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ObjectiveTurner Syndrome is associated with several phenotypic conditions associated with a higher risk of subsequent comorbidity. We aimed to evaluate the prevalence of congenital malformations and the occurrence of age-related comorbid conditions and to determine whether the frequencies of congenital and acquired conditions depend on X chromosome gene dosage, as a function of karyotype subgroup.Design and methodsThis national retrospective observational cohort study includes 1501 patients. We evaluated the prevalence of congenital malformations and the cumulative incidence of subsequent specific comorbidities at five-year intervals, from the ages of 10 to 30 years, with stratification by karyotype subgroup: 45,X (n = 549), 45,X/46,isoXq (n = 280), 46,X,r(X)/46,XX (n = 106), 45,X/46,XX (n = 221), presence of Y (n = 87).ResultsMedian age was 9.4 (3.7–13.7) years at first evaluation and 16.8 (11.2–21.4) years at last evaluation. Congenital heart (18.9%) malformations were more frequent in 45,X patients, and congenital renal (17.2%) malformations were more frequent in 45,X, 45,X/46,isoXq and 46,X,r(X)/46,XX patients than in those with 45,X/46,XX mosaicism or a Y chromosome (P ConclusionThese data suggest that X gene chromosome dosage, particularly for Xp genes, contributes to the risk of developing comorbidities.

Design Hypercortisolism during pregnancy is a risk factor for prematurity. Long-term exposure to hypercortisolism may lead to permanent comorbidities, such as hypertension or diabetes, even after remission. Our aim was to determine whether women with a history of Cushing’s disease (and being eu-, hypo- or hypercortisolic at the time of pregnancy) had the same risks of comorbidities, and especially prematurity, during pregnancy. Methods It was a retrospective multicentric study focusing on mothers with a history of Cushing’s disease or diagnosed during pregnancy, followed in French tertiary referral centers. We compared the outcomes of pregnancies depending on the cortisolic status at the time of pregnancy. Results A total of 60 patients (78 pregnancies including 21 with hypercortisolism, 32 with hypocortisolism and 25 in eucortisolism in 25) were evaluated. The overall rate of preterm birth was 24.3%, with a peak in women diagnosed during pregnancy (62.5%), a high risk in hypercortisolic (33%) and hypocortisolic (19.3%), and a low risk (8%) in eucortisolic women Gestational diabetes and hypertension were observed in 21% and 10.4% of the whole cohort, with a higher risk in hypercortisolic women. Cesarean delivery was performed in 33.7% of the cohort. Conclusions Being non-eucortisolic at the time of pregnancy increases the risk of prematurity and comorbidities compared to the general population. Women with a history of Cushing’s disease should thus be carefully monitored during pregnancy. The high rate of cesarean delivery emphasizes the fact that these pregnancies should always be considered at risk.

Resume Une partie du groupe « Technologies et Therapeutiques Innovantes » de la Societe Francophone du Diabete rapporte dans ce travail les avancees dans le domaine de la sante mobile pour la prise en charge du diabete. Un focus particulier est fait sur la surveillance du glucose en continu et sur la telesurveillance.

Objective Somatostatin receptor ligands (SRL) are useful to control central hyperthyroidism in patients with thyrotropin-secreting pituitary adenoma (TSH pituitary adenoma). The aim of this study was to describe the frequency of thyrotropin deficiency (TSH deficiency) in patients with TSH pituitary adenoma treated by SRL. Design Retrospective study. Methods Patients with central hyperthyroidism due to TSH pituitary adenoma treated by short or long-acting SRL were retrospectively included. TSH deficiency was defined by a low FT4 associated with non-elevated TSH concentrations during SRL therapy. We analysed the frequency of TSH deficiency and the characteristics of patients with or without TSH deficiency. Results Forty-six patients were included. SRL were used as the first-line therapy in 21 of 46 patients (46%). Central hyperthyroidism was controlled in 36 of 46 patients (78%). TSH deficiency appeared in 7 of 46 patients (15%) after a median time of 4 weeks (4–7) and for a median duration of 3 months (2.5–3). The TSH deficiency occurred after one to three injections of long-acting SRL used as first-line therapy in 6/7 cases. There were no differences in terms of clinical and hormonal features, size of adenomas or doses of SRL between patients with or without TSH deficiency. Conclusions SRL can induce TSH deficiency in patients with central hyperthyroidism due to TSH pituitary adenoma. Thyrotropic function should be assessed before the first three injections of SRL in order to track TSH deficiency and reduce the frequency of injections when control of thyrotoxicosis rather than tumour reduction is the aim of the treatment.

Background: Somatostatin analogs (SSA) are efficiently used to control central hyperthyroidism in patients with thyrotropin-secreting pituitary neuroendocrine tumor (TSH-PitNET). The aim of this study was to describe the frequency of thyrotropin (TSH) deficiency under SSA in patients with TSH-PitNET. Methods: We retrospectively recruited patients presenting a central hyperthyroidism due to TSH-PitNET. Inclusion criteria were patients treated in first, second or third line by short or long-acting SSA, with central hyperthyroidism before SSA. Patients treated by radiotherapy or dopamine agonist were excluded. TSH deficiency was defined by either a low FT4 or low FT4 and FT3, associated with non-elevated TSH concentrations during SSA therapy. We analyzed the frequency of TSH deficiency and the characteristics of patients with or without TSH deficiency. Results: 46 patients were included in the study. SSA were used as the first-line therapy in 21 of 46 patients (46%). Central hyperthyroidism was controlled in 36 of 46 patients (78%). TSH deficiency appeared in 7 of 46 patients (15%), after a median time of 4 weeks (4–7) after the starting of SSA, and for a median duration of 3 months (2.5–3). The TSH deficiency occurred after 1 to 3 injections of long-acting SSA. There were no differences in terms of clinical and hormonal features and size of adenomas between patients with or without TSH deficiency. Conclusions: In patients with central hyperthyroidism due to TSH-PitNET, SSA can induce TSH deficiency. Thyrotropic function should be assessed before each injection of SSA in order to adapt the frequency of injection when control of thyrotoxicosis rather than tumor reduction is purpose of the treatment.

Introduction Nous rapportons le cas d’une patiente ayant presente des signes neurologiques focaux aboutissant au diagnostic de myelite associee a une thyroidite d’Hashimoto avec hyperplasie hypophysaire reactionnelle. Observation Patiente de 25 ans, sans antecedent, se presentant aux urgences pour une paresie des membres inferieur puis superieur droit, et une hypoesthesie thermoalgique du membre inferieur gauche. Une IRM cerebrale et medullaire retrouve des hypersignaux T2 du cordon lateral Droit medullaire C3-C4, du bord anterieur du putamen gauche et du cervelet. Une lesion hypophysaire est egalement decrite, suspecte de macroadenome hypophysaire. Le bilan thyroidien retrouve une hypothyroidie profonde (TSHus > 150 mUI/L ; T4L a 3,2 pmol/L (N : 11,5–22,7). Les anticorps anti-thyroperoxydase et anti-thyroglobuline sont fortement positifs (11 100 kU/L [N Discussion Ce cas clinique decrit une association entre dysthyroidie, auto-immunite thyroidienne et maladie demyelinisante. Cette association a deja ete decrite dans la litterature, particulierement dans les cas de myelite, sans prejuger de la causalite1. Notre cas illustre egalement le piege diagnostique classique de l’hyperplasie hypophysaire secondaire a une hypothyroidie profonde.

Resume L’augmentation de la prevalence du diabete gestationnel et l’interet de son traitement incitent les professionnels de sante a optimiser sa prise en charge. Notre service hospitalier a mis en place un projet de telemedecine appele « SUIDIA » (pour SUIvi du DIAbete), developpe avec l’aide de l’Agence regionale de sante (ARS) pour repondre a cette demande. Notre evaluation a montre que le suivi par telemedecine n’a pas d’impact sur les complications materno-fœtales. La majorite des patientes et des professionnels de sante se sont declares satisfaits du suivi et de la prise en charge.

Resume Le domaine de la sante mobile (m-sante) appliquee au diabete poursuit son developpement. Le groupe « Technologies et Therapeutiques Innovantes » faisant partie de la Societe Francophone du Diabete (SFD) a propose une mission a certains de ses membres, afin de rapporter de facon reguliere aux diabetologues les innovations interessantes dans ce domaine. Cet article apporte donc une synthese de ce travail : nouvelles applications et referentiel recent de la Haute Autorite de sante (HAS) sont ainsi detailles.

Resume La technologie mobile, representee notamment par les smartphones, connait une croissance importante depuis plusieurs annees. Les applications de sante mobile (m-sante) sont nombreuses, notamment pour les patients atteints de diabete. Il s’agit principalement de carnets glycemiques virtuels, d’aide dietetique, ou encore d’accompagnement a l’activite physique. Ces differentes applications proposent des contenus varies, mais sont de qualite inegale. Leur developpement et mise a disposition echappent a tout systeme de regulation. Face a cette offre plethorique et anarchique, les patients et les professionnels de sante peuvent etre desempares. Afin de repondre a cette difficulte, les differentes applications francophones dediees au diabete ont ete repertoriees, classees par categories, et leurs principales fonctionnalites ont ete decrites. Ce guide pratique devrait aider les diabetologues a conseiller leurs patients pour l’utilisation de ces nouveaux outils.

Introduction Une nouvelle formulation d’octreotide LP (OCT LP) avec un nouveau solvant a ete developpee pour faciliter la preparation et l’administration. Objectif Evaluer la satisfaction des infirmieres suite a la preparation et a l’administration de l’injection de la precedente (PF) et de la nouvelle formulation (NF) d’OCT LP au moyen d’une echelle analogique de 0 (insatisfait) a 10 (tres satisfait). Methodes 80 medecins endocrinologues ou gastro-enterologues ont participe a cette l’etude. Etaient eligibles tous les patients traites par OCT LP pour acromegalie (ACRO), ou pour tumeur neuroendocrine digestive (TNE). 2 groupes de patients : groupe 1 « PF » et groupe 2 « NF ». Resultats Caracteristiques des patients du Groupe 1 (GR1) : 64 TNE (63,8 ± 10,7 ans ; 33 hommes), 34 ACRO (53,6 ± 12 ans ; 38 hommes) et des patients du groupe 2 (GR2) : 65 TNE (62,4 ± 12,2 ans ; 26 hommes) et 34 ACRO (56,7 ± 11,4 ans ; 12 hommes). 98 et 99 infirmieres ont participe respectivement dans le GR1 et le GR2. La satisfaction globale moyenne des infirmieres etait de 5,3 (IC 95 % : 4,9 – 5,8) avec PF et de 7,5 (IC 95 % : 7 – 7,9) avec NF (p Conclusion Une amelioration significative de la satisfaction globale des infirmieres a ete obtenue avec la nouvelle formulation d’OCT LP.

The burden of hypoglycaemia is important, particularly in elderly type 2 diabetes (T2D) patients. Unfortunately, however, few studies are available concerning this population. GERODIAB is a prospective, multicentre, observational study that aims to describe the 5-year morbidity and mortality of 987 T2D patients aged 70 years and older. After analyzing the frequency of and factors associated with hypoglycaemia in the 6 months prior to study inclusion, it was found that hypoglycaemia was associated with retinopathy, lower levels of LDL cholesterol and altered mini-Geriatric Depression Scale (GDS) scores.

International audience; OBJECTIVES: Several cases of testicular adrenal rest tumours have been reported in men with congenital adrenal hyperplasia (CAH) due to the classical form of 21-hydroxylase deficiency but the prevalence has not been established. The aims of this report were to evaluate the frequency of testicular adrenal rest tissue in this population in a retrospective multicentre study involving eight endocrinology centres, and to determine whether treatment or genetic background had an impact on the occurrence of adrenal rest tissue. MATERIAL AND METHODS: Testicular adrenal rest tissue (TART) was sought clinically and with ultrasound examination in forty-five males with CAH due to the classical form of 21-hydroxylase deficiency. When the diagnosis of testicular adrenal rest tumours was sought, good observance of treatment was judged on biological concentrations of 17-hydroxyprogesterone (17OHP), delta4-androstenedione, active renin and testosterone. The results of affected and non-affected subjects were compared. RESULTS: TART was detected in none of the 18 subjects aged 1 to 15years but was detected in 14 of the 27 subjects aged more than 15years. Five patients with an abnormal echography result had no clinical signs. Therapeutic control evaluated at diagnosis of TART seemed less effective when diagnosis was made in patients with adrenal rest tissue compared to TART-free subjects. Various genotypes were observed in patients with or without TART. CONCLUSION: Due to the high prevalence of TART in classical CAH and the delayed clinical diagnosis, testicular ultrasonography must be performed before puberty and thereafter regularly during adulthood even if the clinical examination is normal.

Proline derivatives with a C(γ)-exo pucker typically display a high amide bond trans/cis (K(T/C)) ratio. This pucker enhances n→π* overlap of the amide oxygen and ester carbonyl carbon, which favors a trans amide bond. If there were no difference in n→π* interaction between the ring puckers, then the correlation between ring pucker and K(T/C) might be broken. To explore this possibility, proline conformations were constrained using a methylene bridge. We synthesized discrete gauche and anti 5-fluoro- and 5-hydroxy-N-acetylmethanoproline methyl esters from 3-syn and 3-anti fluoro- and hydroxymethanopyrrolidines using directed α-metalation to introduce the α-ester group. NBO calculations reveal minimal n→π* orbital interactions, so contributions from other forces might be of greater importance in determining K(T/C) for the methanoprolines. Consistent with this hypothesis, greater trans amide preferences were found in CDCl(3) for anti isomers en-MetFlp and en-MetHyp (72-78% trans) than for the syn stereoisomers ex-MetFlp and ex-MetHyp (54-67% trans). These, and other, K(T/C) results that we report here indicate how substituents on proline analogues can affect amide preferences by pathways other than ring puckering and n→π* overlap and suggest that caution should be exercised in assigning enhanced pyrrolidine C(γ)-exo ring puckering based solely on enhanced trans amide preference.

Introduction Le SITP est une maladie rare caracterisee par une insuffisance hypophysaire variable associee a des anomalies de la tige pituitaire (TP) a l’IRM. Sa physiopathologie est inconnue et sa base genetique heterogene. Objectif Determiner le phenotype gonadotrope/testiculaire d’une large serie d’hommes avec SITP. Patients/Methodes Etude multicentrique : donnees cliniques, hormonales, radiologiques de 70 hommes SITP suivis dans 12 CHU francais (2010–2018). Resultats Âge moyen : 31 ± 7 ans (18-58). Cas sporadiques : 100 %. La taille adulte moyenne : 170 ± 10,5 cm (5 cm 30 kg/m2). PA moyenne : 117/70 mmHg (± 11/9). Le LDLc moyen : 1,28 ± 0,4 g/L. Prevalence des deficits hypophysaires : somatotrope, gonadotrope, corticotrope et thyreotrope dans respectivement 92 %, 77 %, 55 % et 66 % des cas. Deux pour cent des patients avaient une hyperprolactinemie et 92 % avec prolactinemie normale. Parmi les patients, 78,6 % avaient au moins 3 deficits hypophysaires. Aucun diabete insipide. Fonctions gonadotrope/testiculaire : puberte spontanee : 20 % ; 80 % : absence de puberte car hypogonadisme hypogonadotrope (HH). Cryptorchidie 26 %. A l’âge adulte : 82 % avec volume testiculaire reduit (4–16 mL). Chez 85,4 % des patients testosterone basse ( Conclusion Nous decrivons le phenotype gonadotrope dans la plus grande serie d’hommes nes avec SITP. Malgre la forte prevalence d’HH, l’exploration de la fertilite n’est realisee que chez une minorite.

Introduction L’acromegalie est frequemment associee au syndrome de McCune Albright (MAS). Peu de grossesse ont ete rapportees dans ce cadre. Nous rapportons le cas d’une grossesse chez une patiente presentant un MAS et une acromegalie. Observation Le MAS a ete diagnostique a 6 ans devant des poussees d’hyperoestrogenisation, associees a des dysplasies fibreuses, sans signes cutanes. L’acromegalie a ete diagnostique a 26 ans, sans adenome hypophysaire visible a l’IRM. Chez cette patiente en oligo-amenorrhee, deux cycles de stimulation ovarienne ont echoue a l’obtention d’une grossesse. Devant l’augmentation de l’IGF-1, un traitement par lanreotide est ajoute. Apres 2 mois de lanreotide et induction de l’ovulation, une grossesse est obtenue et le traitement est arrete. Les IGF-1, mesurees de maniere mensuelle a partir de 17 semaines de grossesse (SG), etaient comparables aux IGF-1 preconceptionnelles avant la mise sous lanreotide, avec des deviations standard (DS) variant entre +2,2 et 3,3 DS. La grossesse a ete compliquee d’un diabete gestationnel a 10 SG, insulinotraite. L’enfant est ne a 35 SG, par cesarienne devant une contre-indication a la voie basse due a l’atteinte de la branche ischiopubienne par la dysplasie fibreuse, avec un poids de 3470 grammes (88,10e percentile selon audipog). Discussion En accord avec la litterature, le traitement de l’acromegalie semble indispensable a l’obtention d’une grossesse. Chez notre patiente, l’IGF-1 est restee stable au cours de la grossesse, sans traitement. La grossesse a ete compliquee d’un diabete gestationnel et d’une cesarienne.

Objectif Le traitement les femmes MODY2 enceintes n’est theoriquement necessaire que lorsque le fœtus n’est pas porteur de la mutation maternelle GCK. L’objectif de notre etude est d’evaluer l’impact de deux strategies d’instauration de l’insulinotherapie en fonction des glycemies maternelles (groupe G) ou de la croissance fœtale echographique (groupe E). Patientes et methodes Etude observationnelle incluant des femmes enceintes MODY2 ≥ 18 ans et IMC pregestationnel Groupe G : traitement selon les recommandations du diabete pregestationnel. Groupe E : insulinotherapie initiee si le perimetre abdominal fœtal depasse le 75e percentile (surveillance echographique renforcee a 25, 28, 35, 38 SA) ou si les glycemies maternelles depassent les seuils de securite. Le choix de la strategie revient a la patiente et au diabetologue. Resultats Dix-sept inclusions, 11 naissances : 3 dans le groupe G, 8 dans le groupe E. Les terme et poids de naissance medians etaient de 38 ± 2 SA et 3004 g (groupe G) et 38 ± 6 SA et 3448 g (groupe E). Toutes les femmes ont finalement ete traitees par insuline dans le groupe E, du fait de la biometrie fœtale dans 3 cas et des glycemies maternelles des 12 SA dans 5 cas. Discussion Nos donnees preliminaires montrent l’interet des cliniciens pour la prise en charge guidee par l’echographie fœtale. Cette etude permettra de decrire la prise en charge des femmes MODY2 enceintes, le benefice eventuel d’une strategie therapeutique, et dans le cadre d’un projet ancillaire, la mise au point de la determination prenatale non invasive du genotype GCK fœtal.

International audience; Context: Maternally inherited diabetes and deafness (MIDD) is a rare form of diabetes with a matrilineal transmission, sensorineural hearing loss, and macular pattern dystrophy due to an A to G transition at position 3243 of mitochondrial DNA (mtDNA) (m.3243A>G). The phenotypic heterogeneity of MIDD may be the consequence of different levels of mutated mtDNA among mitochondria in a given tissue.Objective: The aim of the present study was thus to ascertain the correlation between the severity of the phenotype in patients with MIDD and the level of heteroplasmy in the blood leukocytes.Participants: The GEDIAM prospective multicenter register was initiated in 1995. Eighty-nine Europid patients from this register, with MIDD and the mtDNA 3243A>G mutation, were included. Patients with MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes) or with mitochondrial diabetes related to other mutations or to deletions of mtDNA were excluded.Results: A significant negative correlation was found between levels of heteroplasmy and age of the patients at the time of sampling for molecular analysis, age at the diagnosis of diabetes, and body mass index. After adjustment for age at sampling for molecular study and gender, the correlation between heteroplasmy levels and age at the diagnosis of diabetes was no more significant. The two other correlations remained significant. A significant positive correlation between levels of heteroplasmy and HbA1c was also found and remained significant after adjustment for age at molecular sampling and gender.Conclusions: These results support the hypothesis that heteroplasmy levels are at least one of the determinants of the severity of the phenotype in MIDD.Heteroplasmy levels are at least one of the determinants of the severity of the phenotype of maternally inherited diabetes and deafness.

Gaseous mixtures of HCl and vinylacetylene were permitted to react in Pyrex IR cells (NaCl windows). Gaseous 4-chloro-1,2-butadiene and 2-chloro-1,3-butadiene (chloroprene) were the major products. Kinetic data (FTIR) generated a rate expression in concert with surface catalysis. Computational studies involving surface associated water provide a view that accounts for the experimentally determined orders and a bifurcated pathway producing both products. The results are in accord with wall-adsorbed reactant(s) as well as previously reported computational studies on the reactants.

The regiochemical outcomes for s -BuLi/TMEDA deprotonations of N -Boc-2-azabicyclo[2.1.1]hexanes had been shown to be temperature dependent. Computational methods have been applied to advance understanding of the complexes that the reagents form, the character of the deprotonations, and hence the experimentally observed regiochemical biases. The tertiary anion is formed more readily than the secondary anion and is also the more stable anion. Computations for the enthalpy of proton abstraction from the analogous N -methoxycarbonyl structure also indicate greater stability for the tertiary carbamate anion.

The ability of Selectfluor to act as a nucleofuge for hydrolysis of beta-anti-halides was investigated with N-alkoxycarbonyl derivatives of 6-anti-Y-7-anti-X-2-azabicyclo[2.2.1]heptanes and 4-anti-Y-8-anti-X-6-azabicyclo[3.2.1]octanes. The azabicycles contained X = I or Br groups in the methano bridge and Y = F, Br, Cl, or OH substituents in the larger bridge. The relative reactivities of the halides were a function of the azabicycle, the halide, and its bridge and the addition of Selectfluor or HgF(2) as a nucleofuge. All halide displacements occurred with retention of stereochemistry. Selectfluor with sodium bromide or sodium chloride, but not sodium iodide, competitively oxidized some haloalcohols to haloketones. A significant 15.6 Hz F...HO NMR coupling was observed with 4-anti-fluoro-8-anti-hydroxy-6-azabicyclo[3.2.1]octane.

Low plasma levels of high-sensitivity C-reactive protein (hs-CRP) have been suggested to differentiate hepatocyte nuclear factor 1 alpha-maturity-onset diabetes of the young (HNF1A-MODY) from type 2 diabetes (T2D). Yet, differential diagnosis of HNF1A-MODY and familial young-onset type 2 diabetes (F-YT2D) remains a difficult challenge. Thus, this study assessed the added value of hs-CRP to distinguish between the two conditions.This prospective multicentre study included 143 HNF1A-MODY patients, 310 patients with a clinical history suggestive of HNF1A-MODY, but not confirmed genetically (F-YT2D), and 215 patients with T2D. The ability of models, including clinical characteristics and hs-CRP to predict HNF1A-MODY was analyzed, using the area of the receiver operating characteristic (AUROC) curve, and a grey zone approach was used to evaluate these models in clinical practice.Median hs-CRP values were lower in HNF1A-MODY (0.25mg/L) than in F-YT2D (1.14mg/L) and T2D (1.70mg/L) patients. Clinical parameters were sufficient to differentiate HNF1A-MODY from classical T2D (AUROC: 0.99). AUROC analyses to distinguish HNF1A-MODY from F-YT2D were 0.82 for clinical features and 0.87 after including hs-CRP. For the grey zone analysis, the lower boundary was set to miss1.5% of true positives in non-tested subjects, while the upper boundary was set to perform 50% of genetic tests in individuals with no HNF1A mutation. On comparing HNF1A-MODY with F-YT2D, 65% of patients were classified in between these categories - in the zone of diagnostic uncertainty - even after adding hs-CRP to clinical parameters.hs-CRP does not improve the differential diagnosis of HNF1A-MODY and F-YT2D.

International audience

International audience; CONTEXT:Primary bilateral macronodular adrenal hyperplasia (PBMAH) is a rare cause of primary adrenal Cushing's syndrome (CS). ARMC5 germline mutations have been identified recently in PBMAH.OBJECTIVE:To determine the prevalence of ARMC5 mutations and analyze genotype-phenotype correlation in a large cohort of unrelated PBMAH patients with subclinical or clinical CS.PATIENTS AND METHODS:ARMC5 was sequenced in 98 unrelated PBMAH index cases. PBMAH was identified by bilateral adrenal nodular enlargement on computed tomography scan. The effect on apoptosis of ARMC5 missense mutants was tested in H295R and HeLa cells. Clinical and hormonal data were collected including midnight and urinary free cortisol levels, ACTH, androgens, renin/aldosterone ratio, cortisol after overnight dexamethasone suppression test, cortisol and 17-hydroxyprogesterone after ACTH 1-24 stimulation and illegitimate receptor responses. Computed tomography and histological reports were analyzed.RESULTS:ARMC5-damaging mutations were identified in 24 patients (26%). The missense mutants and the p.F700del deletion were unable to induce apoptosis in both H295R and HeLa cell lines, unlike the wild-type gene. ARMC5-mutated patients showed an overt CS more frequently, compared to wild-type patients: lower ACTH, higher midnight plasma cortisol, urinary free cortisol, and cortisol after dexamethasone suppression test (P = .003, .019, .006, and

We report the case of a 29-yr-old woman who first presented an aseptic meningitis at the beginning of a pregnancy. She was admitted one month later with headaches and vomiting. Panhypopituitarism with diabetes insipidus was diagnosed. Magnetic resonance imaging (MRI) data suggested the existence of lymphocytic infundibulohypophysitis, with inflammation of the suprasellar area. No new symptoms were noticed until 6 months later when this patient pointed out troubles of the visual field, due to a compression of the optic chiasma. Three boluses of 1 g methylprednisolone were prescribed, with no effects. After delivery, the defects of the visual field increased. A neurosurgical intervention was decided. Diagnosis of Rathke's cleft cyst (RCC) was made. We concluded that this patient presented a rupture of a RCC, which occurred at the beginning of pregnancy, associated later with panhypopituitarism with diabetes insipidus, due to a probable hypophysitis. The end of the pregnancy was marked by consequences of an increased volume of the RCC. To our knowledge, this case is the first described during pregnancy.

Resume Introduction Nous rapportons le cas d’une malade qui a developpe sous propylthiouracil une dermatose neutrophilique (pustulose sous cornee de Sneddon-Wilkinson et pyoderma gangrenosum) associee a l’apparition de p-ANCA (anticorps anticytoplasme des polynucleaires neutrophiles). Il s’agit a notre connaissance du premier cas de la litterature. Observation Une femme de 40 ans etait traitee par propylthiouracil pour une maladie de Basedow. Seize mois apres le debut du traitement, elle notait l’apparition de lesions pustuleuses entourees d’un halo erythemateux. Les lesions evoluaient de facon chronique, sans etre ameliorees par l’application de propionate de clobetasol (Dermoval ® ). En fevrier 2003, ces lesions persistaient, le diagnostic de pustulose sous-cornee de Sneddon-Wilkinson etait evoque cliniquement et confirme par l’examen histologique d’une pustule. Par la suite, apparaissait un placard inflammatoire de la cheville droite dans un contexte d’hyperthermie, qui evoluait rapidement vers une ulceration douloureuse a contour inflammatoire, bordee de clapiers purulents. Cette lesion etait evocatrice de pyoderma gangrenosum. La biopsie cutanee du bord de l’ulceration etait en faveur d’un pyoderma gangrenosum, montrant un infiltrat dermique de polynucleaires neutrophiles, sans vascularite associee. L’immunofluorescence directe etait negative. Depuis octobre 2002, il existait des p-ANCA de type antimyeloperoxydase. Il n’y avait pas de gammapathie monoclonale a IgA. Un traitement par corticotherapie par voie generale a raison d’1 mg/kg/j etait debute. On observait une amelioration clinique spectaculaire et la guerison en 8 semaines. Discussion Le propylthiouracil est connu pour etre responsable de l’apparition d’ANCA chez 20 a 64 p. 100 des sujets traites par propylthiouracil pour une maladie de Basedow. Le mecanisme physiopathologique est mal connu. Cliniquement, on peut observer des vascularites cutanees, des glomerulonephrites et des polychondrites. De rares cas de dermatoses neutrophiliques chez des sujets ayant des ANCA induits par propylthiouracil ont ete observes. Il s’agissait le plus souvent de syndrome de Sweet. Un cas de pyoderma gangrenosum a ete rapporte, associe a des ANCA induits par propylthiouracil, chez une femme de 44 ans. Ces manifestations dermatologiques surviennent comme chez notre malade dans des delais d’environ 2 ans. Les donnees de la litterature nous permettent de rapporter la presence de p-ANCA et d’une dermatose neutrophilique a la prise de propylthiouracil. L’association de pyoderma gangrenosum et de pustulose sous cornee de Sneddon-Wilkinson avec des p-ANCA n’a jamais ete rapportee dans ce contexte endocrinologique. Nous proposons d’inscrire les dermatoses neutrophiliques dans la liste des effets secondaires du propylthiouracil.

Oral manifestations of endocrine dysfunction often may be observed initially by the dentist. Objective manifestations, such as ophtalmos in hyperthyroidism, signs of hypersecretion of GH in acromegaly, are easily recognized. Dentists should have some knowledge of many other diseases in this category that occasionally come in our attention. The present article will discuss the effects of over and under-secretion of each endocrine gland separately, showing its influence on the development and maintenance of the health of the teeth and supporting structures. Diabetes mellitus is the most common endocrinological disease, with an incidence of 3%. Periodontitis risk is three time greater in diabetic patients than in general population and it may worsen the diabetes evolution. Periodontitis in diabetic patients needs an rapid diagnosis and treatment. We also presents the oral aspects of thyroid, parathyroid, suprarenalian, growth hormone and female hormones pathology. The incidence of these troubles is less important, but oral manifestations may reveal an endocrine disfunction.

La voie endoscopique endonasale transphenoidale est la voie preferentielle de la chirurgie de l’adenome hypophysaire. Cette voie traverse la muqueuse sphenoidale (MS). Peu de donnees existent dans la litterature concernant son eventuelle atteinte dans ce contexte. L’objectif de ce travail a ete d’etablir la frequence de l’atteinte de la MS par analyse histologique, et de son interet sur le plan clinique. Methodes Etaient comme suit : – etude prospective observationnelle ; patients operes par voie transphenoidale ; – donnees demographiques, type d’adenome (taille, secretion) etudies ; – histologie : presence d’une inflammation ou d’une infiltration de la MS, d’une infiltration de la dure-mere, du caractere complet ou non de la chirurgie ; – guerison a 3 mois, si absence de recidive sur l’IRM et d’hypersecretion. Resultats Etaient comme suit : – quarante-cinq patients inclus ; âge 56,4 ans (22–86) ; sex-ratio 0,53 ; 91 % macro-adenomes ; 5 cas d’apoplexie ; – secretion : gonadotropes 49 %, somatotropes 27 %, corticotropes 13 %, lactotrope 2 %, mixtes 6 % ; – anatomopathologie : inflammation de la MS dans 89 % des cas (80 % des apoplexies), infiltration dans 9 % (toujours avec inflammation), infiltration de la dure-mere dans 51 %. Exerese complete dans 38 % ; – Guerison dans 33 % ; – Correlation entre infiltration de la MS et infiltration de la dure-mere en histologie ( p = 0,04 ; test de Pearson-Chi 2 ). Absence de correlation avec les autres criteres etudies. Conclusion L’atteinte de la MS semble frequente : son infiltration, contrairement a celle de la dure-mere, apporte peu d’interet sur le plan clinique. D’autres etudes sont necessaires pour determiner l’eventuel role pronostique de son inflammation, notamment dans l’apoplexie hypophysaire comme suggere par ailleurs.

Les mouvements en miroir (MM + ) sont frequemment rapportes chez les patients ayant un syndrome de Kallmann (SK + ), en cas de mutation d’ANOS1 (KAL1) sur le chromosome X. Il n’a jamais ete decrit de MM + chez les femmes ANOS1 + . L’hypothese d’un defaut d’inhibition du faisceau pyramidal controlateral a ete proposee pour expliquer ces MM mais n’a jamais ete demontree. Objectif Tester l’hypothese d’un defaut de decussation et de developpement des voies pyramidales chez des patients SK + MM + . Methodes Analyse genetique dans une famille comprenant 11 hommes SK + MM + et 2 femmes SK-MM + (F1). Analyse par imagerie du faisceau pyramidal par tractographie en tenseur de diffusion chez 2 hommes adultes SK + MM + ANOS1 + analyse anatomopathologique d’un fœtus ANOS1 + (ITG pour agenesie renale bilaterale). Resultats Presence d’un rearrangement complexe d’ANOS1 (C2067-2070AGGA > TCCT ; pGlu642Alafs21) chez les hommes SK + MM + et les femmes MM + de la famille F1. Absence de decussation des faisceaux pyramidaux chez 2 patients SK + MM + ANOS1 + (mutation nonsense c.773G > A ; p.TRP258X, et c.784C > T ; p.Arg262X) Hypoplasie du faisceau pyramidal chez un fœtus ANOS1 + (c.769C > T, p.R257X). Conclusion Les mutations perte de fonction d’ANOS1 peuvent etre associees a des mouvements en miroir avec transmission dominante chez les femmes. Les patients ANOS1 + avec MM ont un defaut de decussation des voies pyramidales. L’anosmine, codee par ANOS1, dont la fonction dans le developpement du bulbe olfactif et la migration des neurones olfactifs etait connue, participe egalement au developpement du faisceau pyramidal.

Objectif La maladie de Cushing est une pathologie rare, responsable d’une morbi-mortalite elevee. La chirurgie hypophysaire ne garantit pas une remission complete et durable. Le but de l’etude est d’evaluer le taux de remission a 3 mois postoperatoire, le taux de recidive au cours du suivi et les facteurs peri-operatoires pronostiques. Materiel et Methodes Les patients majeurs presentant une maladie de Cushing diagnostiquee entre 1990 et 2015, recrutes par l’intermediaire des resultats anatomopathologiques des six CHU, ont ete inclus. Resultats Parmi les 176 patients inclus, 171 ont subi une chirurgie. Le taux de remission des patients a 3 mois postoperatoire etait de 78 %. La mediane de suivi etait de 5 ans. Le taux de recidive etait de 28 % avec un delai median de survenue d’une recidive de 3 ans. La taille des adenomes superieure a 10 mm, l’envahissement du sinus caverneux, l’exerese macroscopiquement incomplete et le cortisol plasmatique postoperatoire immediat non effondre etaient des facteurs de risque de non-remission. Le sexe masculin, le cortisol plasmatique postoperatoire immediat non effondre, le cortisol libre urinaire (CLU) et l’ACTH preoperatoire eleve etaient des facteurs de risque de survenue d’une recidive. Discussion Les taux de remission et de recidive ainsi que les facteurs de risque de non-remission degages par l’etude sont en accord avec les donnees de la litterature. A notre connaissance, le sexe masculin, le CLU et l’ACTH pre-operatoires eleves n’etaient pas decrits comme facteurs pronostiques d’une recidive.

The reactions of N-(alkoxycarbonyl)-2-azabicyclo[2.2.0]hex-5-enes 5 with halonium ion electrophiles were studied in polar and nonpolar aprotic solvents and also in protic media with the aim of controlling nitrogen neighboring group participation. Specifically, for bromonium ions nitrogen participation is facilitated by the polar aprotic solvent nitromethane and by the poorly nucleophilic protic solvent acetic acid. Alkene 5b and bromine/nitromethane afford only the rearranged anti,anti-5,6-dibromo-2-azabicyclo[2.1.1]hexane 6b, and NBS/acetic acid gives an 8:1 mixture favoring rearranged 5-bromo-6-acetate 6f. Conversely, pyridinium bromide perbromide/CH(2)Cl(2) is selective for only unrearranged 5,6-dibromide 7. Iodonium and phenylselenonium ions react with alkenes 5 to give only unrearranged 1,2-addition products 9 and 10, regardless of solvent. Chloronium and fluoronium ions react with alkenes 5 to give 4-aminomethyl-3-hydroxycyclobutene 11, derived by ring cleavage.

Post-surgical surveillance of non-functioning pituitary adenoma (NFPA) is based on magnetic resonance imaging (MRI) at 3 or 6 months then 1 year. When there is no adenomatous residue, annual surveillance is recommended for 5 years and then at 7, 10 and 15 years. In case of residue or doubtful MRI, prolonged annual surveillance monitors any progression. Reintervention is indicated if complete residue resection is feasible, or for symptomatic optic pathway compression, to create a safety margin between the tumor and the optic pathways ahead of complementary radiation therapy (RT), or in case of post-RT progression. In case of residue, unless the tumor displays elevated growth potential, it is usually recommended to postpone RT until progression is manifest, as efficacy is comparable whether treatment is immediate or postponed. The efficacy of the various RT techniques in terms of tumor volume control is likewise comparable. RT-induced hypopituitarism is frequent, whatever the technique. The choice thus depends basically on residue characteristics: size, delineation, and proximity to neighboring radiation-sensitive structures. Reduced rates of vascular complications and secondary brain tumor can be hoped for with one-dose or hypofractionated stereotactic RT, but there has been insufficient follow-up to provide evidence. Somatostatin analogs and dopaminergic agonists have yet to demonstrate sufficient efficacy. Temozolomide is an option in aggressive NFPA resistant to surgery and RT. Après chirurgie, la surveillance des adénomes hypophysaires non fonctionnels (AHNF) repose sur l’imagerie par résonance magnétique (IRM) réalisée 3, voire 6 mois, puis un an après l’intervention chirurgicale. En l’absence de reliquat adénomateux, une surveillance annuelle est recommandée pendant 5 ans, puis 7, 10 et 15 ans après la chirurgie. En cas de reliquat ou d’image douteuse, une surveillance annuelle prolongée précisera l’évolutivité éventuelle de la lésion. Une seconde intervention chirurgicale est justifiée en cas de possibilité d’exérèse complète d’un reliquat, de compression symptomatique des voies optiques, afin de garder une distance de sécurité entre la tumeur et les voies optiques avant irradiation complémentaire ou en cas de progression tumorale après radiothérapie. En présence d’un reliquat, il est le plus souvent justifié (sauf si la tumeur manifeste un potentiel de croissance élevé) de différer la radiothérapie au moment où ce reliquat évolue, son efficacité étant comparable que le traitement soit réalisé d’emblée ou différé. L’efficacité des différentes techniques de radiothérapie sur le contrôle du volume tumoral est comparable. L’hypopituitarisme radio-induit est fréquent, quelle que soit la technique utilisée. Le choix dépendra donc essentiellement des caractéristiques du reliquat (taille, limites, proximité des structures radio-sensibles avoisinantes). Avec les radiothérapies stéréotaxiques en dose unique ou hypo-fractionnées, on espère une fréquence moindre des complications vasculaires et des rares tumeurs cérébrales secondaires ; mais le recul reste insuffisant. Les analogues de la somatostatine et les agonistes dopaminergiques n’ont pas fait la preuve jusqu’alors d’une efficacité suffisante. Le témozolamide peut être discuté chez les patients présentant des AHNF agressifs après chirurgie et radiothérapie.

[reaction: see text] Azabicycle 4 and sec-butyllithium/TMEDA afford the C(1) bridgehead alpha-lithio anion at 0 degrees C. Anion quenching with carbon dioxide, methyl chloroformate, or DMF provide the bridgehead acid 8a (N-BOC-2,4-methanoproline), ester 8b, or aldehyde 8c, respectively. By contrast, at -78 degrees C these same reagents give a mixture of regioisomeric methylene and bridgehead anions whose quenching leads to mixtures of regioisomeric methylene and bridgehead acids 6a/8a, esters 6b/8b, or aldehydes 6c/8c, respectively. The previously unknown 3,5-methanoproline was prepared as its N-BOC methyl ester 6b.

The lipase-catalyzed hydrolysis of castor, coriander, and meadowfoam oils was studied in a two-phase water/oil system. The lipases from Candida rugosa and Pseudomonas cepacia released all fatty acids from the triglycerides randomly, with the exception of castor oil. In the latter case, the P. cepacia lipase discriminated against ricinoleic acid. The lipase from Geotrichum candidum discriminated against unsaturated acids having the double bond located at the Δ-6 (petroselinic acid in coriander oil) and Δ-5 (meadowfoam oil) position or with a hydroxy substituent (ricinoleic acid). The expression of the selectivities of the G. candidum lipase was most pronounced in lipase-catalyzed esterification reactions, which was exploited as part of a two-step process to prepare highly concentrated fractions of the acids. In the first step the oils were hydrolyzed to their respective free fatty acids, in the second step a selective lipase was used to catalyze esterification of the acids with 1-butanol. This resulted in an enrichment of the targeted acids to approximately 95—98% in the unesterified acid fractions compared to the 70—90% content in the starting acid fractions.

The Diels–Alder reaction between (R)-(−)-methyl (Z)-3-(4,5-dihydro-2-phenyl-4-oxazolyl)-2-propenoate (1) and cyclopentadiene in the presence of one equivalent of Et2AlCl gave stereochemical results opposite to those obtained with one equivalent of EtAlCl2. Energy minimizations of proposed complexes of these Lewis acids with the chiral dienophile at the RHF/3–21G level suggest that the aluminum is tetrahedrally complexed with Et2AlCl, but bound in a trigonal bipyramid with EtAlCl2. These complexes expose the diastereotopic faces of the dienophile to reaction with diene.

Introduction Le Xeroderma pigmentosum (XP) est une dermatose genetique rare, autosomique recessive, caracterisee par une sensibilite excessive aux UV entrainant un risque majeur de cancer cutane. Observation Une patiente de 30 ans, presentant un XP diagnostique dans l’enfance, consulte pour une amenorrhee secondaire evoluant depuis plus d’un an. Les explorations hormonales montrent une elevation des gonadotrophines (FSH 36,5 UI/L N 3–7, LH 21,0 UI/L N 3–8) en regard d’un estradiol relativement conserve a 60 pg/mL (N 40–100), associee a une diminution de l’AMH ( Discussion Il existe peu de donnees concernant la fonction gonadique des patients atteints de XP. D’anciennes series de cas decrivaient un retard pubertaire chez 12 % d’entre eux [1] . Recemment, une etude pilote retrouvait une prevalence de l’insuffisance ovarienne prematuree de 15 % [2] . Par ailleurs, les modeles murins de XP ont des performances reproductives reduites, en lien avec une apoptose accrue des cellules germinales [3] . En conclusion, ce cas rapporte une association peu decrite mais peut-etre sous-estimee entre le Xeroderma pigmentosum et l’insuffisance ovarienne prematuree.

Conditions were developed for the selective epoxidation of the double bond of methyl ricinoleate (1) with ethylmethyldioxirane (EMDO) to give the homoallylic epoxyalcohol, methyl (Z)-9,10-oxido-12-hydroxyoctadecanoate (2) in high yields but in poor enantiomeric excess. The diastereomeric ratio for epoxyalcohol 2 was improved modestly when t-butyl-hydroperoxide, coupled with a titanium catalyst and a d-tartrate ligand, was used as oxidizing agent. Reaction of 1 with excess EMDO resulted in the concomitant epoxidation of the double bond and oxidation of the hydroxy group of 1 to give methyl (Z/it)-9,10-oxido-12-oxo-octadecanoate (4), along with methyl 8-(5-hexylfuran-2-yl)octanoate (5). Alternatively, ketoepoxide 4 was prepared by dioxirane oxidation of methyl 12-oxo-(Z)-9-octadecene (3) or by treating epoxyalcohol 2 with sodium hypochlorite. The ketoepoxide 4 is acid-labile and rearranges with loss of water to give furan 5 in high yield.

We compared the concentrations of soluble intercellular adhesion molecule-1 (sICAM-1) and the activities of thyroid-stimulating antibodies (TSAb) and thyrotropin-receptor antibodies (TBIAb) as measured with a commercial kit (TRAK). Sera were obtained from patients with Graves' disease (GD) before, during and after therapy with carbimazole (1-methyl-2-thio-3-carbethoxyimidazole). In all the situations, TSAb method was more sensitive than TBIAb. These two parameters dropped during therapy and were not correlated at any stage of measurement. sICAM-1 levels increased in 56.4% of patients before treatment, remained elevated at the beginning of treatment and decreased after twelve months of therapy. TSAb levels were significantly different between patients in relapse (78%) and those in remission (18%) (Z=−2.250, P = 0.025), with a relapse rate depending on the TSAb positivity (χ2 = 7.103, P = 0.0077). Positive sICAM-1 values were found in 3 of the 9 (33.3%) patients who relapsed after discontinuing the drug but were negative in all the patients remaining in remission with a significant difference (Z = −1.982, P = 0.0475). The relapse rate was also dependent on positive sICAM-1 values (χ2 = 3.958, P = 0.0466). No correlation was found between sICAM-1 levels and anti-TSH receptor antibodies TSAb or TBIAb. We conclude that the TBIAb technique is too insensitive to explore GD. TSAb and sICAM-1 assays in patients with GD are good markers of immune process after treatment withdrawal. Because of its rapid implementation, the sICAM-1 assay may advantageously replace TSAb measurement for forming a prognosis of GD.

Diabetes & Metabolism - In Press.Proof corrected by the author Available online since jeudi 31 octobre 2013

Phase-transfer catalyzed biphasic epoxidation of a series of fats and oils with ethylmethyldioxirane in 2-butanone was conducted. The series of glycerides studied varied from monounsaturated (olive) to highly polyunsaturated (flaxseed) oils. Best conversions for polyunsaturate-containing oils were obtained with a molar ratio of 2.5:1 (oxidant/oil) with two-step addition of oxidant. Conversion to epoxides was monitored by gas-liquid chromatography, and oxirane content was determined by titration. The effect of phase-transfer catalyst or solvent used for the epoxidation reaction also was investigated.

Several chiral naphthylacetic acids have been prepared and evaluated as chiral derivatizing reagents for chiral alcohols. Fluorinated acids provide good general HPLC separations of chiral alcohols, especially 1,2-diglycerides. The separations and the 19F-NMR shift differences of pairs of diastereomers are documented.

Monoglycerides of erucic acid (C22:1, Δ13), prepared by conventional methods, were reacted with caprylic acid (octanoic acid, C8.0) by using lipases as catalysts with the intention of synthesizing a triglyceride that contains two molecules of caprylic acid and one molecule of erucic acid (caprucin). The reaction was carried out by mixing lipase powder, a small quantity of water, and the reactants in a temperature-controlled stirred batch reactor. Organic solvents or emulsifying agents were not required. When the nonspecific lipase fromPseudomonas cepacia was used, a yield of approximately 37% caprucin was obtained, together with a complex mixture of di- and triglycerides that resulted from the random transesterification of the erucic acid. The fatty acid-specific lipase fromGeotrichum candidum promoted minimal transesterification of erucic acid and resulted in a yield of 75% caprucin and approximately 10% interesterification products. Lipase fromCandida rugosa exhibited a similar, although less pronounced, specificity to that fromG. candidum and promoted more transesterification of erucic acid. Optimum conditions forG. candidum lipase were at 50°C and an initial water content of 5.5%. After the reaction, erucic acid was converted to behenic acid by hydrogenation, thereby converting caprucin into caprenin, a commercially available low-calorie triglyceride.

A modified procedure for the regiospecific analysis of triacylglycerols (TAG) with a 1,3-specific lipase is described. After partial lipase hydrolysis of the triacylglycerol, the released free fatty acids (FFA) and 1,2(2,3)-diacylglycerols (DAG) were isolated by thin-layer chromatography (TLC) and converted to fatty acid methyl esters (FAME). The FAME were analyzed by gas-liquid chromatography (GLC). The 1,3-specific lipases used in this study included supported preparations from strains ofMucor miehei andRhizopus oryzae. The method also was applied to the regiospecific analyses of tung nut and Chinese melon seed oil triacyglycerols, both of which contain high proportions of α-elaeostearic acid. The TAG composition of the oils was substantiated in parallel analysis of the oils by highperformance liquid chromatography with chemical ionization mass spectrometric detection of intact TAG.

Introduction Le syndrome de Netherton (SN), maladie rare (incidence 1/200 000 naissances), presente une triade (erythrodermie ichtyosiforme congenitale, trichorrhexie invaginata, atopie) ainsi qu’un retard staturo-ponderal. Autosomique, recessive, la mutation de SPINK5 (5q31–q32) codant pour « the lymphoepithelial Kazal-type-related inhibitor » (LEKTI) entraine une augmentation d’hormone de croissance (hGH) inactive. Ce retard statural n’est pas un deficit mais une inactivation hormonale. Objectif Faire une description phenotypique hypophysaire clinique et biologique du SN et proposer une prise en charge. Materiels et methodes Dans les centres hospitaliers universitaires de Brest, Nantes, Poitiers, Tours et Toulouse, les SN ayant beneficie d’une exploration endocrinologique (entre 1990 et 2015) ont ete collecte avec des donnees demographiques, anamnestiques, cliniques, paracliniques, genetiques et un test dynamique de l’axe somatotrope. Resultats Nous avons 7 cas (1 femme, 6 hommes) de 2 a 72 ans. La taille finale est a la moyenne et proche de la taille cible. Pour les patients en croissance, corrigee a l’âge osseux la taille est entre −1,2 et +0,2 DS versus −4DS et −4,6DS en realite. Les hypophysiogrammes revelent une hypothyroidie centrale, deux retards pubertaires a fonction sertolienne normale, trois insuffisances corticotropes sous dermocorticoides. Les tests de stimulation de la GH sont majoritairement normaux avec des IGF1 basses. Il existerait un lien genotype–phenotype. Les patients les moins severes sur le plan endocrinologique (taille finale normale et puberte spontanee) presentent moins d’elements pathognomoniques. Conclusion Nous preconisons donc cinq axes de soins : dermatologique, endocrinologique (surveillance thyroidienne, supplementation en hGH a 0,030 mg/kg/j, induction pubertaire), allergologique, genetique et biologique.

The γ-linolenic acid (Z,Z,Z-6,9,12-octadecatrienoic acid, GLA) present in borage oil free fatty acids was concentrated in esterification reactions that were catalyzed by several preparations of the acyl-specific lipase ofGeotrichum candidum. In this manner, a 95% recovery of the GLA originally present in borage oil (25% GLA) was obtained as a highly enriched fatty acid fraction with a GLA content of >70%. Other fatty acids concentrated in this fraction were the monounsaturated fatty acids with chainlengths of C-20 and longer that were present in the oil. An immobilized preparation ofG. candidum on silica gel also was used for the enrichment of GLA in borage oil. In this instance, a 75% recovery of GLA was obtained, and the supported lipase was reusable (three cycles) with minimal loss in activity.