AN with no difference according to subtype. The functional impact and the benefit of supplementation remain to be studied.
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Adrenocortical carcinoma (ACC) is a rare cancer. The French ENDOCAN-COMETE network was established in 2009 to coordinate care locally and nationally, and to promote research and education on malignant adrenal tumors. Evidence demonstrating the benefits of this organization is currently lacking. Patients diagnosed with ACC between 2010 and 2017 were identified from the French Network of Cancer Registries (FRANCIM). Patients were categorized based on referral to the ENDOCAN-COMETE network as either referred at diagnosis (R-ACC) or not referred, or referred late (nR-ACC). Median overall survival (OS) and OS rates at 1, 5, and 10 years were compared between the R-ACC and nR-ACC groups after adjustment for prognostic parameters. A total of 134 patients with ACC were identified from the FRANCIM registries, corresponding to an incidence of 1.4 cases per million person-years. Ten patients were excluded because of insufficient information regarding their health care pathway. The final analysis included 124 patients (mean age, 53.6 years; female-to-male ratio, 2:1). At diagnosis, 45.2% had European Network for the Study of Adrenal Tumours (ENSAT) stage I-II disease, 48.4% had stage III-IV disease, and 6.4% had an unknown stage; endocrine and/or tumour-related symptoms were present in 62.9% of patients. Among the analyzed patients, 87 (70%) were R-ACC, whereas 37 (30%) were nR-ACC. In patients with localized stage I-II ACC, OS rates were significantly higher in the R-ACC group than in the nR-ACC group: 1-year OS was 92% versus 85%, 5-year OS was 81% versus 55%, and 10-year OS was 75% versus 35%, respectively. This survival advantage remained significant after adjustment for prognostic factors (hazard ratio, 3.9; P=.026). In contrast, among patients with advanced ACC, OS rates were similar between the 2 groups. Our study demonstrates an OS benefit for patients with stage I-II ACC who were referred early to specialized centers within the ENDOCAN-COMETE network. The combined use of the French cancer registries and dedicated national networks provides the strongest evidence to date demonstrating the impact of such a network.
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Older adults living with type 2 diabetes represent a particularly vulnerable population. We investigated which continuous glucose monitoring (CGM)-derived targets are associated with all-cause mortality in this population. HYPOAGE is prospective multicenter study including 141 insulin-treated older adults living with type 2 diabetes aged 75 and older, under insulin therapy for at least 6 months. All participants underwent standardized geriatric and diabetic assessments and wore an ambulatory blinded CGM (FreeStyle Libre Pro®) for 28 consecutive days. In this ancillary study, multivariable cox regressions were performed to identify factors associated with mortality after adjustment for age, sex, HbA1c, kidney function, geriatric status, and metformin use. At baseline, participants were 81.5 years old on average. After a median follow-up of 44 months, 58 of 141 patients had died. In adjusted model, higher percentages of level 1 time below range (TBR), level 2 TBR and glycemic variability assessed by the coefficient of variation (CV) were independently associated with an increased mortality risk (hazard ratio [95% CI] 1.51 [1.11; 2.06], 1.25 [1.02; 1.53], and 1.76 [1.21; 2.56] for an interquartile range (IQR)% increase of each parameter, respectively). When recommended CGM targets were considered, only glycemic variability (CV ≤ 36%), remained significantly associated with a lower risk of mortality (hazard ratio 0.57 [0.32; 0.99]), whereas TIR > 50% and TBR ≤ 1% were not. Among insulin-treated older adults living with type 2 diabetes, glycemic variability was independently associated with all-cause mortality, highlighting its potential relevance for clinical management in geriatric diabetes care.
Gynecological follow-up of women who have undergone hematopoietic stem cell transplantation (HSCT) is complex, as it has multiple issues: fertility preservation; management of premature ovarian insufficiency or early menopause; infectious risk, particularly related to human papillomavirus; hemorrhagic risk during aplasia; screening for specific complications such as graft-versus-host disease (GVHD, only in the setting of allogeneic transplantation) or radiation-induced breast cancer; sexual and emotional health, etc. Clinical practices vary widely and remain heterogeneous among hospitals. The aim of this article is to provide a synthesis of the main gynecological issues and to propose French clinical practice recommendations in order to harmonize, systematize, and structure the gynecological follow-up of women undergoing HSCT.
Imprinting disorders result from (epi)genetic abnormalities affecting genomic regions whose expression depends on parental origin. Among these, multilocus imprinting disturbances (MLID) constitute a specific entity characterised by simultaneous alterations in several imprinted regions, often leading to complex phenotypes. In recent years, the identification of maternal genetic factors, particularly within the maternal subcortical complex (SCMC), has led to a better understanding of the origin of certain cases of MLID. At the same time, rapid advances in molecular analysis - methylation arrays, targeted NGS panels, and long-read sequencing approaches - have profoundly renewed diagnostic capabilities. Together, these advances now offer a more integrated view of the mechanisms, phenotypes, and genetic determinants of imprinting-related diseases.
According to recent meta-analyses of clinical studies, certain plants and spices improve glycemic control. This article presents several spices with clinically significant hypoglycemic effects that have been studied outside of pregnancy: ginger, psyllium, black cumin, nettle, cinnamon, fenugreek, aloe vera, and bitter melon. Regarding pregnancy, a pilot study conducted at the CHUV evaluated the feasibility of integrating some of these spices in women with gestational diabetes. Adherence was generally satisfactory, despite obstacles related to taste and practicality. When used in conjunction with conventional treatments, these spices could represent an additional dietary resource for diabetes management, provided that their use during pregnancy is supported by larger-scale clinical studies and implemented under appropriate clinical supervision. Selon les méta-analyses d’études cliniques récentes, certaines plantes alimentaires et épices améliorent le contrôle glycémique. Cet article présente plusieurs épices à effet hypoglycémiant cliniquement significatif étudiées en dehors de la grossesse : gingembre, psyllium, cumin noir, ortie, cannelle, fenugrec, aloe vera et melon amer. Pour la grossesse, une étude pilote menée au CHUV a évalué la faisabilité de l’intégration de certaines épices chez des femmes atteintes de diabète gestationnel. L’adhérence était globalement satisfaisante, malgré des obstacles liés au goût et à la praticité. Ces épices, utilisées en complément des traitements conventionnels, pourraient être une ressource diététique supplémentaire dans la gestion du diabète, sous réserve d’études de plus grande ampleur et d’un encadrement clinique pendant la grossesse.
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The Friedewald equation is problematic at high triglyceride or low LDL-c levels. Alternatives, such as the Martin-Hopkins or Sampson-NIH equations, have been proposed. This study aims to compare LDL-c estimates derived from these 3 equations with directly measured LDL-c and to assess whether the choice of equation affects clinical management. LDL-c levels calculated on the 3 equations were compared with measured LDL values. Comparisons were stratified by total triglyceride (TG) (0-400mg/dL, 400-800mg/dL and>800mg/dL) and LDL-c levels (below or above 70mg/dL). Random samples were selected from each category (TG 0-400mg/dL, TG 400-800mg/dL and LDL-c<70mg/dL) and the misclassification rates attributable to each equation were determined in subjects in secondary prevention. In subjects with TG 0-400mg/dL, the misclassification rate was 4.4% on Sampson-NIH, 4.9% on Martin-Hopkins and 6.4% on Friedewald. In subjects with TG 400-800mg/dL, rates were 7.4%, 3.7% and 14.8%, respectively. In subjects with LDL-c<70mg/dL, rates were 14.7%, 14.7% and 17.6%, respectively. This study demonstrated that the 3 methods performed very well in subjects with TG 0-400mg/dL, relatively well for TG 400-800mg/dL and less well for LDL-c<70mg/dL. However, the Sampson and Martin-Hopkins equations were less prone to therapeutic misclassification errors than the Friedewald equation.
Hypophysitis is an inflammation of the pituitary gland or stalk. There are no standardized guidelines for diagnosis and treatment. The present study investigated the role of surgery in diagnosing and treating hypophysitis. A retrospective observational study was conducted in the University referral hospital of Marseille, France. Patients over 15 years of age diagnosed with histologically proven hypophysitis between January 1st, 1994 and October 31st, 2023 were included. Additionally, a literature review was performed, focusing on cases with surgical and/or medical management, during the same period. Immune checkpoint inhibitor-related hypophysitis was not included. In 9 of our 61 patients (14.5%), surgery was indicated mainly for visual disorder (75%). Four showed suspected adenoma. All patients recovered visual function. There was no endocrine improvement. The literature review of surgical management, with 21 studies, included 289 operated patients (40% due to misdiagnosis of adenoma, and 40% for visual impairment). After surgery, 20% developed new endocrine deficits, while 13% showed hormonal improvement. Visual improvement was seen in 80-90% of cases. Non-endocrine complications were rare (5%). The literature review of all forms of management included 661 patients from 22 studies. Glucocorticoids improved endocrine deficits in 30% of cases, and worsened pituitary function in 2%. Patients managed by monitoring had a lower incidence of new deficits than patients managed by surgery. In hypophysitis not related to immune checkpoint inhibitors, surgery should not be performed systematically. It may be indicated in patients with severe visual impairment unresponsive to glucocorticoids or in situations of diagnostic uncertainty after complete medical assessment. In other cases, surgery seems to worsen pituitary function more than glucocorticoids or conservative follow-up, restricting its role to these specific cases after multidisciplinary discussion.
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