GHD reversal common, dependent on GH cutoff in diagnostic stimulation test

medwireNews: A systematic review and meta-analysis confirms a high rate of reversal of idiopathic growth hormone deficiency (IGHD), albeit strongly dependent on the peak GH cutoff used.

The analysis by Wolfgang Högler (Johannes Kepler University Linz, Austria) and colleagues included 25 studies published between 1987 and 2020, with a total of 1589 patients with IGHD, and identified an overall reversal rate of 61%.

However, this varied according to the peak GH threshold used in retesting, with the average reversal rate being 80% at a cutoff of 3–4 ng/mL, 74% at 5–6 ng/mL and 55% at 7.7–10 ng/mL.

The peak GH cutoff used for the initial diagnosis of GHD also varied, being primarily between 5 and 10 ng/mL, although two studies used a cutoff of 20 ng/mL with a GH-releasing hormone plus arginine test, two used multiple cutoffs with different stimulants and two did not state the cutoff used.

The pooled reversal rate was higher among studies with an original GH cutoff of 10 ng/mL than among those with a lower cutoff, at 57–84% depending on the retesting cutoff versus 43% for a retesting cutoff of 3.5–8 ng/mL.

“Thus, adherence to the currently recommended GH cut-off value of 7 ng/ml is likely to reduce the number of children falsely classified GH-deficient”, write the researchers in the European Journal of Endocrinology.

They note that the GH cutoffs used for GHD diagnosis “remain completely arbitrary”, despite being guideline recommended, and highlight other issues such as the poor intra-test reproducibility, differences introduced with the wide range of stimuli used and high inter-assay variability.

“Nonetheless, the peak GH threshold concentration is the crucial parameter determining GH status in IGHD to date”, say Högler and study co-authors.

There was also a higher reversal rate among patients who were retested after attaining their final height compared with those retested earlier, at 75% versus 48%, which the researchers note supports “the hypothesis of GH axis maturation.”

They say there is an argument for retesting prior to final height attainment because “[a]dequate linear growth after GHD reversal and cessation of GH therapy serves as a solid parameter indicating true GHD reversal in absence of a biochemical gold standard marker.”

This would necessitate additional retesting in patients found to have persistent GHD, say Högler and team, but would reduce treatment burden and cost for those able to stop GH therapy early.

“Mid-puberty may be a suitable time-point to safely reevaluate GH status”, they suggest.

By Eleanor McDermid

medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2022 Springer Healthcare Ltd, part of the Springer Nature Group

Eur J Endocrinol 2022; doi:10.1530/EJE-21-1179
Martin Savage
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