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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 forms of CAH affect cortisol levels, and what treatments are available.
Cortisol is a type of steroid hormone called a glucocorticoid. It’s made by the adrenal glands. These two small glands are on top of the kidneys.
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Inside these glands, special proteins called enzymes — specifically 21-hydroxylase — help produce cortisol.
Cortisol is a hormone that helps regulate blood pressure, blood sugar levels, the sleep-wake cycle, and the body’s stress response.Most tissues in the body respond to cortisol, which helps regulate several important functions, including:
Cortisol imbalance, which means having either too much or too little of the hormone, can cause problems in many parts of the body.
A 21-hydroxylase deficiency is the underlying cause of the most common type of CAH.
The main function of 21-hydroxylase is to help make cortisol and another hormone called aldosterone. If 21-hydroxylase is missing or not working properly, the body makes very little cortisol in severe forms of CAH. In salt-wasting CAH, it also makes too little aldosterone.
The effect on cortisol levels depends on the form of CAH a person has.
In classic CAH, changes in the gene that provides instructions for making 21-hydroxylase result in an enzyme that doesn’t work or works poorly. As a result, the adrenal glands don’t make enough cortisol to meet the body’s needs.
In salt-wasting CAH, the body also can’t make enough aldosterone. This hormone helps control salt levels in the blood. Without it, too much salt is lost through urine.
That’s why the most severe form of CAH is called salt-wasting CAH. Less severe forms of CAH may not include salt-wasting, including simple-virilizing CAH. This form of CAH still carries a risk for adrenal crisis (an emergency we’ll discuss below).
In nonclassic CAH, changes in the gene for 21-hydroxylase are less severe but still lead to the body making a smaller amount of working enzyme. People with nonclassic CAH may have 20 percent to 60 percent of normal enzyme activity, which often allows them to make enough cortisol. Symptoms and treatment needs can still vary widely in nonclassic CAH.
About 95 percent of people with CAH have a defect in the 21-hydroxylase enzyme. In other rare types, changes in genes for other adrenal gland proteins can also affect cortisol levels.
For example, a deficiency in 11-beta-hydroxylase, another enzyme involved in making cortisol, can lead to low cortisol levels. When this enzyme is missing, deoxycorticosterone — a hormone that helps control salt and water balance — can build up and raise blood pressure. As a result, people with this type of CAH generally don’t require aldosterone replacement.
Other enzymes that help make cortisol include 3-beta-hydroxysteroid dehydrogenase, 17-alpha-hydroxylase, and the cholesterol side-chain cleavage enzyme.
Rarely, CAH can also be caused by a P450 oxidoreductase deficiency or steroidogenic acute regulatory protein deficiency. People with CAH caused by a deficiency in these other proteins may also have trouble making enough cortisol and require hormone replacement.
Adrenocorticotropic hormone (ACTH) is a hormone made by the pituitary gland
in the brain. When the pituitary gland senses low cortisol in the bloodstream, it releases ACTH. ACTH then signals the adrenal glands to produce more cortisol.
In CAH with low cortisol, the adrenal glands can’t properly respond to the ACTH signals because they don’t have enough of the enzymes needed to convert steroid precursors (substances used to make steroid hormones) into cortisol. In 21-hydroxylase deficiency, one of these precursors is 17-hydroxyprogesterone (17-OHP).
The pituitary gland continues sending out more ACTH signals, which leads to increased levels of 17-OHP that cannot be converted into cortisol. Instead, the adrenal glands use the precursors to make excess amounts of androgens (male hormones). This leads to high androgen levels as a second problem seen in many people affected by 21-hydroxylase deficiency.
These signals are part of the hypothalamic-pituitary-adrenal (HPA) axis, the communication pathway between the brain and the adrenal glands.
Read more about the HPA axis and how CAH affects it.
Common symptoms of low cortisol levels include:
The most serious complication of low cortisol levels is an adrenal crisis, a life-threatening emergency that requires immediate treatment. Cortisol regulates vital functions like blood pressure and circulation, especially during illness or stress. Too little cortisol can reduce blood flow, causing a dangerous drop in blood pressure and possible organ failure.
Symptoms of low cortisol can include fatigue, low blood pressure, decreased appetite, and adrenal crisis — a life-threatening medical emergency.Symptoms of an adrenal crisis include:
If you suspect an adrenal crisis, call 911 or seek emergency care right away.
An adrenal crisis can happen if CAH is not properly treated. Physical stress, such as illness, surgery, or injury, is a common trigger. Strong emotional stress (like grief or extreme worry) has been reported to possibly play a role and can have physical effects on the body over time, but the connection isn’t as well established as it is for physical stressors.
When evaluating possible CAH, doctors may measure cortisol levels with a blood test. Because cortisol levels naturally rise and fall throughout the day, testing is usually done in the early morning, when levels should be at their highest. This helps doctors better understand whether the adrenal glands are working normally.
An ACTH stimulation test may be used during diagnosis to check how well the adrenal glands produce cortisol when stimulated. To diagnose CAH, doctors measure cortisol, 17-OHP, and androgen levels before and after an ACTH injection. In 21-hydroxylase deficiency, 17-OHP rises more than expected after ACTH, while the cortisol response depends on the form of CAH.
The degree of abnormalities seen on testing helps doctors diagnose different forms of CAH, including classic and nonclassic forms.
Checking different hormone precursors can also help doctors diagnose CAH caused by deficiencies in different enzymes.
In countries with newborn screening for CAH, doctors screen for the classic form of the condition by measuring blood levels of 17-OHP. This steroid precursor is necessary for making cortisol in the adrenal glands and builds up when 21-hydroxylase doesn’t function properly.
An endocrinologist (a doctor who treats hormone conditions) and a team of other healthcare providers typically recommend a treatment plan personalized for an individual’s needs.
One goal of treating CAH is to replace missing hormones and prevent problems from low cortisol, such as an adrenal crisis. Treatment also aims to lower excess androgens to keep hormone levels in balance. The type of treatment depends on the type of CAH and how severe the symptoms are.
People with classic forms of CAH need daily glucocorticoid medication to replace cortisol because they don’t make enough on their own. The most common medication for this is hydrocortisone, especially for children who are still growing.
Daily treatment replaces cortisol, with extra doses during illness or other physical stress when needed. It also helps reduce androgen levels.
Newer medicines for CAH can lower the brain signals that drive excess androgen production. For example, crinecerfont (Crenessity) was approved by the U.S. Food and Drug Administration (FDA) in 2024 for adults and children ages 4 and older with classic CAH. It’s used with glucocorticoids to control androgen levels.
Treatment for CAH aims to replace missing hormones, keep hormone levels in balance, and prevent problems from low cortisol.Crinecerfont reduces androgen production from the adrenal gland so that people taking it can work with their endocrinologist to reduce their doses of glucocorticoid medications.
In classic CAH, glucocorticoid treatment usually begins soon after birth and continues for life. People with nonclassic CAH may not need daily steroid treatment for life if they have mild symptoms of excess androgens.
Some people may need medicine if symptoms get worse, even if they’re done growing. People with nonclassic CAH may need glucocorticoids during major illness or surgery if their bodies can’t make enough cortisol under stress.
Additional CAH treatments may be needed depending on symptoms.
Each person’s treatment plan is unique, and regular checkups with doctors help make sure medications are working properly. With the right care and support, people with CAH can lead healthy, active lives.
Ongoing endocrinology research is also improving treatment options, giving people with CAH and their families more ways to care for the condition and plan for the future.
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I was tested at the Medical College of Ga. My sex organs seem normal
But I had a high level of androgens WTH hair on chin st she. 15. Dr . Greenblatt gave meets of something in my stomach. At age 20… read more
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