TOPLINE: 

In transition-age patients with childhood-onset growth hormone deficiency (GHD), peak growth hormone (GH) response to the glucagon stimulation test (GST) appeared to be influenced more by the severity of the pituitary dysfunction than by BMI. Childhood cancer survivors and patients with organic severe etiologies showed the lowest GH responses and the highest likelihood of persistent GHD.

METHODOLOGY:

• GST is increasingly used as an alternative to the insulin tolerance test to diagnose persistent GHD during the transition period from late adolescence to early adulthood, but its accuracy and optimal cutoff values remain unclear.
• This retrospective cohort study included 180 patients with childhood-onset GHD (median age at GHD retesting, 17.39 years; 112 males) and evaluated GH responses to the GST during the transition period, with a focus on the influence of BMI and underlying etiology.
• Participants were grouped according to etiology: idiopathic GHD (n = 80), organic moderate GHD (n = 63; one to two pituitary deficiencies with congenital or acquired anomalies), and organic severe GHD (n = 37; three or more pituitary deficiencies with complex central nervous system abnormalities). Childhood cancer survivors comprised 42% of the cohort.
• All participants underwent a standardized GST (1 mg intramuscular glucagon) after an overnight fast, with serial GH measurements from 0 to 180 minutes after glucagon administration; GH therapy was stopped for at least 1 month before retesting.
• Participants were classified by BMI as having normal weight, overweight, or obesity according to age-appropriate criteria.

TAKEAWAY:

• GH levels peaked at 150 minutes after glucagon administration. The mean GH responses were lowest in patients with organic severe GHD and highest in those with idiopathic GHD. Childhood cancer survivors had lower peaks than other patients; among survivors, patients with organic severe GHD had lower peaks than those with organic moderate GHD.
• The median GH peak in the overall cohort was 5.86 μg/L. Using this cutoff, persistent GHD was confirmed in 50% of patients, with the highest rates in patients with organic severe GHD (91.9%), followed by those with organic moderate GHD (77.8%) and idiopathic GHD (8.8%; P < .001).
• A higher BMI standard deviation score (SDS) correlated with lower GH peaks (Spearman rho = -0.457; P < .001); this association weakened after adjustment for original GHD etiology, which emerged as a stronger determinant of GH response than BMI.
• At the time of the GST, obesity was most common in the organic GHD subgroups: 11.1% in the organic moderate and 35.1% in the organic severe vs 5.0% in the idiopathic GHD group. Two thirds (66.7%) of patients with obesity were childhood cancer survivors, who accounted for the majority of individuals with obesity within the organic subgroups. 

IN PRACTICE:

"This study highlights the GST as a reliable and effective diagnostic tool for assessing persistent GHD during the transition from adolescence to adulthood, especially in individuals with organic or acquired GHD etiologies, such as [childhood cancer survivors]," the authors wrote. 

SOURCE:

The study was led by Daniela Fava, University of Genoa, Genoa, Italy. It was published online on January 12, 2026, in The Journal of Clinical Endocrinology & Metabolism.

LIMITATIONS: 

The retrospective design may have introduced selection and information biases. Because not all patients underwent the insulin tolerance test, the GST results could not be compared with the diagnostic gold standard. A relatively small organic severe GHD subgroup limited the statistical power for subgroup analyses. 

DISCLOSURES:

The study was supported by the Italian Ministry of Health through Ricerca corrente 2024. Some authors were members of the European Reference Network Rare Endocrine Conditions and/or the European Reference Network on Rare Bone Diseases.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.