medwireNews: Children with IGF1 receptor mutations (IGF1RM) have a greater degree of growth retardation and worse response to recombinant human growth hormone (rhGH) therapy than children born small for gestational age (SGA) without the alterations, research shows.

“However, if first-year response is good […], IGF1RM patients potentially can catch up growth to the level of treated SGA children”, Eric Göpel (University of Leipzig, Germany) and co-investigators report in The Journal of Clinical Endocrinology & Metabolism.

The authors therefore believe that children with “IGF1RM should not be excluded from rhGH treatment, but that a critical reevaluation of success should be performed periodically.”

“Then physicians and patients/parents should weigh realistic expectations and potential side effects of hormone treatment”, they write.

The researchers found that IGF1RM carriers (n=17) were a significant 0.70 SDS shorter than wild-type patients (n=34) at rhGH initiation (median height SDS=–3.41 vs –2.71), despite having comparable birth length (–2.57 vs –2.80 SDS).

In addition, IGF1RM patients had a significantly slower response to rhGH during the first year of treatment than controls, with median differences in height SDS from rhGH initiation to follow-up of 0.29 and 0.65, respectively.

After 4 years of treatment, there was no significant difference between the two groups in median near-final height (NFH) SDS, although this tended to be lower in IGF1RM carriers than participants who were SGA (–2.59 vs –2.26 SDS).

Göpel and team also observed a high degree of variability in growth among the IGF1RM patients. This led them to compare the outcomes among good versus poor responders.

They found that more than half (53%) of participants with IGF1RM were poor responders (change in height SDS <0.3 within the first year of treatment), compared with just 17% of SGA participants.

Within the IGF1RM cohort, good responders had a significantly higher 1-year change in height SDS than poor responders (0.61 vs 0.04 SDS) as well as a greater NFH adjusted for birth length (0.92 vs –1.62). Indeed, the researchers note that adjusted change in NFH among the IGF1RM good responders was “comparable to the favorable therapeutic success of SGA controls”, at 0.81 SDS.

They attempted to identify predictors of response to rhGH among the IGF1RM patients but found no differences in auxologic or endocrine measurements between the poor and good responders.

There was, however, a tendency towards a higher proportion of mutations within the extracellular part of the receptor among poor responders, and a higher proportion within the intracellular part of the receptor among good responders.

Finally, Göpel compared outcomes between 11 adult mutation carriers and 11 age and gender-matched SGA controls. They found no difference in the rates of comorbidities such as diabetes, thyroid disease, hearing loss, cancer, wound healing disorders, mental or neurological diseases and abortion between the two groups.

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/clinem/dgz165