Causes, patterns and severity of androgen excess in 487 consecutively recruited pre- and post-pubertal children.

Jan Idkowiak,Nicholas J Shaw,Wolfgang Högler,Rachel Webster,Karen Smith,Melanie Kershaw,Jeremy M Kirk,Ruth E Krone,Pascoe Mannion,Michael W O’Reilly,Vrinda Saraff,Wiebke Arlt,Timothy G Barrett,Yasir S Elhassan,Renuka P Dias,Nils Krone

doi:10.1530/eje-18-0854

Abstract

ObjectiveAndrogen excess in childhood is a common presentation and may signify sinister underlying pathology. Data describing its patterns and severity are scarce, limiting the information available for clinical decision processes. Here, we examined the differential diagnostic value of serum DHEAS, androstenedione (A4) and testosterone in childhood androgen excess.DesignRetrospective review of all children undergoing serum androgen measurement at a single center over 5 years.MethodsSerum A4 and testosterone were measured by tandem mass spectrometry and DHEAS by immunoassay. Patients with at least one increased androgen underwent phenotyping by clinical notes review.ResultsIn 487 children with simultaneous DHEAS, A4 and testosterone measurements, we identified 199 with androgen excess (140 pre- and 59 post-pubertal). Premature adrenarche (PA) was the most common pre-pubertal diagnosis (61%), characterized by DHEAS excess in 85%, while A4 and testosterone were only increased in 26 and 9% respectively. PCOS was diagnosed in 40% of post-pubertal subjects, presenting equally frequent with isolated excess of DHEAS (29%) or testosterone (25%) or increases in both A4 and testosterone (25%). CAH patients (6%) predominantly had A4 excess (86%); testosterone and DHEAS were increased in 50 and 33% respectively. Concentrations increased above the two-fold upper limit of normal were mostly observed in PA for serum DHEAS (>20-fold in the single case of adrenocortical carcinoma) and in CAH for serum androstenedione.ConclusionsPatterns and severity of childhood androgen excess provide pointers to the underlying diagnosis and can be used to guide further investigations.

Highlights

Androgen excess in childhood may present with a variety of symptoms and is thought to have a broad spectrum of underlying pathologies (1)
The diagnosis of Premature adrenarche (PA) and polycystic ovary syndrome (PCOS) require exclusion of other causes of androgen excess such as inborn steroidogenic enzyme defects, most commonly congenital adrenal hyperplasia (CAH), precocious puberty or potentially malignant virilizing adrenal tumors, with the latter being extremely rare in childhood (1, 5, 6)
We have recently reported the utility of simultaneous measurement of serum DHEAS, A4 and testosterone in determining causes, patterns and severity of androgen excess in a large sample of adult women recruited in a single center (12), generating useful guidance for clinicians to predict non-PCOS pathology in adult women presenting with androgen excess

Summary

Introduction

Androgen excess in childhood may present with a variety of symptoms and is thought to have a broad spectrum of underlying pathologies (1). The diagnosis of PA and PCOS require exclusion of other causes of androgen excess such as inborn steroidogenic enzyme defects, most commonly congenital adrenal hyperplasia (CAH), precocious puberty or potentially malignant virilizing adrenal tumors, with the latter being extremely rare in childhood (1, 5, 6). There is a paucity of data from larger cohorts delineating patterns and severity of childhood androgen excess considered predictive for both common and rare underlying pathologies

Methods

Results

Conclusion