Question 8

Outline the causes, consequences and management of adrenal insufficiency in the critically ill.

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College Answer

Causes of adrenal insufficiency in the critically ill can be categorised as primary (ie. diseases of the adrenal gland), secondary (interference with pituitary secretion of ACTH) and tertiary (interference with hypothalamic excretion of CRF).

Primary causes include autoimmune (may have vitiligo), haemorrhage (eg. with sepsis and/or anticoagulant therapy), emboli, sepsis and adrenal vein thrombosis.

Secondary causes include destruction of pituitary by tumour/cellular inflammation, infection, head trauma, and infarction.

Tertiary causes include abrupt cessation of high-dose corticosteroids, and any process that interferes with the hypothalamus (tumours, infiltration, irradiation). The stress of critical illness can unmask adrenal insufficiency in patients at risk

Consequences include shock (which may be refractory), abdominal tenderness, myalgias & arthralgias, nausea and vomiting, volume depletion, fever, and confusion. Electrolyte disturbances include hyperkalemia, and hyponatremia and hypoglycemia.

Management needs to commence before diagnosis is confirmed. Administration of corticosteroids (eg. hydrocortisone 100 mg or dexamethasone [4mg]; dexamethasone interferes least with cortisol assays associated with low or high dose short synacthen tests), fluid resuscitation (reversal of hypovolaemia and electrolyte abnormalities), and treatment for underlying causative and/or co-existing diseases (including sepsis) The diagnosis and treatment of stress induced impairment of the hypothalamic-pituitary–adrenal axis (functional adrenal insufficiency) remains controversial.


Adrenal insufficiency in critical illness is discussed elsewhere.

For the purposes of answering this question, I produce the following tables from the above-linked chapter:

Causes of Adrenal Insufficiency

Vascular aetiologies

Infarction due to arterial embolism

Infarction due to AAA

Postpartum pituitary necrosis







Menigococcal sepsis, purpura fulminans


Neoplastic invasion

Renal cell carcinoma

Adrenal carcinoma

Breast carcinoma

Lung (NSCLC)

Malignant melanoma

Pituitary tumour


Corticosteroid withdrawal

Etomidate (causes primary adrenal insufficiency)
Azole antifungals - Fluconazole, ketoconazole
Rifampicin (increases steroid metabolism)
Phenytoin (increases steroid metabolism)

Infiltrative systemic disease



Congential causes

Adrenal dysgenesis
Impaired steroidogenesis

Autoimmune destruction

Addisons's disease

Traumatic destruction

Trauma is a major cause of adrenal insufficiency

Environmental factors


Clinical Features of Adrenal Insufficiency

Specific features

Hypotension refractory to fluids






Non-specific features

Decreased level of consciousness

Defects of other hormone systems (eg thyroid)

Normocytic anaemia

Hyperdynamic circulation

Metabolic acidosis




Management would have to be approached according tot he well-practiced answer algorithm:

  • Attention to the ABCs;
    • Airway assessment and control (in context of a decreased level of consciousness)
    • Ventilation support (in context of metabolic acidosis)
    • Circulatory support with vasopressors (in context of fluid-refractory shock)
  • Routine investigations, partiuclarly EUCs CMPs and BSL (looking for hypoglycaemia hyponatremia and hyperkalemia)
  • Specific investigations, such as a random cortisol level, and a short synacthen test
  • Specific management, featuring corticosteroid supplementation with hydrocortisone


Oh's Intensive Care manual: Chapter   61   (pp. 660) Adrenocortical  insufficiency  in  critical  illness by Balasubramanian  Venkatesh  and  Jeremy  Cohen


Oelkers, Wolfgang. "Adrenal insufficiency." New England Journal of Medicine335.16 (1996): 1206-1212.


Marik, Paul E. "Mechanisms and clinical consequences of critical illness associated adrenal insufficiency." Current opinion in critical care 13.4 (2007): 363-369.


Cooper, Mark Stuart, and Paul Michael Stewart. "Adrenal insufficiency in critical illness." Journal of intensive care medicine 22.6 (2007): 348-362.