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CDHB

Adrenal Insufficiency

Causes

• Primary adrenal failure:
  • Autoimmune.
  • Haemorrhage/ infarction (e.g., severe sepsis, antiphospholipid syndrome).
  • Metastases.
  • Infection (e.g., tuberculosis, HIV).
• Secondary:
  • ACTH deficiency (pituitary failure)
  • Adrenal suppression, or glucocorticoids stopped or not increased at time of acute stress.

Clinical Features

• Progressive weakness, weight loss, anorexia/nausea.
• Postural hypotension, confusion.
• Symptoms of hypovolaemia (shock) are more prominent in primary failure where skin pigmentation (ACTH effect) is usually also seen.

Investigations

• Na, K, creatinine, urea, glucose - may all be normal (hyponatraemia common). In later phases of primary adrenal deficiency, low Na and high K, high urea, lowish glucose.
• CBC + diff - may be eosinophilia and neutropaenia.
• Draw blood for cortisol, ACTH, renin and aldosterone (10 mL into EDTA tubes). Contact Biochemistry for immediate 4°C centrifugation and freezing of plasma. Urgent Synacthen™ test (plasma cortisol before and 30 minutes after Synacthen™ - 0.25 mg IM/IV) - may be indicated. Contact Endocrine test nurses 80934.
• Interpretation: In primary adrenal insufficiency plasma ACTH and renin are markedly raised. Plasma cortisol can be in the 'normal' range but there is a diminished response to Synacthen. In pituitary failure (ACTH deficiency), plasma cortisol is inappropriately low for the clinical status, plasma ACTH is normal to low, and usually the cortisol response to Synacthen is also diminished - but can be falsely normal. Successive 0800 hr plasma cortisol levels may be indicated, and/or other tests (metyrapone). Consult Endocrine Team.
• In the setting of severe acute illness, a random cortisol >950 nmol/L makes adrenal insufficiency unlikely, <450 nmol/L makes hypoadrenalism a likely possibility. For in-between values (450-950) a cortisol increment of <200 nmol/L after Synacthen suggests adrenal insufficiency and the need for supplemental steroids. Consult Endocrine team.

Treatment

• If hypovolaemic, especially if primary adrenal insufficiency, fluid replacement with sodium chloride 0.9% to restore blood pressure. May require 1 L or more over 2 hours. May require 5-25% glucose to raise glucose levels. Consider empiric antibiotics in cases of profound shock.
• Hydrocortisone 50-100 mg IV then 50 mg q8h for 24 hours, then reduce daily dose of hydrocortisone (e.g., daily dose rapidly reduced to 50-75, 30-50 mg/day on successive days depending on metabolic status) then gradually down to a long term maintenance level of 15-20 mg PO per day. If primary adrenal insufficiency fludrocortisone will usually be required once hydrocortisone dose is less than 50 mg/day.
• Diagnostic work-up and management should be completed in consultation with the Endocrine Department.
• Steroid induced suppression of the hypothalamic-pituitary-adrenal (HPA) axis. Patients receiving long term glucocorticoids (e.g., more than 5-7.5 mg prednisone/day) for conditions other than cortisol deficient states, who are admitted with acute illness, sepsis etc, may require a doubling of the dose (e.g., 20 mg prednisone/day for 1-2 days) then reduce rapidly to normal maintenance doses. If unable to take oral steroids, consider parenteral hydrocortisone e.g., 50 mg q8h for 1-2 days and monitor electrolytes, mental status, blood pressure. Reduce steroid dose rapidly as clinical state allows to maintenance levels.
• All patients with adrenal insufficiency should have a steroid card, medic alert, and information sheet on management of acute illness.

Guidelines for Perioperative Steroids in Patients Already on Steroids

Note: Approximate equivalent doses: prednisone 5 mg ≈ hydrocortisone 20 mg ≈ dexamethasone 0.75 mg ≈ methylprednisolone 4 mg.

• Patients with intrinsic lack of ACTH or with primary adrenal insufficiency are especially sensitive to acute stress illness.
• Patients taking supraphysiological doses of steroids (>5-7 mg prednisone or equivalent per day) for <3 weeks are unlikely to have significant HPA axis suppression, but if in doubt treat as steroid deficient. Patients on high doses of inhaled glucocorticoids (>1500 microgram beclometasone or >750 microgram fluticasone daily) may have HPA axis suppression.

All patients should take their usual steroid doses on day of surgery (or IV equivalent) and supplementation (see table below). Monitor fluid status, electrolytes and glucose daily.

Perioperative guidelines for patient taking steroids

Topic Code: 1359