I have cared for, and published a paper on, many people whose anxiety was being caused, and/or driven, by an inherited condition involving their adrenal gland over-functioning.
This condition is called late-onset congenital adrenal hyperplasia (LOCAH). It’s called late-onset because people develop the symptoms of it a few years before puberty starts, around the “tween” years. It is called congenital because people are born with it, it just waits 9-12 years to express. This tweener time of life is when our adrenal glands mature into their adult form. It’s called hyperplasia, which means “grown larger,” because the adrenal gland of someone with LOCAH works “overtime” to keep up with the body’s needs, and must increase its size to do so.
One of the central functions of our adrenal gland is to make cortisol, the main hormone helping us deal with chronic stress. This process involves cholesterol entering one side of the adrenal gland and then undergoing a 5-step series of bio-transformations before popping out of the other side of the adrenal gland and into the circulation as cortisol.
When a person has LOCAH there is a glitch in one step of the cortisol pathway, so it may initially work at 50% of normal, but the gland quickly bulks up (the hyperplasia) so it can keep up with the body’s demand for cortisol. However, upstream from the block the precursor hormones back up, like in a log jam, and float sideways in the gland to a different pathway that makes testosterone.
This first step in the adrenal testosterone pathway is called dehyroepiandrosterone sulfate (DHEAS). And DHEAS is over produced in LOCAH and is secreted into the circulation. This causes many people with LOCAH have elevated levels of DHEAS in their bloodstreams.
The interesting thing is that DHEAS is a hormone with the power to cause anxiety in people. DHEAS has been referred to as an “anxiogenic neuroactive steroid.” This means it can cause anxiety by acting in our brains. It does this by blocking GABA-A in the brain. GABA-A is the cell surface receptor where GABA binds and acts. GABA normally inhibits brain cell activity. Medications that enhance GABA cause calming, sedation and anesthesia, and inhibit seizures. Blocking GABA causes anxiety, irritability and even seizures in epileptic patients.
This all means that any person with intractable or hard to treat anxiety, or a female with anxiety and signs of too much testosterone, should have a blood test for DHEAS. Finding it elevated probably means they have LOCAH. Testing can be done to prove it and treatment is very effective at normalizing DHEAS, which reduced the person’s anxiety dramatically.