Growth hormone retesting for idiopathic isolated growth hormone deficiency during and after puberty: a systematic review

Context: 

Idiopathic isolated growth hormone deficiency (IIGHD) is difficult to diagnose due to the day-to-day variation in growth hormone (GH) secretion and limitations of GH stimulation testing (GHST). Although recombinant human GH (rhGH) is typically continued until near adult height (NAH), many patients no longer show deficiency at that point. The optimal timing and method for retesting GH secretion remain unclear. 

Objective: 

To summarize the currently available GHSTs in children with IIGHD, with particular focus on diagnostic strategies in the peripubertal period, timing of retesting, and the role of sex steroid priming. 

Methods: 

A systematic literature search was conducted in 4 databases up to June 2025. Studies were included if they reported on GH retesting in children with IIGHD. Data were extracted on patient characteristics, GHST protocols, priming strategies, cutoff values, and reversal rates. Risk of bias was assessed using the ROBINS-I tool. 

Results: 

Thirty-one studies involving 2057 patients were included. Retesting occurred after 1–2 years of rhGH treatment, during mid-puberty, or at (N)AH, with mean reversal rates of 46.4%, 46.3%, and 69.6%, respectively. Priming with sex steroids was inconsistently applied, using testosterone in boys and ethinyl estradiol in girls. A GH peak cutoff of 7 μg/L was most commonly used, though values varied. Mid-pubertal retesting may reduce false-positive diagnoses and treatment burden.

Conclusion: 

Retesting strategies for IIGHD should be individualized based on treatment response and pubertal development. Early retesting is advised for poor responders, while mid-puberty retesting suits most patients with normal development. Priming is recommended in older prepubertal children. Standardization of GHST protocols and long-term outcome studies are needed to optimize care and reduce overtreatment.