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Pegvisomant-primed glucagon stimulation test in assessing GH reserve and GH/IGF kinetics in adults suspected of GH deficiency

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Abstract

Purpose

The accuracy of the glucagon stimulation test (GST) in diagnosing adult GH deficiency (GHD) has recently been questioned. Because pegvisomant (PegV) increases endogenous GH secretion, we hypothesized that priming PegV to the GST (PegV-GST) 72 h beforehand would improve the diagnostic accuracy of this test. This pilot study aimed to prospectively compare PegV-GST to two other diagnostic tests for adult GHD.

Methods

Adults suspected of GHD underwent PegV-GST, GST and insulin tolerance test (ITT) in random order. Growth hormone levels (measured by a PegV insensitive assay) during PegV-GST, GST and ITT were compared, and acute effects of PegV on GH/IGF kinetics were assessed.

Results

Ten subjects with hypothalamic-pituitary disease and 1–4 pituitary hormone deficiencies were studied. Basal and peak GH levels with the PegV-GST were comparable to those of the GST and ITT. The five subjects that failed the GST and ITT were the same subjects that failed the PegV-GST, using the peak GH cutpoint of <3 ng/mL for this test. After PegV priming, basal GH and GH binding protein (GHBP) increased (both P < 0.01) and total IGF-I and bioactive IGF decreased (both P < 0.05), whereas IGF-II and IGFBPs −1, −2 and −3 were unchanged compared to pre-PegV priming. Serum PegV levels correlated positively with basal GH, peak GH, IGFBP-1 and IGFBP-2 levels, and negatively with Δbioactive IGF and ΔGHBP (all P < 0.05).

Conclusion

Single dose PegV administration in adults suspected of GHD increased basal GH and GHBP, with concomitant rapid fall in IGF-I levels and bioactive IGF. PegV priming did not appear to improve the diagnostic accuracy of the GST. Further studies involving larger subject numbers are needed to verify the clinical utility of PegV-GST in evaluating adult GHD.

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Acknowledgments

We thank Pfizer Inc. for kindly providing the PegV injections that was used in this study. The authors are also grateful to Lone Kvist, Elsebeth Hornemann, Lisa Buus, Kirsten Nyborg Rasmussen and Susanne Sorensen for the measurements of IGF-I, bioactive IGF, IGF-II, IGFBP-1, IGFBP-2 and IGFBP-3.

Disclosure statement

KCJY has received research support from Pfizer, Novo Nordisk, Eli Lilly, and Versartis, and has served on the advisory boards for Pfizer, Novo Nordisk and Sandoz.

Funding

KCJY received an investigator-initiated research grant from Oregon Health and Science University through Pfizer, Inc.

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Authors and Affiliations

  1. Departments of Neurosurgery and Neurology, Swedish Pituitary Center, Swedish Neuroscience Institute, 550 17th Ave, Suite 400, Seattle, WA, 98122, USA

    Kevin C. J. Yuen

  2. Division of Endocrinology, Diabetes and Clinical Nutrition, Department of Medicine, Oregon Health and Science University, Portland, OR, 97239, USA

    Kevin C. J. Yuen & Sharon A. Rhoads

  3. Medical Research Laboratory, Department of Clinical Medicine, Aarhus University and Department of Endocrinology, Aarhus University Hospital, 8000, Aarhus C, Denmark

    Jan Frystyk

  4. Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, Munich, 80336, Germany

    Martin Bidlingmaier

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  1. Kevin C. J. Yuen
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  3. Sharon A. Rhoads
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  4. Martin Bidlingmaier
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Correspondence to Kevin C. J. Yuen.

Additional information

Clinical Trials Registry number: NCT01804413.

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Yuen, K.C.J., Frystyk, J., Rhoads, S.A. et al. Pegvisomant-primed glucagon stimulation test in assessing GH reserve and GH/IGF kinetics in adults suspected of GH deficiency. Pituitary 19, 65–74 (2016). https://doi.org/10.1007/s11102-015-0688-8

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