Saturday, July 22, 2017

ICYMI: Primary vs Secondary vs Tertiary Adrenal Insufficiency

In case you missed it, Action for Adrenal Awareness released our video for the month of June. In it, Nichole gives a very brief overview of the different types of Adrenal Insufficiency. She describes primary adrenal insufficiency (a problem with the adrenal glands), secondary adrenal insufficiency (a problem with the pituitary gland), and tertiary adrenal insufficiency (a problem with the hypothalamus).

PAI vs SAI vs TAI Explained

In the purest sense of the words, adrenal insufficiency means that the adrenal glands are insufficient at producing hormones necessary for life. There are three main classifications for how the adrenal glands became insufficient. For primary adrenal insufficiency (Addison's Disease), the issue is caused by the adrenal glands not functioning. In secondary adrenal insufficiency, the issue with the adrenal glands is only a secondary problem. The main cause is the pituitary gland. With tertiary adrenal insufficiency, lack of cortisol is actually the third issue with a sub-par hypothalamus being the main cause.

Photo retrieved from

Primary Adrenal Insufficiency

Primary adrenal insufficiency occurs when the adrenal glands fail to produce adequate cortisol to cover the body's needs. 70% of all cases of primary adrenal insufficiency are caused by idiopathic atrophy of the adrenal cortex. 30% of the cases are caused by a granuloma. It is important to note that Addison's Disease refers specifically to primary adrenal insufficiency caused by an autoimmune disease. There are several other types of primary adrenal insufficiency, such as congenital adrenal hyperplasia (CAH), or the result of a double adrenalectomy.

With PAI, you will have low morning cortisol, low random cortisol, and a high ACTH reading. This is the pituitary gland SCREAMING at the adrenal gland that something is wrong and the adrenal gland is not doing its job. Elevated ACTH levels can also lead to hyper-pigmentation also referred to as the famous Addy "perma-tan."

Often, PAI requires the replacement of all three major hormones produced by the adrenal cortex. Cortisol is replaced with either hydrocortisone, prednisone, or dexamethasone. Aldosterone is replaced with the mineralocorticoid steroid fludrocortisone. And DHEA (a precursor to testosterone) is replaced with DHEA supplements.

There is no cure for primary adrenal insufficiency, and treatment will require lifelong use of steroids.

Secondary Adrenal Insufficiency

Secondary adrenal insufficiency is far more common than primary adrenal insufficiency. It occurs when the pituitary gland fails to produce enough ACTH (adrenocorticotropic hormone). The most common cause of ACTH suppression is use of glucocorticoid steroids to treat other illnesses.

Glucocorticoid steroids are synthetic hormones that act like cortisol. These include cortisone, hydrocortisone, prednisone, prednisolone, and dexamethasone. All of these medications have an effect on ACTH production. The pituitary gland produces ACTH as a response to the body's cortisol need. When the pituitary gland senses any of these medications, it recognizes that cortisol is present and therefore produces less ACTH. This leads to ACTH suppression, and potentially, inadequate cortisol coverage.

ACTH suppression from medication can be classified into three main categories: temporary, short term prolonged, and permanent. The length of suppression depends on the dose, potency, and length of time the medication was used. According to NADF, a few days on prednisone should have a limited ACTH suppression. However, a few weeks of prednisone at a dose of 10 mg a day will diminish the cortisol level along with the body's ability to respond to a stressful situation.

The NADF likes to use the following general guideline: For each month on a suppressive dose of corticoid steroids, it will take the body one month to recover. On more than 10 mg of prednisone a day for three months? Expect to take an additional three months to recover after you have been weaned down. This works up to the 9-12 month mark. If you have been on steroids for longer than 9-12 months, expect it to take many years for your hypothalamus - pituitary - adrenal (HPA) axis to recover, if recovery is even possible.

It is very important to note that SAI is at equal risk of an adrenal crisis to PAI. Secondary adrenal insufficiency is not a less dangerous form of primary adrenal insufficiency. You can still experience an adrenal crisis. It is incredibly important for you to wear a medical alert bracelet and carry an emergency injection.

Tertiary Adrenal Insufficiency

Tertiary adrenal insufficiency is a relatively newer classification in the adrenal insufficiency world. It occurs when the hypothalamus does not produce enough CRH (corticotropin-releasing hormone). CRH is used to tell the pituitary gland to produce ACTH, which then signals the adrenal gland to produce cortisol. It can be caused by long term glucocorticoid steroid use, or after the curing of cushing's disease (too much cortisol).

Tertiary adrenal insufficiency will show low / normal ACTH blood levels at 8AM similar to that of SAI. It can be differentiated from SAI with a CRH stimulation test. This test measures the amount of cortisol in your blood before and after you are given an injection of a synthetic form of CRH.

Closing Remarks

It is incredibly important for a physician to thoroughly review your entire medical history and your symptoms. This will help determine which category you fit into, if your disease can be cured, and help determine the best method of treatment. An inappropriate wean from steroids puts you at a great risk for an Adrenal Crisis.

If you do not believe that your physician is a proper fit for you, seek out a second opinion. Find a doctor that is willing to work with you. Also, reach out to online support groups and others familiar with your disease. Our goal is to help you find the best treatment method possible.

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  1. Great post, Amber! My secondary AI is caused by lymphocytic hypophysitis, which caused my pituitary to no longer produce acth or prolactin.

    1. Thanks for the link! That's fascinating about lymphocytic hypophysitis. I love how ACTH deficiency is more "rare." Congrats on your rareness!

      ~ Amber


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