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Introduction: Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21OHD) or 11-hydroxylase deficiency (11OHD) is characterized by underproduction of cortisol and overproduction of adrenal androgens. These androgens lead to a variable degree of virilization of the female external genitalia in 46,XX individuals. Especially in developing countries, diagnosis is often delayed and 46,XX patients might be assigned as males. This study aims to describe the clinical and biochemical characteristics of a unique cohort of untreated male-reared 46,XX classic CAH patients from Indonesia and discusses treatment challenges. Methods: Nine untreated classic CAH patients with 46,XX genotype and 21OHD (n=6) or 11OHD (n=3), aged 3-46 years old, were included. Biometrical parameters, clinical characteristics, and biochemical measurements including glucocorticoids, renin, androgens, and the pituitary-gonadal axis were evaluated. Results: All patients had low early morning serum cortisol concentrations (median 89 nmol/L) without significant increase after ACTH stimulation. Three patients with salt wasting 21OHD reported one or more periods with seizures and/or vomiting in their past until the age of 6, but not thereafter. The remaining patients reported no severe illness or hospitalization episodes, despite their decreased capacity to produce cortisol. In the 21OHD patients, plasma renin levels were elevated compared to the reference range, and in 11OHD patients renin levels were in the low-normal range. All adult patients had serum testosterone concentrations within the normal male reference range. In 21OHD patients, serum 11-oxygenated androgens comprised 41-60% of the total serum androgen concentrations. Glucocorticoid treatment was offered to all patients, but they refused after counseling as this would reduce their endogenous androgen production and they did not report complaints of their low cortisol levels. Discussion: We describe a unique cohort of untreated classic 46,XX male CAH patients without overt clinical signs of cortisol deficiency despite their cortisol underproduction and incapacity to increase cortisol levels after ACTH stimulation. The described adolescent and adult patients produce androgen levels within or above the normal male reference range. Glucocorticoid treatment will lower these adrenal androgen concentrations. Therefore, in 46,XX CAH patients reared as males an individual treatment approach with careful counseling and clear instructions is needed.
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Hiperplasia Suprarrenal Congénita , Hidrocortisona , Humanos , Hiperplasia Suprarrenal Congénita/genética , Hiperplasia Suprarrenal Congénita/sangre , Hiperplasia Suprarrenal Congénita/complicaciones , Masculino , Adulto , Preescolar , Niño , Adulto Joven , Adolescente , Persona de Mediana Edad , Hidrocortisona/sangre , Femenino , Indonesia/epidemiología , Estudios de CohortesRESUMEN
BACKGROUND: Our Multidisciplinary Team (MDT) is a large specialized team based in Semarang, Indonesia that cares for a wide variety of pediatric and adult individuals with Differences of Sex Development (DSD) from across Indonesia. Here we describe our work over the last 17 years. METHODS: We analyzed phenotypic, hormonal and genetic findings from clinical records for all patients referred to our MDT during the period 2004 to 2020. RESULTS: Among 1184 DSD patients, 10% had sex chromosome DSD, 67% had 46,XY DSD and 23% had 46,XX DSD. The most common sex chromosome anomaly was Turner syndrome (45,X) (55 cases). For patients with 46,XY DSD under-masculinization was the most common diagnosis (311 cases) and for 46,XX DSD a defect of Müllerian development was most common (131 cases) followed by Congenital Adrenal Hyperplasia (CAH) (116 cases). Sanger sequencing, MLPA and targeted gene sequencing of 257 patients with 46,XY DSD found likely causative variants in 21% (55 cases), with 13 diagnostic genes implicated. The most affected gene coded for the Androgen Receptor. Molecular analysis identified a diagnosis for 69 of 116 patients with CAH, with 62 carrying variants in CYP21A2 including four novel variants, and seven patients carrying variants in CYP11B1. In many cases these genetic diagnoses influenced the clinical management of patients and families. CONCLUSIONS: Our work has highlighted the occurrence of different DSDs in Indonesia. By applying sequencing technologies as part of our clinical care, we have delivered a number of genetic diagnoses and identified novel pathogenic variants in some genes, which may be clinically specific to Indonesia. Genetics can inform many aspects of DSD clinical management, and whilst many of our patients remain undiagnosed, we hope that future testing may provide answers for even more.
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[This corrects the article DOI: 10.3389/fendo.2022.1015973.].
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The European Society for Paediatric Endocrinology (ESPE) interactive website, https://www.espe-elearning.org, was first published online in 2012. We describe the various applications of the content of the e-learning website that has been greatly expanded over the last 10 years. A large module on pediatric diabetes was added with the support of the International Society for Paediatric and Adolescent Diabetes (ISPAD). A separate multilingual module was created that focuses on frontline health care providers in limited resource settings. This module has been well received, particularly in targeted parts of the world. e-Learning may also be an opportunity to expand or tailor educational activities for learners according to their differing learning needs. The e-learning website provides guidelines for those interested in general pediatrics, neonatology, clinical genetics, and pediatric gynecology. We also describe various new applications such as master classes in the format of interactive video lectures and joint and complementary e-learning/e-consultation webinars. Finally, international certification was recently realized as e-learning courses were recognized by the European Accreditation Council for Continuing Medical Education (EACCME). As a result of the social distancing measures introduced to control the COVID-19 pandemic, digital education, whether individual or in a virtual classroom setting, has become even more important since e-learning can connect and engage individuals across geographic boundaries as well as those who live in remote areas. The future of education delivery may include hybrid learning strategies, which include in-person and e-learning platforms. Combined e-learning and e-consultation webinars illustrate how international academic institutions, learned medical specialty societies and networks are uniquely placed to deliver balanced, disease-oriented, and patient-centered e-learning education and at the same time provide expert consultation. Moreover, they are well equipped to maintain professional standards and to offer appropriate accreditation.
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COVID-19 , Instrucción por Computador , Diabetes Mellitus , Pediatría , Adolescente , Humanos , Niño , PandemiasRESUMEN
Many women born with disorders or differences of sex development (DSD) report sexual problems, in particular women who have undergone extensive genital reconstruction. Examining cognitions and emotions that hinder or promote sexuality may facilitate understanding these sexual problems and may contribute to the development of specific interventions. In this study, sexual self-concept, body image, and sexual functioning were investigated in relation to genital surgery. To conduct the study, the women's Sexual Self-Concept Scale was translated to Dutch. Evaluation of psychometric properties was conducted in a sample of healthy Belgian and Dutch women participating in an anonymous web-based survey (N = 589, Mdn age, 23 years). The resulting three-factor structure corresponded largely to that of the original version. Compared to control women, women born with a DSD who were included in the Dutch DSD study (N = 99, Mdn age, 26 years) described themselves as being less interested in sex and less sexually active. These women also harbored more negative emotions and cognitions regarding their sexuality and were less satisfied with their external genitalia. In women with a DSD, sexual self-concept was associated with compromised outcomes on sexual functioning and distress. Women who were in a steady relationship, and/or had been sexually active in the past 4 weeks had a more positive sexual self-concept, took a more active role in their sexual relationship, experienced more sexual desire and arousal and less sexual distress than women who were not involved in a partner relationship. Findings in this study indicate that cognitions and emotions related to sexual self-concept play a role in sexual functioning of women with a DSD. A cognitive behavioral counseling approach with focus on coping and exploration of their own sexual needs could prove useful in this group.
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Conducta Sexual , Disfunciones Sexuales Psicológicas , Adulto , Imagen Corporal/psicología , Femenino , Humanos , Autoimagen , Conducta Sexual/psicología , Desarrollo Sexual , Disfunciones Sexuales Psicológicas/psicología , Sexualidad , Encuestas y Cuestionarios , Adulto JovenRESUMEN
OBJECTIVE: Although the provision of e-learning (EL) training for healthcare workers (HCWs) and provider-to-HCW e-consultation (EC) is considered useful for health outcomes, research on their joint use is limited. This scoping review aimed to create an overview of what is currently known in the literature about the use and implementation of EC and EL by HCWs in LMICs and to answer the question of whether there is evidence of complementarity. MATERIALS AND METHODS: Scientific databases were searched and peer-reviewed papers were reviewed systematically according to predefined inclusion/exclusion criteria. Data were extracted including the study focus (EC/EL), year of publication, geographical location, target population, target disease(s) under study, type(s) of study outcomes, and article type. RESULTS: A total of 3051 articles were retrieved and screened for eligibility, of which 96 were kept for analysis. Of these, only 3 addressed both EL and EC; 54 studies addressed EL; and 39 addressed EC. Most studies looked at gain in knowledge/skills usability, efficiency, competence, and satisfaction of HCW, or barriers/challenges to implementation. Descriptive studies focused on the application of EL or EC for targeting specific health conditions. Factors contributing to the success of EC or EL networks were institutional anchoring, multiple partnership, and capacity building of local experts. CONCLUSIONS: Our review found an important gap in the literature in relation to the complementary role of EL and EC for HCWs in LMICs evidenced by outcome measures. There is an important role for national and international academic institutions, learned medical societies, and networks to support regional experts in providing EL and EC for added value that will help the clinical performance of HCWs and improve health outcomes.
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Instrucción por Computador , Países en Desarrollo , Atención a la Salud , Personal de Salud/educación , Humanos , Derivación y ConsultaRESUMEN
Background: Congenital Adrenal Hyperplasia (CAH) due to CYP11B1 is a rare autosomal recessive adrenal disorder that causes a decrease in cortisol production and accumulation of adrenal androgens and steroid precursors with mineralocorticoid activity. Clinical manifestations include cortisol deficiency, ambiguous genitalia in females (differences of sex development (DSD)), and hypertension. Medical treatment recommendations are well defined, consisting of glucocorticoid treatment to substitute glucocorticoid deficiency and consequently normalize adrenal androgen and precursors levels. Current guidelines also emphasize the need for specialized multidisciplinary DSD teams and psychosocial support. In many developing countries, care for DSD patients, especially when caused by an adrenal disease, is challenging due to the lack of infrastructure, knowledge, and medication. Objective: The study aims to report the conflicting decision-making process of medical treatment and sex assignment in late-identified CAH patients in developing countries. Methods: We describe the clinical and biochemical findings and the psychological assessment of five affected but untreated family members with CAH due to CYP11B1 deficiency. Results: All patients had a 46,XX karyotype, ambiguous genitalia, low cortisol levels, and hypertension. Two identified as males, two as females, and one had undecided gender. The patients were counselled that refusing treatment will lead to infertility and the potential risk of developing Addisonian crisis and severe hypertension. However, all 46,XX CAH males refused treatment with glucocorticoids due to the expected lowering of adrenal androgens as their main source of testosterone. None of the patients developed Addisonian crisis, probably due to some residual cortisol activity and glucocorticoid activity of elevated adrenal steroid precursors. Conclusion: Medical treatment and sex assignment in late-identified 46,XX CAH patients in Indonesia may often depend on local and cultural factors. The management of DSD conditions may have to be individualized and integrated into the psychological and social context of the affected family.
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Hiperplasia Suprarrenal Congénita , Trastornos del Desarrollo Sexual , Hipertensión , Femenino , Humanos , Masculino , Hiperplasia Suprarrenal Congénita/tratamiento farmacológico , Hiperplasia Suprarrenal Congénita/genética , Andrógenos/uso terapéutico , Países en Desarrollo , Trastornos del Desarrollo Sexual/genética , Trastornos del Desarrollo Sexual/terapia , Glucocorticoides/uso terapéutico , Hidrocortisona/uso terapéutico , Hipertensión/etiología , Hipertensión/genética , Esteroide 11-beta-Hidroxilasa/genética , Esteroides/uso terapéuticoRESUMEN
BACKGROUND: Electronic learning (e-learning) is a widely accessible, low-cost option for learning remotely in various settings that allows interaction between an instructor and a learner. OBJECTIVE: We describe the development of a free and globally accessible multilingual e-learning module that provides education material on topics in pediatric endocrinology and diabetes and that is intended for first-line physicians and health workers but also trainees or medical specialists in resource-limited countries. METHODS: As complements to concise chapters, interactive vignettes were constructed, exemplifying clinical issues and pitfalls, with specific attention to the 3 levels of medical health care in resource-limited countries. The module is part of a large e-learning portal, ESPE e-learning, which is based on ILIAS (Integriertes Lern-, Informations- und Arbeitskooperations-System), an open-source web-based learning management system. Following a review by global experts, the content was translated by native French, Spanish, Swahili, and Chinese-speaking colleagues into their respective languages using a commercial web-based translation tool (SDL Trados Studio). RESULTS: Preliminary data suggest that the module is well received, particularly in targeted parts of the world and that active promotion to inform target users is warranted. CONCLUSIONS: The e-learning module is a free globally accessible multilingual up-to-date tool for use in resource-limited countries that has been utilized thus far with success. Widespread use will require dissemination of the tool on a global scale.
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OBJECTIVE: The purpose of this study was to describe baseline data on etiological, clinical, laboratory, and management strategies in Kenyan children and adolescents with Disorders of Sex Development (DSD). METHODS: This retrospective study included patients diagnosed with DSD who presented at ages 0-19 years from January 2008 to December 2015 at the Kenyatta National (KNH) and Gertrude's Children's (GCH) Hospitals. After conducting a search in the data registry, a structured data collection sheet was used for collection of demographic and clinical data. Data analysis involved description of the frequency of occurrence of various variables, such as etiologic diagnoses and patient characteristics. RESULTS: Data from the records of 71 children and adolescents were reviewed at KNH (n = 57, 80.3%) and GCH (n = 14, 19.7%). The mean age at the time of diagnosis was 2.7 years with a median of 3 months. Thirty-nine (54.9%) children had karyotype testing done. The median age (IQR) of children with reported karyotypes and those without was 3.3 years (1.3-8.9) and 8.3 years (3.6-12.1), respectively (p=0.021). Based on karyotype analysis, 19 (48.7%) of karyotyped children had 46,XY DSD and 18 (46.2%) had 46,XX DSD. There were two (5.1%) children with sex chromosome DSD. Among the 71 patients, the most common presumed causes of DSD were ovotesticular DSD (14.1%) and CAH (11.3%). Majority (95.7%) of the patients presented with symptoms of DSD at birth. The most common presenting symptom was ambiguous genitalia, which was present in 66 (93.0%) patients either in isolation or in association with other symptoms. An ambiguous genitalia was initially observed by the patient's mother in 51.6% of 62 cases despite the high rate (84.7%) of delivery in hospital. Seventeen (23.9%) of the cases had a gender reassignment at final diagnosis. A psychologist/psychiatrist or counselor was involved in the management of 23.9% of the patients. CONCLUSION: The commonest presumed cause of DSD was ovotesticular DSD in contrast to western studies, which found CAH to be more common. Investigation of DSD cases is expensive and needs to be supported. We would have liked to do molecular genetic analysis outside the country but financial challenges made it impossible. A network for detailed diagnostics in resource-limited countries would be highly desirable. There is a need to train health care workers and medical students for early diagnosis. Psychological evaluation should be carried out for all patients at diagnosis and support given for families.
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Predicting adult height from DNA has important implications in forensic DNA phenotyping. In 2014, we introduced a prediction model consisting of 180 height-associated SNPs based on data from 10,361 Northwestern Europeans enriched with tall individuals (770â¯>â¯1.88 standard deviation), which yielded a mid-ranged accuracy (AUCâ¯=â¯0.75 for binary prediction of tall stature and R2â¯=â¯0.12 for quantitative prediction of adult height). Here, we provide an update on DNA-based height predictability considering an enlarged list of subsequently-published height-associated SNPs using data from the same set of 10,361 Europeans. A prediction model based on the full set of 689 SNPs showed an improved accuracy relative to previous models for both tall stature (AUCâ¯=â¯0.79) and quantitative height (R2â¯=â¯0.21). A feature selection analysis revealed a subset of 412 most informative SNPs while the corresponding prediction model retained most of the accuracy (AUCâ¯=â¯0.76 and R2â¯=â¯0.19) achieved with the full model. Over all, our study empirically exemplifies that the accuracy for predicting human appearance phenotypes with very complex underlying genetic architectures, such as adult height, can be improved by increasing the number of phenotype-associated DNA variants. Our work also demonstrates that a careful sub-selection allows for a considerable reduction of the number of DNA predictors that achieve similar prediction accuracy as provided by the full set. This is forensically relevant due to restrictions in the number of SNPs simultaneously analyzable with forensically suitable DNA technologies in the current days of targeted massively parallel sequencing in forensic genetics.
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Estatura/genética , ADN/genética , Marcadores Genéticos , Polimorfismo de Nucleótido Simple , Población Blanca/genética , Humanos , Modelos Logísticos , Modelos Genéticos , FenotipoRESUMEN
Background: Patients with a disorder of sex development (DSD) are born with atypical genitals or may develop atypical genitals and atypical body appearance, if left untreated. Health related quality of life (HRQoL) was assessed in Indonesian patients to whom diagnostic procedures and medical intervention had been delayed. Method: Comparison of 118 patients born with DSD, aged 6-41 years (60 children, 24 adolescents, and 34 adults) and 118 healthy control subjects matched for gender, age, and residential setting. HRQoL was measured using a translation of the TACQOL/TAAQOL. Results: According to parental and children's report, children with DSD reported more problems in social functioning and had less positive moods. Girls, in particular, reported problems in cognitive functioning. Adult patients reported more depressive moods, especially women, who reported more anger. No differences were found between in the adolescent groups. Conclusion: The data suggest that Indonesian children with DSD experienced more problems in social contact than non-affected Indonesian children, whereas Indonesian adults with DSD suffered from negative emotions more often than non-affected Indonesians. These findings on HRQoL are in line with findings on emotional functioning.
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BACKGROUND: Information sharing in chronic conditions such as disorders of/differences in sex development (DSD) is essential for a comprehensive understanding by parents and patients. We report on a qualitative analysis of communication skills of fellows undergoing training in paediatric endocrinology. Guidelines are created for the assessment of communication between health professionals and individuals with DSD and their parents. METHODS: Paediatric endocrinology fellows worldwide were invited to study two interactive online cases (www.espe-elearning.org) and to describe a best practice communication with (i) the parents of a newborn with congenital adrenal hyperplasia and (ii) a young woman with 46,XY gonadal dysgenesis. The replies were analysed regarding completeness, quality, and evidence of empathy. Guidelines for structured assessment of responses were developed by 22 senior paediatric endocrinologists worldwide who assessed 10 selected replies. Consensus of assessors was established and the evaluation guidelines were created. RESULTS: The replies of the fellows showed considerable variation in completeness, quality of wording, and evidence of empathy. Many relevant aspects of competent clinical communication were not mentioned; 15% (case 1) and 17% (case 2) of the replies were considered poor/insufficient. There was also marked variation between 17 senior experts in the application of the guidelines to assess communication skills. The guidelines were then adjusted to a 3-level assessment with empathy as a separate key item to better reflect the qualitative differences in the replies and for simplicity of use by evaluators. CONCLUSIONS: E-learning can play an important role in assessing communication skills. A practical tool is provided to assess how information is shared with patients with DSD and their families and should be refined by all stakeholders, notably interdisciplinary health professionals and patient representatives.
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Comunicación , Trastornos del Desarrollo Sexual/diagnóstico , Empatía , Endocrinología , Padres/psicología , Relaciones Profesional-Familia , Humanos , Recién Nacido , Revelación de la VerdadRESUMEN
BACKGROUND/AIMS: To assess auxological and safety data for growth hormone (GH)-treated children with SHOX deficiency. METHODS: Data were examined for GH-treated SHOX-deficient children (n = 521) from the observational Genetics and Neuroendocrinology of Short Stature International Study (GeNeSIS). For patients with near-adult height information, GeNeSIS results (n = 90) were compared with a clinical trial (n = 28) of SHOX-deficient patients. Near-adult height was expressed as standard deviation score (SDS) for chronological age, potentially increasing the observed effect of treatment. RESULTS: Most SHOX-deficient patients in GeNeSIS had diagnoses of Leri-Weill syndrome (n = 292) or non-syndromic short stature (n = 228). For GeNeSIS patients with near-adult height data, mean age at GH treatment start was 11.0 years, treatment duration 4.4 years, and height SDS gain 0.83 (95% confidence interval 0.49-1.17). Respective ages, GH treatment durations and height SDS gains for GeNeSIS patients prepubertal at baseline (n = 42) were 9.2 years, 6.0 years and 1.19 (0.76-1.62), and for the clinical trial cohort they were 9.2 years, 6.0 years and 1.25 (0.92-1.58). No new GH-related safety concerns were identified. CONCLUSION: Patients with SHOX deficiency who had started GH treatment before puberty in routine clinical practice had a similar height gain to that of patients in the clinical trial on which approval for the indication was based, with no new safety concerns.
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Estatura , Desarrollo Infantil/efectos de los fármacos , Trastornos del Crecimiento , Proteínas de Homeodominio/genética , Hormona de Crecimiento Humana/administración & dosificación , Osteocondrodisplasias , Estatura/efectos de los fármacos , Estatura/genética , Niño , Femenino , Estudios de Seguimiento , Trastornos del Crecimiento/tratamiento farmacológico , Trastornos del Crecimiento/genética , Trastornos del Crecimiento/fisiopatología , Humanos , Masculino , Osteocondrodisplasias/tratamiento farmacológico , Osteocondrodisplasias/genética , Osteocondrodisplasias/fisiopatología , Proteína de la Caja Homeótica de Baja EstaturaRESUMEN
OBJECTIVES: To assess social stigmatisation related to atypical appearance of the body, including, but not limited to the external genitalia, among Indonesian patients with a disorder of sex development (DSD). Until recently, diagnostic evaluation, information about the underlying causes of DSD and treatment options were sparsely available for these patients. METHODS: Eighty-one parents of children and adolescents with DSD (aged 6-17 years) and 34 adult patients with DSD (aged 18-41 years) completed the Social Stigmatisation Scale towards DSD, an instrument developed to assesses the frequency of stigmatisation and the level of stress associated with these experiences. Open-ended questions investigated detailed information on stigmatisation as well as parents' and patients' emotional and behavioural reactions to these experiences. Differences in stigmatisation were explored across sex of rearing, gender change history, treatment status and DSD characteristics that could be easily identified by others (e.g., masculinisation of the body in women). RESULTS: Social stigmatisation was reported by patients with atypical appearance of their genitalia, atypical appearance of their body aside from their genitals, among those who displayed cross-gender behaviour and those who changed gender. Among participants reared as women and among children and adolescents who changed gender, social stigmatisation was associated with ostracism, depressive symptoms and social isolation. CONCLUSIONS: Patients unable to conceal their condition (those with visible physical atypicality and those who changed gender) experienced social stigmatisation. Stigmatisation was stressful and related to isolation and withdrawal from social interaction. Education about DSD, self-empowerment and medical interventions to prevent atypical physical development may remove barriers to acceptance by others for affected individuals.
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The magnitude of sex differences in human brain and behavior and the respective contributions of biology versus socialization remain a topic of ongoing study in science. The preponderance of evidence attests to the notion that sexual differentiation processes are at least partially hormonally mediated, with high levels of prenatal androgens facilitating male-typed and inhibiting female-typed behaviors. In individuals with Disorders/Differences of Sex Development (DSD), hormonal profiles or sensitivities have been altered due to genetic influences, presumably affecting gender(ed) activity interests as well as gender identity development in a minority of the affected population. While continued postnatal androgen exposure in a number of DSD syndromes has been associated with higher rates of gender dysphoria and gender change, the role of a number of mediating and moderating factors, such as initial gender assignment, syndrome severity and clinical management remains largely unclear. Limited investigations of the associations between these identified influences and gendered development outcomes impede optimization of clinical care. Participants with DSD (n=123), recruited in the context of a Dutch multi-center follow-up audit, were divided in subgroups reflecting prenatal androgen exposure, genital appearance at birth and gender of rearing. Recalled childhood play and playmate preferences, gender identity and sexual orientation were measured with questionnaires and semi-structured interviews. Data were compared to those of control male (n=46) and female participants (n=79). The findings support that (a) prenatal androgen exposure has large effects on (gendered) activity interests, but to a much lesser extent on sexual orientation and that (b) initial gender of rearing remains a better predictor of gender identity contentedness than prenatal androgen exposure, beyond syndrome severity and medical treatment influences. Nonetheless, 3.3% of individuals with DSD in our sample self-reported gender dysphoria from an early age and changed gender, which further underlines the need for thorough long- term follow-up and specific clinical support.
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Trastornos del Desarrollo Sexual/psicología , Identidad de Género , Recuerdo Mental/fisiología , Conducta Sexual/psicología , Adolescente , Adulto , Anciano , Encéfalo/fisiopatología , Estudios de Casos y Controles , Trastornos del Desarrollo Sexual/fisiopatología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Embarazo , Autoinforme , Caracteres Sexuales , Diferenciación Sexual/fisiología , Encuestas y Cuestionarios , Adulto JovenRESUMEN
OBJECTIVE: Atypical sex development is associated with psychosocial vulnerability. We investigated psychosocial well-being in individuals with disorders of sex development (DSD) and hypothesized that psychosocial well-being was related to degree of genital atypicality at birth. METHODS: 120 male (n=16) and female (n=104) persons with DSD, aged 14-60 years, participated in a follow-up audit on psychosocial well-being. They were stratified in: women with 1) 46,XY and female genitalia, 2) 46,XY or 46,XX and atypical genitalia, and 3) men with 46,XY and atypical genitalia. We used the Illness Cognition Questionnaire (ICQ), Checklist Individual Strength (CIS8R), TNO-AZL Quality of Life questionnaire (TAAQOL), Adult Self-Report (ASR), and the Rosenberg Self-Esteem Scale (RSES). RESULTS: Data were compared to reference groups. Participants generally were coping well with DSD (ICQ). Women with DSD reported elevated levels of fatigue (CIS8R) and slightly more attention and memory problems (TAAQOL, ASR). Women with atypical genitalia reported more emotional and behavioral problems. On the ASR Rule-breaking Behavior and Antisocial Personality scales, these women had similar scores as reference men. Women with DSD reported a higher self-esteem (RSES). No differences in psychosocial well-being were found between men with DSD and reference men. CONCLUSION: Individuals with DSD across all diagnostic groups generally reported a good psychosocial well-being. The results further suggest involvement of prenatal androgens in the development of personality traits related to assertiveness and egocentricity. We recommend that individuals with a DSD and their families are involved in decision-making processes and have access to multidisciplinary care.
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Adaptación Psicológica , Trastornos del Desarrollo Sexual/psicología , Calidad de Vida , Adolescente , Adulto , Asertividad , Atención , Fatiga/epidemiología , Femenino , Humanos , Masculino , Trastornos de la Memoria/epidemiología , Trastornos Mentales/epidemiología , Persona de Mediana Edad , Países Bajos , Personalidad , AutoinformeRESUMEN
OBJECTIVE: The objective of this study was to determine the aetiological spectrum of disorders of sex development (DSD) in a large cohort of underprivileged and undiagnosed patients from Indonesia. METHODS: A total of 286 patients with atypical external and/or internal genitalia were evaluated using clinical, hormonal, molecular genetic and histological parameters. RESULTS: The age (years) at presentation was 0-0·5 in 41 (14·3%), >0·5-12 in 181 (63·3%) and >12 in 64 cases (22·4%). 46,XY DSD was most common (68·2%, n = 195), 46,XX DSD was found in 23·4% (n = 67) and sex chromosomal DSD in 8·4% (n = 24). In 61·2% of 46,XX DSD patients, 17·9% of 46,XY DSD patients and all sex chromosome DSD patients (29·4% in total), a final diagnosis was reached based on genetic or histological gonadal tissue evaluation. 17-hydroxyprogesterone and androstenedione levels were the most distinctive parameters in 46,XX DSD patients. In 46,XY DSD, diagnostic groups were identified based on the external masculinization score: androgen action disorder (AAD), unknown male undermasculinization (UMU), and gonadal dysgenesis (GD). LH, FSH and testosterone levels were most informative especially in the older age group. HCG tests were of no additional value as no patients with androgen synthesis disorders were found. Hormonal profiles of patients with sex chromosome DSD and a Y-chromosome sequence containing karyotype showed high levels of LH and FSH, and low levels of AMH, inhibin B and testosterone compared with the normal male range. Gene mutations were found in all patients with CAH, but in only 24·5% and 1·8% of patients with AAD and UMU. In 32% of 46,XY GD patients, copy number variants of different genes were found. CONCLUSION: A stepwise diagnostic approach led to a molecularly or histologically proven final diagnosis in 29·4% of the patients. The most informative parameters were serum levels of 17-hydroxyprogesterone and androstenedione in 46,XX DSD patients, and serum LH, FSH and testosterone levels in 46,XY DSD patients.
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Trastornos del Desarrollo Sexual/diagnóstico , Hormonas/sangre , 17-alfa-Hidroxiprogesterona/sangre , Adolescente , Factores de Edad , Androstenodiona/sangre , Niño , Preescolar , Trastornos del Desarrollo Sexual/sangre , Trastornos del Desarrollo Sexual/genética , Femenino , Hormona Folículo Estimulante/sangre , Genotipo , Disgenesia Gonadal 46 XY , Humanos , Indonesia , Lactante , Recién Nacido , Hormona Luteinizante/sangre , Masculino , Fenotipo , Cromosomas Sexuales/genética , Testosterona/sangreRESUMEN
OBJECTIVE: To determine characteristics of children initially diagnosed with isolated growth hormone deficiency (IGHD) of organic aetiology, who later developed multiple pituitary hormone deficiencies (MPHD). DESIGN: Data were analysed for 716 growth hormone-treated children with organic IGHD, who were growth hormone-naïve at baseline in the multinational, observational Genetics and Neuroendocrinology of Short Stature International Study. METHODS: Development of MPHD was ascertained from investigator-provided diagnoses, adverse events and concomitant medications. Analyses were performed for all patients and separately for those who developed MPHD within 4.5 years or had >3.5 years follow-up and continued to have IGHD (4-year cohort). RESULTS: MPHD developed in 71/716 (9.9%) children overall, and in 60/290 (20.7%) in the 4-year cohort. The most frequent additional deficiencies were thyroid-stimulating hormone (47 patients) and gonadotropins (23 patients). Compared with those who remained with IGHD, children who developed MPHD had more severe GHD at study entry, significantly lower baseline insulin-like growth factor1, peak stimulated growth hormone, and more frequent diagnosis of intracranial tumour or mutation of gene(s) controlling hypothalamic-pituitary development and/or function. Multivariate logistic regression analyses identified female gender, longer follow-up, higher baseline age and lower peak stimulated growth hormone as predictors of MPHD development. CONCLUSIONS: MPHD is more likely to develop in patients with severe organic IGHD, especially those with history of intracranial tumour or mutation of gene(s) controlling hypothalamic-pituitary development and/or function. Older baseline age, female gender and longer follow-up duration were also associated with higher incidence of MPHD. Long-term monitoring of pituitary function is recommended, irrespective of the aetiology of GHD.
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Progresión de la Enfermedad , Gonadotropinas/deficiencia , Hormona de Crecimiento Humana/deficiencia , Hipopituitarismo/epidemiología , Hormonas Hipofisarias/deficiencia , Adolescente , Factores de Edad , Niño , Hipotiroidismo Congénito/epidemiología , Femenino , Estudios de Seguimiento , Humanos , Hipotiroidismo , Masculino , Factores Sexuales , Tirotropina/deficienciaRESUMEN
In most Western countries, clinical management of disorders of sex development (DSD), including ambiguous genitalia, begins at diagnosis soon after birth. For many Indonesian patients born with ambiguous genitalia, limited medical treatment is available. Consequently, affected individuals are raised with ambiguous genitalia and atypical secondary sex characteristics. We investigated gender identity and gender role behavior in 118 Indonesian subjects (77 males, 41 females) with different types of DSD in comparison with 118 healthy controls matched for gender, age, and residential setting (rural, suburban, or urban). In Study 1, we report on methodological aspects of the investigation, including scale adaptation, pilot testing, and determining reliability and validity of measures. In Study 2, we report on gender development in 60 children (42 boys, 18 girls), 24 adolescents (15 boys, 9 girls), and 34 adults (19 men, 15 women) with DSD. The majority of participants with DSD never received any medical or surgical treatment prior to this study. We observed a gender change in all age groups, with the greatest incidence in adults. Among patients who changed, most changed from female to male, possessed a 46,XY karyotype, and had experienced significant masculinization during life. Gender identity confusion and cross-gender behavior was more frequently observed in children with DSD raised as girls compared to boys. Puberty and associated masculinization were related to gender problems in individuals with 46,XY DSD raised female. An integrated clinical and psychological follow-up on gender outcome is necessary prior to puberty and adulthood.
Asunto(s)
Trastornos del Desarrollo Sexual/epidemiología , Identidad de Género , Desarrollo Psicosexual , Diferenciación Sexual , Maduración Sexual , Adolescente , Adulto , Niño , Trastornos del Desarrollo Sexual/diagnóstico , Femenino , Humanos , Indonesia/epidemiología , Relaciones Interpersonales , Masculino , Persona de Mediana Edad , Caracteres Sexuales , Adulto JovenRESUMEN
Diabetes insipidus is a rare but serious endocrine disorder. Paediatric patients were evaluated for polyuria at King Khalid University Hospital, Riyadh, Saudi Arabia, over a decade (2000-13). Relevant clinical examination and/or a triad of high serum osmolality, hypernatremia and low urine osmolality due to increased urine output confirmed the diagnosis. Water deprivation test was required in some cases with non-classic presentations. Appropriate brain imaging was performed whenever central diabetes insipidus (CDI) was suspected. Twenty-eight patients, 15 males (53.6%) and 13 females (46.4%), aged 0-17 years (mean: 6 years) were included. The calculated period prevalence was 7 in 10,000. In our cohort, 60.7% (17 of 28 patients) had CDI, 21.4% (6 of 28) were diagnosed with nephrogenic diabetes insipidus (NDI) and 17.9% (5 of 30) had psychogenic polydipsia. CDI was due to variable aetiology. Though CDI was the commonest, NDI was not a rare encounter in our community, possibly because of high consanguineous marriages.