Addison’s disease is a rare autoimmune endocrine disorder causing primary adrenal insufficiency. Autoantibodies are directed against the adrenal glands resulting in destruction of the adrenal cortex and decreased cortisol release. Adrenal insufficiency is the decreased endocrine function of the adrenal glands and there are many causes of this.
Although Addison’s disease is a rare disorder, it is a PACES favourite and crops up frequently in station 5 and sometimes as part of the history station. In order to be able to competently tackle an Addison’s disease station it is essential to understand adrenal insufficiency, Addison’s disease is just one cause of primary adrenal insufficiency.
Adrenal insufficiency can be divided into primary and secondary. Primary insufficiency is due to a problem within the adrenal glands causing impairment of cortisol production which is a glucocorticoid. 80% of cases of primary adrenal insufficiency are due to Addison’s disease.
Other causes of primary adrenal insufficiency include adrenal adenomas, HIV, TB and congenital adrenal hyperplasia.
Secondary adrenal insufficiency is due to the impairment of the pituitary gland to produce ACTH. The most common cause of this is exogenous steroid use. Other causes include pituitary adenoma or hypothalamic tumour.
Symptoms of adrenal insufficiency are vague and are due to low circulating levels of cortisol.
Symptoms to cover in the history include:
Nausea and vomiting, abdominal pain, diarrhoea
Syncope, dizziness on standing
Obvious skin changes which may suggest hyperpigmentation
Also ask about a personal or family history of associated autoimmune conditions – in particular vitiligo, thyroid disease and type 1 diabetes
Social history including travel and TB and HIV risk assessment
Patients with primary adrenal insufficiency will have widespread hyperpigmentation – particularly evident in the palmar creases, pressure areas (e.g. elbows), buccal mucosa, skin creases, previous surgical scars and light-exposed areas. Patients with secondary adrenal insufficiency will not have evidence of hyperpigmentation.
Women may have a loss of axillary or pubic hair
BP may be low – If BP is raised this would almost exclude a diagnosis of Addison’s disease
Look for evidence of other associated autoimmune conditions – 50% of patients with Addison’s disease have an associated autoimmune condition, most commonly vitiligo therefore look for depigmented skin. Other associated disorders are autoimmune thyroid disease, diabetes, pernicious anaemia, RA, SLE and sjogren’s syndrome
Patients may also have a medicAlert bracelet or necklace so look hard for this as it is important not to miss it.
Frequent examiners questions for the adrenal insufficiency station include:
What investigations would you do for suspected adrenal insufficiency and what would you expect them to show?
Blood tests should be taken which may show:
Deranged electrolytes – in particular hyponatraemia, hyperkalaemia and occasionally hypercalcaemia would be in keeping with adrenal insufficiency.
FBC may show a normocytic anaemia, lymphocytosis or associated eosinophilia
9am cortisol should be taken – a level < 100 is indicative of adrenal insufficiency, > 400 suggests adrenal sufficiency and levels between 100-400 are a grey area and would need a short synacthen test to further investigate.
Short synacthen test should rise >500-550 after 30 minutes – less than that is suggestive of adrenal insufficiency.
Other blood tests are done to distinguish between primary and secondary causes of adrenal insufficiency.
Adrenal autoantibodies should be measured as these are positive in around 70% of cases of Addison’s disease
Serum ACTH is high in cases of primary adrenal insufficiency as the pituitary gland is attempting to stimulate the adrenal glands. ACTH would be low in secondary causes of adrenal insufficiency
Plasma renin and aldosterone should be checked – aldosterone is a mineralocorticoid secreted by the adrenal glands and is often also low in primary adrenal insufficiency with a high renin
Also check TFTs as there is a high incidence of associated autoimmune thyroid disorders
Clinical examination will also help confirm whether this is primary or secondary adrenal insufficiency – hyperpigmentation is due to high levels of ACTH and Melanocyte Stimulating Hormone (MSH) secreted by the pituitary – therefore this is only present in cases of primary adrenal insufficiency and is absent in secondary causes.
What is the treatment of adrenal insufficiency?
If the patient presents with an adrenal crisis this is a medical emergency. The patient will require admission to hospital, often to HDU/ICU for intravenous fluid and electrolyte replacement. Steroids should be replaced intravenously – usually hydrocortisone 100mg 6hrly which has both mineralocortcoid and glucocorticoid actions. It is important to take a random serum cortisol blood test before administering steroids – it is OK to do a random cortisol in this setting as the patient is being highly stressed and a low cortisol level would be diagnostic. Also it is important to establish and treat the precipitant of the adrenal crisis – any underlying bacterial infection should be treated with intravenous antibiotics.
Longer term management includes replacement of glucocorticoids with hydrocortisone and replacement of mineralocorticoids with fludrocortisone. The patients require counselling as to the importance of compliance with medications and to double the dose when unwell. Many patients also carry medic Alert cards/bracelets/or necklaces so look hard for these during your examination of the patient as they can provide you with a vital diagnostic clue.
Do you know of any autoimmune syndromes which Addison’s disease can form a part of?
Addison’s disease can form part of the autoimmune polyglandular syndromes, most commonly autoimmune polyglandular syndrome type 2. Other diseases in this syndrome include autoimmune thyroid disease, and type 1 diabetes.
Written by Jo Corrado
Resources used to write this document are listed in the references section of this webpage