Primary adrenal insufficiency
Primary adrenal failure, or Addison’s disease, arises as a result of a destructive process in the adrenal gland or genetic defects in steroid synthesis. All three zones of the adrenal cortex are typically affected.
Symptoms and signs
The onset is usually gradual. Symptoms may be non-specific, hence it is important to maintain a high index of suspicion for the diagnosis. Most commonly, patients describe fatigue, weakness, anorexia, weight loss, nausea and abdominal pain. Dizziness and postural hypotension occur as a result of mineralocorticoid deficiency whereas glucocorticoid loss leads to hypoglycaemia, and increased pigmentation as a result of ACTH excess (leading to melanocyte stimulation) from reduced cortisol negative feedback. Androgen deficiency in women can lead to reduced libido and loss of axillary and pubic hair.
There are several causes of primary adrenal failure but autoimmune adrenalitis is by far the most common cause in Western populations, and is supported by detection of positive adrenal autoantibodies. Other causes are rare but should be considered when antibody testing is negative (Table 20.1).
Routine laboratory tests show hyponatraemia (>90%), hyperkalaemia, raised urea, hypoglycaemia and a mild anaemia. However, specific tests are needed to make the diagnosis. A low 09.00 cortisol and simultaneously raised ACTH concentration is suggestive of the diagnosis, although a Synacthen test is generally needed for confirmation (Table 20.2).
Emergency treatment of adrenal crisis
This is considered in Figure 20.1 and also in Chapter 35.
Patients with primary adrenal failure need lifelong glucocorticoid and mineralocorticoid replacement therapy. Hydrocortisone is the glucocorticoid of choice, which is given in total daily doses of 15–30 mg, divided into two (e.g. 10 mg twice daily) or three doses (e.g. 10 mg on waking, 5 mg at lunchtime and 5 mg in the early evening). Mineralocorticoid replacement is given as fludrocortisone 50–200 µg once daily.
Patients should be instructed to double the dose of their glucocorticoid at times of illness, and continue on a doubled dose until their illness has resolved. Glucocorticoids need to be administered IV or IM during surgery or in cases of prolonged vomiting or diarrhoea. Patients should be provided with a steroid emergency card (Figure 20.2), encouraged to wear medical alert jewellery and be provided with emergency contact details for their endocrine team.
Secondary adrenal insufficiency
Secondary hypoadrenalism can arise as a result of any cause of hypopituitarism (Chapter 5). Patients display similar symptoms and signs to primary adrenal insufficiency, with the exception that pigmentation is absent, as ACTH is not raised, and mineralocorticoid deficiency is not a feature, because aldosterone secretion is not significantly influenced by ACTH. As with primary adrenal failure, diagnosis relies upon a failure to demonstrate a rise in cortisol following Synacthen administration, coupled with demonstration of an inappropriately low/low–normal plasma ACTH level. The insulin stress test can also be used to diagnose ACTH deficiency (Chapter 2). The principles of hydrocortisone replacement and dose adjustment are the same as for primary adrenal failure but fludrocortisone replacement is not required as mineralocorticoid secretion is intact.
Corticosteroids are frequently prescribed as anti-inflammatory drugs. An important consequence is suppression of the HPA axis, particularly when prescribed in high doses and/or over a long period of time. Consequently, sudden cessation of long-term therapy can lead to adrenal crisis. Patients taking long-term steroids should thus be instructed not to stop their steroids abruptly, at least until an adequate adrenal reserve has been demonstrated. As with other causes of adrenal insufficiency, patients should carry a steroid card and be educated about steroid supplementation at times of illness.