The ESPE e-learning webportal: A global tool for instruction and formative assessment of pediatric endocrinology

The ESPE e-learning portal (http://www.espe-elearning.org) aims at supporting the learning of cognitive objectives, competencies and skills at two levels: core (medical students) and advanced (fellow/postdoc). It provides a rich source of up-to-date information on various Pediatric Endocrinology topics. The ESPE elearning webportal offers a set of functionalities consisting of a general learning content (chapters, problem solving cases, self-tests, glossary, community) and the option to construct specific courses for an event (ESPE school) or organization: a client, university or institution. Moreover, a set of question types has been developed allowing scoring and assessment of competencies. The content is being expanded and includes chapters and/or cases on the topics of growth, puberty, DSD, calcium and bone, diabetes, hyperinsulinism, thyroidal disorders, adrenal disorders, dis-electrolytemia. Since the portal has been moved to its definite address the global use of the portal has increased: during the period September - December 2013 there were 1264 visits; during the period January-April 2014 there were 2393 visits. The availability of the portal for members and non-members of ESPE needs to be emphasized and needs to be made public widely. Moreover, relevant feedback from users should be translated by the editorial board to make practical improvements. As demonstrated during two courses held in Varna, Bulgaria the portal facilitates the combination of online learning and face-to-face instruction: blended learning. Finally, the next step in extending the impact of the e-learning portal is the further development of learning and competency assessment tools. Furthermore, in demonstrating its applicability at a global level, regional and cultural aspects should be fully recognized

Emotional and behavioral problems in late-identified Indonesian patients with disorders of sex development

Objective: The aim of this study is to investigate emotional and behavioral problems among Indonesian patients with disorders of sex development (DSD) who recently came under clinical management. As diagnostic proce-dures and treatment had been delayed, patients progressively developed ambiguous bodies, difficult to conceal from outsiders. Method: We compared 118 Indonesian patients with DSD aged 6–41 years (60 children, 24 adolescents, 34 adults) and 118 healthy control subjects matched for age, gender, and residential settings. We used the Child Be-havioral Checklist (CBCL), Youth Self-Report (YSR), and Adult Self-Report (ASR) to examine differences between patient and control groups as well as differences within patients groups. Results: On the CBCL, parents of young children with DSD reported significantly more emotional and behavioral problems than parents of matched control. Parents of daughters with CAH reported that their daughters withdrew themselves from social interactions. On the ASR, adults with DSD reported significantly more internalizing problems than controls, particularly anxiety and depression. No other differences in emotional functioning were found across different diagnostic groups. Conclusions: Indonesian patients with DSD who were untreated for most of their lives suffered more emotional and behavioral problems than matched controls. Differences and similarities between our findings and observations in patients from Western countries will be discussed

Virilization Due to Androgen Hypersecretion in a Patient with Ovarian Leydig Cell Tumor: Diagnostic and Psychosocial Implications

Virilisasi akibat kelebihan hormon androgen yang terjadi pada wanita akan menimbulkan tanda-tanda seperti pembesaran klitoris, perubahan suara, tumbuhnya rambut di wajah dan tubuh yang menjadi ciri khas laki-laki. Virilisasi yang disebabkan oleh tumor ovarium tidak lebih dari 0,5% dari seluruh penyebab. Kami melaporkan kasus virilisasi akibat tumor sel Leydig pada ovarium kiri wanita usia 36 tahun. Kesalahan interpretasi, informasi medis yang saling bertentangan dan saran dari dokter sebelumnya membuat kebingungan dari pasien tersebut. Kami melakukan evaluasi diagnostik yang meliputi gambaran klinik, hormon, pencitraan, pemeriksaan patologi, molekuler serta pemeriksaan psikologi. Pemeriksaan hormon menunjukkan kadar testosteron yang sangat tinggi. Adanya tumor pada ovarium terdeteksi dari pemeriksaan laparoskopi. Biopsi pada ovarium kiri dilakukan oleh karena pasien menolak dilakukan pengangkatan ovarium. Hasil pemeriksaan patologi menunjukkan tumor sel Leydig tanpa adanya tanda keganasan. Pengelolaan menjadi kurang optimal karena faktor sosial budaya yang menghambat walaupun telah dilakukan konseling secara mendalam. Tumor sel Leydig pada ovarium dicurigai apabila terjadi virilisasi pada wanita usia reproduktif disertai peningkatan hormon androgen, massa ovarium pada pemeriksaan pencitraan dan dibuktikan dengan hasil biopsi. Hal ini penting sebelum memberikan saran maupun pengobatan kepada pasien. Kata kunci: diagnostik work up, virilisasi, sel tumor Leydig. ABSTRACT Virilization due to hyperandrogenism in women causes male signs and symptoms such as swelling of the clitoris, deepening of the voice, facial hair and increase in body hair. Virilization is caused by less than 0.5% of all ovarian tumors. Here we report a case of virilizing Leydig cell tumor of the left ovary in a 36 year old woman. Misinterpretation of symptoms, conflicting medical information and advice from previous doctors had confused the patient. We performed a diagnostic evaluation including clinical, hormonal parameters, imaging, anatomical pathology examinations, and psychological assessment. Blood analysis showed a high testosterone level. The presence of an ovarian tumor was confirmed by laparoscopy. Since the patient refused ovariectomy, a biopsy of the left ovary was performed. Pathology showed a Leydig cell tumor without histological signs of malignancy. In spite of extensive explanation and psychological counseling, cultural barriers prevented appropriate treatment. An ovarian Leydig cell tumor should always be considered for a woman in the reproductive age with symptoms of virilization. The diagnosis is suspected on the basis of an ovarian mass on examination and further investigation and should be proven by biopsy. Key words: diagnostic work up, virilization, Leydig cell tumor

A scoping review of the use of e-learning and e-consultation for healthcare workers in low- and middle-income countries and their potential complementarity

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

New insights into type II germ cell tumor pathogenesis based on studies of patients with various forms of disorders of sex development (DSD)

Disorders of sex development (DSD), previously known as intersex, refer to congenital conditions in which development of chromosomal, gonadal, or anatomical sex is atypical. Patients with specific variants of this disorder have an elevated risk for the development of so-called type II germ cell cancers, i.e., the seminomatous and nonseminatous tumors, referred to as germ cell tumors (GCTs). Specifically DSD patients with gonadal dysgenesis or hypovirilization are at risk. A prerequisite for type II GCT formation is the presence of a specific part of the Y chromosome (referred to as the GBY region), with the TSPY gene being the most likely candidate. Also the octamer binding transcription factor OCT3/4 is consistently expressed in all type II GCTs with pluripotent potential, as well as in the precursor lesions carcinoma in situ (CIS) in case of a testis and gonadoblastoma (GB) in the DSD gonad. The actual risk for malignant transformation in individual DSD patients is hard to predict, because of confusing terminology referring to the different forms of DSD, and unclear criteria for identification of the presence of malignant germ cells, especially in young patients. This is specifically due to the phenomenon of delay of germ cell maturation, which might result in over diagnosis. This review will give novel insight into the pathogenesis of the type II GCTs through the study of patients with various forms of DSD for which the underlying molecular defect is known. To allow optimal understanding of the pathogenesis of this type of cancers, first normal gonadal development, especially regarding the germ cell lineage, will be discussed, after which type II GCTs will be introduced. Subsequently, the relationship between type II GCTs and DSD will be described, resulting in a number of new insights into the development of the precursor lesions of these tumors

Challenges in the treatment of late-identified untreated congenital adrenal hyperplasia due to CYP11B1 deficiency: Lessons from a developing country

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

A human vitamin D receptor mutation causes rickets and impaired Th1/Th17 responses

We present a brother and sister with severe rickets, alopecia and highly elevated serum levels of 1,25-dihydroxyvitamin D (1,25-(OH)2D3). Genomic sequencing showed a homozygous point mutation (A133G) in the vitamin D receptor gene, leading to an amino acid change in the DNA binding domain (K45E), which was described previously. Hereditary vitamin D resistant rickets (HVDRR) was diagnosed. Functional studies in skin biopsy fibroblasts confirmed this. 1,25-(OH)2D3 reduced T helper (Th) cell population-specific cytokine expression of interferon γ (Th1), interleukins IL-17A (Th17) and IL-22 (Th17/Th22) in peripheral blood mononuclear cells (PBMCs) from the patient's parents, whereas IL-4 (Th2) levels were higher, reflecting an immunosuppressive condition. None of these factors were regulated by 1,25-(OH)2D3 in PBMCs from the boy. At present, both patients (boy is 23years of age, girl is 7) have not experienced any major immune-related disorders. Although both children developed alopecia, the girl did so earlier than the boy. The boy showed complete recovery from the rickets at the age of 17 and does not require any vitamin D supplementations to date.In conclusion, we characterized two siblings with HVDRR, due to a mutation in the DNA binding domain of VDR. Despite a defective T cell response to vitamin D, no signs of any inflammatory-related abnormalities were seen, thus questioning an essential role of vitamin D in the immune system. Despite the fact that currently medicine is not required, close monitoring in the future of these patients is warranted for potential recurrence of vitamin D dependence and diagnosis of (chronic) inflammatory-related diseases

Global Application of the Assessment of Communication Skills of Paediatric Endocrinology Fellows in the Management of Differences in Sex Development Using the ESPE E-Learning.Org Portal

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.Fil: Kranenburg, Laura J.C.. Erasmus University Medical Center; Países BajosFil: Reerds, Sam T.H.. Erasmus University Medical Center; Países BajosFil: Cools, Martine. University of Ghent; BélgicaFil: Alderson, Julie. NHS Foundation Trust. University Hospitals Bristol; Reino UnidoFil: Muscarella, Miriam. University of California; Estados UnidosFil: Magrite, Ellie. Ffounder And Trustee;Fil: Kuiper, Martijn. Erasmus University Medical Center;Fil: Abdelgaffar, Shereen. Cairo University; EgiptoFil: Balsamo, Antonio. Universidad de Bologna; ItaliaFil: Brauner, Raja. Universite de Paris V; FranciaFil: Chanoine, Jean Pierre. British Columbia Children’s Hospital. Department of Paediatrics; CanadáFil: Deeb, Asma. Mafraq Hospital; Emiratos Arabes UnidosFil: Fechner, Patricia. University of Washington; Estados UnidosFil: German, Alina. Technion - Israel Institute of Technology; IsraelFil: Holterhus, Paul Martin. Universitätsklinikum Schleswig-Holstein; Alemania. Christian-Albrechts-Universität zu Kiel; AlemaniaFil: Juul, Anders. Universidad de Copenhagen; DinamarcaFil: Mendonca, Berenice B.. Universidade de Sao Paulo; BrasilFil: Neville, Kristen. Sydney Children's Hospital; AustraliaFil: Nordenstrom, Anna. Karolinka Institutet; SuizaFil: Oostdijk, Wilma. Leiden University; Países BajosFil: Rey, Rodolfo Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; ArgentinaFil: Rutter, Meilan M.. University of Cincinnati; Estados UnidosFil: Shah, Nalini. Seth GS Medical College & KEM Hospital; IndiaFil: Luo, Xiaoping. Tongji Hospital; ChinaFil: Grijpink, Kalinka. Delft University of Technology; Países BajosFil: Drop, Stenvert L.S.. Erasmus University Medical Center; Países Bajo

Severity of Virilization Is Associated with Cosmetic Appearance and Sexual Function in Women with Congenital Adrenal Hyperplasia: A Cross-Sectional Study

Item does not contain fulltextIntroduction. Women with the classical form of congenital adrenal hyperplasia (CAH) are born with different degrees of virilization of the external genitalia. Feminizing surgery is often performed in childhood to change the appearance of the genitalia and to enable penile-vaginal intercourse later in life. There are suggestions that this affects sexual functioning. Aims. The aim is to study the anatomical, surgical, cosmetic, and psychosexual outcomes in women with CAH. Methods. Forty women with CAH, aged over 15 years, from two referral centers for management of Disorders of Sex Development in the Netherlands were included. Physical and functional status were assessed by a gynecological interview and examination. Sexual functioning was assessed with the Female Sexual Function Index and Female Sexual Distress Scale-Revised scales and compared with a reference group. Mean Outcome Measures. Surgery performed, anatomy, cosmetic score, sexual function and distress. Results. Thirty-six of the 40 women had undergone feminizing surgery; 25 women (69%) underwent more than one operation. Resurgery was performed in seven of the 13 (54%) women who had had a single-stage procedure. Anatomical assessment showed reasonable outcomes. Multiple linear regression showed that only level of confluence had a significant effect on cosmetic outcome, the impact depending on the number of surgeries performed. Cosmetic evaluations did not differ between the women and the gynecologists. Only 20 women had experience of intercourse. Eight women reported dyspareunia; seven women reported urinary incontinence. The women's perceived sexual functioning was less satisfactory than in the reference group, and they reported more sexual distress. Conclusion. The level of confluence was the major determinant for cosmetic outcome; the impact depended on the number of surgeries performed. Fifty-four percent of the women required resurgery after a single-stage procedure in childhood. Anatomical assessment showed reasonable outcomes. The women evaluated their sexual functioning and functional outcome less favorable than the reference group, and they experienced less often sexual intercourse. van der Zwan YG, Janssen EHCC, Callens N, Wolffenbuttel KP, Cohen-Kettenis PT, van den Berg M, Drop SLS, Dessens AB, Beerendonk C. Severity of virilization is associated with cosmetic appearance and sexual function in women with congenital adrenal hyperplasia: A cross-sectional study. J Sex Med 2013;10:866-875