Intended for healthcare professionals

Practice Rational Testing

Investigating cortisol excess or deficiency: a practical approach

BMJ 2019; 367 doi: (Published 26 November 2019) Cite this as: BMJ 2019;367:l6039
  1. Fahmy W F Hanna, professor of endocrinology and metabolism1 2,
  2. Basil G Issa, consultant physician and endocrinologist3,
  3. Brian Kevil, professor of clinical biochemistry3,
  4. Anthony A Fryer, professor of clinical biochemistry1 4
  1. 1University Hospital of North Midlands, Stoke-on-Trent, UK
  2. 2Staffordshire University, Stoke-on-Trent, UK
  3. 3Manchester University Foundation Trust, Manchester, UK
  4. 4Institute for Applied Clinical Sciences, Keele University, Stoke-on-Trent, UK
  1. Correspondence to: F W F Hanna fahmy.hanna{at}

What you need to know

  • Random, untimed cortisol levels are of limited clinical value

  • Cortisol measured at around 8-9 am (when the level is expected to be highest) is the preferred initial screening test for cortisol deficiency

  • If high clinical suspicion for hypercortisolaemia, patients should be referred to specialist care for testing and interpretation of results

  • Dynamic testing is often required to confirm cortisol deficiency or excess given the pulsatile nature of cortisol secretion and the influence of diurnal variation, feedback control and stress.

  • Salivary cortisol has better specificity for diagnosis of Cushing’s syndrome than urinary cortisol and is easier to collect; if this test is available, it is increasingly preferred to urinary free cortisol

A 67 year old woman with no significant medical history required urgent orthopaedic surgery after a fall. In preparation, her bloods were collected and a random cortisol was requested, which came back at 763 nmol/L. She did not have diabetes or hypertension. The anaesthetist reviewed and commented: “High cortisol, not safe for surgery until further evaluation.”

A 24 year old man with previously well controlled type 1 diabetes presented with repeated hypoglycaemic episodes. Serum cortisol in clinic at 9 am came back as 143 nmol/L.

Cortisol, secreted by the adrenal cortex, regulates blood pressure, glucose metabolism, and physiological responses to stress. Both cortisol over-secretion (hypercortisolism, Cushing’s syndrome) and under-secretion (hypocortisolism such as in Addison’s disease) are uncommon: the prevalence of Addison’s disease is 6-9 per 100 000,1 while that of Cushing’s syndrome is 4/100 000.2 However, given the potential for life threatening consequences (such as in acute adrenal crisis) and the range of associated non-specific symptoms, it is critical for clinicians to understand how to interpret and manage cortisol status. Cortisol excess could be due to an adrenal cortisol-secreting tumour or to a functional pituitary tumour (Cushing’s disease), or, less commonly, malignant tumours can …

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