Glucocorticoid Psychosis usually occurs at very high doses of Hydrocortisone or Prednisone. Usually, I would associate it with doses of Prednisone near 90 mg a day (450 mg of Hydrocortisone). Symptoms can include hallucinations, delusions, agitation, mania, severe depression, etc. At these doses, the adrenal cortex stops working. The dose of the glucocorticoid is so high, significant insulin resistance occurs. The supraphysiologic doses of glucocorticoid can start destroying brain cells, with prolonged treatment.

At lower, sub-physiologic levels (e.g. hydrocortisone at or below 15-20 mg in women, 20-25 mg in men a day), then the dose doesn’t result in excessive overall cortisol levels. The cortisol levels are maintained by negative-feedback control from the brain.

However, treatment of adding hydrocortisone does suppress or slow down adrenal cortex function. The negative feedback control senses the added hydrocortisone, reduces ACTH production, and slows down the adrenal cortex production of hydrocortisone AND THE OTHER SIGNALS (HORMONES) OF THE ADRENAL CORTEX. This can cause a deficit in the production of pregnenolone, progesterone, DHEA, aldosterone, testosterone, estradiol, etc. etc.

It is this deficit of the other adrenal signals (hormones) that causes problems.

Excessive norepinephrine signaling is a contributing factor for anxiety. Norepinephrine is the primary signal for stress. At high levels, it can cause fear (or irritability and anger). At higher levels it can cause paranoia and paranoid delusions, and stimulate hallucinations. At high levels, norepinephrine can also trigger obsessive-compulsive behavior.

Progesterone, for example, is a very calming signal to the brain. Losing progesterone can lead to anxiety or worse in a nervous system that is already excessively producing norepinephrine.

The loss of production of the other signals makes treatment with hydrocortisone monotherapy problematic. Many patients do not have a problem with hydrocortisone monotherapy. But some patients are very sensitive to the loss of the other hormones/signals. It is difficult to tell which ones are going to be sensitive – other than through trial and error in therapy.

Generally, I would consider replacement of one or more additional adrenal hormones to make up the difference at the start of treatment.

For example, when adding hydrocortisone, I would at minimum add an androgen, like DHEA. This would help reduce the risk of bone density loss, for example, from treatment with hydrocortisone alone, though the risk is low to begin with. DHEA also has calming effects on the brain – helping increase dopamine. It also is a precursor for testosterone and estradiol, helping support their production and effects on brain function as well as general health.

With women and some men, I would consider adding progesterone. Progesterone is not only calming, it is a precursor for many of the other signals from the adrenal glands.

I would also consider adding pregnenolone, particularly if memory and attention are affected.

If needed, such as when lightheadedness is frequent, then treatment with aldosterone or Florinef (Fludrocortisone) may be necessary.

Supporting adrenal function through hormone replacement therapy is complicated because so many hormones many need to be replaced to restore normal function and avoid problems.

One of my colleagues, Thierry Hertoghe MD, is fond of saying one should consider replacing all the hormones at once (or at least optimizing all of them at once) when considering replacement of one.

@BlackJack 569 wrote:

Dr. M whats your usual dose of Cortef for male patients?

If I was to use hydrocortisone, the usual adult male can take about 20-25 mg a day in divided doses. This would be a generally sub-replacement dose which does not fully suppress adrenal function. The liver will destroy about 40% of this before it goes into the general circulation.

An excellent reference book to hormone treatments is Thierry Hertoghe MD’s The Hormone Handbook. https://ucprx.com/index.php?page=shop.product_details&flypage=shop.flypage&product_id=20&option=com_virtuemart&Itemid=6&vmcchk=1&Itemid=6

This would be the book to refer to when it comes to dosing of cortisol and other hormones.

Note that if one is considering using hydrocortisone (Cortef), then one has to also consider adding the other adrenal signals (hormones) such as pregnenolone, progesterone, DHEA, aldosterone, testosterone, estradiol.

When one does not also consider adding one or more of the other adrenal signals when one is adding hydrocortisone, then one will often develop problems with treatment.

Note that when a person has low cortisol production because of hypothalamic-pituitary-adrenal axis dysregulation (which includes conditions previously referred to as adrenal fatigue), then addressing these problems may be more important than supporting adrenal output. Addressing the cause of the low adrenal output would more directly treat the problem – if the problem can be found. Often, for example, nutritional deficiencies are a cause of adrenal problems. Mental health and stresses are other causes. Etc. etc.

@mylilcappi 576 wrote:

Dr. M,
You mention adding DHEA. My Dhea is high. 237 (0-150)
I don’t know why, but it’s looking like thank can’t take that.
thanks

If DHEA is already high, it doesn’t need to be added.

@mylilcappi 579 wrote:

Dr. M,
So basically you are saying, that possibly the reason why HC does this to my MIND is because I don’t have enough progesterone, estradiol, etc. And If these hormones were where they are supposed to be, that HC would not do this to me? Trying to understand here..

thanks….

The addition of hydrocortisone to the body causes a reduction in ACTH production which then causes the adrenals to slow down production of their hormones.

This causes a deficiency in the hormones other than hydrocortisone. All of the adrenal cortex hormones (except aldosterone and to a certain extent DHEA), are produced all at once in response to ACTH. Since ACTH is reduced by the addition of exogenous hydrocortisone, one can expect some deficiency in these other hormones – progesterone, DHEA, testosterone, estradiol, estrone, androstenedione, androstenediol, pregnenolone, etc. etc.

So the question would be what would happen if a person has a deficiency in these other hormones? This is particularly true when a person is under high stress, has anxiety, etc. During the time such a person is having anxiety, their adrenal cortex output is expected to respond to stress signaling by outputting even more DHEA, progesterone, testosterone, etc. etc. The lack of such a response because the adrenal output is reduced by hydrocortisone can be significant.

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Realize that from my perspective, the adrenal glands are part of the mind. Their output fully and directly affects mental function.

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Note that I assume you were taking Hydrocortisone in divided doses. When too high a single dose of hydrocortisone occurs – such as perhaps 20 mg all at once in some people – then the adrenal output is shut down for that time.

@mylilcappi 602 wrote:

Also I am very interested in many topics that include the nervous system…

How is the world would I go about seeing if my nervous system needs attention.. What kinds of tests, what kinds of doctors? As you can probably tell, I’m desperate..

so you don’t think the klonopin interfered with the HC enough to give me those serious side effects.. especially my MIND.

thanks again…………

Usually a psychiatrist would be the one addressing the functional side of the nervous system.