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Hormones

Cortisol

The body's main stress hormone — cortisol regulates metabolism, blood pressure, and the stress response, and is key to diagnosing adrenal disorders.

SampleBlood (serum) FastingNot required (timed morning sample, around 9am) Results1–2 days
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Summary

Cortisol is the body's primary stress hormone, produced by the adrenal glands. It regulates metabolism, blood sugar, blood pressure, immune function, and the response to stress. Cortisol follows a strong daily rhythm — highest in the morning and lowest at night — so a correctly timed sample is essential. It is the central test for diagnosing both adrenal insufficiency (too little) and Cushing's syndrome (too much).

Cortisol is released by the adrenal glands under the control of ACTH from the pituitary, which is in turn driven by CRH from the hypothalamus — the HPA axis. Cortisol levels peak around waking, fall through the day, and reach their lowest point around midnight.

This daily rhythm is why timing matters: a 9am sample is standard. A low 9am cortisol may indicate adrenal insufficiency (Addison’s disease), while a high or non-suppressible cortisol suggests Cushing’s syndrome. Dynamic tests (such as the short Synacthen test or dexamethasone suppression test) are used to confirm abnormalities.

Chronic stress, depression, and disrupted sleep can all alter cortisol patterns. Cortisol is also assessed alongside DHEA-S in evaluating overall adrenal function and the stress response.

What It Is

Cortisol is a glucocorticoid steroid synthesised in the adrenal zona fasciculata from cholesterol under ACTH stimulation. It binds intracellular glucocorticoid receptors to regulate gene transcription, with widespread effects: increasing blood glucose (gluconeogenesis), mobilising fatty acids and amino acids, modulating immune and inflammatory responses, and maintaining vascular tone and blood pressure.

Most circulating cortisol is bound to cortisol-binding globulin (CBG) and albumin; only free cortisol is active. The HPA axis is regulated by negative feedback, with cortisol suppressing CRH and ACTH.

Reference ranges depend on timing: 9am serum cortisol approximately 166–507 nmol/L; midnight levels much lower. A 9am cortisol > 500 nmol/L makes adrenal insufficiency unlikely, while < 100 nmol/L is concerning; intermediate values require dynamic testing.

Cortisol must be interpreted with timing in mind, as it follows a strong circadian rhythm. Oestrogen (e.g. the contraceptive pill) raises cortisol-binding globulin and total cortisol without raising free, active cortisol — a common source of misinterpretation.

Functions

Stress response

Cortisol is the principal hormone of the stress response, mobilising energy and sharpening alertness during physical and psychological stress.

Metabolism and blood sugar

Raises blood glucose and mobilises fats and proteins for energy — chronically high cortisol promotes weight gain and insulin resistance.

Immune and inflammation regulation

Modulates immune activity and suppresses excessive inflammation — the basis for therapeutic corticosteroids.

Blood pressure maintenance

Supports vascular tone and blood pressure; deficiency causes low blood pressure and collapse.

Reference Ranges

Cortisol (9am serum)

Measured in nmol/L
Low < 100
Indeterminate 100–350
Normal 350–507
High > 507
Status Range (nmol/L) Range (μg/dL) What it means
Low < 100 < 3.6 Low morning cortisol — concerning for adrenal insufficiency; confirm with dynamic testing.
Indeterminate 100–350 3.6–12.7 Intermediate — adrenal insufficiency cannot be excluded; a Synacthen test is advised.
Normal 350–507 12.7–18.4 Reassuring morning cortisol — adrenal insufficiency unlikely.
High > 507 > 18.4 Elevated — consider stress, Cushing's syndrome, or raised binding globulin (oestrogen).

Cortisol must be interpreted with the time of sampling (ideally 9am). Oestrogen raises total cortisol without raising free cortisol. Diagnosis of adrenal disorders requires dynamic testing (Synacthen, dexamethasone suppression), not a single value.

Symptoms of Imbalance

Cortisol abnormalities produce distinct clinical pictures depending on whether levels are too low or too high.

Low — Deficiency
  • Fatigue and weakness
  • Dizziness and low blood pressure (especially on standing)
  • Weight loss and poor appetite
  • Nausea and abdominal pain
  • Salt craving
  • Skin darkening (in Addison's disease)
  • Risk of adrenal crisis (collapse) under stress
High — Excess
  • Weight gain, especially around the abdomen and face ('moon face')
  • High blood pressure
  • Easy bruising and thin skin
  • Purple stretch marks (striae)
  • Muscle weakness
  • High blood sugar
  • Mood changes, anxiety, and insomnia

Causes of Imbalance

Causes of Low
  • Primary adrenal insufficiency (Addison's disease)
  • Secondary adrenal insufficiency (pituitary failure)
  • Long-term corticosteroid use then sudden withdrawal
  • Adrenal haemorrhage or infarction
Causes of High
  • Acute or chronic stress
  • Cushing's syndrome (adrenal or pituitary tumour, or ectopic ACTH)
  • Exogenous corticosteroid therapy
  • Oestrogen (raises cortisol-binding globulin and total cortisol)
  • Severe depression and alcohol excess (pseudo-Cushing's)

FAQs

Cortisol follows a strong daily rhythm, peaking in the early morning and falling to its lowest at night. Reference ranges and diagnostic thresholds are based on a 9am sample. A morning level helps assess whether the adrenal glands are producing enough cortisol; a midnight or late-night level is sometimes used to detect the loss of normal rhythm seen in Cushing’s syndrome.

A low morning cortisol raises concern for adrenal insufficiency — the adrenal glands not producing enough cortisol. This can be primary (Addison’s disease) or secondary to pituitary problems or steroid withdrawal. Symptoms include fatigue, dizziness, weight loss, and low blood pressure. A low or borderline result is confirmed with a dynamic test such as the short Synacthen (ACTH stimulation) test.

Yes. Acute physical or psychological stress — including anxiety about the blood test itself — raises cortisol. This is a normal physiological response, not a disease. Because of this, a single elevated cortisol does not diagnose Cushing’s syndrome; specific tests that assess the cortisol rhythm and its suppressibility (such as a dexamethasone suppression test) are needed to confirm true cortisol excess.

Yes. Oestrogen, including in the combined contraceptive pill and some HRT, increases cortisol-binding globulin — the protein that carries cortisol. This raises total cortisol measured in blood without raising the free, active hormone. It is a common reason for an apparently high cortisol in an otherwise well person, and is important to flag when interpreting results.

References

  1. Bornstein SR, et al. Diagnosis and treatment of primary adrenal insufficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2016;101(2):364–389. View source
  2. Nieman LK, et al. The diagnosis of Cushing's syndrome: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2008;93(5):1526–1540. View source
  3. Chrousos GP. Stress and disorders of the stress system. Nat Rev Endocrinol. 2009;5(7):374–381. View source

Last medically reviewed: June 2026 · Reviewed by the Trupoint Health Clinical Team.

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