Nursing care
Why does Addison disease cause hyperpigmentation? The ACTH feedback loop explained
Written and reviewed by Nicole Ramirez, BSN, RN, CMSRN · 4 min read · Updated November 2026
Short answer
Addison disease causes hyperpigmentation because damaged adrenal glands stop making cortisol, so the pituitary keeps raising ACTH to push them harder. ACTH, along with beta-lipotropin released with it, has melanocyte-stimulating activity, so the skin darkens. Secondary adrenal insufficiency does not cause dark skin, because the pituitary is the failing gland and ACTH stays low.
Low cortisol, high ACTH: a feedback loop stuck on
Cortisol normally switches off its own signal. When cortisol is high enough, the pituitary releases less ACTH. In Addison disease, the adrenal cortex is damaged and cannot answer, so cortisol stays low and the pituitary keeps increasing ACTH in an attempt to make the glands respond.
MSD Manuals describes exactly this chain: a falling cortisol level raises pituitary ACTH and blood beta-lipotropin. It also gives the lab pattern that confirms primary disease, an ACTH of 50 pg/mL or more alongside a cortisol below 5 mcg/dL, which it applies particularly to stressed or critically ill clients. High ACTH with low cortisol is the fingerprint of a gland that has stopped responding.
How a stress hormone ends up darkening skin
ACTH is not only an adrenal messenger. According to MSD Manuals, beta-lipotropin has melanocyte-stimulating activity and, together with ACTH, causes the hyperpigmentation. Melanocytes respond by making more melanin, and the skin slowly deepens in color.
Because the change is gradual, it is easy to miss. NIDDK notes that adrenal insufficiency symptoms develop slowly and can be overlooked or blamed on other illnesses. A client may describe it as a tan that never faded, or family may notice it before the client does, so ask about it directly rather than waiting for it to be mentioned.
Where to look on assessment
The darkening is not limited to sun-exposed skin. MSD Manuals describes it on exposed and, to a lesser extent, unexposed areas, especially pressure points over bony prominences, skin folds, scars and extensor surfaces. NIDDK lists elbows, knees, knuckles and toes, the lips, and the lining of the cheek.
Mucous membranes are the most useful clue, particularly in clients with darker skin tones where a general change is hard to judge. MSD Manuals describes bluish black discoloration of the areolae and mucous membranes, and NIDDK lists the lips. Look inside the cheek and at the gums with a penlight, check scars and knuckle creases, and compare with photos or the client's own description of their usual color.
Why skin color separates primary from secondary insufficiency
MSD Manuals states that adrenal insufficiency caused by pituitary failure does not cause hyperpigmentation. In secondary disease, the pituitary is the gland that has failed, so ACTH is low, not high, and there is no excess signal to drive the melanocytes. Pale or unchanged skin with low cortisol points away from Addison disease.
This finding pairs with the electrolyte pattern. In primary disease, aldosterone is also lost, which explains the high potassium and low sodium covered on the linked potassium page. A stem that combines dark skin creases, salt craving and high potassium is describing primary disease. A stem with low cortisol, normal skin and normal potassium suggests a pituitary cause.
Hypothetical practice scenario
Hypothetical scenario, not a real exam item: a client reports months of fatigue, dizziness on standing and craving salty food. The nurse notices dark patches inside the cheek and darkened knuckle creases. Which lab result fits this picture: high ACTH with low cortisol, low ACTH with low cortisol, or high cortisol with low ACTH?
High ACTH with low cortisol fits, because the pituitary is pushing hard against adrenal glands that cannot respond, and that excess ACTH is what darkens the skin. Low ACTH with low cortisol describes secondary insufficiency, which does not darken skin. High cortisol with suppressed ACTH belongs to a cortisol excess state, the opposite problem.
Sources and further reading
MSD Manual Professional Version: Addison Disease. Cortisol to ACTH and beta-lipotropin chain, melanocyte-stimulating activity, distribution of pigmentation, mucous membrane patches, no hyperpigmentation in pituitary failure, diagnostic ACTH and cortisol values.
NIDDK: Symptoms and Causes of Adrenal Insufficiency and Addison's Disease. Skin darkening sites in Addison disease, salt craving, positional dizziness, gradual onset that can be overlooked.
The next step on this is the same as on everything else here: answer questions and read the rationales. Our endocrine practice questions are the closest set to what this page covers.
Common questions
Why is ACTH high in Addison disease?
The adrenal glands cannot make enough cortisol, so the normal brake on the pituitary is gone. The pituitary keeps raising ACTH to stimulate glands that cannot respond. MSD Manuals uses an ACTH of 50 pg/mL or more with cortisol below 5 mcg/dL to indicate primary disease, particularly in stressed or critically ill clients.
Does secondary adrenal insufficiency cause dark skin?
No. In secondary insufficiency, the pituitary itself is failing, so ACTH is low and there is no excess hormone to stimulate pigment cells. MSD Manuals states that insufficiency due to pituitary failure does not cause hyperpigmentation.
Is Addison skin darkening just a tan?
No. It appears on unexposed skin too, especially skin folds, scars, knuckles, elbows and knees, and inside the mouth. Dark patches on the gums or inner cheek are a strong clue that sun exposure cannot explain.