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Why is there hyperpigmentation in Addison disease?

Posted Jul 22 2012 12:39am

Q. How come patients with Addison disease have hyperpigmented skin?

A. Addison disease is an autoimmune disorder in which the body attacks the adrenal glands, effectively shutting them down. Patients end up with a whole host of problems, including hypotension (from the lack of mineralocorticoids) and hypoglycemia (from the lack of cortisol).

As the disease progresses, the adrenals put out less and less cortisol. The pituitary sees that drop in cortisol levels and responds by making more ACTH. ACTH is derived from a bigger precursor molecule called pro-opiomelanocortin (POMC). POMC is also a precursor for beta endorphin and melanocyte stimulating hormone (MSH)…so if you make more POMC (in order to make more ACTH), you’ll make more beta endorphin and MSH.

The beta endorphin doesn’t do much, as far as I know, but the MSH stimulates melanocytes, giving the skin a bronze color. Sometimes it’s an all-over bronze, like a tan (as in the photo above), and sometimes it’s more localized (in the gums, or in areas subjected to increased pressure, like over the knuckles or in skin folds).

However the bronze color manifests, it’s a telltale sign that the patient’s adrenal failure is primary (localized to the adrenal) and not secondary (due to hypopituitarism). In adrenal failure due to hypopituitarism, the whole problem is that the patient isn’t making ACTH (and thus the adrenals aren’t putting out their products) – so there’s no increase in MSH production and no hyperpigmentation.

Note: the photo is from the original book in which Thomas Addison described Addison disease (On the constitutional and local effects of disease of the supra-renal capsules). It is located at the Hardin Library for the Health Sciences at the University of Iowa.

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