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



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.


Longitudinal cohort study.


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.


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.


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.

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We thank Kari Abelsen and Ansgar Heck for assistance and support. This study was based on routine practice at the Section of Specialized Endocrinology, Rikshospitalet, Oslo University Hospital in Oslo, and did not receive additional funding.

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Corresponding author

Correspondence to Anders Jensen Kolnes.

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All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements) or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the hospital authority, regional ethics committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study.

Additional information


This is a welcome update regarding the most recent and most logical method of post operative assessment of adrenal insufficiency and the need for and calibration of cortisol replacement therapy, assessed initially and over time.

E.R. Laws

Boston, MA, USA

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This article is part of the Topical Collection on Pituitaries

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Kolnes, A.J., Øystese, K.A., Dahlberg, D. et al. Cut-off values for sufficient cortisol response to low dose Short Synacthen Test after surgery for non-functioning pituitary adenoma. Acta Neurochir 162, 845–852 (2020).

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  • Non-functioning pituitary adenoma
  • Short Synacthen Test
  • Secondary adrenal insufficiency
  • Pituitary surgery