Two situations are often confused: replacement therapy in adrenal insufficiency (which must be increased under stress) and pharmacological anti-inflammatory treatment (which must be tapered in a controlled fashion). The management is the opposite in each case.
Equivalent doses
| Agent | Equivalent glucocorticoid dose | Mineralocorticoid effect | Biological half-life |
|---|---|---|---|
| Hydrocortisone (cortisol) | 20 mg | Marked | Short, 8–12 hours |
| Prednisolone | 5 mg | Moderate | Intermediate, 12–36 hours |
| Methylprednisolone | 4 mg | Low | Intermediate |
| Betamethasone | 0.6 mg | None | Long, 36–54 hours |
| Dexamethasone | 0.75 mg | None | Long, 36–54 hours |
The equivalences apply to the anti-inflammatory effect. They say nothing about the mineralocorticoid effect or about suppression of the HPA axis, where a long half-life produces more marked suppression.
Stress dosing in known adrenal insufficiency
A patient with primary adrenal insufficiency (Addison's disease), secondary adrenal insufficiency or long-term corticosteroid treatment cannot increase their own cortisol production.
| Situation | Action |
|---|---|
| Fever, infection or gastroenteritis at home | Double or triple the oral daily dose during the days of illness (the patient's sick-day rules) |
| Vomiting or diarrhoea, unable to keep tablets down | Parenteral hydrocortisone. The patient must have an emergency injection at home |
| Acute illness, trauma, surgery | Parenteral hydrocortisone, at a dose according to the local protocol. Usually a bolus followed by repeated doses or an infusion |
| Suspected adrenal crisis | Give the corticosteroid immediately. Do not wait for laboratory results. Take a serum cortisol and ACTH first only if this does not delay treatment. Plus fluid and glucose |
Adrenal crisis: hypotension that does not respond to fluid, abdominal pain, vomiting, fever, hyponatraemia, hyperkalaemia, hypoglycaemia. Give hydrocortisone and an isotonic crystalloid. Exact doses according to the local protocol.
Tapering after pharmacological treatment
| Duration and dose | Risk of HPA suppression | Tapering |
|---|---|---|
| < 3 weeks, at any dose | Low | Can be stopped straight away |
| > 3 weeks, prednisolone < 5 mg/day | Low to moderate | Can usually be stopped without a prolonged taper |
| > 3 weeks, prednisolone ≥ 5 mg/day | Substantial | A stepwise taper. More quickly down to the physiological level, then slowly |
| Months to years | Marked | A slow taper, often over months. Consider an ACTH test before stopping |
During and after the taper the patient must be informed about the stress-dosing rules and about the symptoms of adrenal insufficiency.
Prophylaxis during longer corticosteroid treatment
| Risk | Action |
|---|---|
| Osteoporosis | Calcium and vitamin D. A bisphosphonate with longer treatment and risk factors, according to the guideline |
| Hyperglycaemia | Glucose measurement, above all in the afternoon and evening. See the quick reference on inpatient insulin therapy |
| Peptic ulcer | A proton pump inhibitor with concomitant NSAID use or a history of ulcer, not routinely |
| Infection | Consider Pneumocystis prophylaxis with high doses over a long period, according to the local protocol |
| Psychiatric symptoms | Sleep disturbance, hypomania, confusion. Commonest early on and at high doses |
| Muscle weakness | Steroid myopathy, with proximal weakness |
Red flags and pitfalls
- Stopping a corticosteroid abruptly after longer-term treatment.
- Not giving a stress dose to a patient with adrenal insufficiency during acute illness.
- Confusing dexamethasone 0.75 mg with prednisolone 0.75 mg. A tenfold difference in effect.
- Giving the morning dose late in the day, which causes sleep disturbance and more marked HPA suppression.
- Inhaled and topical steroids in high doses can also cause systemic suppression.
- Corticosteroids mask fever and peritonitis. The abdomen of a patient on corticosteroids can be silent despite perforation.
Sources
- Endocrine Society clinical practice guideline on the diagnosis and treatment of primary adrenal insufficiency.
- The summary of product characteristics for each glucocorticoid preparation.
- Internetmedicin, Adrenal insufficiency and Addisonian crisis.
