medwireNews: Many children with congenital adrenal hyperplasia (CAH) may be receiving excessively high hydrocortisone doses, especially during the earliest months of life, a study suggests.
The researchers’ analysis included 1288 patients with CAH, drawn from a German/Austrian registry. The children were a median age of 7.2 years, 46.9% were boys, and the majority (63.4%) had salt-wasting CAH.
All study participants received hydrocortisone three times daily, at a median daily dose of 14.4 mg/m2 body surface area (BSA), with a range of 12.3 to 16.7 mg/m2 BSA.
Heike Hoyer-Kuhn (University of Cologne, Germany) and study co-authors observe that this dose falls within the recommended range of 10 to 15 mg/m2 BSA.
However, they stress that this median dose “also implies that 44% of all patients (41% of the patients older than 3 months) received a dosage higher than 15 mg/m2 BSA, which represents overdosage according to guidelines.”
Overtreatment was most common in the very youngest age group, with 73.3% of patients aged 0–3 months receiving a dose higher than 15 mg/m2 BSA.
“To the best of our knowledge, there is no evidence that higher dosages in the neonatal period reduce life-threatening events”, write the researchers in Endocrine Connections.
“Furthermore, there are different trials available showing an association between high dose glucocorticoid treatment and short stature in adulthood.”
They suggest that the higher doses in this very young age group could result from doctors minimising the risk of underdosing in the context of the need for frequent dose adjustments due to rapid growth and changes in BSA.
Overtreatment was also more frequent from the onset of puberty, at 50.6%, while rates of overtreatment of prepubertal children older than 3 months ranged from 33.6% to 38.3%.
The researchers cite research showing the potential for reduced final height in patients given hydrocortisone at a dose higher than 17 mg/m2 BSA during puberty, and say their data “should initiate a (re-)debate on dosing and weight adjusted [hydrocortisone] preparations in the participating centers.”
There were no significant dose differences between boys and girls, including within the different age categories. And there were no clear associations between overtreatment and the patients’ BMIs, height standard deviation scores or blood pressures. The 955 (74.1%) patients additionally receiving fludrocortisone (median dose 88.8 µg/day) received higher hydrocortisone doses than other patients at midday and in the evening, but not in the morning.
The team also found the median hydrocortisone dose to be significantly lower after the introduction of general CAH screening in 2005 than before, at 14.6 versus 16.4 mg/m2 BSA, which they say “goes along with the updated recommendations from the Endocrine Society to treat with the lowest effective dosage”.
By Eleanor McDermid
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Endocr Connect 2021; 10: 561–569