Results and predictors of outcome of endoscopic endonasal surgery in Cushing's disease: 20-year experience of an Italian referral Pituitary Center

J Endocrinol Invest. 2020 Oct;43(10):1463-1471. doi: 10.1007/s40618-020-01225-5. Epub 2020 Mar 25.

Abstract

Purpose: To assess outcomes and predictors of early and long-term remission in patients with Cushing's disease (CD) due to ACTH-secreting adenomas treated via endoscopic endonasal approach (EEA).

Methods: This is a retrospective study. Consecutive patients operated for CD from 1998 to 2017 in an Italian referral Pituitary Center were enrolled. Clinical, radiological, and histological data at enrollment and follow-up were collected.

Results: 151 patients (107 F) were included; 88.7% were naïve for treatment, 11.3% had been treated surgically and 11.2% medically. At pre-operative magnetic resonance imaging (MRI), 35 had a macroadenoma and 80 a microadenoma, while tumor was undetectable in 36 patients. Mean age at surgery was 41.1 ± 16.6 years. Diagnosis was confirmed histologically in 82.4% of the cases. Patients with disease persistence underwent second surgery and/or medical and/or radiation therapy. Mean follow-up was 92.3 ± 12.0 (range 12-237.4) and median 88.2 months. Remission rate was 88.1% after the first surgery and 90.7% at last follow-up. One patient died of pituitary carcinoma. Post-surgical cortisol drop (p = 0.004), tumor detection at MRI (p = 0.03) and size < 1 cm (p = 0.045) increased the chance of disease remission; cavernous sinus invasion was a negative predictor of outcome (p = 0.002). Twenty-seven patients developed diabetes insipidus and 18 hypopituitarism. Surgery repetition increased the risk of hypopituitarism (p = 0.03), but not of other complications, which included epistaxis (N = 2), cerebrospinal fluid leakage (1), pneumonia (3), myocardial infarction (1), and pulmonary embolisms (2).

Conclusions: Selective adenomectomy via EEA performed by experienced surgeons, supported by a multidisciplinary dedicated team, allows long-term remission in the vast majority of CD patients with low complication rate.

Keywords: ACTH-secreting pituitary adenoma; Cortisol; Cushing’s disease; Outcome; Pituitary unit; Predictor; Transsphenoidal surgery.

MeSH terms

  • ACTH-Secreting Pituitary Adenoma / complications
  • ACTH-Secreting Pituitary Adenoma / diagnosis
  • ACTH-Secreting Pituitary Adenoma / metabolism
  • ACTH-Secreting Pituitary Adenoma / surgery
  • Adenoma / complications
  • Adenoma / diagnosis
  • Adenoma / metabolism
  • Adenoma / surgery
  • Adult
  • Endoscopy / methods*
  • Female
  • Humans
  • Italy
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Neurosurgical Procedures / methods*
  • Nose / surgery
  • Pituitary ACTH Hypersecretion / diagnosis*
  • Pituitary ACTH Hypersecretion / etiology
  • Pituitary ACTH Hypersecretion / metabolism
  • Pituitary ACTH Hypersecretion / surgery*
  • Prognosis
  • Referral and Consultation
  • Retrospective Studies
  • Treatment Outcome
  • Young Adult