Endocrine Abstracts

Introduction: Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders that arise from enzyme deficiencies in biosynthetic pathways of the adrenal. The most common enzyme deficiency, 21-hydroxylase deficiency, results in cortisol deficiency, androgen excess and variable aldosterone deficiency. Current guidelines recommend a standard dose short Synacthen test (SDSST) is performed between 24 and 48 hours of life, with measurement of cortisol and androgens. Cortisol is measured routinely by chemiluminescent immunoassay (CLIA). However, there is cross-reactivity of cortisol with 17α-hydroxyprogesterone and 21-deoxycortisol in most CLIA assays, which are elevated in patients with 21-hydroxylase deficiency, giving a falsely higher cortisol level. Liquid chromatography–tandem mass spectrometry (LC–TMS) is highly specific and eliminates this risk.

Method: Retrospective, observation study of infants, presenting between June 2022 and February 2023 with clinical and biochemical profiles suggestive of CAH and paired measurements of cortisol made by CLIA and LC–TMS.

Results: Three infants (2M, 1F) were noted to have discrepancies in cortisol concentrations measured by CLIA and LC–TMS. The female patient had virilised genitalia. All patients had hyponatremia, hyperkalaemia but remained normoglycemic. Cortisol concentrations were healthy on SDSST analysed by CLIA in two patients, however other biochemical parameters were consistent with a diagnosis of CAH. Samples were therefore reanalysed by LC–TMS and were found to be low. The third patient had low cortisol on SDSST, with a healthy random cortisol measurement. Cortisol measurements by CLAI and LC–TMS are given in Table 1.Table 1 Cortisol concentrations on baseline and peak samples on SDSST, and random samples measured by CLIA and LC–TMS, and 17-hydroxyprogesterone in three infants with CAH.

Conclusion: Cortisol measured by CLIA is unreliable in infants with very high levels of 17-hydroxyprogesterone, and it’s metabolites, secondary to 21-hydroxylase deficiency CAH. Therefore, we recommend cortisol is measured by LC–TMS.