Addison's Disease

 

• Causes

  Primary adrenocortical failure

  • Autoimmune: antibodies against adrenal cortex and/or 21-hydroxylase, an enzyme involved in steroid synthesis.
  • Metastases.
  • Infection: TB, CMV in HIV.
  • Surgery.
  • Congenital: congenital adrenal hyperplasia, adrenoleukodystrophy.

  Results in ↓glucocorticoids and ↓mineralocorticoids.

  Secondary adrenocortical failure

  • Withdrawal of glucocorticoid treatment, as long term use suppresses the pituitary adrenal axis.
  • Hypopituitarism.

  Results in ↓glucocorticoids only.

• Presentation

  General:

  • Tired all the time (TATT).
  • Malaise
  • Depression
  • Dizzy
  • Postural hypotension.

  GI:

  • Weight loss
  • Anorexia
  • Nausea and vomiting.
  • Abdo pain.
  • Dehydration

  Musculoskeletal and derm:

  • Skin pigmentation: especially in mucosa, sun-exposed areas, creases, and scars. Caused by reduced -ve feedback of hormones on pituitary, leading to ↑ACTH production. ACTH is made from same precursor (POMC) as melanocyte stimulating hormone. Also seen in ↑ACTH-driven Cushing's.
  • Myalgia

  Onset:

  • If cause is autoimmune or malignant, onset is insidious, with TATT, anorexia, and GI symptoms common.
  • However, in some cases adrenal crisis can be the first presentation.

• Investigations

  Basic bloods

  • U&E: ↓Na+, ↑K+, ↑Ca2+ (rare), ↑urea (due to hypovolaemia).
  • ↓Glucose
  • FBC: normocytic anaemia (commoner) or co-morbid pernicious anaemia.

  Diagnostic tests

  Morning serum ↓cortisol (8-9am), when levels should peak.

  High dose ACTH stimulation test (aka short Synacthen test):

  • Use if cortisol test not clear. Can be done any time of day.
  • Baseline cortisol measured → high dose IM/IV Synacthen given → cortisol re-checked after 30 mins.
  • Primary adrenocortical failure → small or no rise in cortisol.
  • Secondary adrenocortical failure → early secondary disease would lead to a sharp rise, but in established hypopituitarism there would just be a small rise as adrenals eventually atrophy without ACTH.
  • Glucocorticoid withdrawal → looks like primary failure, as adrenals don't regain function for some time after withdrawal.

  Serum ↓ACTH = secondary cause.

  Other tests

  • Mineralocorticoid function: ↓aldosterone, ↑renin.
  • 21-hydroxylase adrenal Ab.

• Management

  Corticosteroid replacement:

  • Hydrocortisone (glucocorticoid): PO 2/day, AM + late afternoon.
  • Prednisolone (glucocorticoid) is 1/day PO alternative to hydrocortisone if there are adherence problems. However, its longer half life may lead to high levels at night which disrupt sleep.
  • Fludrocortisone (mineralocorticoid): PO, given in addition to glucocorticoid if cause is primary adrenal failure.

  Other considerations:

  • Double the glucocorticoids (but not mineralocorticoids) in infection, trauma, or surgery.
  • Consider a bracelet or card to carry indicating long-term steroid use.

• Adrenal crisis

  A sudden glucocorticoid drop.

  Causes and triggers

  • Glucocorticoid withdrawal, or relative shortage due to ↑needs e.g. during surgery
  • Metastases
  • Un(der)treated Addison's e.g. ↓steroid dose due to surgery NBM, ↑need during infection.
  • Bilateral adrenal haemorrhage due to meningococcal sepsis (Waterhouse-Friderichsen's syndrome) or MI.
  • Physiological stress: infection, trauma, surgery, pregnancy, general anaesthetic.

  Presentation

  • Postural ↓BP.
  • Weakness
  • Confusion
  • Feeble rapid pulse.
  • Fever, especially if triggered by infection.
  • GI: severe abdo pain (can present as an acute abdomen), anorexia, nausea, vomiting.
  • If severe: shock, coma.

  Investigations

  • As with Addison's, though note that Na+/K+ may be normal.
  • Non-anion gap metabolic acidosis.

  Management

  If suspected, treat before results:

  1. ABC including saline, glucose check, and IV glucose if needed.
  2. Hydrocortisone 100 mg IV stat.
  3. Investigate and treat underlying cause, which may require antibiotics.
  4. Further hydrocortisone 100 mg every 6 hours until they can take PO steroids.

  In short, 5S:

  • Supportive treatment.
  • Saline
  • Sugar
  • Steroids
  • Search for cause.

• Congenital adrenal hyperplasia

  Pathophysgiology

  • 95% are due to an autosomal recessive 21-hydroxylase deficiency ('classic CAH'), resulting in impaired cortisol production and – in severe cases – aldosterone deficiency ('salt-wasting CAH').
  • Compensatory ↑ACTH causes adrenal hyperplasia, leading to excess androgens (testosterone).
  • The rarer 11 β-Hydroxylase deficiency form can cause hyperaldosteronism.

  Presentation

  • Addisonian symptoms.
  • Hyperandrogenism: ambiguous genitalia in females, precocious puberty, infertility.

  Investigations

  ↑17-Hydroxyprogesterone (17-OHP).