Hormone Journal

Cortisol

Medically reviewed by Hormone Journal Editorial Team · Last reviewed 2026-05-17

Cortisol is a steroid hormone made by the adrenal glands that regulates metabolism, immune function, and the body's response to stress.

Cortisol is a steroid hormone made by the adrenal glands that regulates metabolism, immune function, and the body's response to stress.

What it is

Cortisol is the body's primary glucocorticoid (a class of steroid hormone that affects glucose metabolism and immune activity). It is synthesized from cholesterol in the zona fasciculata, the middle layer of the adrenal cortex — the outer shell of the adrenal glands that sit atop each kidney. In healthy adults, the adrenal glands secrete roughly 10–20 mg of cortisol per day, with levels peaking within 30–45 minutes of waking and falling to their lowest point around midnight.

Causes and mechanism

Cortisol production is controlled by the hypothalamic-pituitary-adrenal (HPA) axis — a three-part signaling chain. The hypothalamus (a small brain region) releases corticotropin-releasing hormone (CRH), which prompts the pituitary gland to secrete adrenocorticotropic hormone (ACTH). ACTH then travels through the bloodstream to the adrenal glands and triggers cortisol synthesis. Cortisol feeds back to suppress both the hypothalamus and pituitary, keeping levels in a normal range. Physical stress, illness, low blood sugar, and psychological threat can all activate this axis and raise cortisol acutely. Chronic activation — from ongoing psychological stress, poor sleep, or certain medications such as long-term corticosteroids — can keep levels persistently elevated.

Symptoms and diagnosis

High cortisol (hypercortisolism) may cause central weight gain, easy bruising, stretch marks, high blood pressure, elevated blood sugar, muscle weakness, and mood changes. When caused by a tumor or gland problem, this is called Cushing syndrome. Low cortisol (adrenal insufficiency, including Addison disease) typically presents with fatigue, low blood pressure, unintentional weight loss, salt craving, and darkening of the skin.

Diagnosis relies on blood, urine, or saliva tests. Common options include:

  • Morning serum cortisol — drawn between 8–9 a.m. when levels are naturally highest
  • 24-hour urinary free cortisol — measures total daily output
  • Late-night salivary cortisol — useful for detecting Cushing syndrome, since levels should be very low at midnight
  • Low-dose dexamethasone suppression test — checks whether cortisol can be appropriately suppressed

Note: "adrenal fatigue" — the idea that chronic stress depletes the adrenal glands — is not a recognized medical diagnosis. No validated test supports it, and symptoms attributed to it overlap with many other conditions.

Treatment options

Treatment depends entirely on the underlying cause:

  • Cushing syndrome: Surgery to remove the causative tumor is first-line. Steroidogenesis inhibitors (e.g., metyrapone, ketoconazole) or the cortisol-receptor blocker mifepristone may be used when surgery is not possible.
  • Adrenal insufficiency / Addison disease: Daily oral hydrocortisone replacement (typically 15–25 mg/day in divided doses) plus fludrocortisone for mineralocorticoid replacement. Patients need sick-day rules and an emergency hydrocortisone injection kit.
  • Stress-related cortisol elevation: No approved drug targets cortisol in otherwise healthy people. Evidence supports regular aerobic exercise, consistent sleep schedules, and cognitive behavioral therapy (CBT) for reducing HPA axis activation. Mindfulness-based stress reduction (MBSR) has shown modest cortisol-lowering effects in controlled trials, though effect sizes vary.

When to see a clinician

Seek evaluation if you notice unexplained weight gain concentrated around the abdomen and face, new stretch marks wider than 1 cm, muscle weakness, or blood pressure that is difficult to control — these can signal Cushing syndrome. Persistent fatigue, dizziness on standing, and darkening skin warrant testing for adrenal insufficiency. An acute adrenal crisis (severe vomiting, confusion, very low blood pressure) is a medical emergency requiring immediate care. Routine cortisol testing in the absence of specific symptoms is generally not recommended, as single measurements are highly variable and context-dependent.

FAQs

What is a normal cortisol level?

A morning serum cortisol drawn between 8–9 a.m. is typically 10–20 mcg/dL (275–555 nmol/L) in healthy adults, though reference ranges vary slightly by laboratory. Levels fall throughout the day, reaching below 5 mcg/dL by late evening. A single result is rarely diagnostic on its own — timing, collection method, and clinical context all matter, so your clinician will usually order confirmatory tests.

What is the difference between cortisol and adrenaline?

Both are stress hormones, but they work on different timescales. Adrenaline (epinephrine) is released within seconds from the adrenal medulla and drives the immediate fight-or-flight response — faster heart rate, dilated pupils, and a burst of energy. Cortisol is released minutes later from the adrenal cortex and sustains the response by raising blood glucose and modulating inflammation. Adrenaline effects fade in minutes; elevated cortisol can persist for hours.

Can high cortisol cause weight gain?

Yes. Chronically elevated cortisol promotes fat storage, particularly in the abdomen and around the face and upper back — a pattern sometimes called central or visceral obesity. It also increases appetite and can drive cravings for high-calorie foods. In Cushing syndrome, weight gain is one of the most consistent findings, present in more than 90% of cases. Stress-related cortisol elevation may contribute to modest weight gain, though the effect size in otherwise healthy people is smaller and harder to isolate.

Does cortisol affect sleep?

Yes, in both directions. Cortisol follows a circadian rhythm, rising sharply in the early morning to promote wakefulness and falling at night to allow sleep. Elevated evening cortisol — from chronic stress, shift work, or HPA axis disorders — delays sleep onset and reduces slow-wave (deep) sleep. Conversely, poor or short sleep (less than 6 hours) raises next-day cortisol levels, creating a cycle that can be difficult to break without addressing both stress and sleep habits.

Is adrenal fatigue a real diagnosis?

No — "adrenal fatigue" is not recognized by the Endocrine Society, the American Association of Clinical Endocrinology, or any major medical body. The concept suggests that chronic stress gradually exhausts the adrenal glands, but no peer-reviewed evidence supports this mechanism or a reliable test for it. Symptoms like fatigue, brain fog, and low energy are real but have many evidence-based explanations. If you have these symptoms, ask your clinician to test for thyroid disorders, anemia, sleep apnea, and true adrenal insufficiency before accepting an "adrenal fatigue" label.

Sources

All glossary termsUpdated 2026-05-17