Abstract
Biological assessment of abnormal genitalia is based on an ordered sequence of endocrine
and genetic investigations that are predicated on knowledge obtained from a suitable
history and detailed examination of the external genital anatomy. Investigations are
particularly relevant in 46,XY DSD where the diagnostic yield is less successful than
in the 46,XX counterpart. Advantage should be taken of spontaneous activity of the
pituitary-gonadal axis in early infancy rendering measurements of gonadotrophins and
sex steroids by sensitive, validated assays key to assessing testicular function.
Allied measurement of serum anti-Müllerian hormone completes a comprehensive testis
profile of Leydig and Sertoli cell function.
Genetic assessment is dominated by analysis of a plethora of genes that attempts to
delineate a cause for gonadal dysgenesis. In essence, this is successful in up to
20% of cases from analysis of SRY and SF1 (NR5A1) genes. In contrast, gene mutation
analysis is highly successful in 46,XY DSD due to defects in androgen synthesis or
action. The era of next generation sequencing is increasingly being applied to investigate
complex medical conditions of unknown cause, including DSD. The challenge for health
professionals will lie in integrating vast amounts of genetic information with phenotypes
and counselling families appropriately. How tissues respond to hormones is apposite
to assessing the range of genital phenotypes that characterise DSD, particularly for
syndromes associated with androgen resistance. In vitro methods are available to undertake
quantitative and qualitative analysis of hormone action. The in vivo equivalent is some assessment of the degree of under-masculinisation in the male,
such as an external masculinisation score, and measurement of the ano-genital distance.
This anthropometric marker is effectively a postnatal readout of the effects of prenatal
androgens acting during the masculinisation programming window. For investigation
of the newborn with abnormal genitalia, a pragmatic approach can be taken to guide
the clinician using appropriate algorithms.
Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Journal of Pediatric UrologyAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- The effect of dihydrotestosterone exposure during or prior to the masculinization programming window on reproductive development in male and female rats.Int J Androl. 2012; 35: 330-339
- Holistic management of DSD.Best Pract Res Clin Endocrinol Metab. 2010; 24: 335-354
- The role of a clinical score in the assessment of ambiguous genitalia.BJU Int. 2000; 85: 120-124
- Phenotypic classification of male pseudohermaphroditism due to steroid 5 alpha-reductase 2 deficiency.Am J Med Genet. 1996; 63: 223-230
- Androgen receptor defects: historical, clinical, and molecular perspectives.Endocr Rev. 1995; 16: 271-321
- AMH determination is essential for the management of 46, XY DSD patients.Horm Res. 2009; 72: 365
- UK guidance on the initial evaluation of an infant or an adolescent with a suspected disorder of sex development.Clin Endocrinol. 2011;
- Hypophyso-gonadal function in humans during the first year of life. 1. Evidence for testicular activity in early infancy.J Clin Invest. 1974; 53: 819-828
- A novel ultrapressure liquid chromatography tandem mass spectrometry method for the simultaneous determination of androstenedione, testosterone and dihydrotestosterone in paediatric blood samples: age-and sex-specific reference data.J Clin Endocrinol Metab. 2010; 95: 239-409
- Gas chromatography/mass spectrometry (GC/MS) remains a pre-eminent discovery toll in clinical steroid investigations even in the ear of fast liquid chromatography tandem mass spectrometry (LC/MS/MS).J Steroid Biochem Mol Biol. 2010; 121: 496-504
- Consensus statement on management of intersex disorders.Arch Dis Child. 2006; 91: 554-563
Bashamboo A, McElreavey K. Gene mutations associated with anomalies of human gonad formation. Sex Dev 2012 Oct 3 [Epub ahead of print].
- Studies of a cohort of 46, XY with DSD including steroid biosynthesis deficiencies.Adv Exp Med Biol. 2011; 707: 15-17
- Molecular mechanisms of androgen action – a historical perspective.Methods Mol Biol. 2011; 776: 3-24
- Androgen insensitivity syndrome.Lancet. 2012; ([Epub ahead of print])
- Anogenital distance from birth to 2 years: a population study.Environ Health Perspect. 2009; 117: 1786-1790
- The relationship between anogenital distance, fatherhood and fertility in adult men.PLoS One. 2011; 6: e18973
- Caucasian male infants and boys with hypospadias exhibit reduced anogenital distance.Hum Reprod. 2012; 27: 1577-1580
- Increased activation of the alternative ‘backdoor’ pathway in patients with 21-hydroxylase deficiency: evidence from urinary steroid hormone analysis.J Clin Endocrinol Metab. 2012; 97: 367-375
- New technologies for the identification of novel genetic markers of disorders of sex development (DSD).Sex Dev. 2012; 4: 213-224
- Exome sequencing: dual role as a discovery and diagnostic tool.Ann Neurol. 2012; 71: 5-14
- Incidental medical information in whole-exome sequencing.Pediatrics. 2012; 129: 1605-1611
Article info
Publication history
Published online: November 19, 2012
Accepted:
October 2,
2012
Received:
September 21,
2012
Identification
Copyright
© 2012 Journal of Pediatric Urology Company. Published by Elsevier Inc. All rights reserved.
