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Cortisol: ACTH ratio to test for primary hypoadrenalism: a pilot study
  1. Mark K V Lee1,
  2. Samuel Vasikaran2,
  3. James C G Doery3,
  4. Nilika Wijeratne3,
  5. David Prentice1
  1. 1Department of Internal Medicine, Royal Perth Hospital, Perth, Western Australia, Australia
  2. 2Department of Clinical Biochemistry, PathWest-Royal Perth Hospital, Perth, Western Australia, Australia
  3. 3Department of Pathology, Monash Health and Department of Medicine, Monash University, Melbourne, Victoria, Australia
  1. Correspondence to Dr Samuel Vasikaran, Department of Clinical Biochemistry, PathWest-Royal Perth Hospital, GPO Box X2213, Perth, WA 6847, Australia; samuel.vasikaran{at}


Introduction A standard short Synacthen test (SST) is the conventional diagnostic test for primary hypoadrenalism. Measuring simultaneous plasma cortisol and adrenocorticotrophin hormone (ACTH) and using the cortisol: ACTH ratio as a first-line test may be safer and more convenient than performing a SST.

Methods A retrospective study of 349 patients who had a SST with simultaneous baseline plasma cortisol and ACTH performed between 2005 and 2010 in two separate Australian health centres. The plasma cortisol: ACTH ratio was calculated for each patient and their final diagnosis was determined based on their SST result and a review of their clinical notes.

Results Eighteen patients had primary hypoadrenalism, 46 patients had secondary hypoadrenalism and 285 patients had normal adrenal function. All the patients with primary hypoadrenalism had a plasma cortisol: ACTH ratio <3, while none of the patients with normal adrenal function or secondary hypoadrenalism had a cortisol: ACTH ratio <3. Therefore, a cortisol: ACTH ratio <3 had a 100% sensitivity and specificity for the diagnosis of primary hypoadrenalism. Patients with secondary hypoadrenalism had a cortisol: ACTH ratio >3, while subjects with normal adrenal function had a cortisol: ACTH ratio >15. There was overlap in cortisol: ACTH ratios of patients with secondary hypoadrenalism and normal adrenal function.

Conclusions Although the cortisol: ACTH ratio predicts primary hypoadrenalism, its value is limited to diagnosing primary hypoadrenalism as it does not distinguish secondary hypoadrenalism from normal adrenal function. Larger prospective studies that include patients with early primary hypoadrenalism are needed to confirm the reliability of plasma cortisol: ACTH ratio as a diagnostic test for primary hypoadrenalism.

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