Synopsis
Recognise cortisol deficiency early, distinguish adrenal from pituitary or glucocorticoid-induced disease, investigate safely and establish replacement that prevents avoidable adrenal crisis.
- Primary adrenal insufficiency is failure of the adrenal cortex: cortisol and often aldosterone are deficient, ACTH rises, and hyperpigmentation, salt craving, postural hypotension, hyponatraemia and hyperkalaemia may occur.
- Secondary or tertiary insufficiency reflects pituitary/hypothalamic disease or suppression by exogenous glucocorticoids. ACTH is low or inappropriately normal, aldosterone is usually preserved and hyperkalaemia is not a typical isolated feature.
- Symptoms are non-specific: fatigue, weight loss, anorexia, nausea, abdominal discomfort and dizziness. Recurrent unexplained hyponatraemia or deterioration during infection should raise the diagnostic priority.
- Ask about every glucocorticoid route, including oral, injected, inhaled, intranasal, topical and rectal preparations, recent repeated courses and CYP3A4 inhibitors that increase systemic exposure.
- Use an 08:00 to 09:00 serum cortisol as the initial non-acute test in adults, interpreted with the local assay, sleep pattern and current steroid exposure. Random cortisol is difficult to interpret outside an emergency.
- A short Synacthen test assesses adrenal response but does not safely delay treatment in an unwell patient. Early central deficiency can occasionally retain a response before adrenal atrophy develops.
- Paired ACTH separates primary from central disease after cortisol deficiency is established. Renin and aldosterone assess mineralocorticoid loss; primary disease usually needs fludrocortisone as well as glucocorticoid.
- Patients need more than a prescription: education, NHS Steroid Emergency Card, sick-day rules, extra tablets, emergency injection access and peri-procedure planning are core treatment.
- Do not start levothyroxine in a patient with possible untreated adrenal insufficiency without addressing cortisol, because increased cortisol clearance and metabolic demand can precipitate crisis.
Key red flags
Worsening vomiting, diarrhoea, abdominal pain, profound weakness, confusion, hypotension, hypoglycaemia or shock demands emergency hydrocortisone and fluids. A normal potassium does not exclude crisis.
Investigation priorities
Screen for impaired morning cortisol production in a stable adult not taking interfering glucocorticoid.
Management branches
Chronic compatible symptoms or unexplained hyponatraemia without current haemodynamic instability.
- Review all steroid exposures, timing, shift work and comorbidity; arrange an 08:00 to 09:00 cortisol with electrolytes and glucose using the local testing instructions.
- If cortisol is low or indeterminate, seek endocrinology advice for paired ACTH and dynamic testing, while giving interim emergency precautions when clinical risk is material.
- Once deficiency is confirmed, localise primary versus central disease, establish cause, assess other pituitary or autoimmune deficits and issue safety education before routine discharge.
Key medicines
Hydrocortisone physiological replacementNICE adult total 15 to 25 mg daily by mouth in two to four divided doses, individualised by endocrinology and clinical response.Both under- and over-replacement cause harm. Assess weight, postural symptoms, blood pressure, glucose, bone risk and sleep; never omit sick-day education or stop abruptly.
Prednisolone replacement alternativeNICE lists 3 to 5 mg orally daily in one or two doses for adults when hydrocortisone is unsuitable or adherence favours longer action.Longer exposure may increase metabolic and bone effects and makes clinical titration important. It still requires stress dosing, an emergency card and peri-operative cover.