4th April 2024

Pathophysiology

Addison’s disease, or primary adrenal insufficiency, is a rare condition whereby the adrenal glands are not able to secrete enough adrenocortical hormones to sustain normal bodily functions. It is usually an autoimmune condition where the individual’s immune system destroys healthy adrenal tissue. In normal health, these hormones – mainly cortisol, aldosterone and dehydroepiandrosterone (DHEA) – are vital in maintaining various balances within the body as well as responding to acute demands placed on the body in day-to-day life.

An understanding of the role of each of these hormones is useful in recognising the symptoms and signs in a patient presenting with Addison’s disease (see Table 1).

In addition to the symptoms and signs elicited directly from the hormone deficiencies, the adrenal gland’s place within the hypothalamic-pituitary-adrenal axis results in the classical sign of Addison’s disease: hyperpigmentation. This is because the low levels of adrenal hormones (specifically cortisol) are detected and lead to increased secretion of adrenocorticotropic hormone (ACTH) from the pituitary gland via a negative feedback loop. The pituitary gland continues to secrete more and more ACTH in an attempt to stimulate the damaged adrenal gland. The high levels of ACTH have a stimulant effect on melanocytes to produce melanin, leading to hyperpigmented or ‘bronzed’ skin.

The onset of Addison’s disease is usually prolonged over several months of gradually progressive symptoms. In rare cases, the initial presentation may be an Addisonian crisis, where the levels of adrenal hormones (mainly cortisol) are so low as to be life-threatening. Addisonian crisis presents more commonly in patients with established Addison’s disease who experience an acute physiological stress, e.g., infection or abrupt removal of steroids.  Patients will commonly have reduced GCS, be hypotensive and have significant electrolyte disturbances.