RESUMEN
Congenital hypopituitarism is a genetically heterogeneous condition that is part of a spectrum disorder that can include holoprosencephaly. Heterozygous mutations in SIX3 cause variable holoprosencephaly in humans and mice. We identified two children with neonatal hypopituitarism and thin pituitary stalk who were doubly heterozygous for rare, likely deleterious variants in the transcription factors SIX3 and POU1F1. We used genetically engineered mice to understand the disease pathophysiology. Pou1f1 loss-of-function heterozygotes are unaffected; Six3 heterozygotes have pituitary gland dysmorphology and incompletely ossified palate; and the Six3+/-; Pou1f1+/dw double heterozygote mice have a pronounced phenotype, including pituitary growth through the palate. The interaction of Pou1f1 and Six3 in mice supports the possibility of digenic pituitary disease in children. Disruption of Six3 expression in the oral ectoderm completely ablated anterior pituitary development, and deletion of Six3 in the neural ectoderm blocked the development of the pituitary stalk and both anterior and posterior pituitary lobes. Six3 is required in both oral and neural ectodermal tissues for the activation of signaling pathways and transcription factors necessary for pituitary cell fate. These studies clarify the mechanism of SIX3 action in pituitary development and provide support for a digenic basis for hypopituitarism.
Asunto(s)
Holoprosencefalia , Hipopituitarismo , Niño , Humanos , Heterocigoto , Hipopituitarismo/genética , Factores de Transcripción/genética , Mutación , Hormonas Hipofisarias/genética , Factor de Transcripción Pit-1/genéticaRESUMEN
Pituitary hormone deficiency occurs in â¼1:4,000 live births. Approximately 3% of the cases are due to mutations in the alpha isoform of POU1F1, a pituitary-specific transcriptional activator. We found four separate heterozygous missense variants in unrelated individuals with hypopituitarism that were predicted to affect a minor isoform, POU1F1 beta, which can act as a transcriptional repressor. These variants retain repressor activity, but they shift splicing to favor the expression of the beta isoform, resulting in dominant-negative loss of function. Using a high-throughput splicing reporter assay, we tested 1,070 single-nucleotide variants in POU1F1. We identified 96 splice-disruptive variants, including 14 synonymous variants. In separate cohorts, we found two additional synonymous variants nominated by this screen that co-segregate with hypopituitarism. This study underlines the importance of evaluating the impact of variants on splicing and provides a catalog for interpretation of variants of unknown significance in POU1F1.
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Ensayos Analíticos de Alto Rendimiento/métodos , Hipopituitarismo/patología , Mutación , Hormonas Hipofisarias/deficiencia , Empalme del ARN/genética , Factor de Transcripción Pit-1/genética , Adolescente , Adulto , Niño , Preescolar , Humanos , Hipopituitarismo/etiología , Hipopituitarismo/metabolismo , Masculino , LinajeRESUMEN
The SFE-AFCE-SFMN 2022 consensus deals with the management of thyroid nodules, a symptom that is a frequent reason for consultation in endocrinology. Thyroid nodules are very common and mostly benign. Thyroid ultrasound and thyroid fine-needle aspiration biopsy (FNAB) are the reference tests for the analysis of these nodules. The aim of this article is to describe for the cytopathologist the key points of the SFE-AFCE-SFMN 2022 consensus involving thyroid cytology: the indications for thyroid FNAB, the technique and analysis, and the management (treatment, follow-up) following this cytological screening examination, a key element in the management of the thyroid nodule.
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Neoplasias de la Tiroides , Nódulo Tiroideo , Humanos , Nódulo Tiroideo/diagnóstico , Nódulo Tiroideo/terapia , Nódulo Tiroideo/patología , Neoplasias de la Tiroides/diagnóstico , Neoplasias de la Tiroides/terapia , Neoplasias de la Tiroides/patología , Consenso , Biopsia con Aguja Fina/métodos , Estudios RetrospectivosRESUMEN
BACKGROUND: Previous quantitative studies have shown a reduced quality of life in patients treated for craniopharyngioma (CP). However, few have assessed their sexual quality of life and other issues related to patient intimacy have not yet been addressed. Standardized questionnaires limit the approach to sexuality and the exploration of patient experiences. A qualitative study, which allows in-depth analysis, may represent an interesting approach to explore intimacy in women with a history of CP. OBJECTIVE: To assess the impact of a CP history on femininity and relationships in women. DESIGN AND PATIENTS: A qualitative study with semi-structured interviews was conducted with 15 adult women treated for CP during childhood, adolescence or at childbearing age up to 40 years of age. Interviews were audio recorded, anonymized and transcribed literally. Data analysis was carried out with an inductive approach according to the grounded theory method. RESULTS: Three main themes were identified: (a) apparent changes leading to altered self-perception that may impact on femininity and generate lower self-esteem; (b) managing the hidden disabilities of the disease inducing a need for permanent control; and (c) building parenthood and couple relationships: coping with sexual dysfunction and infertility. CONCLUSIONS: Our study highlighted alterations in self-perception and femininity due to body change and disability resulting from CP treatment, impacting both couple and social relationships. Interviewing women who underwent CP surgery at different ages highlighted specific needs and different expectations of medical professionals which emphasize the importance of offering both global and personalized care.
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Craneofaringioma , Neoplasias Hipofisarias , Adolescente , Adulto , Femenino , Feminidad , Humanos , Percepción , Calidad de VidaRESUMEN
PURPOSE: Surgical indications for pituitary tumors during pregnancy are rare, and are derived from a balance between expected benefits, particularly for maternal benefits, and anesthetic/surgical risks. METHODS: A literature review was performed to define the optimal surgical indications for pituitary adenomas (PA) and other pituitary tumors during pregnancy. RESULTS: Main benefits are expected in case of critical visual impairment and/or life-threatening endocrine disturbances. Multidisciplinary patient management is systematically required although nonobstetric surgery presents a reasonable risk during pregnancy. The risks of congenital malformation during the first trimester and those of premature birth during the third trimester make the second trimester the optimal period for surgery. In prolactin-secreting, nonsecreting, GH- and TSH-secreting PAs, transsphenoidal surgery (TS) is recommended in cases involving severe visual impairment, characterized by severe visual field deficit, visual acuity impairment, and abnormal optical coherence tomography findings, and when no other medical alternatives are possible and/or sufficient. Uncontrolled and severe Cushing's disease (CD) during pregnancy increases both maternal and fetal morbimortality, thus justifying TS or sometimes dopamine agonist therapy as a safer alternative. Finally, metyrapone, ketoconazole, or bilateral adrenalectomy could be recommended in certain cases after the failure of medical therapies and/or TS. Surgery is also required for suprasellar meningiomas, craniopharyngiomas, and pituitary cysts in the case of severe visual deficit. CONCLUSION: Surgical indications for pituitary tumors are rare during pregnancy; therefore, surgery should be avoided when possible. Further, the second trimester should be considered as the optimal surgical period. Severe visual disturbance and uncontrolled CD are the main surgical indications during pregnancy.
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Neoplasias Hipofisarias/cirugía , Craneofaringioma/cirugía , Femenino , Humanos , Meningioma/cirugía , Hipersecreción de la Hormona Adrenocorticotrópica Pituitaria (HACT)/cirugía , EmbarazoRESUMEN
Steroidogenic acute regulatory protein (StAR) mutations are the most frequent aetiologies of congenital lipoid adrenal hyperplasia (CLAH). Phenotypes may vary, and puberty may be absent in affected individuals. To date, only two pregnancies have been described in 46,XX CLAH patients with StAR mutations; these patients exhibited ovarian steroidogenesis along with spontaneous puberty and menarche and normal menses. The patient described here presented with CLAH caused by the homozygous (unreported, 1 bp) deletion c.719del in the StAR gene, which was diagnosed after acute adrenal insufficiency when the patient was 10 days old. The patient did not undergo spontaneous puberty, so puberty was induced by HRT when the patient was 13 years old. At the age of 25 years, the patient was referred to our reproductive unit because she desired to conceive. An initial cycle of clomiphene, stimulation produced follicular growth with two mature follicles measuring 18 and 15 mm, respectively, but the plasma oestradiol levels remained low (18 pg/ml) and the endometrium was thin (3 mm). Pregnancy was finally achieved after ovarian stimulation, IVF and transfer of frozen-thawed embryos after endometrial preparation with HRT. A normal female child was delivered following a 40 weeks' uneventful pregnancy. We therefore report the first IVF pregnancy achieved in a 46,XX CLAH patient homozygous for a StAR mutation, with inadequate ovarian steroidogenesis and no spontaneous puberty.
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Hiperplasia Suprarrenal Congénita/genética , Trastorno del Desarrollo Sexual 46,XY/genética , Fertilización In Vitro , Infertilidad Femenina/genética , Hiperplasia Suprarrenal Congénita/tratamiento farmacológico , Adulto , Trastorno del Desarrollo Sexual 46,XY/tratamiento farmacológico , Femenino , Glucocorticoides/uso terapéutico , Terapia de Reemplazo de Hormonas , Humanos , Infertilidad Femenina/terapia , Mutación , Fosfoproteínas/genética , Embarazo , Resultado del EmbarazoRESUMEN
STUDY QUESTION: What are the prevalence and the outcomes of spontaneous pregnancies (SP) in a large cohort of French women with Turner syndrome (TS)? SUMMARY ANSWER: Amongst 480 women with TS, 27 women (5.6%) had a total of 52 SP, with 30 full-term deliveries for 18 women. WHAT IS KNOWN ALREADY: Primary ovarian insufficiency is a classic feature of TS. So far, few studies have evaluated the rate of SP in these patients. STUDY DESIGN, SIZE, DURATION: The French Ministry of Health set up a National Reference Centre for Rare Growth Disorders (CRMERC), including TS. We studied a cohort of adult TS patients from seven endocrine units (Saint-Antoine, Pitié-Salpêtrière, Bicêtre, Lyon, Marseille, Brest, Reims Hospitals) belonging to this centre, between January 1999 and January 2014. PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 480 adult patients with TS were included. The patients' clinical characteristics, karyotypes and reproductive histories had been collected, after informed consent, in a web database called CEMARA. Our reference population was issued from a database belonging to the French Health Ministry, collecting pregnancy outcomes in the French general population. In order to find predictive characteristics of SP, TS with spontaneous pregnancies were compared with non-pregnant TS patients from our cohort. MAIN RESULTS AND THE ROLE OF CHANCE: There were 27 patients (5.6%) who had a total of 52 SP. The two predictive factors which correlated with occurrence of a SP were spontaneous menarche and mosaic karyotype. The median delay to conception was 6 months (range 0-84). Miscarriage occurred in 16 pregnancies, 30.8% versus 15% in the general French population (P < 0.01). The remaining pregnancy outcomes were legal abortion (n = 2), medical interruption (n = 3), intrauterine fetal death (n = 1) and delivery at term (n = 30). Caesarean section rates were higher than in the general population, respectively 46.7% versus 21% (P < 0.001). Pregnancy-induced hypertensive disorders (PHDs) occurred in four cases (13.3%), including two cases of mild pre-eclampsia (6.7%). Neither aortic root dilatation nor aortic dissection were observed. The median birthweight was 3030 g (range 2020-3460). Two cases of TS were identified in the 17 daughters issued from this cohort. LIMITATIONS, REASONS FOR CAUTION: It would have been interesting to evaluate AMH levels and SP occurrence, as a predictive factor. Unfortunately, hormonal measurements were missing for some patients. Prospective studies are necessary to display prognostic values of AMH for SP and thus better target fertility preservation programmes in TS patients. WIDER IMPLICATIONS OF THE FINDINGS: This study suggests that pregnancy outcomes in SPs are more favourable than those after oocyte donation in TS patients. However, the risk of fetal chromosomal abnormalities remains high. Our study will be useful in order to give patients with TS, their families, paediatricians and physicians involved in reproduction, better counselling concerning their fertility. STUDY FUNDING/COMPETING INTERESTS: Funding was provided by the Association pour la recherche Claude Bernard, Paris France All authors claim no competing interests. TRIAL REGISTRATION NUMBER: NA.
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Fertilidad , Complicaciones Cardiovasculares del Embarazo/fisiopatología , Insuficiencia Ovárica Primaria/etiología , Síndrome de Turner/fisiopatología , Adolescente , Adulto , Anciano , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Francia/epidemiología , Humanos , Menarquia , Persona de Mediana Edad , Mosaicismo , Embarazo , Complicaciones Cardiovasculares del Embarazo/genética , Resultado del Embarazo , Índice de Embarazo , Sistema de Registros , Historia Reproductiva , Tiempo para Quedar Embarazada , Síndrome de Turner/genética , Adulto JovenRESUMEN
STUDY QUESTION: What is the exact prevalence of Kisspeptin Receptor (KISS1R) mutations in the population of patients with normosmic congenital hypogonadotrophic hypogonadism (nCHH) by comparison with other genes, involved in gonadotrophin-releasing hormone (GnRH) release or action? SUMMARY ANSWER: KISS1R mutants are responsible for the nCHH phenotype in only a small minority of cases and were less prevalent than GnRH Receptor (GNRHR) mutations. WHAT IS KNOWN ALREADY: The respective prevalence of each of the genetic causes of nCHH is unclear. Large series of patients are very rare and suffer from heterogeneity of the population of CHH studied. STUDY DESIGN, SIZE, DURATION: Patients with nCHH were consecutively enrolled in a single French referral centre and were gradually tested for KISS1R between January 2006 and April 2015. PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 603 patients with nCHH (399 men and 204 women) were diagnosed at the Bicêtre Hospital and underwent KISS1R analysis. The GNRHR, tachykinin receptor 3 (TACR3), gonadotrophin-releasing hormone 1 (GNRH1), tachykinin 3 (TAC3) and KISS1 genes were also sequenced. Functional characterization of KISS1R mutations included a study of signal transduction using a reporter gene (serum response element-luciferase (SRE-Luc) involved in the mitogen-activated protein (MAP) kinase pathway. MAIN RESULTS AND THE ROLE OF CHANCE: We detected 15 KISS1R variants (10 novel), in 12 of the 603 patients (2.0%, 95% CI [0.9-3.1]. KISS1R mutations were less prevalent than GNRHR (4.7%) and TACR3 (2.6%) mutations but more prevalent than GNRH1 (1.5%), TAC3 (1.0%) and KISS1 (0%) mutations. KISS1R mutants were present in the biallelic state in 8 of the 12 patients concerned. Among 5 men with biallelic KISS1R mutations, 4 had either micropenis or cryptorchidism. In vitro analysis of the 5 new variants present in the biallelic state (C95W, Y103*, C115W, P176R and A287E) showed a loss of function. LIMITATIONS, REASONS FOR CAUTION: The prevalence of TACR3, GNRH1, TAC3 and KISS1 mutations was calculated from a smaller number of nCHH patients than KISS1R and GNRHR. This should prompt caution concerning the reported prevalence of mutations in these four genes. WIDER IMPLICATIONS OF THE FINDINGS: We show that KISS1R mutants are responsible for the nCHH phenotype in only a small minority of cases. Together, the genes analysed here were mutated in fewer than 15% of patients, suggesting a role of other genes in nCHH. The presence of cryptorchidism and/or micropenis in the majority of men with biallelic KISS1R mutations strongly suggests that this gene is essential for prenatal GnRH secretion. STUDY FUNDING, COMPETING INTERESTS: This work was supported in part by grants from Paris-Sud University (Bonus Qualité Recherche, and Attractivité grants) to J.B., French Ministry of Health, Hospital Clinical Research Program on Rare Diseases. Assistance Publique Hôpitaux de Paris, Programme Hospitalier de Recherche Clinique (PHRC # P081212 HYPOPROTEO) to J.Y. C.P. was supported by student fellowships 'Année Recherche' from Agence Régionale de Santé Provence Alpes Côtes d'Azur. The authors have nothing to disclose.
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Hipogonadismo/genética , Mutación , Receptores de Kisspeptina-1/genética , Adolescente , Adulto , Análisis Mutacional de ADN , Femenino , Estudios de Asociación Genética , Humanos , Sistema de Señalización de MAP Quinasas , Masculino , Persona de Mediana Edad , Receptores LHRH/genética , Receptores de Neuroquinina-3/genética , Transducción de SeñalRESUMEN
OBJECTIVE: Predicting the outcome of patients operated on for Cushing's disease (CD) is a challenging task. Our objective was to assess the accuracy of immediate postsurgical plasma cortisol, desmopressin test and the coupled dexamethasone-desmopressin test (CDDT) as predictors of outcome. DESIGN AND PATIENTS: Sixty-seven patients with initial remission and a minimal postsurgical follow-up greater than 18 months were included in this retrospective bicentre study. MEASUREMENTS: Follow-up included 3-6 months followed by yearly 24-h urinary-free cortisol, ACTH and cortisol plasmatic levels, a 1-mg overnight dexamethasone suppression test (1-mg DST), desmopressin test and the CDDT. ROC curves were performed to define the optimal threshold of immediate postsurgical cortisol level and 3- to 6-month desmopressin test and CDDT, as predictors of final outcome in comparison with classical biological markers of recurrence. RESULTS: Eleven patients presented recurrence. The patient's median follow-up was 52 months (range, 18-180). As early predictors of outcome, immediate postsurgical plasma cortisol level <35 nmol/l predicted the lack of recurrence with 93% negative predictive value (NPV), whereas predictive positive value (PPV) was 25%. During the follow-up, the CDDT was more precise than the desmopressin test in predicting the lack of recurrence (100% NPV) when performed in the first 3 years after surgery. Positivity of the CDDT was defined based on ROC curves by ACTH and cortisol increments >50%. The CDDT was highly reproducible, as the same response was observed every year in 91% of the patients. CONCLUSIONS: Adding the CDDT the first 3 years after surgery to immediate postsurgical cortisol evaluation should allow obtaining an optimal follow-up management of patients operated for Cushing's disease.
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Desamino Arginina Vasopresina/sangre , Dexametasona/sangre , Hidrocortisona/sangre , Hipersecreción de la Hormona Adrenocorticotrópica Pituitaria (HACT)/sangre , Hipersecreción de la Hormona Adrenocorticotrópica Pituitaria (HACT)/cirugía , Adolescente , Hormona Adrenocorticotrópica/sangre , Adulto , Anciano , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Hipersecreción de la Hormona Adrenocorticotrópica Pituitaria (HACT)/patología , Periodo Posoperatorio , Valor Predictivo de las Pruebas , Curva ROC , Recurrencia , Inducción de Remisión , Estudios Retrospectivos , Adulto JovenRESUMEN
CONTEXT: Diagnosis announcement of a chronic disease is a crucial moment for patients as well as for their families and an important step in the management of severe conditions such as rare endocrine diseases. Little is known of how diagnosis is communicated to patients and families. The FIRENDO network was created by the third French Plan for Rare Diseases, to promote autonomy, care and research on rare endocrine diseases. OBJECTIVES: The aim of this study was to characterize, for the first time, the experience and needs of patients and/or their parents around the announcement of diagnosis to ensure optimal quality of care. METHODS: A quantitative self-administered survey on diagnosis announcement procedures in rare endocrine diseases was launched in April 2017 by the ad hoc FIRENDO thematic working group in collaboration with its 11 partnering patient associations and support groups. The questionnaire was designed and revised by patient support group representatives, adult and pediatric endocrinologists, psychologists and biologists, all expert in rare endocrine diseases. It was made available on the FIRENDO network website and distributed mainly by email with electronic links on their respective websites to members of all affiliated patient support groups. RESULTS: Questionnaires were filled out by 391 patients and 223 parents (median age of patients: 39 years). The following conditions were associated with at least 30 answers: Addison's disease, classical forms of congenital adrenal hyperplasia (CAH), Russell-Silver syndrome, Cushing's syndrome, acromegaly and craniopharyngioma. Overall, some announcement modalities were judged favorably by patients: physician's empathy, availability and use of clear terms, and presence of family at the time of announcement. However, a lack of psychological care and information documents was reported, as well as some inadequate procedures such as postal mail announcements. CONCLUSION: This work suggests that better knowledge of the patient's experience is useful for improving the diagnosis announcement of rare endocrine disorders. The main recommendations derived from the survey were the need for several announcement visits, information on patient support groups and reference centers, imperatively avoiding impersonal announcement, and the usefulness of a written accompanying document.
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Hiperplasia Suprarrenal Congénita , Síndrome de Cushing , Enfermedades del Sistema Endocrino , Adulto , Niño , Humanos , Enfermedades Raras/diagnóstico , Enfermedades Raras/terapia , Enfermedades del Sistema Endocrino/diagnóstico , Enfermedades del Sistema Endocrino/terapia , Encuestas y CuestionariosRESUMEN
Pituitary deficiency, or hypopituitarism, is a rare chronic disease. It is defined by insufficient synthesis of one or more pituitary hormones (growth hormone, TSH, ACTH, LH-FSH, prolactin), whether or not associated with arginine vasopressin deficiency (formerly known as diabetes insipidus). In adult patients, it is usually acquired (notably during childhood), but can also be congenital, due to abnormal pituitary development. The present study focuses on congenital pituitary deficiency in adults, from diagnosis to follow-up, including special situations such as pregnancy or the elderly. The clinical presentation is highly variable, ranging from isolated deficit to multiple deficits, which may be part of a syndromic form or not. Diagnosis is based on a combination of clinical, biological (assessment of all hormonal axes), radiological (brain and hypothalamic-pituitary MRI) and genetic factors. Treatment consists in hormonal replacement therapy, adapted according to the period of life and the deficits, which may be progressive. Comorbidities, risk of complications and acute decompensation, and the impact on fertility and quality of life all require adaptative multidisciplinary care and long-term monitoring.
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Hipopituitarismo , Humanos , Hipopituitarismo/diagnóstico , Hipopituitarismo/terapia , Francia/epidemiología , Adulto , Femenino , Embarazo , Terapia de Reemplazo de Hormonas/métodos , Masculino , Anciano , Hipófisis/anomalíasRESUMEN
INTRODUCTION: Given the new therapeutic options in acromegaly, it seemed important to evaluate the outcome of operated acromegalic patients today. OBJECTIVE: To analyse the characteristics and short- and long-term surgical outcome of patients who underwent transsphenoidal surgery for a growth hormone (GH)-secreting adenoma in our centre and to determine predictive factors of remission. DESIGN AND PATIENTS: This retrospective 10-year study included 115 newly diagnosed acromegalic patients operated on at Timone University Hospital, Marseille, France, between 1997 and 2007. MEASUREMENTS: Initial and long-term outcomes were evaluated using stringent and current remission criteria, associating GH nadir after oral glucose tolerance test <0·4 µg/l and normal insulin-like growth factor-1 (IGF-1) at 3 months, and a normal IGF-1 at the end of follow-up (52·4 ± 36·8 months, median 41 months, range 6·7-135·4 months, n = 99). RESULTS: At the end of follow-up, 90·9% of patients had controlled disease. Overall, 49·5% of patients were in long-term remission after surgery alone, and only 2·0% of patients experienced recurrent disease. Multivariate predictors of 3-month remission included mean GH at diagnosis (P = 0·033), tumour invasion (P = 0·013) and surgeon report of incomplete or uncertain macroscopic resection (P = 0·003 and P = 0·047, respectively). Multivariate predictors at diagnosis of long-term remission included mean GH level (P = 0·048), adenoma size (P = 0·007) and absence of pituitary deficit (P = 0·026). CONCLUSIONS: In long-term follow-up after surgery of acromegaly, half of the patients achieved remission after surgery alone and more than 90% had their disease controlled. With stringent 3-month remission criteria, recurrence was rare.
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Acromegalia/terapia , Adenoma/terapia , Agonistas de Dopamina/uso terapéutico , Somatostatina/análogos & derivados , Somatostatina/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del Tratamiento , Adulto JovenRESUMEN
Few studies have assessed the role of cross-sex hormones on psychological outcomes during the period of hormonal therapy preceding sex reassignment surgery in transsexuals. The objective of this study was to assess the relationship between hormonal therapy, self-esteem, depression, quality of life (QoL), and global functioning. This study incorporated a cross-sectional design. The inclusion criteria were diagnosis of gender identity disorder (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision) and inclusion in a standardized sex reassignment procedure. The outcome measures were self-esteem (Social Self-Esteem Inventory), mood (Beck Depression Inventory), QoL (Subjective Quality of Life Analysis), and global functioning (Global Assessment of Functioning). Sixty-seven consecutive individuals agreed to participate. Seventy-three percent received hormonal therapy. Hormonal therapy was an independent factor in greater self-esteem, less severe depression symptoms, and greater "psychological-like" dimensions of QoL. These findings should provide pertinent information for health care providers who consider this period as a crucial part of the global sex reassignment procedure.
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Afecto/efectos de los fármacos , Hormonas Esteroides Gonadales/administración & dosificación , Calidad de Vida/psicología , Autoimagen , Personas Transgénero/psicología , Adulto , Afecto/fisiología , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Over the past decade, the development of ICI (immune checkpoint inhibitors) has constituted a revolution in the treatment of many cancers, but with a specific toxicity profile including endocrine IRAEs (immune-related adverse events). As the indications for these molecules are constantly increasing due to their efficacy, it is important that endocrinologists and oncologists know how to detect, manage and monitor this type of toxicity. Many guidelines and recommendations have been proposed in the last few years for the management of endocrinopathies. French guidelines on immunotherapy-related endocrine IRAEs were published in 2018, with a specific algorithm for hypophysitis and primary adrenal insufficiency (PAI), based on clinical suspicion followed by biochemical and imaging evaluation, and are still relevant today. Here we present the general pathophysiological mechanisms of these toxicities, and discuss the incidence, diagnosis, treatment, progression, management and monitoring of pituitary and adrenal disorders in patients treated by immunotherapy, with emphasis on hypophysitis, which is much more frequent than PAI with this type of molecule. We also highlight several key points, such as the need for emergency treatment by hydrocortisone with the possibility of continuing immunotherapy in these endocrinopathies, and the long-term persistence of corticotropin or adrenal deficiency in most cases, requiring specific "hydrocortisone education". These points should be kept in mind by oncologists and endocrinologists who treat and monitor patients treated by immunotherapy.
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Enfermedades de las Glándulas Suprarrenales , Enfermedades del Sistema Endocrino , Hipofisitis , Neoplasias , Humanos , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Hidrocortisona/efectos adversos , Antígeno CTLA-4 , Enfermedades del Sistema Endocrino/inducido químicamente , Enfermedades del Sistema Endocrino/terapia , Enfermedades de las Glándulas Suprarrenales/inducido químicamente , Enfermedades de las Glándulas Suprarrenales/diagnóstico , Enfermedades de las Glándulas Suprarrenales/terapia , Neoplasias/tratamiento farmacológico , Neoplasias/complicaciones , Hipofisitis/inducido químicamente , Hipofisitis/terapiaRESUMEN
Acromegaly is a rare disease with prevalence of approximately 60 cases per million, slight female predominance and peak onset in adults in the fourth decade. Clinical diagnosis is often delayed by several years due to the slowly progressive onset of symptoms. There are multiple clinical criteria that define acromegaly: dysmorphic syndrome of insidious onset, symptoms related to the pituitary tumor (headaches, visual disorders), general signs (sweating, carpal tunnel syndrome, joint pain, etc.), complications of the disease (musculoskeletal, cardiovascular, pneumological, dental, metabolic comorbidities, thyroid nodules, colonic polyps, etc.) or sometimes clinical signs of associated prolactin hypersecretion (erectile dysfunction in men or cycle disorder in women) or concomitant mass-induced hypopituitarism (fatigue and other symptoms related to pituitary hormone deficiencies). Biological confirmation is based initially on elevated IGF-I and lack of GH suppression on oral glucose tolerance test or an elevated mean GH on repeated measurements. In confirmed cases, imaging by pituitary MRI identifies the causal tumor, to best determine management. In a minority of cases, acromegaly can be linked to a genetic predisposition, especially when it occurs at a young age or in a familial context. The first-line treatment is most often surgical removal of the somatotroph pituitary tumor, either immediately or after transient medical treatment. Medical treatments are most often proposed in patients not controlled by surgical removal. Conformal or stereotactic radiotherapy may be discussed on a case-by-case basis, especially in case of drug inefficacy or poor tolerance. Acromegaly should be managed by a multidisciplinary team, preferably within an expert center such as a reference or skill center for rare pituitary diseases.
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Acromegalia , Hormona de Crecimiento Humana , Neoplasias Hipofisarias , Masculino , Adulto , Humanos , Femenino , Acromegalia/diagnóstico , Acromegalia/etiología , Acromegalia/terapia , Hormona de Crecimiento Humana/uso terapéutico , Hormona de Crecimiento Humana/metabolismo , Neoplasias Hipofisarias/cirugía , Prueba de Tolerancia a la Glucosa , Protocolos ClínicosRESUMEN
INTRODUCTION: Although the impact of sex reassignment surgery on the self-reported outcomes of transsexuals has been largely described, the data available regarding the impact of hormone therapy on the daily lives of these individuals are scarce. AIMS: The objectives of this study were to assess the relationship between hormonal therapy and the self-reported quality of life (QoL) in transsexuals while taking into account the key confounding factors and to compare the QoL levels between transsexuals who have, vs. those who have not, undergone cross-sex hormone therapy as well as between transsexuals and the general population (French age- and sex-matched controls). METHODS: This study incorporated a cross-sectional design that was conducted in three psychiatric departments of public university teaching hospitals in France. The inclusion criteria were as follows: 18 years or older, diagnosis of gender identity disorder (302.85) according to the Diagnostic and Statistical Manual, fourth edition text revision (DSM-IV TR), inclusion in a standardized sex reassignment procedure following the agreement of a multidisciplinary team, and pre-sex reassignment surgery. MAIN OUTCOME MEASURE: QoL was assessed using the Short Form 36 (SF-36). RESULTS: The mean age of the total sample was 34.7 years, and the sex ratio was 1:1. Forty-four (72.1%) of the participants received hormonal therapy. Hormonal therapy and depression were independent predictive factors of the SF-36 mental composite score. Hormonal therapy was significantly associated with a higher QoL, while depression was significantly associated with a lower QoL. Transsexuals' QoL, independently of hormonal status, did not differ from the French age- and sex-matched controls except for two subscales of the SF-36 questionnaire: role physical (lower scores in transsexuals) and general health (lower scores in controls). CONCLUSION: The present study suggests a positive effect of hormone therapy on transsexuals' QoL after accounting for confounding factors. These results will be useful for healthcare providers of transgender persons but should be confirmed with larger samples using a prospective study design.
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Terapia de Reemplazo de Hormonas/métodos , Calidad de Vida , Transexualidad/tratamiento farmacológico , Adulto , Estudios Transversales , Femenino , Humanos , Masculino , Análisis Multivariante , Psicometría , Encuestas y Cuestionarios , Resultado del TratamientoRESUMEN
Transsphenoidal surgery is the first-line treatment for acromegaly. However, several factors can modify surgical remission rates, such as the initial hormone levels, the size and invasiveness of the tumor, and the degree of experience of the surgeon. Physicians treating patients with acromegaly should thus consider how to improve surgical remission rates. As stated in recent guidelines, the major point is to consider that any patient with acromegaly should be referred to an expert neurosurgeon to maximize the chances of surgical sure. The benefits of presurgical medical treatment, mainly using somatostatin receptor ligands (SRLs), given 3 to 6 months before surgery, remain controversial. By normalizing growth hormone and insulin-like growth factor 1 levels, SRLs may improve the overall condition of the patient, thus decreasing anesthetic and surgical complications. By decreasing the tumor size and modifying the consistency of the tumor, SRLs might also make surgical excision easier. This is however theoretical as published data are contradictory on both points, and only limited data support the use of a systematical presurgical medical treatment. The aim of this review is to analyze the potential benefits and pitfalls of using presurgical medical treatment in acromegaly in view of the contradictory literature data. We also attempt to determine the profile of patients who might most benefit from this presurgical medical treatment approach as an individualized therapeutic management of acromegaly.
RESUMEN
Introduction: A gonadectomy is currently recommended in patients with Turner syndrome (TS) and a 45,X/46,XY karyotype, due to a potential risk of gonadoblastoma (GB). However, the quality of evidence behind this recommendation is low. Objective: This study aimed to evaluate the prevalence of GB, its characteristics, as well as its risk factors, according to the type of Y chromosomal material in the karyotype. Methods: Our study within French rare disease centers included patients with TS and a 45,X/46,XY karyotype, without ambiguity of external genitalia. Clinical characteristics of the patients, their age at gonadectomy, and gonadal histology were recorded. The regions of the Y chromosome, the presence of TSPY regions, and the percentage of 45,X/46,XY mosaicism were evaluated. Results: A total of 70 patients were recruited, with a median age of 29.5 years (21.0-36.0) at the end of follow-up. Fifty-eight patients had a gonadectomy, at a mean age of 15 ± 8 years. GB was present in nine cases. Two were malignant, which were discovered at the age of 14 and 32 years, without metastases. Neither the percentage of XY cells within the 45,X/46,XY mosaicism nor the number of TSPY copies was statistically different in patients with or without GB (P = 0.37). However, the entire Y chromosome was frequent in patients with GB (6/9). Conclusions: In our study, including a large number of patients with 45,X/46,XY TS, the prevalence of gonadoblastoma is 12.8%. An entire Y chromosome appears as the main risk factor of GB and should favor early gonadectomy. Significant statement: About 10% of patients with TS have a karyotype containing Y chromosomal material: 45,X/46,XY. Its presence is related to the risk of GB. Therefore, a prophylactic gonadectomy is currently recommended in such patients. However, the quality of evidence is low. Our objective was to evaluate the prevalence of GB according to the type of Y-chromosomal material. We found a prevalence of GB of 12.8% in a cohort of 70 TS patients. No sign of hyperandrogenism was observed. The entire Y chromosome was the most frequent type of Y-material in patients with GB. As the prognosis of these tumors was good, a delay of surgery might be discussed.
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Gonadoblastoma , Neoplasias Ováricas , Síndrome de Turner , Femenino , Humanos , Niño , Adolescente , Adulto Joven , Adulto , Gonadoblastoma/epidemiología , Gonadoblastoma/genética , Gonadoblastoma/patología , Síndrome de Turner/epidemiología , Síndrome de Turner/genética , Síndrome de Turner/diagnóstico , Prevalencia , Estudios de Seguimiento , Neoplasias Ováricas/patología , Cariotipo , MosaicismoRESUMEN
Turner syndrome (TS; ORPHA 881) is a rare condition in which all or part of one X chromosome is absent from some or all cells. It affects approximately one in every 1/2500 liveborn girls. The most frequently observed karyotypes are 45,X (40-50%) and the 45,X/46,XX mosaic karyotype (15-25%). Karyotypes with an X isochromosome (45,X/46,isoXq or 45,X/46,isoXp), a Y chromosome, X ring chromosome or deletions of the X chromosome are less frequent. The objective of the French National Diagnosis and Care Protocol (PNDS; Protocole National de Diagnostic et de Soins) is to provide health professionals with information about the optimal management and care for patients, based on a critical literature review and multidisciplinary expert consensus. The PNDS, written by members of the French National Reference Center for Rare Growth and Developmental Endocrine disorders, is available from the French Health Authority website. Turner Syndrome is associated with several phenotypic conditions and a higher risk of comorbidity. The most frequently reported features are growth retardation with short adult stature and gonadal dysgenesis. TS may be associated with various congenital (heart and kidney) or acquired diseases (autoimmune thyroid disease, celiac disease, hearing loss, overweight/obesity, glucose intolerance/type 2 diabetes, dyslipidemia, cardiovascular complications and liver dysfunction). Most of the clinical traits of TS are due to the haploinsufficiency of various genes on the X chromosome, particularly those in the pseudoautosomal regions (PAR 1 and PAR 2), which normally escape the physiological process of X inactivation, although other regions may also be implicated. The management of patients with TS requires collaboration between several healthcare providers. The attending physician, in collaboration 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 designed to provide such support.
Asunto(s)
Diabetes Mellitus Tipo 2 , Síndrome de Turner , Adulto , Cromosomas Humanos X/genética , Femenino , Humanos , Cariotipo , Cariotipificación , Síndrome de Turner/diagnóstico , Síndrome de Turner/genética , Síndrome de Turner/terapiaRESUMEN
OBJECTIVE: A relative can be an asset in dealing with chronic illnesses, such as acromegaly, where quality of life (QoL) is altered even after remission. However, it has been shown that quality of life of caregivers can also be impacted. Our main objective was to compare the perception of acromegaly in remission in the patient-relative dyad. METHODS: In this observational study, 27 patients in remission and relatives were first asked to complete QoL, anxiety/depression and coping strategy questionnaires. Then, the patient's body image and self-esteem were evaluated from both the patient's and the relative's point of view using the same questionnaires with modified instructions. RESULTS: Relatives had overall an accurate estimation of patient body image using the Figure Rating Scale by Stunkard. However, there were wide variations between the patient's and the relative's responses regarding self-esteem and body perception. The QoL of relatives was not altered and was significantly higher in the social domain than for the patient. CONCLUSIONS: Our results show that relatives require education concerning all the steps involved in the management of acromegaly, as they likely do not fully understand the sequelae of acromegaly.