Cortisol Blood Test

What is cortisol?

Cortisol is a steroid hormone produced by the adrenal cortex (the outer layer of the adrenal glands, which sit on top of the kidneys). It follows a strong diurnal (daily) rhythm: highest in the early morning (peaking around 8am) and lowest at midnight. Cortisol regulates: blood sugar, blood pressure, anti-inflammatory response, metabolism of fats/proteins/carbohydrates, and the body's response to stress. Cortisol testing must be interpreted carefully in the context of the time of day and clinical situation.

Cortisol normal range

Questions to ask your doctor

• Is my cortisol taken at the right time of day?
• Do I need a short Synacthen test (cortisol stimulation test)?
• Should I have an ACTH level and a dexamethasone suppression test?
• If I am on long-term steroids, how do I safely reduce them?
• Do I need a pituitary or adrenal MRI/CT scan?

References

The clinical information on this page is drawn from peer-reviewed sources indexed by the US National Library of Medicine. Links go to the source so you can read it yourself.

1. Physiology, Endocrine Hormones. In: StatPearls. Treasure Island (FL): StatPearls Publishing. NCBI Bookshelf NBK538498

References

Sources cited on this page. PubMed links open the original abstract.

1. Bornstein SR, Allolio B, Arlt W, et al. Diagnosis and treatment of primary adrenal insufficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2016;101(2):364–389. PMID 26789536 · doi:10.1210/jc.2015-1710

Why timing matters – the cortisol diurnal rhythm

Cortisol is not produced at a constant rate – it follows a circadian rhythm that is essential to understand before interpreting any result. Cortisol peaks between 6 and 9 am (reaching 400–700 nmol/L), falls gradually throughout the day, and reaches its nadir at midnight (typically below 50 nmol/L). A 9 am cortisol reflects peak physiological output; a random cortisol taken at any other time is largely uninterpretable without knowing the exact time of collection.

Reference ranges on laboratory reports are typically given for early morning samples. A "normal" 9 am cortisol does not indicate normal cortisol function throughout the day – for suspected Cushing's syndrome, late-night cortisol (which should be suppressed) is more diagnostically sensitive than a morning cortisol (which may be normal in Cushing's due to preserved, though dysregulated, morning rhythm).

Tests for cortisol deficiency (adrenal insufficiency)

• 9 am serum cortisol: Above 450–500 nmol/L is virtually normal (adrenal insufficiency unlikely). Below 100 nmol/L is virtually diagnostic of adrenal insufficiency. Between 100 and 450 nmol/L is a "grey zone" requiring dynamic testing.
• Short synacthen test (SST): The gold standard for diagnosing primary adrenal insufficiency. Synthetic ACTH (250 µg IV or IM) is given at time zero; cortisol is measured at 30 and 60 minutes. A peak cortisol above 420–500 nmol/L (laboratory-dependent) is a normal response – adrenal insufficiency is excluded. A subnormal peak confirms adrenal insufficiency. The SST does not reliably detect secondary adrenal insufficiency (pituitary problem) in the first weeks after pituitary damage – the adrenals are not yet atrophied and may respond normally. Insulin tolerance test (ITT) is used in this context but is only performed in specialist centres due to hypoglycaemia risk.
• ACTH: A simultaneous ACTH measurement localises the cause. High ACTH + low cortisol = primary adrenal insufficiency (Addison's disease – adrenal glands failing). Low ACTH + low cortisol = secondary adrenal insufficiency (pituitary or hypothalamic cause, or long-term steroid suppression).

Tests for cortisol excess (Cushing's syndrome)

• Late-night salivary cortisol: The most sensitive and convenient screening test. A midnight salivary cortisol above 9.0 nmol/L (laboratory-specific) on two occasions is strongly suggestive of Cushing's syndrome. Salivary collection is non-invasive and can be done at home.
• 24-hour urinary free cortisol (UFC): Measures integrated daily cortisol production. Above the upper limit of normal on two collections suggests Cushing's. False positives occur in stress, exercise excess, depression, and pseudo-Cushing's (alcohol-related).
• Overnight 1 mg dexamethasone suppression test (DST): The pituitary should suppress ACTH (and hence cortisol) when dexamethasone is given. A cortisol above 50 nmol/L the following morning indicates failure to suppress – seen in Cushing's syndrome and pseudo-Cushing's states. Sensitivity approximately 90%; needs confirmatory testing.