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Characterization of a paradoxical post-operative increase in serum cortisol in Cushing disease

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Abstract

Purpose

In Cushing disease, early post-operative serum cortisol fluctuations have not been adequately characterized, and their association with initial remission and recurrence is unclear.

Methods

A retrospective cohort study of patients with Cushing disease was conducted at two institutions. A “riser” was defined a priori as a paradoxical increase in serum cortisol with an immediate incremental increase in serum cortisol over three consecutive cortisol draws separated by roughly 6-h (definition 1). Post hoc analyses used a definition of two consecutive increases (definition 2). Risers were compared to non-risers for initial remission and time-to-recurrence.

Results

A total of 505 patients with Cushing disease were screened, and 469 had adequate data for group assignment. Analysis of post-operative cortisol showed a subgroup of “risers” with a frequency of 3.6% for definition 1 and 42.6% for definition 2. In these patients, cortisol levels were significantly higher until approximately 36 h post-operatively, and cortisol had a significantly longer mean serum half-life. In the post hoc analysis, definition 2 risers had a lower remission rate compared to non-risers (162/196, 82.7%, versus 243/264, 92.0%) with an odds ratio of 0.41 (0.23–0.73; p = 0.003). For both definitions, recurrence was similar between groups.

Conclusions

We found that almost half of Cushing disease patients experienced a temporary increase in serum cortisol level during the early post-operative period. Serum cortisol half-life was longer, and the remission rates were lower, however, recurrence rates were similar to non-risers.

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Data availability

Available upon reasonable request.

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Funding

No specific funding was received for this piece of work.

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Authors and Affiliations

  1. Department of Neurosurgery, University of North Carolina Hospitals, Chapel Hill, NC, USA

    Michael P. Catalino & Aaron Gelinne

  2. Department of Neurosurgery, University of Virginia Health System, Charlottesville, VA, USA

    Natasha Ironside & John A. Jane Jr

  3. School of Medicine, University of Virginia, Charlottesville, VA, USA

    Justin Coley & Kathryn Kearns

  4. Department of Otolaryngology, University of Virginia Health System, Charlottesville, VA, USA

    Rachel Jonas

  5. Harvard Medical School, MIT Health Sciences and Technology, Boston, MA, USA

    Alexander Munoz & Edward R. Laws Jr

  6. Department of Neurosurgery, Brigham and Women’s Hospital/Harvard Medical School, Boston, MA, USA

    Alaa Montaser

  7. Division of Endocrinology, University of Virginia Health System, Charlottesville, VA, USA

    Mary Lee Vance

  8. Mass General Brigham Hospitals, Boston, MA, USA

    Edward R. Laws Jr

  9. Department of Neurosurgery, Mayo Clinic Florida, Jacksonville, FL, USA

    Alaa Montaser

Authors
  1. Michael P. Catalino
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  2. Aaron Gelinne
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  3. Natasha Ironside
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  4. Justin Coley
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  5. Rachel Jonas
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  6. Kathryn Kearns
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  7. Alexander Munoz
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  8. Alaa Montaser
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  9. Mary Lee Vance
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  10. John A. Jane Jr
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  11. Edward R. Laws Jr
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Contributions

Made substantial contributions to the conception or design: MPC, AG, MLV, JAJ Jr, ERL Jr. Drafted and revised it critically for important intellectual content: MPC, AG, NI, MLV, JAJ Jr, ERL Jr; Approved the final version to be published: All authors. Agree to be accountable for all aspects of the work: All authors.

Corresponding author

Correspondence to Michael P. Catalino.

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Conflict of interest

The authors report no conflicts of interest.

Ethical approval

The authors certify that the study was performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. Institutional review board approval was obtained from each institution.

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A waiver of informed consent was granted for this retrospective study.

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Catalino, M.P., Gelinne, A., Ironside, N. et al. Characterization of a paradoxical post-operative increase in serum cortisol in Cushing disease. Pituitary 25, 340–347 (2022). https://doi.org/10.1007/s11102-021-01203-x

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  • DOI: https://doi.org/10.1007/s11102-021-01203-x

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