medwireNews: Growth hormone (GH) treatment of children with Silver-Russell Syndrome (SRS) is associated with early adrenarche, but this does not compromise their growth response, report researchers.

The 34 boys and 28 girls in the study reached adrenarche (dehydroepiandrosterone sulphate [DHEAS] level >500 ng/mL) at a median age of 9.2 and 8.1 years, respectively, which the researchers say is only about 1 year ahead of the population norm.

However, 13% percent of the patients – all boys – had premature adrenarche, defined as the finding of clinical pubarche in boys younger than 9 years, which the team says “is certainly more frequent than in the general population”.

Age at adrenarche was closely associated with age at gonadarche in boys (median 11.9 years), but not in girls (10.2 years). Just one patient of the 51 followed up to puberty had central precocious puberty – a boy who had gonadarche at the age of 6.9 years, following adrenarche at 2.3 years.

After accounting for confounding factors, low birthweight was a moderate predictor of early adrenarche in boys, but not girls, whereas low age at initiation of GH treatment was moderately to highly predictive. GH was initiated at a median age of 5.8 years in boys and 5.4 years in girls.

Gerhard Binder (University Children’s Hospital, Tübingen, Germany) and co-researchers note that early GH initiation may not actually cause early adrenarche, because factors such as the severity of SRS and of growth failure influence the age at presentation and treatment, as could increasing recognition of SRS in the medical community.

However, they observe that studies in children born small for gestational age have reported a rise in DHEAS levels during GH treatment, suggesting that it could be a direct effect of GH.

“Importantly, the effects of early adrenarche on final height were negligible”, the team writes in The Journal of Clinical Endocrinology & Metabolism.

Neither adult height, difference between adult height and target height, nor treatment-related gain in height standard deviation scores were associated with age at adrenarche. The median residual growth after adrenarche was 36.7 cm in boys and 27.7 cm in girls, but there was greater residual growth in patients with earlier adrenarche and post-adrenarche growth was not influenced by age at GH initiation.

“Therefore, our data do not support a general therapeutic intervention in SRS aiming to enhance growth by suppressing adrenarche or inhibiting the aromatization of adrenal androgens”, conclude the researchers.

By Eleanor McDermid

J Clin Endocrinol Metab 2017; Advance online publication

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