Adrenal insufficiency

• Adrenal insufficiency is where the adrenal glands do not produce enough steroid hormones, particularly cortisol and aldosterone. Steroids are essential for life. Therefore, the condition is life-threatening unless the hormones are replaced.
• Addison's disease:

  • Damage to the adrenal glands - most commonly autoimmune
  • Primary adrenal insufficiency
  • Results in reduced cortisol and aldosterone secretion
• Secondary adrenal insufficiency:

  • Loss or damage to the pituitary gland - tumours, surgery, trauma
  • Inadequate ACTH and lack of stimulation of the adrenal glands - leading to low cortisol and aldosterone
• Tertiary adrenal insufficiency:

  • Inadequate CRH release from the hypothalamus
  • Usually the result of patients taking long-term steroids
  • Suppression of the hypothalamus via negative feedback
• Symptoms of adrenal insufficiency:

  • Fatigue
  • Muscle weakness and cramps
  • Dizziness and fainting - postural hypotension
  • Polydipsia and craving salt
  • Weight loss
  • Abdominal pain
  • Depression
  • Reduced libido
• Signs of adrenal insufficiency:

  • Bronze hyperpigmentation of the skin, particularly in the creases - ACTH stimulates melanin production
  • Hypotension - postural hypotension
• A key biochemical finding in adrenal insufficiency is hyponatraemia - lack of aldosterone causes loss of sodium and water
• Key biochemical findings:

  • Hyponatraemia - may be only sign
  • Hyperkalaemia - aldosterone usually excretes potassium in the urine
  • Hypoglycaemia - cortisol raises blood glucose
  • Raised creatinine and urea due to dehydration - AKI
  • Hypercalcaemia - reduced calcium removal by the kidney
• The short synacthen test is the first line investigation:

  • Synacthen is a synthetic ACTH
  • IM/IV 250 microgram synacthen
  • Measure cortisol 30 minutes and 60 minutes after
  • A failure of cortisol to double indicates either Addison's disease or secondary adrenal insufficiency - adrenal cortex is unresponsive to stimulation
• ACTH can be measured directly:

  • High in primary adrenal insufficiency - Addison's
  • Low in secondary adrenal insufficiency
• CT or MRI of the adrenal glands can be helpful if suspecting structural pathology. They are not routinely required.

  MRI of the pituitary gives further information about pituitary pathology.
• Management:

  • Hydrocortisone (glucocorticoid) is used to replace cortisol - 2/3 doses over the day to mimic the circadian rhythm
  • Fludrocortisone (mineralocorticoid) is used to replace aldosterone
  • Steroid card, ID tag and emergency letter
  • Patients and close contacts are taught to give IM hydrocortisone in an emergency
• Sick day rules:

  • Double dose of hydrocortisone for 48 hours during acute illness
  • Taper dose back down
  • If unable to keep oral hydrocortisone down - IM 100mg hydrocortisone and seek immediate medical help
• Of people with autoimmune Addison's disease, about two-thirds have an autoimmune polyendocrine syndrome.

  Type 1 - Triad of Addison's disease, hypoparathyroidism, and chronic candidiasis

  Type 2 - Usually involves Addison's disease and autoimmune thyroid disease or type 1 diabetes mellitus
• • Secondary adrenal insufficiency results from inadequate adrenocorticotropic hormone (ACTH) and a lack of stimulation of the adrenal glands, leading to low cortisol. This is the result of loss or damage to the pituitary gland. Secondary adrenal insufficiency can be due to:
  • Tumours (e.g., pituitary adenomas)
  • Surgery to the pituitary
  • Radiotherapy
  • Sheehan’s syndrome (where major post-partum haemorrhage causes avascular necrosis of the pituitary gland)
  • Trauma
• The most common auto-antibody associated with Addison's disease is the 21-hydroxylase auto-antibody