CAH starts with a missing enzyme and leads to a domino effect of hormonal impacts
Congenital adrenal hyperplasia (CAH) disrupts hormonal pathways across your body. The result? A mix of symptoms and effects that may seem unrelated — until you understand how hormones are connected.
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It’s like that old kids’ rhyme about the leg bone being connected to the knee bone: One small change at the biochemical level can cause a ripple effect around your body.
We talked with endocrinologist Pratibha Rao, MD, about the hormonal pathways impacted by CAH. Why do they happen? And how do they affect you?
In about 95% of people with CAH, a certain enzyme — called 21-hydroxylase — is missing or doesn’t work fully. It happens because of an inherited genetic change, or mutation.
That might sound like no big deal. The human body has tens of thousands of enzymes after all. But each of them is important.
Enzymes are the catalysts that make chemical reactions, like hormone production, happen. And when 21-hydroxylase isn’t up to speed, it creates a domino effect across your body.
“The defect in 21-hydroxylase can happen in varying stages,” Dr. Rao explains. “In classic CAH, the deficiency is more severe. In non-classic CAH, it can be milder, so you may not have symptoms until later in life, or have no symptoms at all.”
The hormonal impacts of CAH are vast and incredibly complex. But let’s take a deeper look at some of the relevant hormones impacted by CAH.
Among its other jobs, 21-hydroxylase helps create aldosterone. That’s a hormone that helps regulate blood pressure, sodium and potassium in your body. People with salt-wasting CAH typically have a severe form of 21-hydroxylase deficiency — meaning they can’t make aldosterone at all.
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That causes them to lose too much sodium when they pee. That leads to problems like:
People with salt-wasting CAH may take salt supplements or mineralocorticoids — prescription replacements for aldosterone.
Cortisol is commonly called the “stress hormone” because your body produces it in response to ... you guessed it, stress. That includes emotionally stressful times, like grief and trauma. But also physical stressors, like injuries and illnesses.
21-hydroxylase is a key enzyme for creating cortisol. It does that by taking a steroid hormone called 17-hydroxyprogesterone (17-OHP) and converting it into cortisol. (Keep that in mind because we’ll be coming back to 17-OHP in a bit.)
As people with CAH don’t have the enzyme to make that switch happen, your body can’t make cortisol. Or it can’t make enough to keep up.
“Your body is meant to automatically increase cortisol production to deal with stress,” Dr. Rao reports. “When it doesn’t get the cortisol it needs, it can lead to adrenal crisis.” That’s a dangerous, and potentially life-threatening condition. Left unmanaged, it can lead to seizures or a coma.
That’s why CAH treatment includes medications called glucocorticoids. Those are synthetic cortisol-like hormones. Getting a proper dosage of those medications is vital for your health and well-being.
“It’s really important that people with CAH know they may need to increase their dosage during increased times of stress,” Dr. Rao states. “We also advise them to carry emergency injectable medication with them, wear a medical alert bracelet and keep a wallet card.”
Remember how 21-hydroxylase is supposed to turn 17-OHP into cortisol? When that doesn’t happen, 17-OHP builds up in your body.
It can’t become cortisol, but it needs to go somewhere. So, it winds up taking another path. It gets rerouted and used to produce androgens, a group of sex hormones that includes testosterone and androstenedione.
Extra androgens are responsible for CAH symptoms like:
Extra progesterone in your body normally gets converted into 17-OHP, which, as we now know, is supposed to become cortisol.
But for people with CAH, that doesn’t happen. So, progesterone builds up and contributes to hormone imbalance.
This buildup can then contribute to menstrual irregularities, fertility issues, mood swings and more.
When your body senses low cortisol, it tries to compensate — boosting production signals that also increase melanocyte-stimulating hormone (MSH).
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That’s because cortisol and MSH share the same chemical origin: POMC, a molecule that breaks down into ACTH, which signals cortisol, and MSH.
What does that do?
“MSH goes into the skin and stimulates the formation of melanin, a substance that gives your skin its color,” Dr. Rao explains.
Excess melanin can lead to hyperpigmentation — dark patches of skin that often show up on your gums, palms and soles of your feet. Staying on top of your CAH medication regimen can help manage or prevent this.
No one said that managing CAH is easy or convenient. It can be tedious, overwhelming and relentless.
But keeping your hormones balanced is key to living a healthy life. Stay connected with your healthcare team. Speak up about any new symptoms. And most of all, take care of yourself. You matter.
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