Cortisol
Medically reviewed by Hormone Journal Editorial Team · Last reviewed 2026-05-22
Cortisol is the body's primary stress hormone, produced by the adrenal glands, with chronically elevated levels linked to heart disease, weight gain, and immune dysfunction.
What it is
Cortisol is the body's principal glucocorticoid hormone, secreted by the adrenal cortex in response to stress, and chronically elevated levels are associated with at least 9 major health conditions including cardiovascular disease, type 2 diabetes, and depression. Also called hydrocortisone in its pharmaceutical form, cortisol is the primary glucocorticoid produced by the zona fasciculata of the adrenal cortex and the central output of the hypothalamic-pituitary-adrenal (HPA) axis. In Canada, abnormal cortisol levels are investigated through serum, salivary, or 24-hour urinary free cortisol tests available at national laboratory networks including LifeLabs and Dynacare, typically ordered by a family physician or endocrinologist.
In healthy adults, cortisol follows a diurnal rhythm: levels peak within 30–45 minutes of waking (the cortisol awakening response) and decline steadily through the day, reaching their lowest point around midnight. This rhythm governs energy metabolism, immune tone, blood pressure, and mood. When the rhythm is disrupted — by shift work, chronic psychological stress, or HPA-axis disease — the downstream effects touch nearly every organ system.
Causes and mechanism
The HPA axis controls cortisol release through a hormonal cascade. The hypothalamus releases corticotropin-releasing hormone (CRH), which signals the anterior pituitary to secrete adrenocorticotropic hormone (ACTH). ACTH then stimulates the adrenal cortex to synthesize and release cortisol from cholesterol. Cortisol feeds back to suppress both CRH and ACTH, keeping levels within a normal range under ordinary conditions.
This self-limiting loop breaks down under two main circumstances:
- Chronic psychosocial stress — sustained activation of the fight-or-flight response keeps cortisol elevated, impairing immune function, disrupting sleep, and promoting visceral fat accumulation.
- HPA-axis pathology — tumours or gland dysfunction cause either excess (Cushing syndrome) or deficiency (Addison disease).
| Condition | Cortisol direction | Primary cause | Key features |
|---|---|---|---|
| Cushing syndrome | Elevated | Pituitary adenoma (most common), adrenal tumour, or exogenous glucocorticoids | Central obesity, hypertension, muscle wasting, glucose intolerance |
| Addison disease | Deficient | Autoimmune adrenal destruction | Fatigue, hypotension, weight loss, hyperpigmentation |
| Chronic stress response | Mildly to moderately elevated | Sustained psychosocial stressors | Sleep disruption, anxiety, metabolic changes |
| Congenital adrenal hyperplasia | Variable (often deficient) | Enzyme deficiency in cortisol synthesis | Androgen excess, ambiguous genitalia in severe forms |
Endogenous Cushing syndrome is rare, affecting an estimated 40–70 people per million; it occurs about three times more often in women than men and most commonly presents between ages 30 and 50.
Symptoms and diagnosis
Symptoms depend on whether cortisol is chronically high, chronically low, or acutely dysregulated. Elevated cortisol over time produces central weight gain, easy bruising, stretch marks (striae), high blood pressure, poor wound healing, and cognitive difficulties including problems with memory and focus. Chronically low cortisol causes profound fatigue, low blood pressure, salt craving, and darkening of the skin in sun-exposed areas.
Diagnosis begins with a clinical history and one or more of the following tests:
- Late-night salivary cortisol (two measurements on separate nights) — reflects the nadir of the diurnal curve; elevated values suggest Cushing syndrome
- 24-hour urinary free cortisol — measures total daily cortisol output
- 1 mg overnight dexamethasone suppression test — a suppressed morning cortisol (below 50 nmol/L) rules out Cushing syndrome in most cases
- Morning serum cortisol + ACTH — used to distinguish adrenal insufficiency and to localize the defect within the HPA axis
In Canada, these tests are covered under provincial health plans when ordered for a clinical indication; reference ranges may vary slightly between LifeLabs and Dynacare, so results should always be interpreted alongside the reporting laboratory's own intervals.
Treatment options
Treatment targets the underlying cause rather than cortisol itself.
For Cushing syndrome, surgical removal of the causative tumour (transsphenoidal pituitary surgery for Cushing disease; adrenalectomy for adrenal adenoma) is first-line. Steroidogenesis inhibitors such as metyrapone or ketoconazole are used when surgery is not immediately possible. Radiation and the glucocorticoid receptor antagonist mifepristone are reserved for refractory cases.
For adrenal insufficiency (Addison disease), lifelong oral hydrocortisone replacement — typically 15–25 mg/day in divided doses, timed to mimic the natural diurnal rhythm — is standard. Fludrocortisone replaces the mineralocorticoid function also lost in primary adrenal insufficiency. Patients require sick-day rules and injectable hydrocortisone for emergencies; Canadian pharmacies dispense emergency kits on prescription.
For chronic stress-related cortisol dysregulation without a diagnosable HPA-axis disorder, evidence-based interventions include cognitive behavioural therapy (CBT), structured aerobic exercise (30 minutes most days), sleep hygiene, and mindfulness-based stress reduction (MBSR). These approaches have demonstrated measurable reductions in salivary cortisol in randomized trials. No Health Canada-approved pharmaceutical is indicated solely for stress-related cortisol elevation in the absence of a formal endocrine diagnosis.
When to see a clinician in Canada
See your family physician if you notice unexplained weight gain concentrated around the abdomen and face, new stretch marks, easy bruising, persistent fatigue, or blood pressure that is difficult to control. These may warrant cortisol screening. Referral to an endocrinologist is appropriate when initial screening tests are abnormal. In Canada, endocrinology wait times vary by province; if your GP suspects Cushing syndrome or adrenal insufficiency, ask for an urgent or semi-urgent referral given the cardiovascular risks of untreated disease. Virtual care platforms (Maple, Felix, Cleo, and others) can facilitate initial assessment and GP referral but are not a substitute for specialist workup when HPA-axis disease is suspected.
Limitations and open questions
Research is still emerging on the long-term cardiovascular consequences of subclinical cortisol excess — elevations that do not meet the threshold for a formal Cushing diagnosis but may still increase cardiometabolic risk. The optimal cortisol replacement regimen for Addison disease (dose, timing, formulation) remains an active area of study; modified-release hydrocortisone is available in some countries but not yet widely accessible in Canada. Health Canada has not issued specific guidance on salivary cortisol testing as a standalone diagnostic tool, and inter-laboratory variability in salivary assays means results require careful clinical interpretation. The relationship between cortisol and neurodegenerative disease risk — while biologically plausible — has not been established with sufficient evidence to inform screening recommendations. Commercial "adrenal fatigue" testing and supplement protocols are not recognized by Canadian endocrinology societies and lack clinical validation.
FAQs
What is a normal cortisol level in Canada, and how is it tested?
Normal morning serum cortisol in most Canadian laboratories falls between roughly 170 and 540 nmol/L, measured between 8 and 9 a.m. Testing options include serum cortisol, 24-hour urinary free cortisol, and late-night salivary cortisol; the right test depends on what your clinician suspects. LifeLabs and Dynacare both offer these panels, and reference ranges are printed on each report — always compare your result to the interval from the lab that processed your sample. A single abnormal value rarely confirms a diagnosis; most guidelines require at least two abnormal results before further workup.
How is high cortisol different from everyday stress?
Everyday stress causes a short-lived cortisol spike that resolves once the stressor passes, with levels returning to baseline within an hour or two. Pathologically high cortisol — as seen in Cushing syndrome — means levels remain elevated around the clock, including at night when they should be at their lowest. Cushing syndrome affects only about 40–70 people per million, whereas stress-related cortisol fluctuations are nearly universal. The clinical distinction matters because Cushing syndrome requires specific medical or surgical treatment, while stress-related elevation responds to lifestyle and psychological interventions.
Can high cortisol cause weight gain, and if so, where?
Yes — chronically elevated cortisol promotes fat redistribution toward the abdomen, face (sometimes called 'moon face'), and upper back ('buffalo hump'), while limbs may lose muscle mass. This pattern occurs because glucocorticoid receptors are especially dense in visceral adipose tissue, and cortisol stimulates both fat storage and appetite. In Cushing syndrome, central obesity is present in the majority of patients and is one of the most recognizable diagnostic features. Even in people without a formal diagnosis, sustained high cortisol from chronic stress is associated with increased waist circumference over time.
Is cortisol testing covered by provincial health insurance in Canada?
Serum cortisol ordered by a physician for a clinical indication is covered under all provincial and territorial health plans. Salivary cortisol and 24-hour urinary free cortisol are also generally covered when requisitioned by a physician, though coverage rules vary slightly by province. Direct-to-consumer cortisol tests purchased without a physician requisition are not covered and are not recommended as a substitute for clinically ordered testing. If you are paying out of pocket, salivary cortisol kits at LifeLabs or Dynacare typically cost between $50 and $100 CAD.
What happens if low cortisol goes untreated?
Untreated adrenal insufficiency (Addison disease) can progress to an adrenal crisis — a life-threatening emergency characterized by severe hypotension, vomiting, and loss of consciousness, often triggered by illness or injury. Without immediate intravenous hydrocortisone, an adrenal crisis can be fatal. In Canada, patients with confirmed adrenal insufficiency are advised to carry an emergency hydrocortisone injection kit and to wear medical alert identification. Long-term, even mild untreated adrenal insufficiency impairs quality of life, with fatigue and cognitive difficulties reported by the majority of patients in observational studies.
Sources
- Physiology, Cortisol — StatPearls, NCBI Bookshelf
- Cushing's Syndrome — National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Chronic stress puts your health at risk — Mayo Clinic
- The Role of Cortisol in Chronic Stress and Neurodegenerative Diseases — PMC / NCBI
- Diagnosis of Cushing's Syndrome — The Endocrine Society Clinical Practice Guideline
- Adrenal Insufficiency and Addison's Disease — Health Canada / Canadian context via CMAJ