medwireNews: Steroid hormone profiles can identify the majority of children with non-congenital adrenal hyperplasia (CAH) primary adrenal insufficiency (PAI), say researchers.
“The present study provides, for the first time, a comprehensive steroid profiling of patients with non-CAH PAI”, say Tulay Guran (Marmara University School of Medicine, Istanbul, Turkey) and study co-authors.
“Our results revealed a profound and generalized reduction of adrenocortical steroid production in these patients, which is evident even in early infancy.”
All of the 41 children (median age 3 months, range 0–8 years) had severe cortisol deficiency, as well as elevated adrenocorticotropic hormone (ACTH). In addition, 95.1% had adrenal androgen deficiency, 58.5% had mineralocorticoid deficiency and 31.7% had gonadal sex steroid deficiency.
The researchers report that the combination of cortisol levels below 4 ng/mL, cortisone below 11 ng/mL and corticosterone of less than 0.11 ng/mL had 96% accuracy for distinguishing between non-CAH PAI patients and 324 healthy infants (age 3 days to 6 months).
The team also found that sequencing a target panel of genes provided a genetic diagnosis for most patients, whereas whole-exome sequencing offered no additional information.
“In this highly selected cohort, molecular etiologies were distributed in eleven genes including MC2R, STAR, NNT, NR0B/DAX1, CYP11A1, MRAP, SGPL1, ABCD1, AIRE, AAAS and HSD3B2”, say Guran and colleagues.
This provided a genetic diagnosis for 29 (70.7%) of the 41 children in the current study. The researchers say that, in combination with other published studies, this suggests that variations in around 20 genes account for 65–80% of non-CAH PAI cases.
Therefore, “targeted panel sequencing is the easiest and the most cost-effective first-line approach to perform the genetic analysis”, they write in The Journal of Clinical Endocrinology & Metabolism.
The study participants came from 40 unrelated families, 60% of which had consanguinity. The patients carried a total of 24 mutations in the 11 affected genes; eight of the mutations were previously unreported.
Whole-exome sequencing was carried out for the 12 patients who remained without a genetic diagnosis, but this did not provide any additional information.
These children were older than other patients when diagnosed, were more likely to be male, less likely to have parental consanguinity and had lower ACTH levels and less severe steroid hormone deficiencies.
By Eleanor McDermid
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