Basal, ACTH-stimulated adrenal steroid tests unmask non-classical CAH underlying precocious puberty

medwireNews: Basal adrenal androgen levels can help identify girls with non-classical congenital adrenal hyperplasia who present as central precocious puberty (CPP), but adrenocorticotrophic hormone (ACTH) stimulation may be needed for a firm diagnosis, say researchers.

This recommendation is based on the findings of a case–control study of 177 girls from a tertiary paediatric endocrinology institute in Israel who were diagnosed with CPP following gonadotropin-releasing hormone and ACTH stimulation tests.

Liat de Vries and colleagues from Tel Aviv University in Israel note that “the routine performance of basal androgen and/or ACTH tests as part of the work-up for CPP is controversial, and most centers apply them only when adrenarche is prominent.”

They add: “Our policy [to routinely use the test] is based on previous reports by our group and others showing that CPP may be a presenting sign of NCCAH.”

The team found no statistically significant differences in height, weight, BMI, bone age and age at onset of puberty between the 37 girls ultimately diagnosed with NCCAH and the 140 with idiopathic CPP.

Tanner stage tended to be lower in the NCCAH group, with patients more likely to present in stage 1 or 2 than later stages. Conversely, patients with idiopathic CPP were more likely to present in Tanner stage 3 or 4 than earlier stages.

The girls with NCCAH did, however, have significantly higher mean basal levels of androstenedione (5.0 vs 2.2 nmol/L), 17- hydroxyprogesterone (17-OHP; 32.6 vs 1.9 nmol/L) and dehydroepiandrosterone (3.6 vs 1.5 nmol/L) than those with idiopathic CPP, but the researchers note that the ranges overlapped considerably between the groups.

Furthermore, stepwise logistic regression analysis of these three hormones showed that only 17-OHP was significantly associated with a diagnosis of NCCAH, at an odds ratio of 2.17. The researchers calculated that, at a cutoff of 6.0 nmol/L, 17-OHP predicted NCCAH with a sensitivity of 97.1% and a specificity of 97.2%.

Basal oestradiol and luteinising hormone levels were similar between the two groups, whereas the stimulated levels of both hormones, as well as cortisol, were significantly lower in the NCCAH group than in the in the idiopathic CPP group.

In addition, girls with NCCAH were significantly more likely to have a family history of the condition than those with idiopathic CPP (16.7 vs 0.0%), but significantly less likely to have a family history of PP (8.1 vs 40.4%).

Writing in The Journal of Clinical Endocrinology & Metabolism, de Vries and co-authors point out that the prevalence of NCCAH in their cohort was “significantly higher than that reported in the general population and supports previous data showing that NCCAH may trigger early activation of the hypothalamic-pituitary-gonadal axis.”

“Thus, it seems that in girls with true CPP, from populations where the disorder is prevalent, an assessment of adrenal androgen levels is required and an ACTH test should be considered”, they remark.

The researchers add: “The decision to perform an ACTH stimulation test should be based on clinical parameters, including family history and level of basal 17-OHP and possibly androstenedione.”

By Laura Cowen

medwireNews is an independent medical news service provided by Springer Healthcare. © 2019 Springer Healthcare part of the Springer Nature group

J Clin Endocrinol Metab 2019; doi:10.1210/jc.2018-02605
Martin Savage
Programme Director

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