Endocrine Profiling in DSD

Differences in sex development (DSD) are conditions in which there is an inconsistency between chromosomal, gonadal, and genital/anatomical development. Among the tools available for their evaluation, endocrine profiling is the least reliable owing to the dynamic nature of hormone secretion and limitations in the currently used methods for assay. Nevertheless, when employed appropriately, it provides immense insight into the possible etiology. With the introduction of liquid chromatography-tandem mass spectroscopy, the assay sensitivity and specificity have improved significantly; however, a standardization of laboratory values and normal reference ranges is needed. The source of androgens in humans is either the adrenal gland or the gonads and the pathology of most DSDs originates from either of these. In suspected isolated hypofunctioning of the testes, the work-up focuses on the assessment of the presence and functionality of testicular tissue. As the steroidogenic pathway is similar in the adrenal and the gonads, deficiency of any of the enzymes involved can present with both gonadal and adrenal failure. If adrenal involvement is evident, a complete adrenal steroid profile is the preferred approach. In a 46 XX infant with atypical genitalia, the commonest etiology being 21 hydroxylase deficiency, the initial work-up is geared toward ruling out adrenal insufficiency and confirming hyperandrogenism. In this chapter, we discuss common clinical scenarios at birth, beyond mini-puberty and at puberty; and suggest appropriate timing and choice of hormonal evaluation.