Causes
The most common cause of tertiary adrenal insufficiency, also known as glucocorticoid-induced adrenal insufficiency, is exposure to long-term or high-dose glucocorticoid (steroid) medication.
When people are prescribed steroid medication as a treatment for conditions such as asthma, skin conditions, arthritis, Crohn's disease or multiple sclerosis, they are taking these steroids for extended periods, which can interfere with the normal control mechanisms between the brain and the adrenal glands, known as the hypothalamic-pituitary-adrenal (HPA) axis.
The production of cortisol (a steroid hormone, or glucocorticoid) from fully functioning adrenal glands is controlled by two areas of the brain called the hypothalamus and the pituitary gland.
Tertiary adrenal insufficiency starts in the hypothalamus, which makes corticotropin-releasing hormone (CRH), a hormone that tells the pituitary to make ACTH. When the hypothalamus doesn’t make enough CRH, the pituitary gland doesn’t make enough ACTH. In turn, the adrenal glands don’t make enough (or any) cortisol.
When people stop taking artificial glucocorticoids suddenly, their adrenal glands may not return to normal cortisol production, which results in adrenal insufficiency.
FAQs
Thank you to Ruth Howard, an educational psychologist who has a diagnosis of TAI, for her research into Tertiary adrenal insufficiency, and for pulling together the information below:
It is important to emphasise that even if a person stops taking artificial glucocorticoids, they may never recover adrenal function, or it may take many years.
Up to 15% of people diagnosed with tertiary adrenal insufficiency experience chronic adrenal insufficiency, and between 2% and 7% will never recover adrenal function.
Alessandro Prete & Irina Bancos (2021) Glucocorticoid induced adrenal insufficiency. BMJ 2021;374:n1380 http://dx.doi.org/10.1136/bmj.n1380
Tertiary Adrenal Insufficiency (TAI), also known as Glucocorticoid-Induced Adrenal Insufficiency (GI-AI), is the most common form of adrenal insufficiency.
Glucocorticoids (GCs) were first introduced in 1948 and are the most widely used medications worldwide, treating inflammatory and autoimmune diseases and conditions. Tertiary adrenal insufficiency is thought to be highly prevalent in people taking glucocorticoids, but remains under-recognised and under-diagnosed
Just to demonstrate the scale of the challenge with tertiary adrenal insufficiency, an excellent review published in the BMJ in 2021 demonstrated a 48.7% risk of developing adrenal insufficiency in patients taking oral glucocorticoids, and a 20.3% to 43.7% risk in those using inhaled glucocorticoids, particularly when used for more than a year and used alongside oral steroids (a common combination for the treatment of asthma).
These figures suggest a huge number of individuals could be affected by this condition, given that 1-3% of the population use glucocorticoids to manage acute and long-term health conditions.
Alessandro Prete & Irina Bancos (2021) Glucocorticoid induced adrenal insufficiency. BMJ 2021;374:n1380 http://dx.doi.org/10.1136/bmj.n1380
Yes, the higher the dose and the longer the use of glucocorticoids, the more likely it is that someone will develop tertiary adrenal insufficiency.
Those on one of the most common forms of asthma inhalers are particularly at risk (the use of the inhaled glucocorticoids Fluticasone propionate is a particular risk factor, despite there being safer alternatives for the treatment of asthma and COPD).
Diagnosis, Treatment & Medication
As with the other types of adrenal insufficiency, diagnosis is identified through measuring morning cortisol levels in the blood and a subsequent Short Synacthen Test.
Treatment with replacement glucocorticoids (e.g. hydrocortisone or prednisolone) will depend on an individual's level of adrenal function. A time-critical medication regimen is required to replace the missing cortisol.
Sick Day Rules must be followed, and patients with secondary adrenal insufficiency are at risk of adrenal crisis, so they should carry an emergency injection kit.
Please see below for further information on all of these important topics:
