Guide to Cortisol

WRITTEN BY

The Levels Team

Updated: 05/22/2025|12 min read

Summary

Cortisol is a steroid hormone produced by the adrenal glands. It plays a role in the body's stress response and also affects metabolism, immune function, and inflammation.

Why It Matters

Cortisol increases in response to stress, but it affects many systems in the body. When functioning properly, cortisol helps regulate blood sugar levels, metabolism, immune response, blood pressure, and inflammation. It ebbs and flows throughout the day, with levels typically highest in the morning (typically 30 minutes after waking) and lowest at night, helping to regulate the sleep-wake cycle.

The production of cortisol begins in the brain's hypothalamus, which releases corticotropin-releasing hormone (CRH) in response to stress or daily rhythms. CRH then stimulates the pituitary gland to secrete adrenocorticotropic hormone (ACTH), which then signals the adrenal glands to produce and release cortisol. This is referred to as the hypothalamic-pituitary-adrenal (HPA) axis.

The Total Cortisol test using liquid chromatography/mass spectrometry (LC/MS) precisely measures the total amount of cortisol circulating in the bloodstream.

High or low cortisol levels may suggest adrenal disorders, such as Cushing's syndrome or Addison's disease. Beyond diagnosing specific adrenal disorders, cortisol testing can provide insights into chronic stress and the body's response to stress management interventions, medication adjustments, or other treatments aimed at normalizing adrenal function.

Associated Symptoms

Cortisol levels themselves are laboratory findings rather than medical conditions. However, abnormal levels may be associated with various health issues, each with its own symptoms.

Common symptoms that may indicate conditions associated with high cortisol (hypercortisolism):

• Central weight gain: Fat accumulation in the abdomen (increased visceral fat), face (moon face), and upper back (buffalo hump) may be due to cortisol's effects on fat distribution
• Muscle weakness: Particularly in the limbs, can occur as cortisol breaks down muscle protein for energy production
• Thin, fragile skin: Easily bruising and poor wound healing can result from cortisol's inhibition of collagen formation
• Mood changes: Anxiety, irritability, or depression can result from cortisol's effects on brain neurotransmitters
• Elevated blood pressure: Increased sensitivity to adrenaline and enhanced sodium retention may increase blood pressure
• Blood sugar issues: Insulin resistance and elevated glucose can result from cortisol's promotion of gluconeogenesis
• Sleep disturbances: Difficulty falling asleep may be due to disrupted circadian rhythm of cortisol secretion

Common symptoms that may indicate conditions associated with low cortisol (hypocortisolism):

• Profound fatigue: Extreme tiredness unrelieved by rest can be due to impaired metabolism and energy production
• Muscle weakness: Decreased strength, especially with exertion, may result from inadequate energy metabolism
• Orthostatic hypotension: Dizziness or fainting when standing up can be due to insufficient blood pressure regulation
• Salt cravings: Intense desire for salty foods may result from impaired sodium retention
• Gastrointestinal symptoms: Nausea, vomiting, or abdominal pain may be due to reduced stress response and metabolic imbalances
• Weight loss: Unintentional decrease in body weight can result from reduced appetite and altered metabolism
• Hyperpigmentation: Darkening of skin creases, scars, and mucous membranes (in primary adrenal insufficiency) may be due to increased ACTH

It's important to note that symptoms of cortisol imbalances often develop gradually and may be mistaken for other conditions. The pattern, severity, and progression of symptoms, along with laboratory findings, help determine the underlying cause and guide appropriate treatment.

Clinical Ranges

Lab Reference Ranges:

• 8:00 - 10:00 AM: 4.6-20.6 mcg/dL
• 4:00 - 6:00 PM: 1.8-13.6 mcg/dL

Lifestyle Factors That Can Impact It

Activities that can negatively impact cortisol levels include:

• Chronic stress (physical and emotional): Chronic stress keeps the body in "fight or flight" mode, leading to consistently elevated cortisol levels.
• Poor sleep habits: Irregular sleep schedules, insufficient sleep, and sleep disorders can disrupt the normal diurnal pattern of normal cortisol production.
• Excessive caffeine: Caffeine stimulates cortisol production, and the effect is amplified in people also experiencing stress.
• Alcohol and drug use: Substance use can disrupt the HPA axis, leading to abnormal cortisol levels.
• Crash dieting or chronic caloric restriction: Severe dietary restriction signals the body to increase cortisol as a stress response to perceived famine.

Ways to support healthy cortisol levels:

• Incorporating mindfulness-based stress reduction techniques such as meditation, deep breathing, and yoga. Prioritize regular physical activity and aim for consistent, restorative sleep each night to help balance stress hormones.
• Nourish your body with a balanced, whole-foods-based diet that includes plenty of fruits, vegetables, whole grains, lean proteins, and healthy fats. Limit intake of caffeine, alcohol, and added sugars to prevent cortisol spikes. Include magnesium-rich foods like leafy greens, nuts, seeds, and legumes, which may promote relaxation and support adrenal health.
• Finally, cultivate a strong social support network and consider professional counseling or therapy to address deeper stressors and enhance emotional well-being.

Other Factors That Can Impact It

Genetic Conditions

• Gene variations, like polymorphisms in the glucocorticoid receptor gene can affect cortisol sensitivity.
• Variations in genes encoding enzymes involved in cortisol metabolism can influence cortisol clearance rates.

Medical Conditions

• Cushing's syndrome: Caused by excessive cortisol, often due to a pituitary or adrenal tumor or long-term corticosteroid medication use or a pituitary or adrenal tumor. The excess cortisol disrupts normal metabolic processes throughout the body.
• Addison's disease: Most commonly caused by an autoimmune response where the immune system attacks the adrenal glands, causing low cortisol.
• Pituitary disorders: Tumors or damage to the pituitary gland can affect ACTH production, disrupting cortisol production.
• Hypothalamic dysfunction: Damage or disorders affecting the hypothalamus can disrupt CRH production, affecting the entire HPA axis.
• Chronic inflammatory conditions: Conditions like rheumatoid arthritis can affect cortisol regulation.
• Major depression and anxiety disorders: These can alter the HPA axis, causing high cortisol levels.
• Chronic fatigue syndrome and fibromyalgia: These conditions may involve abnormal cortisol rhythms, often showing a flattened cortisol curve throughout the day.

Medications and Supplements

• Glucocorticoid medications (prednisone, dexamethasone)
• Estrogen (oral contraceptives, hormone replacement therapy)
• Certain antidepressants (particularly SSRIs)
• Herbal adaptogens: ashwagandha, Rhodiola, and holy basil. Licorice root (can cause hypertension, monitor blood pressure)
• Vitamins and Minerals: Vitamin C, B Vitamins (B5, B6, B12), Magnesium, Zinc
• Omega-3 fatty acids (from food or supplements)
• Opioids
• Ketoconazole and similar antifungals
• Licorice root
• Adaptogenic herbs (ashwagandha, Rhodiola)

Individual Factors

• Age: Some studies show higher average levels of cortisol in older adults.
• Sex: Women demonstrate different cortisol responses to stressors than men and cortisol levels fluctuate throughout the menstrual cycle.
• Pregnancy: Cortisol levels naturally increase during pregnancy, and peak in the third trimester.
• Body composition: Higher body fat is associated with altered cortisol metabolism.

Testing Accuracy and Stability

Total Cortisol testing using LC/MS is very accurate, but several day-to-day factors can affect test results.

Factors That Can Affect the Accuracy of Your Test

• Time of collection: Samples collected at different times of day will show natural variation due to cortisol's daily rhythm.
• Acute stress before testing can temporarily elevate cortisol levels.
• Disrupted sleep the night before testing can affect morning cortisol levels.
• Food intake, particularly high-protein meals, can temporarily affect cortisol levels.
• Recent intense physical activity can increase cortisol.
• Menstrual cycle phase: Women may show variations in cortisol levels throughout their cycle.
• Pregnancy: Significantly alters normal reference ranges.
• Recent glucocorticoid medication use can suppress cortisol production.

How It Relates to Other Markers

Doctors may look at other tests alongside cortisol results to provide insights about health status. These tests may include:

• ACTH (adrenocorticotropic hormone): Measures the pituitary hormone that stimulates cortisol production.
• Dexamethasone suppression test: Helps distinguish causes of cortisol excess. Lack of suppression may suggest Cushing's syndrome or an adrenal or pituitary tumor.
• Cortisol rhythm testing (diurnal pattern): Multiple samples throughout the day reveal if normal daily rhythm is preserved. Loss of normal rhythm may suggest Cushing's syndrome, and chronic stress.
• Salivary cortisol: Measures free (unbound) cortisol and is particularly useful for assessing diurnal rhythm.
• 24-Hour urinary-free cortisol: Provides a measure of cortisol production over an entire day, eliminating the issue of diurnal variation.

What Results May Mean in the Context of Other Markers

• High cortisol + High ACTH: May suggest pituitary tumor (Cushing's disease) or ectopic ACTH production.
• High cortisol + Low ACTH: May suggest adrenal tumors or long-term usage of steroid medication.
• Low cortisol + High ACTH: May suggest primary adrenal insufficiency (Addison's disease).
• Low cortisol + low or normal ACTH: Can indicate secondary adrenal insufficiency, where the problem originates in the pituitary or hypothalamus.
• Normal total cortisol + abnormal free cortisol: May indicate issues with cortisol-binding globulin (CBG) levels, which can be affected by estrogen, kidney or liver disease, or protein malnutrition.

Follow-up Considerations

If cortisol is abnormal, your provider may make some of the following recommendations. You should always speak to your doctor if you have medical questions or before making medical decisions.

When Re-Testing May be Appropriate

• After beginning treatment for cortisol abnormalities, usually within 4-12 weeks
• When symptoms persist or worsen
• Following changes in medications that affect cortisol metabolism
• When testing was performed during acute illness or stress, as these can temporarily alter results
• For monitoring known cortisol disorders at intervals recommended by an endocrinologist

Additional Testing Your Doctor May Consider

• Imaging studies (CT, MRI) of the pituitary and adrenal glands to identify tumors or structural abnormalities
• 24-hour salivary cortisol testing
• CRH stimulation test to distinguish between pituitary and adrenal causes of cortisol abnormalities
• Glucose tolerance testing when metabolic causes are suspected
• Bone density scan for people with prolonged high cortisol levels
• Thyroid function tests as thyroid disorders frequently co-occur with adrenal dysfunction

When Additional Care May be Warranted

• Sudden onset of severe symptoms such as extreme weakness, confusion, or severe abdominal pain
• Unexplained weight changes
• Progressive worsening of symptoms despite initial treatment
• Development of complications such as diabetes, hypertension, or osteoporosis
• Pregnancy or planning pregnancy with known cortisol disorders

Further Reading

How does cortisol affect metabolic health?

Bibliography