Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Dec 18;110(1):78-90.
doi: 10.1210/clinem/dgae408.

Accuracy of Glucagon Testing Across Transition in Young Adults With Childhood-Onset GH Deficiency

Daniela Fava  1   2 , Davide Guglielmi  2 , Carlotta Pepino  1 , Alessia Angelelli  1   2 , Emilio Casalini  1   2 , Carolina Varotto  1 , Marta Panciroli  1 , Caterina Tedesco  2 , Tiziana Camia  1 , Alessandro Naim  1 , Anna Elsa Maria Allegri  2 , Giuseppa Patti  1   2 , Flavia Napoli  2 , Roberto Gastaldi  2 , Stefano Parodi  3 , Mariacarolina Salerno  4 , Mohamad Maghnie  1   2 , Natascia Di Iorgi  1   2
Affiliations

Accuracy of Glucagon Testing Across Transition in Young Adults With Childhood-Onset GH Deficiency

Daniela Fava et al. J Clin Endocrinol Metab. .

Abstract

Context: The 2019 American Association of Clinical Endocrinologists guidelines suggested peak GH-cutoffs to glucagon test (GST) of ≤3 and ≤1 µg/L in the diagnosis of permanent GH deficiency (GHD) during the transition phase.

Objective: The aim of the study was to evaluate the accuracy of GST compared to insulin tolerance test (ITT) in the definition of GHD at adult height achievement.

Patients and methods: Ninety-seven subjects with childhood-onset GHD (median age, 17.39 years) underwent ITT, GST, and IGF-1 testing; 44 subjects were idiopathic (isolated GHD), 35 moderate organic GHD (0-2 hormone deficiencies) and 18 severe organic GHD (≥3 hormone deficiencies).

Results: Bland and Altman analysis showed a high consistency of GH peak measures after ITT and GST. Receiver operating characteristic analysis identified 7.3 μg/L as the optimal GH peak cutoff to GST [95% confidence interval (CI) 4.15-8.91; sensitivity 95.7%, specificity 88.2%, positive predictive value (PPV) 88.0%, negative predictive value (NPV) 95.7%] able to correctly classify 91.8% of the entire cohort while 5.8 μg/L was the best GH peak cutoff able to correctly classify 91.4% of moderate organic GHD patients (95% CI 3.16-7.39; sensitivity 96.0%, specificity 80.0%, PPV 92.3%, NPV 88.9%). Patients with ≥3 hormone deficiencies showed a GH peak <5 μg/L at ITT and <5.8 μg/L at GST but 1. The optimal cutoff for IGF-1 was -1.4 SD score (95% CI -1.94 to 0.77; sensitivity 75%, specificity 94%, PPV 91.7%, NPV 81.0%) that correctly classified 85.1% of the study population.

Conclusion: A GH peak to GST <5.8 μg/L represents an accurate diagnostic cutoff for young adults with childhood-onset GHD and high pretest probability of permanent GHD.

Keywords: GH deficiency; ITT; brain tumors; congenital hypopituitarism; glucagon; pituitary stalk interruption syndrome; posterior pituitary ectopia; transition; young adults.

PubMed Disclaimer

Figures

Figure 1.
Figure 1.
Etiological diagnosis of 97 patients with childhood-onset GHD at the time of the study subdivided in 3 groups: I-GHD, OM-GHD, OS-GHD. Abbreviations: GHD, GH deficiency; I-GHD, idiopathic growth hormone deficiency; OM-GHD, organic moderate GHD; OS-GHD, organic severe GHD.
Figure 2.
Figure 2.
(A) Box plots show median (thick line), the IQR, delimited by the first and third quartile (margins of the box), and the range of values between ± 1.5 IQR from the margin of the box (whiskers) of peak GH at GST in the 3 groups: I-GHD, OM-GHD, OS-GHD. P-value from the Kruskal–Wallis nonparametric test. Outliers are also shown for each group. (B) Box plots show median (thick line), first and third quartile (margins of the box), minimum and maximum values of IGF-1 SD score at retesting in the 3 groups: I-GHD, OM-GHD, OS-GHD. P-value from the Kruskal–Wallis nonparametric test is indicated. Abbreviations: GHD, GH deficiency; GST, glucagon stimulation test; I-GHD, idiopathic growth hormone deficiency; IQR, interquartile range; OM-GHD, organic moderate GHD; OS-GHD, organic severe GHD.
Figure 3.
Figure 3.
(A) Mean (SD) GH values curve at each time point of GST in patients withI-GHD, OM-GHD, OS-GHD. (B) Mean (SD) blood glucose value curve at each time point of GST in patients with I-GHD, OM-GHD, OS-GHD. Abbreviations: GHD, GH deficiency; GST, glucagon stimulation test; I-GHD, idiopathic growth hormone deficiency; OM-GHD, organic moderate GHD; OS-GHD, organic severe GHD.
Figure 4.
Figure 4.
Agreement between peak GH values at the ITT and at the GST, evaluated by the Bland and Altman plot. The P-value associated with the Pitman's test is shown. Abbreviations: GST, glucagon stimulation test; ITT, insulin tolerance test.
Figure 5.
Figure 5.
(A-C) ROC curve analyses of peak GH to GST in the entire cohort (A) and in OM-GHD group (C). (B-D) ROC curve analyses of IGF-1 SDS in the entire cohort (B) and in OM-GHD group (D). Abbreviations: OM-GHD, organic moderate GHD; ROC, receiver operating curve; SDS, SD score.
Figure 6.
Figure 6.
Algorithm for the evaluation of GH function in childhood-onset GHD after adult at the time of transition. Abbreviation: GHD, GH deficiency.
See this image and copyright information in PMC

References

    1. Tauber M, Moulin P, Pienkowski C, Jouret B, Rochiccioli P. Growth hormone (GH) retesting and auxological data in 131 GH-deficient patients after completion of treatment. J Clin Endocrinol Metab. 1997;82(2):352‐356. - PubMed
    1. Maghnie M, Strigazzi C, Tinelli C, et al. Growth hormone (GH) deficiency (GHD) of childhood onset: reassessment of GH status and evaluation of the predictive criteria for permanent GHD in young adults. J Clin Endocrinol Metab. 1999;84(4):1324‐1328. - PubMed
    1. Loche S, Bizzarri C, Maghnie M, et al. Results of early reevaluation of growth hormone secretion in short children with apparent growth hormone deficiency. J Pediatr. 2002;140(4):445‐449. - PubMed
    1. Thomas M, Massa G, Maes M, et al. Growth hormone (GH) secretion in patients with childhood-onset GH deficiency: retesting after one year of therapy and at final height. Horm Res. 2003;59(1):7‐15. - PubMed
    1. Hilczer M, Smyczynska J, Stawerska R, Lewinski A. Final height and growth hormone secretion after completion of growth hormone therapy in patients with idiopathic growth hormone deficiency and with abnormalities of the hypothalamic-pituitary region. Neuro Endocrinol Lett. 2005;26(1):19‐24. - PubMed