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Glucocorticoid-induced adrenal insufficiency after therapy with intravenous methylprednisolone in patients with moderate-to-severe and active Graves’ orbitopathy: assessment with a low-dose corticotropin test

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Abstract

Purpose

We aimed to assess adrenal function following treatment of moderate-to-severe and active Graves’ orbitopathy (GO) with intravenous methylprednisolone (IVMP) in weekly pulses in a cumulative dose of 4.5 or 7.5 g. We evaluated the impact of IVMP pulses on adrenal reserve using a low-dose (1 μg) ACTH stimulation test (LDT) for the first time.

Methods

In this prospective study we evaluated adrenal function in 21 patients with moderate-to-severe and active GO treated with 12 weekly IVMP pulses according to the European Group on Graves’ Orbitopathy (EUGOGO) recommendations. We assessed serum cortisol, plasma adrenocorticotropic hormone (ACTH), and dehydroepiandrosterone sulfate (DHEA-S) levels before the 1st and 12th IVMP pulse. We performed dynamic testing using LDT before the 12th IVMP pulse in all patients. In those who failed LDT, adrenal function was reassessed with LDT and the overnight metyrapone test after 4–7 weeks.

Results

Two patients failed to achieve serum cortisol levels ≥ 18.1 μg/dL at 30 and 60 min in LDT and were diagnosed with glucocorticoid-induced adrenal insufficiency (GC-induced AI). They were recommended to take hydrocortisone in situations of acute stress. Both patients were reassessed within 4–7 weeks after treatment cessation and showed an adequate response in LDT and overnight metyrapone test. We observed a statistically significant decrease in DHEA-S levels (p = 0.004) before the 12th IVMP pulse compared to baseline in all patients.

Conclusion

For the first time, our research shows that administering IVMP in 12 weekly pulses can result in GC-induced AI. We suggest that patients should undergo careful evaluation for GC-induced AI, including LDT, after therapy with IVMP according to EUGOGO guidelines. Screening for altered adrenal reserve could prevent life-threatening complications, particularly during acute stress situations.

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Data availability

The datasets generated and analysed during the current study are available from the corresponding author upon reasonable request.

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Funding

This study received no funding.

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Authors and Affiliations

  1. Department of Internal Medicine and Endocrinology, Medical University of Warsaw, 02-091, Warsaw, Poland

    K. Pelewicz & P. Miśkiewicz

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Contributions

KP and PM conceived and designed the study. KP collected the data, drafted the manuscript, and performed statistical analysis, tables, and figures. KP and PM performed data analysis and interpretation. PM critically revised the manuscript for important intellectual content and guided the study design and data interpretation. All authors read and approved the final manuscript.

Corresponding author

Correspondence to P. Miśkiewicz.

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The authors report no potential conflict of interest.

Ethical approval

This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Commission of Bioethics at the Medical University of Warsaw, Poland (KB 61/A2021; 02 July 2021).

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Informed consent was obtained from all individual participants included in the study.

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Pelewicz, K., Miśkiewicz, P. Glucocorticoid-induced adrenal insufficiency after therapy with intravenous methylprednisolone in patients with moderate-to-severe and active Graves’ orbitopathy: assessment with a low-dose corticotropin test. J Endocrinol Invest (2024). https://doi.org/10.1007/s40618-024-02304-7

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