Mutations in the aryl hydrocarbon receptor interacting protein gene are not highly prevalent among subjects with sporadic pituitary adenomas.

CONTEXT: Limited screening suggests that three germline mutations in the aryl hydrocarbon receptor interacting protein (AIP) gene are not involved in sporadic pituitary tumorigenesis. Multiple novel mutations of this gene have since been identified in familial isolated pituitary adenoma cohorts. OBJECTIVE: The objective of the study was to undertake full AIP coding sequence screening to assess for the presence of germline and somatic mutations in European Union subjects with sporadic pituitary tumors. DESIGN: The study design was the analysis of DNA from peripheral blood lymphocytes and analysis of exons 1-6 and paraexonic intron sequences of AIP. Multiplex ligation-dependent probe amplification was used to screen separate sporadic pituitary tumor tissue samples for discrete and extensive deletions or mutations of the AIP gene. Setting: The study was conducted in university tertiary referral Clinical Genetics, Molecular Biology, and Endocrinology Departments. RESULTS: In 107 patients [prolactinomas (n =49), nonfunctioning tumors (n = 29), somatotropinomas (n = 26), ACTH-secreting tumors (n = 2), TSH-secreting tumors (n = 1)], no germline mutations of AIP were demonstrated. Among a group of 41 tumor samples from other subjects, a novel AIP mutation (R22X) was found in one sample in which the corresponding allele was deleted; follow-up screening of the patient demonstrated a germline R22X AIP mutation. CONCLUSIONS: AIP mutations do not appear to play a prominent role in sporadic pituitary tumorigenesis in this population of European subjects

Tumorigenèse endocrine et voie de l'AMPc

LE KREMLIN-B.- PARIS 11-BU Méd (940432101) / SudocSudocFranceF

Coexistence of Autoimmune Hyper-and Hypothyroidism in a Kindred with Reduced Sensitivity to Thyroid Hormone

International audienceIntroduction: Resistance to thyroid hormone beta (RTHβ) is a rare disease with an autosomal dominant transmission. Diagnosis may be challenging especially in patients with hyper-or hypothyroidism. Case Presentation: A 31-year-old male patient with suppressed thyroid-stimulating hormone (TSH), elevated free thyroxine and free triiodothyronine, along with high thyroid receptor antibodies was diagnosed with Graves' disease. Benzylthiouracil was started. One month later, reduced sensitivity to thyroid hormones was suspected because of persistently high thyroid hormone levels contrasting with high TSH level. Molecular analysis highlighted a 10c.1357C>T p.P453S mutation in the thyroid hormone receptor beta gene (THRB). RTHβ was diagnosed. Several relatives also had RTHβ (the mother, the young son, and 2 out of 3 siblings). Autoimmune hypothyroidism was present in the mother, whereas 2 out of 3 siblings had asymptomatic autoimmunity. Discussion/Conclusion: Both Graves' disease and autoimmune hypothyroidism were described in patients with RTHβ. We show here for the first time that autoimmune hypo-and hyperthyroidism may coexist in kindred with RTHβ. Seven previously published cases of Graves' disease and RTHβ were retrieved and analyzed. Treatments and thyroid hormone level targets are discussed as well as the possible link between RTHβ and autoimmune thyroid diseases

Méningiomes et utilisation prolongée d’acétate de cyprotérone: à propos de 28 cas opérés

Introduction L’acétate de cyprotérone (ACYP) est contre-indiqué en cas de méningiome car il favorise leur développement. L’objectif de l’étude est de déterminer les caractéristiques phénotypiques et génotypiques des patients opérés de méningiomes traités de façon prolongée par ACYP. Méthodes Nous avons analysé en rétrospectif les caractéristiques phénotypiques de 28 patients, traités par ACYP qui ont été opérés de méningiomes dans le service de neurochirurgie de l’hôpital Foch à Suresnes entre 2003 et 2010. La recherche de mutation PIK3CA et TRAF7 a été réalisée chez 18 patientes. Résultats Vingt-huit patients, d’âge moyen 48±6,5 ans, ont été inclus : 27 femmes et 1 homme. Dix-huit présentent un méningiome unique et 10 des méningiomes multiples. Quarante-sept pour cent des méningiomes sont développés dans la région sellaire, 40 % près des lobes cérébraux, 9 % sur la faux du cerveau et 4 % dans la fosse postérieure. La durée de traitement par ACYP a tendance à être plus longue dans le groupe méningiomes multiples que dans le groupe méningiome unique (16 ans 95 % IC[12–19] vs 12 ans 95 IC[9–20] NS, p = 0,29). La dose cumulée estimée d’ACYP tend à être plus élevée en cas de méningiome multiple (276 575 mg ± 406 567 vs 107 585 mg ± 119 231, NS, p = 0,11). Les mutations somatiques sont présentes dans 6/11 méningiomes uniques versus chez tous les méningiomes multiples (p = 0,035). Discussion Les mutations somatiques PIK3CA ou TRAF7 sont significativement associées aux méningiomes multiples ; elles sont présentes chez toutes les patientes. La longue durée d’exposition à l’ACYP s’associe au caractère multiple des méningiomes

Evaluating the satisfaction and utility of social networks in medical practice and continuing medical education

Abstract Background Digital health has surged during the Covid health crisis, and the use of social media, already prevalent in medicine, has significantly increased. There are Social Networks groups dedicated to physicians with an educational purpose. These groups also facilitate peer discussions on medical questions and the sharing of training materials. Objectives The aim of our study was to assess the value of these new tools and their contribution to medical education. Methods An anonymous questionnaire was conducted among members of a Social Networks community group for physicians. The survey received responses from 1451 participants. Results The majority of participants believed they had enriched their medical knowledge and accessed documents they would not have accessed without the group. Subgroup analysis showed that the contribution of this tool is more pronounced for general practitioners and doctors practicing in limited healthcare access. Conclusion It is essential to develop digital tools that enhance physician training, and social networks represent a valuable educational tool

Structural analysis of the impact of a novel androgen receptor gene mutation in two adult patients with mild androgen insensitivity syndrome

International audienceAndrogen receptor gene (AR) mutations are responsible for androgen insensitivity syndrome (AIS) presenting with a clinical phenotype that ranges from gynaecomastia and/ or infertility in mild AIS (MAIS) to complete testicular feminisation in complete AIS. We report a novel AR gene mutation in two unrelated adult patients with MAIS and we studied its functional impact using 3D modelling. Patient 1, referred for infertility, presented with gynaecomastia, mild hypospadias and bilateral testicular hypotrophy contrasting with high testosterone levels, an elevated FSH, an elevated androgen sensitivity index (ASI) and oligoasthenoteratospermia. In vitro fertilisation and intracytoplasmic sperm injection resulted in a successful twin pregnancy. Patient 2 referred for a decrease in athletic performance had surgically treated gynaecomastia, oligoasthenospermia, high testosterone levels and an elevated ASI. Despite his impaired spermogram, he fathered two children without assisted reproductive technology. AR gene sequencing in the two patients revealed a common novel missense mutation, Ala699Thr, in exon 4 within the ligand-binding domain. 3D modelling studies showed that this mutation may impact dimer stability upon ligand binding or may affect allosteric changes upon dimerisation. This study illustrates the value of structural analysis for the functional study of mutations and expands the database of AR gene mutations

Management of nonfunctioning pituitary incidentaloma

International audiencePrevalence of pituitary incidentaloma is variable: between 1.4% and 27% at autopsy, and between 3.7% and 37% on imaging. Pituitary microincidentalomas (serendipitously discovered adenoma \textless1cm in diameter) may increase in size, but only 5% exceed 10mm. Pituitary macroincidentalomas (serendipitously discovered adenoma\textgreater1cm in diameter) show increased size in 20-24% and 34-40% of cases at respectively 4 and 8years' follow-up. Radiologic differential diagnosis requires MRI centered on the pituitary gland. Initial assessment of nonfunctioning (NF) microincidentaloma is firstly clinical, the endocrinologist looking for signs of hypersecretion (signs of hyperprolactinemia, acromegaly or Cushing's syndrome), followed up by systematic prolactin and IGF-1 assay. Initial assessment of NF macroincidentaloma is clinical, the endocrinologist looking for signs of hormonal hypersecretion or hypopituitarism, followed up by hormonal assay to screen for hypersecretion or hormonal deficiency and by ophthalmologic assessment (visual acuity and visual field) if and only if the lesion is near the optic chiasm (OC). NF microincidentaloma of less than 5mm requires no surveillance; those of≥5mm are not operated on but rather monitored on MRI at 6months and then 2years. Macroincidentaloma remote from the OC is monitored on MRI at 1year, with hormonal exploration (for anterior pituitary deficiency), then every 2years. When macroincidentaloma located near the OC is managed by surveillance rather than surgery, MRI is recommended at 6months, with hormonal and visual exploration, then annual MRI and hormonal and visual assessment every 6months. Surgery is indicated in the following cases: evolutive NF microincidentaloma, NF macroincidentaloma associated with hypopituitarism or showing progression, incidentaloma compressing the OC, possible malignancy, non-compliant patient, pregnancy desired in the short-term, or context at risk of apoplex

Genotypic prediction of HIV-1 subtype D tropism.

International audienceUNLABELLED: ABSTRACT: BACKGROUND: HIV-1 subtype D infections have been associated with rapid disease progression and phenotypic assays have shown that CXCR4-using viruses are very prevalent. Recent studies indicate that the genotypic algorithms used routinely to assess HIV-1 tropism may lack accuracy for non-B subtypes. Little is known about the genotypic determinants of HIV-1 subtype D tropism. RESULTS: We determined the HIV-1 coreceptor usage for 32 patients infected with subtype D by both a recombinant virus phenotypic entry assay and V3-loop sequencing to determine the correlation between them. The sensitivity of the Geno2pheno10 genotypic algorithm was 75% and that of the combined 11/25 and net charge rule was 100% for predicting subtype D CXCR4 usage, but their specificities were poor (54% and 68%). We have identified subtype D determinants in the V3 region associated with CXCR4 use and built a new simple genotypic rule for optimizing the genotypic prediction of HIV-1 subtype D tropism. We validated this algorithm using an independent GenBank data set of 67 subtype D V3 sequences of viruses of known phenotype. The subtype D genotypic algorithm was 68% sensitive and 95% specific for predicting X4 viruses in this data set, approaching the performance of genotypic prediction of HIV-1 subtype B tropism. CONCLUSION: The genotypic determinants of HIV-1 subtype D coreceptor usage are slightly different from those for subtype B viruses. Genotypic predictions based on a subtype D-specific algorithm appear to be preferable for characterizing coreceptor usage in epidemiological and pathophysiological studies

Additional file 1 of Evaluating the satisfaction and utility of social networks in medical practice and continuing medical education

Supplementary Material