Society for Endocrinology UK Guidance on the Initial Evaluation of a Suspected Difference or Disorder of Sex Development (Revised 2021)

S. Faisal Ahmed; John Achermann; Julie Alderson; Naomi S. Crouch; Sue Elford; Ieuan A. Hughes; Nils Krone; Ruth McGowan; Talat Mushtaq; Stuart O'Toole; Leslie Perry; Martina E. Rodie; Mars Skae; Helen E. Turner


Clin Endocrinol. 2021;95(6):818-840. 

In This Article

Steroid Measurement and its Interpretation

Steroid hormone analysis is a vital component of the biochemical evaluation, but the method of analysis can have a significant impact on the result. Liquid chromatography linked with tandem mass spectrometry (LC-MS/MS) allows multiple analyte analysis from a single sample whilst maintaining analytical specificity[64] and, in cases of DSD, plasma or serum steroids should be measured by LC-MS/MS which is available increasingly widely in the UK.[65] It is expected that over the next few years, further advances in the range of steroids that can be routinely measured in diagnostic laboratories in the UK will lead to greater diagnostic accuracy. For instance, LC-MS/MS-based analysis of multiple steroids including 17OHP, 21-deoxycortisol and 11-deoxycortisol may provide greater diagnostic precision at an earlier stage in a newborn with CAH.[66] However, there is a need for a sustained effort at ensuring that these diagnostic services contribute to external quality assessment. Close communication between the clinical and biochemistry personnel within the DSD team is vital to enable correct interpretation of laboratory results and awareness that results should be available in a timely manner. In addition to serum steroid analysis, USP analysis by gas chromatography mass spectrometry (GC-MS) can provide additional and more comprehensive qualitative and quantitative data on excretion of steroid metabolites. As gonadotrophins, androgens and precursors, fluctuate markedly over the first few months of life and may lead to a diagnostically blind window there is a place to consider an early neonatal collection as well as further samples at a later stage. A urine sample can be frozen and stored for many years and may help with a review of the diagnosis at a later stage. USP is not appropriate for suspected cases of 5α-reductase type 2 deficiency until after 3 months of age as diagnostic pairs of 5β to 5α reduced metabolites are not detectable until then.[67] As urine metabolites may also fluctuate during the day,[68] in cases where there is a high level of suspicion, the clinician should consider a 24-h urine collection. The number of steroid metabolites that can be measured on a USP has also increased dramatically over the past few years and whilst ratios of individual metabolites may provide greater discriminatory power[69] their utility in routine clinical practice needs further review.[70] Normally, infants, particularly boys, have significant changes in steroid and other endocrine hormone concentrations during the first 100 days of birth.[64] In boys, serum testosterone and DHT may initially be high at birth but decline to less than 1 nmol/L or undetectable, respectively. Concentrations then rise from around day 30 after birth to peak at day 70 before declining to normal prepubertal concentrations.[71] These normal variations may influence the interpretation of sex steroid and gonadotrophin measurements as well as the results of the hCG stimulation test. Furthermore, the actual value for the hormone concentration will vary depending on the assay methodology.