How long does a patient have to have ACTH deficiency with basal morning ACTH at about 10 ng/L in order to develop such adrenal gland atrophy that there is an inadequate response to low dose Synacthen test?

I found here that in the first 4-6 weeks after the onset of ACTH deficiency, the response to Synacthen might be normal because there is no arenal gland atrophy yet. Does anyone have any other sources analysing how long it takes for the adrenal glands to atrophy?

  • In your own words can you describe what "adrenal gland atrophy" is? Commented Aug 4, 2023 at 17:03
  • 1
    @BrendanDarrer Shrinking of the adrenal gland. Commented Aug 8, 2023 at 12:55

1 Answer 1


Some Endocrinology

The hypothalamic-pituitary-adrenal (HPA) axis can be summarised in this diagram, with the hormones released at each level creating a negative feedback loop with the level above.

HAP axis

Image from Empowered Health Institute

Corticotrophin releasing hormone (CRH) from the hypothalamus stimulates the pituitary to produce adrenocorticotrophic hormone (ACTH), which in turn stimulates the adrenal gland (specifically its outer cortex) to produce glucocorticoids like cortisol.

The adrenal gland is made up of the cortex and medulla. The cortex produces steroid hormones including glucocorticoids, mineralocorticoids, and adrenal androgens, and the medulla produces the catecholamines, epinephrine, and norepinephrine.

Adrenal Atrophy

ACTH is a growth factor for the adrenal cortex. The presence of exogenous glucocorticoids (such as prescribed steroids) will suppress ACTH production and eventually lead to adrenal atrophy.

It seems that a period of 4-6 weeks of insufficient ACTH will cause some degree of adrenal atrophy.

This is taken from Glucocorticoid Withdrawal—An Overview on When and How to Diagnose Adrenal Insufficiency in Clinical Practice:

A prolonged (more than 4–6 weeks) insufficient ACTH secretion leads to an atrophy of the zona fasciculata and reticularis and decreased ability to secrete cortisol.

In turn, it referenced the following chapter in a book, which I do not have full access to:

Carroll T.B., Aron D.C., Findling J.W., Tyrrell J.B. Glucocorticoids and Adrenal Androgens. In: Gardner D.G., Shoback D., editors. Greenspan’s Basic & Clinical Endocrinology. 10th ed. McGraw-Hill Education; New York, NY, USA: 2017.

During this period, a synthetic ACTH (“Synacthen test”) may yield a normal result as the adrenal gland can still respond.

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