medwireNews: Children with idiopathic growth hormone deficiency (GHD) should be retested at mid-puberty, say researchers who found a substantial proportion no longer required GH treatment.
And withdrawing GH treatment in those with normalised GH did not adversely affect their growth outcomes, say Paolo Cavarzere (University Hospital of Verona, Italy) and study co-authors.
“On the contrary, in such cases, discontinuation may reduce potential side effects and unnecessary discomfort to patients and their families, as well as reduce costs for the National Health care system”, they write in the European Journal of Endocrinology.
The team assessed 46 boys and 34 girls, who had started GH therapy at 0.033 mg/kg for 6 days/week at an average age of 9.88 and 9.64 years, respectively, when their height standard deviation scores (SDSs) were –2.57 and –2.34.
When the children reached Tanner stage 3, GH therapy was withdrawn for 12 weeks, after which they underwent a repeat GH stimulation test. Forty-four (55%) children (23 boys and 21 girls) had a GH peak of 8 µg/L or more in response to arginine, and GH therapy was stopped. The remaining 23 boys and 13 girls had persistent GHD, and restarted GH treatment.
The researchers say that normalisation of GH secretion “may, at least in part, represent maturation of the pituitary gland.”
But they also acknowledge issues with the diagnosis of GHD, such as the usual peak GH cutoff not accounting for factors like age, pubertal status and adiposity.
After mid-puberty testing, children who discontinued treatment continued to grow at an average velocity of 7.4 cm/year, which was not significantly different from the previous 8.0 cm/year velocity, and the corresponding rates for those who restarted GH were 4.1 and 4.4 cm/year.
When the children had attained near-adult height, the shortfall between height SDS and their genetic target height SDS was –0.69 for boys who stopped GH treatment and –0.34 for those who continued, with corresponding values of –0.70 and –0.28 for girls. These differences were not statistically significant.
“Our findings contrast with other studies that, on the contrary, suggested increasing the GH dose during puberty in order to optimize the GH effect”, say Cavarzere and team, but they note that a previous study found no benefit for this approach.
“In this context, our results might offer a good alternative”, they suggest. “[I]t might be beneficial to retest all GHD patients at mid-puberty and then evaluate in a subsequent study whether only patients with persistent GHD benefit from higher doses in order to improve their final stature.”
The team found just one factor that was significantly associated with the likelihood of persistent GHD: lower levels of insulin-like growth factor (IGF)-1 after 1 year of treatment. The association was nonlinear, with the effect only appearing below an IGF-1 level of 50 nmol/L.
A 1-year IGF-1 level below 32.5 nmol/L (or SDS –0.45) was 67% sensitive and 76% specific for persistent GHD, and the researchers suggest that children who fall into this category can be assumed to have ongoing GHD and may not need to be retested at mid-puberty.
But they caution that this cutoff should be confirmed in a larger prospective study.
By Eleanor McDermid
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Eur J Endocrinol 2020; 182: 559–567