medwireNews: Nearly two-thirds of children with non-classic congenital adrenal hyperplasia (NCCAH) have an inadequate cortisol response, report researchers.

“The clinical implications of this finding remain unclear and deserve evaluation given the potential risk for adrenal crisis when patients with an inadequate cortisol response to stimulation are exposed to stress”, say Michel Polak (Hôpital Universitaire Necker-Enfants Malades, Paris, France) and study co-authors.

Although current guidelines do not advocate glucocorticoid treatment of asymptomatic NCCAH patients, the team suggests that it may be advisable in those with a blunted cortisol response in the event of major stress, such as surgery, trauma or childbirth.

“Special attention is required during puberty, a period with physiological changes in cortisol metabolism and pharmacokinetics”, they note in Hormone Research in Paediatrics.

The researchers found an insufficient cortisol response (peak cortisol <18 μg/dL) to tetracosactide in 21 (60%) of 35 children with genetically confirmed NCCAH, compared with just one (2.1%) of 47 control patients with premature pubarche.

The majority (68.6%) of the NCCAH patients (26 girls; nine boys) were seen for premature growth of pubic and/or axillary hair, with the others identified via family screening. They were aged an average of 7.0 years at first investigation, and there was a significant difference in average age between the NCCAH patients with inadequate and normal cortisol responses, at 8.3 versus 5.1 years.

Despite their blunted cortisol response, the patients with NCCAH had significantly higher baseline cortisol levels than the control group, at 12.9 versus 9.7 μg/dL. They also had increased adrenocorticotropic hormone levels, at 51.3 versus 29.5 pg/mL.

“One possible explanation is chronic adrenal gland overstimulation to achieve sufficient cortisol levels in patients with NCCAH”, suggest the researchers.

Besides premature body hair growth, the NCCAH patients commonly had an accelerated growth rate (37.1%), bone age advancement (48.6%) and acne (17.1%). Two patients had severe fatigue, which improved when they received hydrocortisone therapy, which Polak et al say implies a role for adrenal insufficiency in severe fatigue, especially as a recent study reported this symptom in 41% of patients with classic CAH.

But they caution: “Fatigue is a common complaint in patients with adrenal insufficiency and should be evaluated using objective tools, such as validated questionnaires, which can measure both chronic and momentary fatigue.”

By Eleanor McDermid, Senior medwireNews Reporter

Horm Res Paediatr 2015; Advance online publication

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