Addison’s disease (primary adrenal insufficiency) is caused by destruction of the adrenal cortex.

This results in reduced production of glucocorticoids (such as cortisol), mineralocorticoids (such as aldosterone), and adrenal androgens (such as dehydroepiandrosterone)

Adrenal insufficiency may also be caused by long-term administration of corticosteroids or disorders of the hypothalamus or pituitary gland, but this is not Addison’s disease.

In the developed world, Addison’s disease is most commonly caused by autoimmune disease.Worldwide, tuberculosis is the most common cause of Addison’s disease. It should be stressed that Addison’s disease is rare.

Diagnosis of Addison’s disease is often delayed because symptoms are non-specific, common, and overlap with many other conditions

A person with Addison’s disease may present with a sudden crisis precipitated by intercurrent infection or stress. Features include hypotension, hypovolaemic shock, acute abdominal pain, low-grade fever, and vomiting.

Addison’s disease should also be considered in a person with persistent, non-specific symptoms, such as: fatigue; hyper pigmentation; gastrointestinal symptoms; cravings for salt, soy sauce, or liquorice; musculoskeletal symptoms; or postural dizziness due to hypotension.

The possibility of Addison’s disease should also be considered in people with:

hypothyroidism whose symptoms worsen when thyroxine is started; type 1 diabetes mellitus with recurrent unexplained hypoglycaemic episodes; other autoimmune diseases; or low sodium and high potassium levels on blood biochemistry.

In adults,

if adrenal insufficiency is suspected on the basis of clinical features, a serum cortisol level and urea and electrolytes should be requested. As a general guide:If the serum cortisol level is less than 100 nanomol/L, the person should be admitted to hospital. Adrenal insufficiency is highly likely.

If the serum cortisol level is 100-500 nanomol/L, the person should be referred to an endocrinologist for further investigations.If the serum cortisol level is more than 400 nanomol/L, the diagnosis of Addison’s disease is unlikely.

If the person is acutely unwell or hypotensive, the person should be admitted to hospital.
Serum cortisol values are not reliable in this situation, as they increase during illness

In children, investigations should be urgently carried out in secondary care if adrenal insufficiency is suspected. Admission to hospital may be required depending on the clinical picture and clinical judgement.

The diagnosis of Addison’s disease is usually confirmed in secondary care. An adrenocorticotrophic hormone stimulation (Synacthen®) test should be done.

Treatment for Addison’s disease is usually initiated and adjusted by a specialist endocrinologist, but repeat prescriptions may be provided in primary care under a shared care arrangement.

Hydrocortisone is usually used for glucocorticoid replacement, but longer-acting glucocorticoids, such as prednisolone and dexamethasone, are sometimes used to avoid the peaks and troughs which may occur with hydrocortisone.
Fludrocortisone is usually used for mineralocorticoid replacement.Dehydroepiandrosterone (unlicensed) may be prescribed by some specialists for androgen replacement.

It is important for people with Addison’s disease to increase their corticosteroid cover if they are under physical stress, such as illness. If an adrenal crisis is suspected, emergency admission to hospital should be arranged. Hydrocortisone intramuscularly or intravenously should be administered before transfer to hospital. Emergency administration of fludrocortisone is not required.

G Mohan.