Non-classic congenital adrenal hyperplasia (NCAH) is a relatively common disorder regardless of ethnicity, but most cases are never diagnosed, especially in males. A baseline 17-hydroxyprogesterone measurement may be used for screening, but 17-hydroxyprogesterone measurement after ACTH stimulation is the gold standard. We advocate a CYP21A2 mutation analysis to verify the diagnosis, for genetic counselling and for better prognostic and treatment guidance. Most patients are diagnosed in adolescence and adult life with hirsutism, acne, a PCOS-like picture and fertility issues. Many men with NCAH never seek medical attention and escape diagnosis. Although treatment is somewhat controversial, an early diagnosis and start of treatment may have positive implications on growth and be relevant for preventing and ameliorating the symptoms and consequences of androgen excess that develop over time, including fertility issues. Long-term treatment with glucocorticoids will improve the androgen symptoms but may result in long-term complications, such as obesity, insulin resistance, hypertension, osteoporosis and fractures. The glucocorticoid doses should be kept low. However, complications seen in NCAH, assumed to be caused by the glucocorticoid treatment, may also be associated with long-term androgen exposure. Oral contraceptive pills are a common treatment option for young females with NCAH. Regular clinical monitoring to improve the clinical outcome is recommended. It is important to acknowledge that glucocorticoid treatment will lead to secondary cortisol insufficiency and the need for stress dosing. Studies focusing on the specific difficulties patients with NCAH face, both those with a late clinical diagnosis and those with a neonatal diagnosis obtained by screening, are warranted.
Anna Nordenström and Henrik Falhammar
Tatja Hirvikoski, Anna Nordenström, Torun Lindholm, Frank Lindblad, E Martin Ritzén, and Svetlana Lajic
To investigate the long-term effects of prenatal treatment of congenital adrenal hyperplasia (CAH) with emphasis on behavioural problems and temperament.
A population-based long-term follow-up study of Swedish children at risk for virilising CAH, who had received treatment prenatally with dexamethasone (DEX). The questionnaire-based follow-up was performed when the children had reached school age.
Standardised parent-completed questionnaires were used to evaluate adaptive functioning, behavioural/emotional problems and psychopathology, social anxiety and temperament in DEX-exposed school-aged children (n=26) and matched controls (n=35). In addition, the association between parental questionnaires and children's self-ratings was investigated.
There were no statistically significant differences between DEX-exposed children and controls in measures of psychopathology, behavioural problems and adaptive functioning. In a questionnaire on temperamental traits, DEX-exposed children were described by their parents as being more sociable than controls (P=0.042). The correlation analysis showed only modest parent–child agreement on social anxiety, i.e. the increased social anxiety in children's self-ratings was not confirmed by their parents.
DEX-treated children showed good overall adjustment. The parent–child agreement with respect to social anxiety was modest, highlighting the importance of multiple information sources and assessment methods. The clinical significance of the observed difference in sociability cannot be determined within the frameworks of this study. Additional studies of larger cohorts are essential to make more decisive conclusions on the safety of the treatment. Until then, it is important that parents are thoroughly informed about the benefits and potential risks and uncertainties of this controversial treatment.
Christa Flück, Anna Nordenström, S Faisal Ahmed, Salma R Ali, Marta Berra, Joanne Hall, Birgit Köhler, Vickie Pasterski, Ralitsa Robeva, Katinka Schweizer, Alexander Springer, Puck Westerveld, Olaf Hiort, Martine Cools, and the COST Action BM1303 Working Group
The treatment and care of individuals who have a difference of sex development (DSD) have been revised over the past two decades and new guidelines have been published. In order to study the impact of treatments and new forms of management in these rare and heterogeneous conditions, standardised assessment procedures across centres are needed. Diagnostic work-up and detailed genital phenotyping are crucial at first assessment. DSDs may affect general health, have associated features or lead to comorbidities which may only be observed through lifelong follow-up. The impact of medical treatments and surgical (non-) interventions warrants special attention in the context of critical review of current and future care. It is equally important to explore gender development early and refer to specialised services if needed. DSDs and the medical, psychological, cultural and familial ways of dealing with it may affect self-perception, self-esteem, and psychosexual function. Therefore, psychosocial support has become one of the cornerstones in the multidisciplinary management of DSD, but its impact remains to be assessed. Careful clinical evaluation and pooled data reporting in a global DSD registry will allow linking genetic, metabolomic, phenotypic and psychological data. For this purpose, our group of clinical experts and patient and parent representatives designed a template for structured longitudinal follow-up. In this paper, we explain the rationale behind the selection of the dataset. This tool provides guidance to professionals caring for individuals with a DSD and their families. At the same time, it collects the data needed for answering unsolved questions of patients, clinicians, and researchers. Ultimately, outcomes for defined subgroups of rare DSD conditions should be studied through large collaborative endeavours using a common protocol.
Angela K Lucas-Herald, Jillian Bryce, Andreas Kyriakou, Marie Lindhardt Ljubicic, Wiebke Arlt, Laura Audí, Antonio Balsamo, Federico Baronio, Silvano Bertelloni, Markus Bettendorf, Antonia Brooke, Hedi L Claahsen-van der Grinten, Justin Davies, Gloria Hermann, Liat de Vries, Ieuan A Hughes, Rieko Tadokoro-Cuccaro, Feyza Darendeliler, Sukran Poyrazoglu, Mona Ellaithi, Olcay Evliyaoglu, Simona Fica, Lavinia Stejereanu, Aneta Gawlik, Evgenia Globa, Nataliya Zelinska, Tulay Guran, Ayla Güven, Sabine Hannema, Olaf Hiort, P-m Holterhus, Violeta Iotova, Vilhelm Mladenov, Vandana Jain, Rajni Sharma, Farida Jennane, Colin Johnston, Gil Guerra-Junior, Daniel Konrad, Odile Gaisl, Nils P Krone, Ruth Krone, Katherine Lachlan, Dejun Li, Corina Lichiardopol, Lidka Lisá, Renata Levoni Markosyan, Inas Mazen, Klaus Mohnike, Marek Niedziela, Anna Nordenstrom, Rodolfo A Rey, Mars Skae, Lloyd JW Tack, Jeremy W Tomlinson, Naomi Weintrob, Martine Cools, and S Faisal Ahmed
Objectives: To determine trends in clinical practice for individuals with DSD requiring gonadectomy.
Design: Retrospective cohort study.
Methods: Information regarding age at gonadectomy according to diagnosis; reported sex; time of presentation to specialist center; and location of center from cases reported to the International DSD Registry and who were over 16 years old in January 2019.
Results: Data regarding gonadectomy were available in 668 (88%) individuals from 44 centers. Of these, 248 (37%) (median age (range) 24 (17, 75) years) were male and 420 (63%) (median age (range) 26 (16, 86) years) were female. Gonadectomy was reported from 36 centers in 351/668 cases (53%). Females were more likely to undergo gonadectomy (n=311, p<0.0001). The indication for gonadectomy was reported in 268 (76%). The most common indication was mitigation of tumour risk in 172 (64%). Variations in the practice of gonadectomy were observed; of the 351 cases from 36 centers, 17 (5%) at 9 centers had undergone gonadectomy before their first presentation to the specialist center. Median age at gonadectomy of cases from high income countries and low/middle income countries (LMIC) was 13.0 yrs (0.1, 68) years and 16.5 yrs (1, 28), respectively (p<0.0001) with the likelihood of long-term retention of gonads being higher in LMIC countries.
Conclusions: The likelihood of gonadectomy depends on the underlying diagnosis, sex of rearing and the geographical setting. Clinical benchmarks, which can be studied across all forms of DSD will allow a better understanding of the variation in the practice of gonadectomy.