Cut-off values for sufficient cortisol response to low dose Short Synacthen Test after surgery for non-functioning pituitary adenoma

Acta Neurochir (Wien). 2020 Apr;162(4):845-852. doi: 10.1007/s00701-019-04068-z. Epub 2020 Jan 6.


Objective: The aim was to study the prevalence of secondary adrenal insufficiency before and after surgery for non-functioning pituitary adenomas, as well as determine risk factors for developing secondary adrenal insufficiency. A secondary aim was to determine adequate p-cortisol response to a 1-μg Short Synacthen Test after surgery.

Design: Longitudinal cohort study.

Methods: One hundred seventeen patients (52/65 females/males, age 59 years) undergoing primary surgery for clinically non-functioning pituitary adenomas were included. P-cortisol was measured in morning blood samples. Three months after surgery, a Short Synacthen Test was performed.

Results: All tumours were macroadenomas (mean size 26.9 mm, range 13-61 mm). The surgical indications were visual impairment (93), tumour growth (16), pituitary apoplexy (6) and headache (2). Before surgery, 17% of the patients had secondary adrenal insufficiency (SAI), decreasing to 15% 3 months postoperatively. Risk of SAI was increased in patients operated for pituitary apoplexy (p < 0.001), while age, sex, tumour size and complication rate were not different from the remaining cohort. Three months after surgery, all patients with baseline p-cortisol ≥ 172 nmol/l (6.2 μg/dl) and peak p-cortisol during Short Synacthen Test ≥ 320 nmol/l (11.6 μg/dl) tapered cortisone unproblematically. In patients with intact hypothalamic-pituitary-adrenal axis, p-cortisol peaked < 500 nmol/l (18.1 μg/dl) during Short Synacthen Test in 48% of patient.

Conclusion: Pituitary surgery is safe and transsphenoidal surgery rarely causes new SAI. Relying solely on morning p-cortisol for diagnosing secondary adrenal insufficiency gives false positives and the Short Synacthen Test remains useful. A peak p-cortisol ≥ 320 during (11.6 μg/dl) Short Synacthen Test indicates a sufficient response, while < 309 nmol/l (11.2 μg/dl) indicates secondary adrenal insufficiency.

Keywords: Non-functioning pituitary adenoma; Pituitary surgery; Secondary adrenal insufficiency; Short Synacthen Test.

MeSH terms

  • Adenoma / blood
  • Adenoma / physiopathology
  • Adenoma / surgery*
  • Adrenal Insufficiency / blood
  • Adrenal Insufficiency / diagnosis*
  • Adult
  • Aged
  • Diagnostic Tests, Routine
  • Female
  • Humans
  • Hydrocortisone / blood*
  • Hypothalamo-Hypophyseal System / physiopathology
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Pituitary Neoplasms / blood
  • Pituitary Neoplasms / physiopathology
  • Pituitary Neoplasms / surgery*
  • Pituitary-Adrenal System / physiopathology
  • Postoperative Period


  • Hydrocortisone