Addison’s disease

Clinical features

A high index of suspicion is required for the diagnosis of Addison’s disease. Doctors need to be alert to the possibility of Addison’s disease. A cluster of common symptoms, although non-specific in themselves, may point to Addison’s disease. A cohort study of 108 patients with Addison’s disease found that they had all experienced fatigue, weakness, anorexia, and unintentional weight loss.7 Other symptoms included gastrointestinal complaints such as nausea and vague abdominal pain (56%), postural dizziness (12%), and musculoskeletal pains (6%).7 Hyperpigmentation of skin and mucous membranes is a characteristic feature of Addison’s disease; however, it is absent in about 10% of cases, which may delay diagnosis.7 8 Postural hypotension is common in Addison’s disease; however, low blood pressure without a postural drop can also occur.

Autoimmune Addison’s disease is associated with other autoimmune conditions. For example, vitiligo often coexists with Addison’s disease.7 It is important to consider Addison’s disease if a patient with type 1 diabetes starts developing unexplained recurrent hypoglycaemia or the patient’s insulin requirement falls as this may signal adrenal insufficiency.9 Likewise, worsening of symptoms in a patient with autoimmune hypothyroidism after the start of thyroxine treatment should also raise the suspicion of Addison’s disease as thyroxine replacement in a patient with untreated Addison’s disease can precipitate an adrenal crisis.10

About half of patients with Addison’s disease are diagnosed only after an acute adrenal crisis.1 It is a medical emergency often precipitated by an infection or other forms of stress in an undiagnosed or inadequately treated patient with Addison’s disease. In this condition, patients present acutely unwell with severe dehydration, hypotension, or circulatory shock.

Investigations

On routine blood tests, unexplained electrolyte disturbances such as hyponatraemia and hyperkalaemia may provide a clue to the diagnosis of Addison’s disease. Other biochemical abnormalities, including raised urea concentration, hypoglycaemia, hypercalcaemia, and raised concentrations of serum thyroid stimulating hormone, may be present.

A clinical suspicion of Addison’s disease must be confirmed biochemically by demonstrating inadequate cortisol production. Owing to the pulsatile nature and diurnal variation of cortisol secretion, random measurement of serum cortisol concentration is inadequate to assess adrenal function in most cases. A short Synacthen test is the investigation of choice to confirm or exclude Addison’s disease; it is a safe test, which can be done either in primary care by a general practitioner or in secondary care via referral. In the test, 250 μg of tetracosactide (an analogue of corticotropin) is injected intramuscularly or intravenously, and blood samples for serum cortisol are taken immediately, at 30 minutes, and at 60 minutes. A rise in serum cortisol level to above 500 nmol/l 30 minutes or 60 minutes after the tetracosactide injection is considered a normal response,1 although this threshold cortisol concentration indicating a normal response may vary according to the reference ranges of local laboratory assays. If the cortisol response to tetracosactide is inadequate, patients should be referred to secondary care for further evaluation and management. A plasma adrenocorticotrophic hormone concentration should be measured as a raised concentration will distinguish Addison’s disease from secondary adrenal insufficiency. Plasma renin activity is raised in Addison’s disease, and its measurement is also sometimes useful in differentiating between Addison’s disease and secondary adrenal insufficiency. Once the diagnosis of Addison’s disease is made, further investigations are needed to determine the underlying cause.