Cortisol is a hormone that helps control many important functions in the body. People living with congenital adrenal hyperplasia (CAH) may have lower-than-normal cortisol levels, depending on their type of CAH.

This article will explain what cortisol does, how different types of CAH affect cortisol levels, and what treatments are available.

What Is Cortisol?

Cortisol is a type of steroid hormone called a glucocorticoid. It’s made by the adrenal glands, two small glands located on top of the kidneys. Inside these glands, a special protein called an enzyme — specifically, 21-hydroxylase — helps produce cortisol.

Most tissues in the body respond to cortisol, which helps regulate several important functions, including:

• Stress response
• Blood pressure
• Inflammation
• Metabolism (how the body converts food into energy)
• Blood sugar levels
• Sleep-wake cycle

Cortisol imbalance — having either too much or too little of the hormone — can cause problems in many parts of the body.

How Does Congenital Adrenal Hyperplasia Affect Cortisol Levels?

People with CAH don’t have enough 21-hydroxylase. That’s why CAH is sometimes referred to as 21-hydroxylase deficiency.

The main function of 21-hydroxylase is to help make cortisol and another hormone called aldosterone. If this enzyme is missing or not working properly, the body makes less of these important hormones. The effect on cortisol levels depends on the type of CAH a person has.

Cortisol Levels in Classic CAH

In classic CAH, mutations (changes) in the gene that makes 21-hydroxylase result in a nonfunctional enzyme. This means that the adrenal glands don’t make any cortisol.

In addition, a nonfunctional 21-hydroxylase enzyme can’t make enough aldosterone. This hormone helps control sodium (salt) levels in the blood, so without it, too much salt gets lost through urine. That’s why this type of CAH is called salt-wasting CAH.

Some people with classic CAH still have some working 21-hydroxylase enzyme. Their condition is less severe, and their adrenal glands may make some cortisol. This type of classic CAH is called simple-virilizing CAH.

Cortisol Levels in Nonclassic CAH

In nonclassic CAH, changes in the gene for 21-hydroxylase lead to lower levels of the enzyme. However, most people with nonclassic CAH still have between 20 percent and 60 percent of normal enzyme activity, so their cortisol levels are usually similar to those of people without CAH.

Cortisol Levels in Rare Types of CAH

About 95 percent of people with CAH have either classic or nonclassic CAH, but other rare forms exist. Mutations in different enzymes can also affect cortisol levels.

For example, a deficiency in 11-beta-hydroxylase, an enzyme involved in making cortisol, and a mineralocorticoid (deoxycorticosterone, a hormone that helps control salt and water balance), can lead to low cortisol levels.

Another enzyme, 17-hydroxylase, found in the adrenal glands, helps produce aldosterone, sex hormones, and cortisol. People with CAH caused by a 17-hydroxylase deficiency may also have trouble making enough cortisol.

CAH Symptoms Related to Low Cortisol Levels

Common symptoms of low cortisol levels include:

• Extreme tiredness
• Hypotension (low blood pressure)
• Decreased appetite
• Weight loss

The most serious complication of low cortisol levels is an adrenal crisis, a life-threatening emergency that requires immediate treatment. Cortisol helps regulate many vital body functions, including maintaining blood pressure and circulation. Cortisol levels that drop too low can lead to a lack of proper blood flow, resulting in a dangerous drop in blood pressure and potential organ failure. Symptoms of an adrenal crisis include:

• Stomach pain, nausea and vomiting, or diarrhea
• Weakness
• Headache
• Fever
• Fast heart rate and breathing rate
• Sluggish movement or confusion
• Coma

An adrenal crisis can happen if CAH goes untreated. Increased stress, either physical or emotional, can also trigger an adrenal crisis in people with CAH.

Low cortisol levels can also be caused by Addison’s disease, an autoimmune condition in which the body’s immune system attacks the adrenal glands using 21-hydroxylase antibodies. Doctors test for these antibodies to tell Addison’s disease apart from CAH because they are not present in CAH. Both conditions have similar symptoms and can lead to an adrenal crisis. In some countries, past tuberculosis infections can also damage the adrenal glands.

Low Cortisol Levels and Other CAH Symptoms

CAH also affects other hormones made by the adrenal glands. When 21-hydroxylase doesn’t work properly, cortisol precursors (substances that normally help make cortisol) build up in the adrenal glands. Instead of turning these precursors into cortisol, the body converts them into androgens, a type of sex hormone. This leads to high androgen levels in the body.

In classic CAH, a 21-hydroxylase deficiency can lead to low cortisol and aldosterone levels but higher-than-normal androgen levels, which may cause:

• Ambiguous genitalia (genitals that don’t look typically male or female)
• An enlarged penis
• Early puberty
• Rapid growth
• Deep voice or excess body hair
• Infertility (trouble becoming pregnant)

In nonclassic CAH, cortisol levels may be normal. However, excess cortisol precursors can still lead to high levels of androgens, including testosterone and 17-hydroxyprogesterone. This can cause symptoms such as:

• Early puberty
• Acne
• Rapid growth
• An enlarged penis with small testicles
• Irregular menstrual periods
• Excess facial or body hair
• Infertility

Tests To Check Cortisol Levels

Cortisol levels can be measured with a blood test or a urine test.

An adrenocorticotropic hormone (ACTH) stimulation test checks how well the adrenal glands produce cortisol when stimulated. ACTH is a hormone from the pituitary gland that signals the adrenal glands to make more cortisol. During this test, doctors measure cortisol and 17-hydroxyprogesterone, a cortisol precursor, after injecting ACTH. In people with CAH, cortisol levels remain low, while 17-hydroxyprogesterone rises quickly, helping doctors diagnose or monitor CAH. This test must be done in a hospital under medical supervision.

In countries with newborn screening for CAH, doctors diagnose the condition by measuring blood levels of 17-hydroxyprogesterone. This substance is necessary for making cortisol, but it builds up when 21-hydroxylase doesn’t function properly. In healthy newborns, 17-hydroxyprogesterone is high at birth but decreases quickly. However, in babies with CAH, this substance stays high.

Treatments That Target Cortisol Levels

Treatment of CAH focuses on preventing complications of low cortisol levels, such as an adrenal crisis. The type of treatment depends on the type of CAH and the severity of symptoms. A team of healthcare providers and specialists is typically involved in finding the best treatment plan for an individual’s needs.

People with classic CAH need daily glucocorticoid medication to replace cortisol because they don’t make any on their own. The most common medication for this is hydrocortisone (Cortef). This treatment not only helps the body manage stress but also helps reduce androgen levels.

In classic CAH, glucocorticoid treatment usually begins soon after birth and continues for life. Because cortisol is key to helping the body handle stress, the glucocorticoid dose may need to be adjusted when the body is stressed, such as during illness or emotional stress.

People with nonclassic CAH may not need any glucocorticoid treatment if they’re not experiencing symptoms. However, some may need treatment if their cortisol levels are low or during times of stress.

Additional CAH treatments may be needed depending on symptoms. For example, people with salt-wasting classic CAH may need salt supplements and mineralocorticoid medications to help balance sodium and fluid levels.

Each person’s treatment plan is unique, and regular checkups with doctors help make sure medications are working properly. With the right care, people with CAH can lead healthy, active lives​​​.

Talk With Others Who Understand

On CAHteam, the site for those with congenital adrenal hyperplasia and their loved ones, people come together to gain a new understanding of CAH and share their stories with others who understand life with the condition.

How has CAH affected your cortisol levels? What treatments have helped balance your cortisol levels? Share your experience in the comments below.