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Corticotroph tumor progression during long-term therapy with osilodrostat in a patient with persistent Cushing’s disease

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Abstract

Purpose

Corticotroph tumor progression (CTP) or Nelson’s syndrome (NS) can occur in patients with Cushing’s disease (CD) following bilateral adrenalectomy. It has rarely been observed in patients treated with long-term medical therapy for persistent CD. Osilodrostat (LCI699) is a new steroidogenesis inhibitor of 11β-hydroxylase (CYP11β1) that induced remission of hypercortisolism in 86% of patients with refractory CD in the randomized placebo-controlled trial LINC-3 (NCT02180217).

Methods

A 40-year-old woman with persistent CD following transsphenoidal surgery was treated with osilodrostat in the LINC-3 trial and was followed with regular hormonal assessments and imaging of residual corticotroph tumor.

Results

Under oral therapy with osilodrostat 10 mg twice daily, urinary free cortisol (UFC) normalized and clinical signs of CD regressed during therapy. However after 4 years of treatment, ACTH levels increased from 73 to 500 pmol/L and corticotroph tumor size increased rapidly from 3 to 14 mm, while UFCs remained well controlled. Surgical resection of an atypical tumor with weak ACTH expression and increased proliferative index (Ki-67 ≥ 8%) resulted in current remission but will require close follow-up.

Conclusion

This case highlights the importance of monitoring ACTH and corticotroph tumor size in patients with persistent CD, either under effective treatment with steroidogenesis inhibitors or after bilateral adrenalectomy.

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Data availability

Available from authors upon request.

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Author information

Authors and Affiliations

  1. Division of Endocrinology, Department of Medicine, Centre de Recherche du Centre hospitalier de l’Université de Montréal (CHUM), Université de Montréal, 900 Saint-Denis Street, Montréal, Québec, H2X 0A9, Canada

    Cédric Fontaine-Sylvestre & André Lacroix

  2. Neuroradiology Division, Department of Radiology, Centre hospitalier de l’Université de Montréal (CHUM), Université de Montréal, Montréal, Québec, Canada

    Laurent Létourneau-Guillon

  3. Neurosurgery Division, Department of Surgery, Centre hospitalier de l’Université de Montréal (CHUM), Université de Montréal, Montréal, Québec, Canada

    Robert A. Moumdjian

  4. Neuropathology Division, Department of Pathology, Centre hospitalier de l’Université de Montréal (CHUM), Université de Montréal, Montréal, Québec, Canada

    France Berthelet

Authors
  1. Cédric Fontaine-Sylvestre
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  2. Laurent Létourneau-Guillon
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  3. Robert A. Moumdjian
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  4. France Berthelet
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  5. André Lacroix
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Contributions

CFS and AL designed the analysis, data collection and wrote the manuscript; LLG analyzed pituitary MRI imaging, RAM performed the pituitary surgeries and FB the pathology studies. All authors revised and approved the final version of the manuscript.

Corresponding author

Correspondence to André Lacroix.

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Conflict of interest

AL received funding as an investigator for participation in the LINC-3 trial from Novartis.

Ethical approval

LINC-3 study was approved by the CHUM ethics committee.

Informed consent

Patient provided informed signed consent to participate in the study and to publish results.

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Fontaine-Sylvestre, C., Létourneau-Guillon, L., Moumdjian, R.A. et al. Corticotroph tumor progression during long-term therapy with osilodrostat in a patient with persistent Cushing’s disease. Pituitary 24, 207–215 (2021). https://doi.org/10.1007/s11102-020-01097-1

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  • DOI: https://doi.org/10.1007/s11102-020-01097-1

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