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

Pituitary. 2021 Apr;24(2):207-215. doi: 10.1007/s11102-020-01097-1. Epub 2020 Oct 19.


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.

Keywords: Corticotroph tumor progression; Cushing’s disease; Nelson’s syndrome; Osilodrostat.

Publication types

  • Case Reports

MeSH terms

  • Adrenocorticotropic Hormone / metabolism
  • Adult
  • Corticotrophs / drug effects
  • Corticotrophs / pathology
  • Dexamethasone / therapeutic use
  • Female
  • Humans
  • Hydrocortisone / urine*
  • Imidazoles / therapeutic use*
  • Pituitary ACTH Hypersecretion / drug therapy*
  • Pituitary ACTH Hypersecretion / pathology*
  • Pyridines / therapeutic use*


  • Imidazoles
  • Pyridines
  • Osilodrostat
  • Dexamethasone
  • Adrenocorticotropic Hormone
  • Hydrocortisone

Associated data