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1.
Gynecol Obstet Fertil Senol ; 50(10): 675-681, 2022 10.
Artigo em Francês | MEDLINE | ID: mdl-35609786

RESUMO

Postmenopausal hyperandrogenism is an androgen excess originating from either the adrenals and/or the ovaries. Clinically, symptoms can be moderate (increase in terminal hair growth, acnea) or severe with signs of virilization (alopecia, clitoridomegaly). In either setting, physicians need to exclude relatively rare but potentially life-threatening underlying tumorous causes, such as adrenal androgen-secreting tumors. The objectives of this review are to evaluate which hormonal measurements (T, delta 4 androstenedione, 17 OH progesterone, SDHEA, FSH, LH) and/or imaging (pelvic ultrasound, MRI or adrenal CT-scan) could be useful identifying the origin of the androgen excess. Our review illustrates that the rate of progression of hirsutism and/or alopecia, and serum testosterone levels are in favor of tumors. Pelvic MRI and adrenal CT-scan are useful tools for identifying the different causes of androgen excess.


Assuntos
Neoplasias das Glândulas Suprarrenais , Hiperandrogenismo , Neoplasias das Glândulas Suprarrenais/complicações , Alopecia/complicações , Androgênios , Androstenodiona , Feminino , Hormônio Foliculoestimulante , Humanos , Hiperandrogenismo/etiologia , Menopausa , Ovário , Progesterona , Testosterona
2.
Orphanet J Rare Dis ; 17(Suppl 1): 170, 2022 04 19.
Artigo em Inglês | MEDLINE | ID: mdl-35440056

RESUMO

Dunnigan syndrome, or Familial Partial Lipodystrophy type 2 (FPLD2; ORPHA 2348), is a rare autosomal dominant disorder due to pathogenic variants of the LMNA gene. The objective of the French National Diagnosis and Care Protocol (PNDS; Protocole National de Diagnostic et de Soins), is to provide health professionals with a guide to optimal management and care of patients with FPLD2, based on a critical literature review and multidisciplinary expert consensus. The PNDS, written by members of the French National Reference Center for Rare Diseases of Insulin Secretion and Insulin Sensitivity (PRISIS), is available on the French Health Authority website (in French). Dunnigan syndrome is characterized by a partial atrophy of the subcutaneous adipose tissue and by an insulin resistance syndrome, associated with a risk of metabolic, cardiovascular and muscular complications. Its prevalence, assessed at 1/100.000 in Europe, is probably considerably underestimated. Thorough clinical examination is key to diagnosis. Biochemical testing frequently shows hyperinsulinemia, abnormal glucose tolerance and hypertriglyceridemia. Elevated hepatic transaminases (hepatic steatosis) and creatine phosphokinase, and hyperandrogenism in women, are common. Molecular analysis of the LMNA gene confirms diagnosis and allows for family investigations. Regular screening and multidisciplinary monitoring of the associated complications are necessary. Diabetes frequently develops from puberty onwards. Hypertriglyceridemia may lead to acute pancreatitis. Early atherosclerosis and cardiomyopathy should be monitored. In women, polycystic ovary syndrome is common. Overall, the management of patients with Dunnigan syndrome requires the collaboration of several health care providers. The attending physician, in conjunction with the national care network, will ensure that the patient receives optimal care through regular follow-up and screening. The various elements of this PNDS are described to provide such a support.


Assuntos
Hipertrigliceridemia , Resistência à Insulina , Lipodistrofia Parcial Familiar , Lipodistrofia , Pancreatite , Doença Aguda , Feminino , Humanos , Hipertrigliceridemia/complicações , Lipodistrofia Parcial Familiar/diagnóstico , Lipodistrofia Parcial Familiar/genética , Lipodistrofia Parcial Familiar/terapia
3.
Hum Reprod ; 35(10): 2391-2398, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-32810206

RESUMO

STUDY QUESTION: Is there an added diagnosis value of buccal cell FISH analysis compared with blood lymphocyte chromosomal investigations in patients with Turner syndrome (TS)? SUMMARY ANSWER: Buccal cell FISH analysis, a non-invasive technique, modified the chromosomal results obtained with the blood karyotype in 17 patients (12%) of our cohort. WHAT IS KNOWN ALREADY: Few studies have evaluated buccal cell FISH analysis and compared them with blood karyotype in patients with TS. STUDY DESIGN, SIZE, DURATION: A prospective, monocentric cohort study was conducted in a rare diseases centre (CMERC) between July 2017 and August 2019. PARTICIPANTS/MATERIALS, SETTING, METHODS: In total, 142 adult patients with TS, and at least 5% 45,X cells in a previous blood karyotype, were recruited. All the patients' files were included in the CEMARA database. This national database has been declared to the French data protection agency (CNIL approval number 1187326). In compliance with French law, consent regarding non-opposition to collect and use the data was obtained from each patient. A FISH analysis on a buccal smear was performed. MAIN RESULTS AND THE ROLE OF CHANCE: The percentage of 45,X cells was identical between the two tissues in only 32.4% of cases. The discrepancy was higher than 41% for 12% of the cohort. The percentage of 45,X cells was higher in blood in 53 (37.3%) patients, and higher in buccal cells in 43 (30.3%) of cases. In 17 (12%) cases, the blood karyotype had to be reconsidered in regard to the buccal cell analysis. LIMITATIONS, REASONS FOR CAUTION: It would have been interesting to evaluate karyotypes in cells from other tissues such as cells from skin biopsy or from the urinary tract and even from blood vessels or gonads in case of surgery and to compare them with each patient's phenotype. However, most of the time, these tissues are not available. WIDER IMPLICATIONS OF THE FINDINGS: Although blood lymphocyte karyotype remains the gold standard for the diagnosis of TS, buccal cell FISH analysis is an efficient tool to evaluate the global chromosomal constitution in these patients, thus allowing them to have better care and follow-up. For instance, identifying a Y chromosome can prevent the occurrence of a gonadoblastoma, as gonadectomy should be discussed. On the other hand, finding normal XX cells in a patient with a previous diagnosis of homogenous 45,X TS, may be psychologically helpful and relevant for gynaecological care. STUDY FUNDING/COMPETING INTEREST(S): No specific funding was sought for the study. The authors declare no competing interests. TRIAL REGISTRATION NUMBER: N/A.


Assuntos
Neoplasias Ovarianas , Síndrome de Turner , Adulto , Estudos de Coortes , Feminino , Humanos , Mosaicismo , Mucosa Bucal , Estudos Prospectivos , Síndrome de Turner/diagnóstico , Síndrome de Turner/genética , Síndrome de Turner/terapia
5.
Gynecol Endocrinol ; 35(11): 941-944, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31155980

RESUMO

Adrenal infarction is usually associated with bilateral adrenal hemorrhage in the setting of antiphospholipid syndrome or hemodynamic variation. Few cases of unilateral nonhemorrhagic adrenal infarction (NHAI) have been described in the literature. Here, we report a case occurring during pregnancy. A 30-year-old woman presented at 32 weeks of gestation with sudden-onset right abdominal pain and contractions. Unilateral adrenal infarction was diagnosed following computed tomography (CT). It showed an enlarged right adrenal, without hyperenhancement. Because of persisting contractions, despite medical care, she delivered a healthy, albeit premature, girl. Abdominal pain decreased right after delivery. Three month later, CT imaging showed atrophy of the right adrenal and a normal left adrenal. The patient's adrenal hormonal function was normal. Accurate diagnosis of NHAI remains difficult as its clinical presentation is not specific. It can only be performed with adrenal imaging. Magnetic resonance imaging shows diffuse enlargement of one or both adrenals and an edema on T2-weighted images. Anticoagulation therapy may be discussed. Patients should be evaluated between 3 and 6 months after the event to assess adrenal size and function. In summary, NHAI during pregnancy is probably underdiagnosed and obstetricians should be aware of this or diagnostic difficulty.


Assuntos
Dor Abdominal/etiologia , Glândulas Suprarrenais/irrigação sanguínea , Infarto/diagnóstico por imagem , Complicações na Gravidez/diagnóstico por imagem , Glândulas Suprarrenais/diagnóstico por imagem , Adulto , Feminino , Humanos , Infarto/complicações , Gravidez , Complicações na Gravidez/etiologia , Tomografia Computadorizada por Raios X
6.
Ann Pharm Fr ; 77(1): 62-73, 2019 Jan.
Artigo em Francês | MEDLINE | ID: mdl-30243470

RESUMO

The peripheral insertion central catheter (PICC-Line) is indicated for long term intravenous medication administration. Some adverse events (AE) might occur, especially for patients after hospital discharge. Therefore, patient empowerment about the side effects and precaution for use is essential to prevent potential patient harm. A multidisciplinary working group met and designed support program for outpatient living with PICC-line. Pharmacy consultations (PC) were proposed to patient before and after PICC-line insertion. A strip cartoon and card game were created to facilitate patient education. The aim of the study was to assess the comprehension of patient then secondarily to follow up AE awareness. During 10 months, 30 patients of mean age 65.9±14 years were included. Thirty-sixPICC-Line were installed and followed on 1659days of catheterization. 4, 9 and 13patients received respectively no, at least one and two PCs before discharge from the hospital. Although the differences were not statistically significant, comprehension tends to improve when patients benefit from both PCs especially when it concerns complications. Twenty-fiveambulatory AEs were recorded including 9infections or suspicion of infection, 2 thrombosis and 2 displacements of PICC-line. Among the patients who had no PC, four experienced delayed care. In comparison, it occurred in only one patient in the group who received at least one PC after PICC-line insertion. Further studies are warranted to confirm this trend.


Assuntos
Cateterismo Venoso Central/métodos , Cateterismo Periférico/métodos , Idoso , Idoso de 80 Anos ou mais , Assistência Ambulatorial , Recursos Audiovisuais , Infecções Relacionadas a Cateter/prevenção & controle , Cateterismo Venoso Central/efeitos adversos , Cateterismo Periférico/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pacientes Ambulatoriais , Educação de Pacientes como Assunto , Projetos Piloto
7.
Hum Reprod ; 33(8): 1408-1416, 2018 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-29912343

RESUMO

STUDY QUESTION: What are the consequences of radioactive iodine (RAI) therapy for testicular function? SUMMARY ANSWER: A single activity of 3.7 GBq RAI for differentiated thyroid carcinoma (DTC) treatment in young men transiently altered Sertoli cell function and induced sperm chromosomal abnormalities. WHAT IS KNOWN ALREADY: Few studies, mainly retrospective, have reported the potential impacts of RAI on endocrine and exocrine testicular function. STUDY DESIGN, SIZE, DURATION: A longitudinal prospective multi-center study on testicular function performed in DTC patients before a single 131I ablative activity of 3.7 GBq (V0) and at 3 months (V3) and 13 months (V13) after treatment. PARTICIPANTS/MATERIALS, SETTING, METHODS: Forty male patients, aged 18-55 years, with DTC participated. Hormonal analysis included FSH, LH, testosterone and inhibin B serum levels at V0, V3 and V13. Furthermore, sperm parameters, DNA fragmentation and sperm chromosomal abnormalities were evaluated at each time points. The differences in all parameters, between V0-V3, V0-V13 and V3-V13, were analyzed, using a Wilcoxon test. MAIN RESULTS AND THE ROLE OF CHANCE: Prior to RAI administration, all patients had normal gonadal function. At V3, a statistically significant increase in FSH levels and a decrease in inhibin B levels were observed and sperm concentration, as well as the percentage of morphologically normal spermatozoa, were significantly decreased (P < 0.0001). These modifications were transient as both sperm concentration and normal morphology rate returned to baseline values at V13. However, at this later time point, FSH and inhibin B levels were still impacted by RAI administration but remained in the normal range. Although no DNA fragmentation was observed at V3 nor V13, our study revealed a statistically significant increase in the number of sperm chromosomal abnormalities both at V3 (P < 0.001) and V13 (P = 0.01). LIMITATIONS, REASONS FOR CAUTION: Among the 40 patients included in the study, only 24 had all the parameters available at all visits. WIDER IMPLICATIONS OF THE FINDINGS: Prospective studies with longer term follow up would be helpful to determine whether the chromosome abnormalities persist. These studies would be required before sperm banking should be suggested for all patients. However, sperm preservation for DTC patients who require cumulative radioiodine activities higher than 3.7 GBq should be proposed. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by the Programme Hospitalier de Recherche Clinique, AP-HP (No. P040419). The authors report no conflict of interest in this work. TRIAL REGISTRATION NUMBER: NCT01150318.


Assuntos
Carcinoma/radioterapia , Infertilidade Masculina/etiologia , Radioisótopos do Iodo/efeitos adversos , Doses de Radiação , Lesões por Radiação/etiologia , Testículo/efeitos da radiação , Neoplasias da Glândula Tireoide/radioterapia , Adolescente , Adulto , Biomarcadores/sangue , Carcinoma/patologia , Diferenciação Celular , Aberrações Cromossômicas , Fragmentação do DNA , França , Hormônios/sangue , Humanos , Infertilidade Masculina/sangue , Infertilidade Masculina/genética , Infertilidade Masculina/patologia , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Lesões por Radiação/sangue , Lesões por Radiação/genética , Lesões por Radiação/patologia , Radioterapia Adjuvante/efeitos adversos , Medição de Risco , Fatores de Risco , Espermatozoides/patologia , Espermatozoides/efeitos da radiação , Testículo/metabolismo , Testículo/patologia , Neoplasias da Glândula Tireoide/patologia , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
8.
Diagn Interv Imaging ; 99(4): 247-253, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29196222

RESUMO

PURPOSE: To investigate the possible relationships between sigmoid diverticula, the volume of the left lateral segment of the liver and sigmoid colon volvulus. MATERIAL AND METHODS: The presence of sigmoid diverticula was analyzed in 36 patients (24 men, 12 women; mean age, 70.77±19.86 [SD] years) with sigmoid volvulus (group 1). The volumes of left lateral segment of the liver (i.e., segments 2 and 3 and further referred to as liver 1), liver 2 (i.e., segments 1, 4, 5, 6, 7 and 8), total liver volume and liver volume ratio (LVR) (i.e., [liver 1/liver 2]×100) were calculated from abdominal CT performed distantly from the acute episode of sigmoid volvulus. Results of volumetric measurements in group 1 were compared with those of two groups of age and gender-matched control patients without hepatopathy: one patient group with sigmoid diverticula (group 2) and one group without sigmoid diverticula (group 3). RESULTS: No patients with sigmoid volvulus had diverticulum. Liver 1 volume was lower in group 1 (193.8cm3) than in group 2 (273.75cm3) (P=0.0003). Mean LVR was greater in group 2 (24.18%) than in group 1 (14.46%) (P=1×10-7) and group 3 (18.36%) (P=0.003). Mean LVR was greater in group 3 than in group 1 (P=0.01). No significant differences in liver 2 volume and total liver volumes were found between the 3 groups. CONCLUSION: Elasticity of colon wall associated with relative hypotrophy of left lateral segment of the liver are significantly associated with sigmoid volvulus. Further studies are needed to elucidate the pathophysiological mechanisms behind this association.


Assuntos
Colo Sigmoide , Divertículo/complicações , Volvo Intestinal/complicações , Fígado/diagnóstico por imagem , Fígado/patologia , Doenças do Colo Sigmoide/complicações , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Humanos , Hipertrofia , Imageamento Tridimensional , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X , Adulto Jovem
9.
Ann Endocrinol (Paris) ; 78 Suppl 1: S31-S40, 2017 Oct.
Artigo em Francês | MEDLINE | ID: mdl-29157487

RESUMO

The endocrine and exocrine functions of the gonads are controlled by the gonadotrope axis, whose master regulator is the hypothalamic decapeptide GnRH. The Kisspeptin/Neurokinin B (Kp/NkB) neuronendocrine system is the main physiologic regulator of GnRH neurons. The Kp/NkB system is currently considered the key mediator for the hypothalamic negative feedback exerted by sex steroids and prolactin, as well as by various metabolic signals. Intrinsic alterations or regulatory abnormalities of Kp/NkB system lead to various gonadotrope axis puberty and fertility dysfunctions. Molecular inactivations of Kp/NkB system actors are associated with some forms of congenital hypogonadotropic hypogonadism without anosmia. The Kp/NkB System is also involved in a few forms of precocious puberty. Finally, the Kp/NKB system is also implicated in gonadotrope axis alterations leading to functional hypothalamic amenorrhea or hyperprolactinemia. NkB is particularly and directly involved in vasomotor menopausal hot flushes mechanism. Various Kp/NkB agonist/antagonist compounds have been developed during the last ten years, and are currently being evaluated in humans. These molecules have potential applications not only in rare genetic diseases with Kp/NkB alterations, but also in various gonadotrope axis-related diseases or in vitro fertilization. The administration of NkB antagonists in menopausal women represents a real therapeutic advance because of their impressive effect in controlling vasomotor menopausal hot flushes.


Assuntos
Hormônio Liberador de Gonadotropina/análogos & derivados , Hormônio Liberador de Gonadotropina/uso terapêutico , Gônadas/fisiologia , Antagonistas de Hormônios/uso terapêutico , Sistema Hipotálamo-Hipofisário/fisiologia , Sistema Hipófise-Suprarrenal/fisiologia , Animais , Feminino , Gonadotrofos/metabolismo , Hormônio Liberador de Gonadotropina/agonistas , Hormônio Liberador de Gonadotropina/antagonistas & inibidores , Gônadas/efeitos dos fármacos , Gônadas/metabolismo , Humanos , Hipogonadismo/terapia , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Sistema Hipotálamo-Hipofisário/metabolismo , Kisspeptinas/agonistas , Kisspeptinas/antagonistas & inibidores , Kisspeptinas/metabolismo , Masculino , Menopausa/efeitos dos fármacos , Neurocinina B/agonistas , Neurocinina B/antagonistas & inibidores , Neurocinina B/metabolismo , Sistema Hipófise-Suprarrenal/efeitos dos fármacos , Sistema Hipófise-Suprarrenal/metabolismo , Maturidade Sexual/efeitos dos fármacos , Maturidade Sexual/fisiologia
10.
Klin Monbl Augenheilkd ; 234(4): 561-563, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28147402

RESUMO

Without appropriate treatment, Group A streptococcal infections can lead to post-streptococcal syndrome, including post-streptococcal uveitis. This should be kept in mind in young patients with acute bilateral non-granulomatous anterior uveitis, in order to avoid ocular and systemic complications. We report two cases of bilateral post-streptococcal anterior uveitis, in young men, of respectively 20 and 16 years old, that presented to Jules Gonin Eye Hospital.


Assuntos
Antibacterianos/administração & dosagem , Infecções Estreptocócicas/diagnóstico , Infecções Estreptocócicas/tratamento farmacológico , Uveíte Supurativa/diagnóstico , Uveíte Supurativa/tratamento farmacológico , Administração Oftálmica , Adolescente , Diagnóstico Diferencial , Humanos , Masculino , Doenças Raras/diagnóstico , Doenças Raras/tratamento farmacológico , Doenças Raras/microbiologia , Infecções Estreptocócicas/microbiologia , Resultado do Tratamento , Uveíte Supurativa/microbiologia
11.
J Clin Endocrinol Metab ; 101(5): 2099-104, 2016 05.
Artigo em Inglês | MEDLINE | ID: mdl-27003306

RESUMO

CONTEXT: Premature ovarian insufficiency (POI) may be secondary to chemotherapy, radiotherapy, or environmental factors. Genetic causes are identified in 20-25% of cases, but most POI cases remain idiopathic. OBJECTIVE: This study aimed to identify new genes involved in POI and to characterize the implication of CPEB1 gene in POI. DESIGN AND SETTING: This was a case report and cohort study replicate conducted in academic medical centers. PATIENTS AND METHODS: A deletion including CPEB1 gene was first identified in a patient with primary amenorrhea. Secondly, 191 sporadic POI cases and 68 familial POI cases were included. For each patient, karyotype was normal and FMR1 premutation was excluded. Search for CPEB1 deletions was performed by quantitative multiplex PCR of short fluorescent fragments or DNA microarray analysis. Gene sequencing of CPEB1 was performed for 95 patients. RESULTS: We identified three patients carrying a microdeletion in band 15q25.2. The proximal breakpoint, for the three patients, falls within a low-copy repeat region disrupting the CPEB1 gene, which represents a strong candidate gene for POI as it is known to be implicated in oocyte meiosis. No mutation was identified by sequencing CPEB1 gene. Therefore, heterozygous deletion of CPEB1 gene leading to haploinsufficiency could be responsible for POI in humans. CONCLUSION: Microdeletions of CPEB1 were identified in 1.3% of patients with POI, whereas no mutation was identified. This microdeletion is rare but recurrent as it is mediated by nonallelic homologous recombination due to the existence of low-copy repeats in the region. This result demonstrates the importance of DNA microarray analysis in etiological evaluation and counseling of patients with POI.


Assuntos
Deleção de Genes , Menopausa Precoce/genética , Insuficiência Ovariana Primária/genética , Fatores de Transcrição/genética , Fatores de Poliadenilação e Clivagem de mRNA/genética , Adulto , Estudos de Coortes , Feminino , Humanos , Mutação
12.
Gynecol Obstet Fertil ; 44(3): 181-6, 2016 Mar.
Artigo em Francês | MEDLINE | ID: mdl-26966035

RESUMO

Prolactin is a major hormone, involved in gonadotroph axis regulation. Hyperprolactinemia induces gonadotropin deficiency and therefore hypogonadotropic hypogonadism. It should be suspected in front of menstrual cycle abnormalities, infertility and/or galactorrhea. If drugs and/or PRL adenoma represent the vast majority of causes of hyperprolactinemia, other etiologies and misleading diagnosis of hyperprolactinemia should be searched for. After eliminating a pregnancy, in women of childbearing age, the first step is to interpret the result of hyperprolactinemia, according to the assay technique used. Indeed, the major active form of prolactin is the 23kDA non-glycosylated prolactin. However, some assays interfere with macroprolactinemia, an inactive form of prolactin, including glycosylated prolactin bound to an IgG immunoglobulin. Its presence in the serum is misleading as it may induce increased levels of prolactin, usually below 100 ng/mL. The diagnosis of macroprolactinemia has major issues as pituitary MRI does not need to be performed. Furthermore, neither treatment nor follow-up of patients with macroprolactinemia are necessary. It should be suspected in the presence of normal menstrual cycles. Drugs inducing hyperprolactinemia usually raise prolactin levels below 100 ng/mL. If prolactin level is higher than 250 ng/mL, the main diagnosis is pituitary macro-adenoma. If prolactin ranges between 100 and 250 ng/mL, it is usually related to a micro-adenoma or a necrotic macro-adenoma. A mixed PRL/GH should always be suspected. If prolactin level is below 150 ng/mL, in the presence of a large hypothalamic-pituitary tumor, the major diagnosis is hyperprolactinemia due to pituitary disconnection. Ectopic secretions of prolactin remain very rare. A new etiology of hyperprolactinemia is loss of function mutation of prolactin receptor.


Assuntos
Hiperprolactinemia/diagnóstico , Hiperprolactinemia/etiologia , Adenoma/complicações , Erros de Diagnóstico , Feminino , Humanos , Hipogonadismo , Imageamento por Ressonância Magnética , Ciclo Menstrual , Mutação , Hipófise/diagnóstico por imagem , Neoplasias Hipofisárias/complicações , Gravidez , Prolactina/análogos & derivados , Prolactina/sangue , Receptores da Prolactina/genética
13.
Eur J Endocrinol ; 173(6): 819-26, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26392472

RESUMO

BACKGROUND: MEN1, which is secondary to the mutation of the MEN1 gene, is a rare autosomal-dominant disease that predisposes mutation carriers to endocrine tumors. Most studies demonstrated the absence of direct genotype-phenotype correlations. The existence of a higher risk of death in the Groupe d'étude des Tumeurs Endocrines-cohort associated with a mutation in the JunD interacting domain suggests heterogeneity across families in disease expressivity. This study aims to assess the existence of modifying genetic factors by estimating the intrafamilial correlations and heritability of the six main tumor types in MEN1. METHODS: The study included 797 patients from 265 kindred and studied seven phenotypic criteria: parathyroid and pancreatic neuroendocrine tumors (NETs) and pituitary, adrenal, bronchial, and thymic (thNET) tumors and the presence of metastasis. Intrafamilial correlations and heritability estimates were calculated from family tree data using specific validated statistical analysis software. RESULTS: Intrafamilial correlations were significant and decreased along parental degrees distance for pituitary, adrenal and thNETs. The heritability of these three tumor types was consistently strong and significant with 64% (s.e.m.=0.13; P<0.001) for pituitary tumor, 65% (s.e.m.=0.21; P<0.001) for adrenal tumors, and 97% (s.e.m.=0.41; P=0.006) for thNETs. CONCLUSION: The present study shows the existence of modifying genetic factors for thymus, adrenal, and pituitary MEN1 tumor types. The identification of at-risk subgroups of individuals within cohorts is the first step toward personalization of care. Next generation sequencing on this subset of tumors will help identify the molecular basis of MEN1 variable genetic expressivity.


Assuntos
Neoplasias das Glândulas Suprarrenais/genética , Neoplasias Brônquicas/genética , Neoplasia Endócrina Múltipla Tipo 1/genética , Tumores Neuroendócrinos/genética , Neoplasias Pancreáticas/genética , Neoplasias das Paratireoides/genética , Neoplasias Hipofisárias/genética , Neoplasias do Timo/genética , Adolescente , Neoplasias das Glândulas Suprarrenais/epidemiologia , Adulto , Distribuição por Idade , Neoplasias Brônquicas/epidemiologia , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Predisposição Genética para Doença , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Tumores Neuroendócrinos/epidemiologia , Neoplasias Pancreáticas/epidemiologia , Neoplasias das Paratireoides/epidemiologia , Linhagem , Neoplasias Hipofisárias/epidemiologia , Neoplasias do Timo/epidemiologia , Adulto Jovem
14.
J Clin Endocrinol Metab ; 100(4): 1568-77, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25594862

RESUMO

CONTEXT: Multiple endocrine neoplasia Type-1 (MEN1) in young patients is only described by case reports. OBJECTIVE: To improve the knowledge of MEN1 natural history before 21 years old. METHODS: Obtain a description of the first symptoms occurring before 21 years old (clinical symptoms, biological or imaging abnormalities), surgical outcomes related to MEN1 Neuro Endocrine Tumors (NETs) occurring in a group of 160 patients extracted from the "Groupe d'étude des Tumeurs Endocrines" MEN1 cohort. RESULTS: The first symptoms were related to hyperparathyroidism in 122 cases (75%), pituitary adenoma in 55 cases (34%), nonsecreting pancreatic tumor (NSPT) in 14 cases (9%), insulinoma in 20 cases (12%), gastrinoma in three cases (2%), malignant adrenal tumors in 2 cases (1%), and malignant thymic-NET in one case (1%). Hyperparathyrodism was the first lesion in 90 cases (56%). The first symptoms occurred before 10 years old in 22 cases (14%) and before 5 years old in five cases (3%). Surgery was performed before age 21 in 66 patients (41%) with a total of 74 operations: pituitary adenoma (n = 9, 16%), hyperparathyroidism (n = 38, 31%), gastrinoma (n = 1, 33%), NSPT (n = 5, 36%), and all cases of insulinoma, adrenal tumors, and thymic-NET. One patient died before age 21 due to a thymic-NET. Overall, lesions were malignant in four cases. CONCLUSIONS: Various MEN1 lesions occurred frequently before 21 years old, but mainly after 10 years of age. Rare, aggressive tumors may develop at any age. Hyperparathyroidism was the most frequently encountered lesion but was not always the first biological or clinical abnormality to appear during the course of MEN1.


Assuntos
Neoplasia Endócrina Múltipla Tipo 1/epidemiologia , Adenoma/diagnóstico , Adenoma/epidemiologia , Adolescente , Neoplasias das Glândulas Suprarrenais/diagnóstico , Neoplasias das Glândulas Suprarrenais/epidemiologia , Adulto , Idade de Início , Criança , Pré-Escolar , Estudos de Coortes , Feminino , França/epidemiologia , Humanos , Lactente , Insulinoma/diagnóstico , Insulinoma/epidemiologia , Masculino , Neoplasia Endócrina Múltipla Tipo 1/diagnóstico , Tumores Neuroendócrinos/diagnóstico , Tumores Neuroendócrinos/epidemiologia , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/epidemiologia , Neoplasias Hipofisárias/diagnóstico , Neoplasias Hipofisárias/epidemiologia , Adulto Jovem
15.
Ann Endocrinol (Paris) ; 76(6 Suppl 1): S39-50, 2015 Oct.
Artigo em Francês | MEDLINE | ID: mdl-26776288

RESUMO

Pregnancy is an immunological paradox that implies that a semi-allogeneic fetus is not rejected by the maternal immune system, from implantation of the embryo to delivery. Progesterone (P4), estradiol (E2) and human chorionic gonadotropin (hCG), contribute to the transformation of immune cells in a transient tolerance state, necessary to the maintenance of pregnancy. The effects of pregnancy hormones depend probably of their maternal plasma level. hCG is dangerous at high concentrations because it can stimulate autoantibodies production, whereas in physiological concentrations, hCG, P4 and E2 upregulate immune response expanding regulatory T and B cells, allowing the fetus to grow within the maternal uterus in a protective environment. A second example of fetal-maternal relation found recently is the role of maternal nutrition on development of the fetal hypothalamic neurons. Experiments in mice fed on a high fat diet reveal a critical timing when altered maternal metabolism affect formation of hypothalamic neurocircuits of the offspring and predispose him to long-term metabolic disorders.


Assuntos
Gonadotropina Coriônica/fisiologia , Estradiol/fisiologia , Troca Materno-Fetal/fisiologia , Progesterona/fisiologia , Animais , Doenças Autoimunes , Feminino , Humanos , Hipotálamo/embriologia , Imunidade , Camundongos , Gravidez
16.
Rev Med Suisse ; 10(426): 846-50, 852-3, 2014 Apr 16.
Artigo em Francês | MEDLINE | ID: mdl-24834642

RESUMO

Adverse food reactions can be classified into two main categories depending on wether an immune mechanism is involved or not. The first category includes immune mediated reactions like IgE mediated food allergy, eosinophilic oesophagitis, food protein-induced enterocolitis syndrome and celiac disease. The second category implies non-immune mediated adverse food reactions, also called food intolerances. Intoxications, pharmacologic reactions, metabolic reactions, physiologic, psychologic or reactions with an unknown mechanism belong to this category. We present a classification of adverse food reactions based on the pathophysiologic mechanism that can be useful for both diagnostic approach and management.


Assuntos
Hipersensibilidade Alimentar/diagnóstico , Alimentos/efeitos adversos , Doença Celíaca/imunologia , Esofagite Eosinofílica/imunologia , Hipersensibilidade Alimentar/imunologia , Humanos , Imunoglobulina E/imunologia
17.
Ann Endocrinol (Paris) ; 75 Suppl 1: S13-20, 2014 Oct.
Artigo em Francês | MEDLINE | ID: mdl-25617918

RESUMO

Men reproductive health has long been ignored although it is responsible for 50% of couple's infertility. However, in recent years, the understanding of endocrine physiology underlying testis development and spermatogenesis has enabled the development of new therapeutic strategies. Some concern the management of male infertility. Others are dealing with finding an effective male contraceptive. In this review, we first present the management of infertility, in patients with congenital hypogonadotropic hypogonadism. We then describe the major improvements for Klinefelter patient's infertility. Finally, we review the different hormonal and non-hormonal methods for male contraception, currently in development. Efficacy and safety of the some non-hormonal methods remain to be demonstrated so far in humans.


Assuntos
Infertilidade Masculina/terapia , Anticoncepcionais Masculinos , Hormônio Foliculoestimulante/uso terapêutico , Gonadotropinas Hipofisárias/fisiologia , Hormônios/fisiologia , Humanos , Hipogonadismo/complicações , Hipogonadismo/terapia , Hipotálamo/fisiologia , Infertilidade Masculina/tratamento farmacológico , Infertilidade Masculina/etiologia , Síndrome de Klinefelter/complicações , Síndrome de Klinefelter/terapia , Hormônio Luteinizante/uso terapêutico , Masculino , Hipófise/fisiologia , Injeções de Esperma Intracitoplásmicas , Espermatogênese , Testículo/embriologia , Testículo/crescimento & desenvolvimento , Testículo/fisiologia , Testosterona/uso terapêutico
18.
Arch Pediatr ; 20(7): 817-22, 2013 Jul.
Artigo em Francês | MEDLINE | ID: mdl-23727374

RESUMO

Amenorrhea in adolescents can be primary, with or without breast development, or secondary. Whether amenorrhea is primary or secondary, height, body mass index, food intake, the level of physical activity per week, the presence of hirsutism or galactorrhea, pelvic pain and past history of intercourse need to be investigated. Initially, blood tests should include hCG, FSH, estradiol, testosterone and prolactin serum levels. This screening will discriminate between hypogonadotropic hypogonadism and amenorrhea from primary ovarian insufficiency (POI). In case of primary amenorrhea, hypogonadism may be due to congenital hypogonadotropic hypogonadism (HH) or more rarely acquired HH. If FSH is elevated, amenorrhea is due to primary ovarian failure, mainly related to Turner syndrome. If pubertal development is normal, a pelvic ultrasound should be performed. It may visualize a hindering of menses output or less frequently an absence of uterus, as in Rokitansky syndrome or androgen insentivity syndrome. The most frequent etiologies of secondary amenorrhea are polycystic ovarian syndrome (PCOS), functional hypothalamic amenorrhea and less frequently POI and hyperprolactinemia. The differential diagnoses of PCOS are late-onset 21-hydroxylase deficiency and very rare ovarian or adrenal tumors. When contraception is not necessary, hormonal replacement therapy, including estrogen and progestins should be administered in order to avoid hypoestrogenism. In case of PCOS, sequential progestins can be prescribed. A contraceptive pill can be considered when contraception is needed and/or when hyperandrogenism needs to be treated.


Assuntos
Amenorreia/diagnóstico , Amenorreia/etiologia , Adolescente , Amenorreia/tratamento farmacológico , Síndrome de Cushing/diagnóstico , Árvores de Decisões , Feminino , Humanos , Hipogonadismo/diagnóstico , Síndrome do Ovário Policístico/diagnóstico , Insuficiência Ovariana Primária/diagnóstico , Puberdade Tardia
19.
Arch Pediatr ; 20(8): 910-4, 2013 Aug.
Artigo em Francês | MEDLINE | ID: mdl-23727373

RESUMO

Menometrorrhagia is a common symptom in adolescents. It is idiopathic in most cases. In case of menometrorrhagia, it is necessary to exclude a pregnancy, a disorder of hemostasis, particularly the von Willebrand disease, as it represents the most common inherited disorder, and more rarely a chronic disease or an endocrinopathy. History of the bleedings, menstrual blood loss quantification by the Higham score and tolerance of the bleedings (blood pressure) should be evaluated. Laboratory testing includes hCG, ferritin level, a complete blood count, a prothrombin time, an activated partial thromboplastin. Management of menometrorrhagia is related to the severity of the blood loss. It associates antifibrinolytics or non-steroidal anti-inflammatory agents (NSAIDS) with hormonal treatments, such as estrogen-progestin oral contraceptive pill or cyclic oral progestins. Primary or functional dysmenorrhea concerns 40 to 90% of the teenagers and represents a frequent cause of school absenteeism. Management of primary dysmenorrhea is primarily based on a treatment by NSAIDS. In case of its inefficacy or if contraception is needed hormonal treatments, such as estrogen-progestin combined pill should be prescribed. It is very important when pelvic pain is chronic and not soothed by simple medications to look for a secondary dysmenorrhea, mainly endometriosis. In such cases, pelvic magnetic resonance imaging should be performed.


Assuntos
Dismenorreia/etiologia , Metrorragia/etiologia , Adolescente , Anti-Inflamatórios não Esteroides/uso terapêutico , Antifibrinolíticos/uso terapêutico , Transtornos da Coagulação Sanguínea/complicações , Anticoncepcionais Orais Hormonais/uso terapêutico , Doenças do Sistema Endócrino/complicações , Endometriose/complicações , Feminino , Humanos , Gravidez
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