Adrenal insufficiency

Classification

Primary (Addison disease)

• • Aetiology
    • Congenital adrenal dysgenesis/hypoplasia
    • Defective steroidogenesis
    • Adrenal destruction
      • Autoimmune
      • Infectious
        • TB
        • Fungal
        • Viral
      • Malignant
      • Haemorrhage (Waterhouse-Friderichsen syndrome)
        • Occurs in setting of septicaemia caused by meningococcal or other organisms
        • More common in children and asplenic patients

Secondary

• • ACTH deficiency
  • Aetiology
    • Generally from pharmacologic steroid withdrawal
      • Occurs in patients receiving >20mg of prednisolone (or equivalent) daily for >5 days, or those receiving  low supra-physiologic doses for >3 weeks
      • Rate of recovery varies according to the curation and severity of previous glucocorticoid excess, and may need supplementation for several years
    • Surgical cure of Cushing syndrome
    • Pan-hypopituitarism caused by neoplastic or infiltrative disease
    • Granulomatous disease
    • Pituitary haemorrhage or infarction
      • Can occur in the setting of severe post-partum haemorrhage (Sheehan syndrome)
    • Chronic high-dose opioids
      • Occurs in up to 30% of high-dose long-term opioid users
      • Cessation of opioids results in reversion to normal
      • Glucocorticoids seems to improve symptoms (energy, mood) and it is therefore probably prudent to treat with glucocorticoids, if weaning opioids is impossible

Adrenal insufficiency in the critically ill

• • Acute reversible dysfunction of the HPA axis with sepsis or SIRS
  • Maybe occurs due to reduced responsiveness of target tissues to glucocorticoids or adrenal ACTH resistance

Presentation

• Weakness and fatigue, anorexia, nausea or vomiting, weight loss
• Hypotension
• Electrolyte disturbances
  • Hyperkalaemia
  • Hyponatraemia
• Hyperpigmentation
  • Particularly seen in primary adrenal insufficiency due to high ACTH levels causing melanogenesis

Diagnosis

• Morning cortisol level can effectively exclude adrenal insufficiency
  • >15microg/dL in serum (>413nmol/L)
  • >5.8ng/mL in saliva
• Levels below those levels should have provocative testing to confirm (cosyntropin test)
  • Measure serum cortisol before, and 30-60 minutes after administration of ACTH
  • Failure to mount an adequate response usually indicated adrenal insufficiency
• Morning ACTH level differentiates between primary and secondary ACTH deficiency
  • Increased: Primary
  • Decreased or normal: Secondary

Treatment

• Replace glucocorticoid (prednisolone) and mineralocorticoid (fludrocortisone)

Adrenal crisis

• Typically occurs in patients with already marginal adrenocortical function who are subjected to a significant acute physiologic stressor, such as infection or trauma
• Presents with shock, abdominal pain, fever, nausea, vomiting, electrolyte disturbance, hypoglycaemia
• Mineralocorticoid deficiency results in an inability to maintain sodium and intravascular volume
• Treatment
  • 1-2L IV saline
  • Hydrocortisone - 100mg IV bolus then 75mg q8h OR dexamethasone 4mg IV every 24 hours
    • Dexamethasone has the advantage of not interfering with biochemical assays of endogenous glucocorticoid production

Perioperative prophylactic steroid administration

• The need for hydrocortisone is probably overstated
• Primary adrenal insufficiency carries a greater risk for crisis - generally require 100mg hydrocortisone before induction
• Secondary adrenal insufficiency due to glucocorticoid treatment have only a 1-2% risk of hypotensive crisis
• Unilateral adrenalectomy should have supplementary glucocorticoids only if the underlying diagnosis is Cushing syndrome