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  • Clinical Research Article
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The utility of IGF1 in the evaluation of pediatric patients with endogenous hypercortisolemia

Pediatric Research volume 95, pages 758–761 (2024)Cite this article

Abstract

Background

Cushing Disease (CD) is a rare endocrine disorder associated with impaired growth hormone (GH) and short stature. Insulin-like growth factor-1 (IGF-1) is a marker of GH secretion.

Methods

Patients with young onset CD (<21 years old) and available IGF-1 levels at diagnosis and/or follow-up were studied (total = 194, diagnosis = 174, follow-up = 104). IGF-1 was reported as z-score (IGF1z).

Results

IGF1z was lower than expected in the general population (median IGF1z: −0.92 [−1.54, 0.07], p < 0.0001) at diagnosis and remained low at follow-up (median: −1.13 [−1.78, −0.66], p < 0.0001). There was no correlation of IGF1z at diagnosis with BMI; there was a weak correlation with height (rs = 0.19, p = 0.035). IGF1z was inversely correlated with markers of hypercortisolemia, including morning (rs = −0.31, p < 0.0001) and midnight cortisol (rs = −0.30, p < 0.0001), and with insulin resistance (Homeostatic Model Assessment for Insulin Resistance, HOMA-IR, rs = −0.27, p < 0.01).

Conclusions

IGF-1 levels in CS are on the lower side of the normal range during active disease and remain low at one year after treatment. IGF-1 levels correlated mainly with markers of hypercortisolemia rather than the short stature of patients and should not be used in the assessment of growth in this population.

Impact

  • We report that IGF-1 levels in childhood during active hypercortisolemia and up to 1 year after resolution are on the lower side of the normal range.

  • Our results demonstrate that IGF-1 levels during active hypercortisolemia correlate mainly with markers of Cushing syndrome.

  • This report adds data to the current literature where reports of IGF-1 in Cushing syndrome have shown variable results.

  • Understanding the lack of utility of IGF-1 in assessing growth parameters in the pediatric Cushing syndrome population is important for physicians caring for these patients who should not use IGF-1 for diagnostic or treatment decisions.

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Fig. 1: Distribution of IGF-1 levels in patients with Cushing disease before and after treatment.

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Data availability

Some datasets generated during and/or analyzed during the current study are not publicly available but are available from the corresponding author on reasonable request if patient confidentiality is preserved.

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Acknowledgements

This study was funded by the intramural research program of the Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD), National Institutes of Health (NIH), Bethesda, MD 20892, USA.

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Authors and Affiliations

  1. Unit on Hypothalamic and Pituitary Disorders, Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD), National Institutes of Health (NIH), Bethesda, MD, USA

    Jessica R. Weinberg, Mariana Voudouri, Meg Keil, Constantine A. Stratakis & Christina Tatsi

  2. Office of the Clinical Director, Eunice Kennedy Shriver National Institute of Child Health and Human development (NICHD), National Institutes of Health (NIH), Bethesda, MD, USA

    Meg Keil

  3. Human Genetics & Precision Medicine, IMBB, FORTH, Heraklion, Crete, Greece

    Constantine A. Stratakis

  4. ELPEN Research Institute, Athens, Greece

    Constantine A. Stratakis

Authors
  1. Jessica R. Weinberg
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  2. Mariana Voudouri
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  3. Meg Keil
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  4. Constantine A. Stratakis
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  5. Christina Tatsi
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Contributions

C.T., J.W. : conception, design, data collection, analysis, and interpretation. M.V., and M.K.: collection the data. C.A.S.: critical revision of the study. All the authors contributed to the manuscript and approved the submitted version.

Corresponding author

Correspondence to Christina Tatsi.

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Competing interests

Dr. Stratakis holds patents on the function of the PRKAR1A, PED11A, and GPR101 genes and related issues; his laboratory has also received research funding on the GPR101 gene, and on abnormal growth hormone secretion and its treatment by Pfizer, Inc. He is currently employed by ELPEN, SA and has been consulting for Lundbeck Pharmaceuticals and Sync, SA. Dr. Tatsi received funding by Pfizer, Inc., for unrelated studies.

Consent statement

All study procedures were approved by the Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD) Institutional Review Board. Consent was obtained from participants and/or their parent or legal guardian to participate in the study.

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Weinberg, J.R., Voudouri, M., Keil, M. et al. The utility of IGF1 in the evaluation of pediatric patients with endogenous hypercortisolemia. Pediatr Res 95, 758–761 (2024). https://doi.org/10.1038/s41390-023-02906-6

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  • DOI: https://doi.org/10.1038/s41390-023-02906-6

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