Adrenal insufficiency and steroid sick-day rules: AU general practice guide

Adrenal insufficiency (AI) is the clinical state of inadequate glucocorticoid production — and, in primary AI, concurrent mineralocorticoid deficiency. It spans a spectrum from autoimmune Addison’s disease, where the adrenal cortex is progressively destroyed, to the far commoner iatrogenic form, in which months of exogenous steroid therapy suppresses the hypothalamic–pituitary–adrenal (HPA) axis.

In Australian general practice, adrenal insufficiency carries three urgent clinical implications. First, any patient taking more than 7.5 mg prednisolone equivalent daily for more than three weeks may have HPA suppression — a threshold relevant across virtually every specialty prescribing long-term steroids for asthma, rheumatological disease, inflammatory bowel disease, and transplant medicine. Second, autoimmune Addison’s disease is often diagnosed late because its cardinal features — fatigue, weight loss, and postural hypotension — overlap with many common presentations. Third, adrenal crisis is a life-threatening emergency that is largely preventable through patient education and written sick-day protocols.

Therapeutic Guidelines (eTG) and the Endocrine Society of Australia provide the clinical reference framework for Australian GPs managing this condition. Addisons Australia is the peak Australian patient organisation and distributes steroid emergency cards that every diagnosed patient should carry.

A. Core clinical — the AU general-practice framework

Classification

Primary AI (Addison’s disease) means the adrenal cortex itself is damaged. Autoimmune disease accounts for approximately 80% of Australian cases, with anti-21-hydroxylase antibodies identified on testing; both glucocorticoid and mineralocorticoid production are lost. Other causes include adrenal haemorrhage (Waterhouse-Friderichsen syndrome in meningococcaemia, anticoagulant therapy), bilateral adrenal metastases (lung, breast, GI cancers — usually require ≥90% cortical destruction), infiltrative disease (sarcoidosis, haemochromatosis), and drugs (ketoconazole, abiraterone, mitotane, etomidate).

Secondary AI means the pituitary is not producing adequate ACTH. The commonest cause overall is iatrogenic: any dose above 7.5 mg prednisolone equivalent daily for more than three weeks can suppress pituitary ACTH release, leaving the adrenals atrophied. Other secondary causes include pituitary adenoma, pituitary surgery or radiotherapy, Sheehan syndrome (postpartum pituitary infarction), and immune checkpoint inhibitor-induced hypophysitis (pembrolizumab, nivolumab, ipilimumab — increasingly seen in oncology settings).

Tertiary AI = hypothalamic CRH deficiency; most clinically relevant in long-term opioid users.

Clinical features

Chronic AI is insidious. The classic constellation seen in general practice:

• Fatigue and weakness — present in over 90% of Addison’s cases
• Weight loss and anorexia
• Postural hypotension / dizziness — postural drop of ≥20 mmHg systolic is common
• Hyperpigmentation — primary AI only — gums, palmar creases, scars, knuckles; ACTH drives melanocyte stimulation; absent in secondary AI
• Salt craving — mineralocorticoid deficiency (primary only)
• Nausea, diarrhoea, abdominal discomfort
• Low mood, depression, irritability
• Hypoglycaemia — especially in children and insulin-treated diabetics
• Menstrual irregularity, low libido, loss of axillary and pubic hair in women (adrenal androgen deficiency)

Hyperpigmentation is essentially pathognomonic for primary AI. Its absence in secondary AI — where ACTH is low — is a useful differentiating feature.

Adrenal crisis is a life-threatening emergency: refractory hypotension unresponsive to fluid resuscitation, vomiting, severe abdominal pain sometimes mimicking an acute abdomen, fever, and altered consciousness. Laboratory abnormalities: hyponatraemia, hyperkalaemia, hypoglycaemia. Precipitants include intercurrent infection, surgery, gastroenteritis with vomiting (absorption of oral steroid fails), missed doses, and any physiological stressor.

Diagnosis

Step 1 — 9 am cortisol with simultaneous ACTH:

Per eTG, sample in the morning before 9 am and at least 12–24 hours after any glucocorticoid dose:

Cortisol	Interpretation
<100 nmol/L	Strongly suggests AI
100–500 nmol/L	Indeterminate — proceed to dynamic testing
>500 nmol/L	Generally excludes AI (lab-specific cut-off)

ACTH elevated → primary AI; ACTH low or normal → secondary AI.

Step 2 — Synacthen (cosyntropin) stimulation test:

• 250 mcg IV or IM
• Cortisol measured at baseline, 30 min, 60 min
• Peak cortisol below 500–550 nmol/L (lab-specific) confirms AI
• Note: the 250 mcg test can miss recent secondary AI (pituitary not yet atrophied, adrenals still responsive); 1 mcg low-dose test preferred for suspected mild or early secondary AI

Step 3 — Cause investigation:

• Anti-21-hydroxylase antibodies — autoimmune Addison’s confirmation
• CT adrenals — bilateral atrophy, calcification (TB, old haemorrhage), enlargement (malignancy, infiltration)
• Pituitary MRI — secondary AI aetiology
• Renin/aldosterone — mineralocorticoid axis assessment (primary AI)
• Polyglandular autoimmune screen: anti-TPO, GAD/IA-2 antibodies, parathyroid antibodies (Polyglandular Autoimmune Syndrome Type 1 and 2)

Chronic replacement treatment

Glucocorticoid replacement per eTG and Endocrine Society 2016 guidelines:

Agent	Typical dose	Notes
Hydrocortisone	15–25 mg/day in 2–3 divided doses	Standard: 10 mg on waking, 5 mg lunch, 5 mg mid-afternoon; last dose by 3–4 pm
Prednisolone	3–5 mg morning	Once daily; convenient; less physiological diurnal profile
Plenadren (modified-release HC)	20–30 mg morning	Better circadian profile; not PBS-listed (~$300+/month private)

Mineralocorticoid replacement (primary AI only):

• Fludrocortisone 0.05–0.2 mg morning (typical 0.1 mg)
• Adjust by BP, postural drop, plasma renin activity, sodium, potassium
• Increase in hot weather and during heavy exercise

Every patient requires a MedicAlert bracelet, a written steroid emergency card (available from Addisons Australia), and documented sick-day education — reviewed at every follow-up visit.

B. Sick-day rules — the essential patient safety protocol

Sick-day rules are not optional: they are the frontline prevention strategy against adrenal crisis. Addisons Australia and the Endocrine Society of Australia distribute patient cards summarising these rules and they should be provided in writing at diagnosis and reinforced at every subsequent contact.

Minor illness (mild fever <38°C, cold, mild dental pain, minor GI upset without vomiting):

• Double the usual oral hydrocortisone dose for 2–3 days
• Example: usual 20 mg/day → 40 mg/day during illness
• Resume normal dose once recovered

Moderate illness (fever ≥38°C, dental or minor surgical procedure, URI requiring antibiotics):

• Triple the usual oral dose for the duration of illness plus 24 hours post-recovery
• Example: 20 mg/day → 60 mg/day

Severe illness, vomiting, diarrhoea (unable to absorb oral tablets, major surgery, sepsis, trauma, obstetric labour):

• Inject hydrocortisone 100 mg IM immediately using the Solu-Cortef Act-O-Vial
• Proceed directly to an emergency department
• Hospital management: hydrocortisone 100 mg IV followed by 200 mg/24 h by continuous IV infusion or 50 mg IV q6h, plus IV fluid resuscitation

Surgical cover (per eTG):

• Minor (local anaesthetic only): double oral dose pre-operatively and for 24 hours post-procedure
• Moderate (colonoscopy, hernia repair, laparoscopy): hydrocortisone 50 mg IV/IM at induction; double oral dose for 24–48 hours
• Major (cardiac, abdominal, orthopaedic): hydrocortisone 100 mg IV at induction, then 50 mg IV q6h × 24 hours, taper thereafter

Document that sick-day education has been provided, and ensure the patient’s next-of-kin or partner is also trained in IM injection technique.

C. Iatrogenic glucocorticoid-induced adrenal insufficiency

This is the most prevalent form of AI seen in Australian general practice. Any GP managing patients on long-term steroids for asthma, COPD, inflammatory bowel disease, osteoporosis, or autoimmune and rheumatological conditions should assess HPA status when steroid tapering or cessation is planned.

Threshold for clinically significant HPA suppression (per ESE 2020 guidelines):

• ≥7.5 mg prednisolone equivalent/day for >3 weeks: suppression possible
• Higher doses and longer duration → greater suppression risk
• High-dose chronic inhaled corticosteroids (fluticasone ≥1000 mcg/day equivalent): possible but less common
• Standard-dose intranasal or topical steroids: low risk; high-potency agents on large surface areas occasionally cause systemic suppression

Tapering strategy per eTG:

• Once below 7.5 mg prednisolone equivalent, taper slowly: 7.5 → 5 mg → 3 mg → 2 mg → cessation, each step over weeks to months
• At ≤5 mg, consider Synacthen testing to assess HPA recovery
• HPA recovery may take 6–12 months after prolonged high-dose therapy
• Provide sick-day cover throughout the taper and for approximately 12 months post-cessation

A practical minimum: provide every patient who has taken supraphysiological steroids for more than three weeks with a verbal and written sick-day plan before tapering or stopping, regardless of whether Synacthen testing has been performed.

D. Australian operations

MBS items

Item	Purpose
23 / 36 / 44	Standard GP consultation items
132 / 133	Endocrinologist initial and subsequent consultations
66825 / 66828	Cortisol assay (used in Synacthen testing)
66845	ACTH
12306 / 12320	DEXA bone densitometry (osteoporosis monitoring on long-term steroid)
965 / 967	GPCCMP (chronic disease care plan; replaces GPMP/TCA from 1 July 2025)

PBS medications

All the following are General Schedule (no authority required):

• Hydrocortisone 4 mg and 20 mg tablets (brands: Hysone, generics)
• Hydrocortisone sodium succinate 100 mg vials (Solu-Cortef) — for emergency IM and IV use
• Prednisolone 1 mg, 5 mg, 25 mg tablets
• Fludrocortisone 0.1 mg tablets

Note: Plenadren (modified-release hydrocortisone) is NOT PBS-listed — private prescription only (~$300+/month). This is a clinically relevant cost barrier for patients who would benefit from the more physiological circadian profile.

Australian patient resources

• Addisons Australia — peak consumer organisation; free steroid emergency cards, sick-day plan templates, education resources, peer support
• Endocrine Society of Australia — clinician guidelines and education
• MedicAlert Australia — bracelet and pendant supplier
• Healthdirect 1800 022 222 — 24/7 telephone health advice
• Better Health Channel — Addison’s disease — consumer information

E. Special populations

Pregnancy. Adrenal insufficiency does not preclude pregnancy but requires joint management with an endocrinologist and obstetrician. Hydrocortisone is the preferred glucocorticoid in pregnancy (crosses the placenta minimally at physiological replacement doses). Requirements typically increase by approximately 50% in the third trimester. At the onset of active labour, hydrocortisone 100 mg IV should be given, then repeated every six hours until 24 hours post-delivery; fludrocortisone is continued as usual.

Paediatric presentation. Congenital adrenal hyperplasia (21-hydroxylase deficiency) is screened for on the Newborn Screening Test in all Australian states. In the salt-wasting form, life-threatening hyponatraemia, hyperkalaemia, and collapse can occur in the neonatal period if the diagnosis is missed. Paediatric endocrinologist involvement is essential. Older children with Addison’s disease require weight-based hydrocortisone dosing, school sick-day plans, and close monitoring during illness.

Older adults. Falls risk is not significantly elevated by physiological replacement doses of hydrocortisone, but bone health surveillance (DEXA, calcium, vitamin D) is important given the osteoporosis risk associated with long-term exogenous glucocorticoid use. Hydrocortisone requirements may decrease slightly with age due to lower cortisol clearance.

Immune checkpoint inhibitor-induced hypophysitis. Patients treated with pembrolizumab, nivolumab, ipilimumab, or atezolizumab are at risk of pituitary gland inflammation and permanent secondary AI. ACTH deficiency is common and often irreversible. Any patient on these agents presenting with headache, fatigue, or visual disturbance warrants urgent pituitary MRI and endocrinology review.

Long-term opioid users. Chronic opioid therapy can suppress CRH and ACTH secretion, causing tertiary AI. This is an under-recognised cause of fatigue and postural hypotension in patients managed for chronic pain — consider cortisol and ACTH testing in this setting before attributing symptoms to the primary pain disorder.

Polyglandular Autoimmune Syndrome. Autoimmune Addison’s often coexists with autoimmune thyroid disease (Hashimoto’s or Graves’), type 1 diabetes, pernicious anaemia, coeliac disease, and premature ovarian insufficiency. Annual screening with TSH, fasting glucose, B12, and TTG IgA is warranted in all confirmed autoimmune Addison’s patients.

When to escalate

Refer to endocrinology or emergency as appropriate when:

• Suspected adrenal crisis — emergency department immediately; do not wait for a cortisol result; hydrocortisone 100 mg IV + fluid resuscitation first
• New diagnosis of AI — endocrinologist for cause investigation, replacement initiation, and comprehensive patient education
• Pregnancy in a patient with known AI — joint endocrinology and obstetric care from conception
• Complex steroid tapering — recurrent symptomatic AI below physiological dose, failed Synacthen recovery at six to twelve months
• Immune checkpoint inhibitor hypophysitis — urgent endocrinology and oncology liaison
• Congenital adrenal hyperplasia — paediatric endocrinology
• Pituitary apoplexy (sudden thunderclap headache, visual loss, collapse) — neurosurgical emergency
• Polyglandular autoimmune syndrome management — endocrinology for coordinating multisystem autoimmune surveillance

What this article is and is not

This is general health information based on current Australian clinical guidelines — Therapeutic Guidelines, Australian Medicines Handbook, Endocrine Society guidelines, ESE guidelines, and Addisons Australia resources. It is not personal medical advice and does not create a doctor–patient relationship. Decisions about medication doses, sick-day protocols, and steroid tapering are individual decisions made with your own GP and endocrinologist.

For acute emergencies: call 000 or present to the nearest emergency department. For non-urgent health advice: Healthdirect 1800 022 222.

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Sources cited

1. Therapeutic Guidelines — Adrenal insufficiency
2. Australian Medicines Handbook
3. RACGP — AFP resources on adrenal insufficiency
4. Addisons Australia — patient education and emergency cards
5. Endocrine Society — Diagnosis and Treatment of Primary Adrenal Insufficiency (2016)
6. European Society of Endocrinology — Glucocorticoid-Induced Adrenal Insufficiency (2020)
7. Endocrine Society of Australia
8. MedicAlert Australia
9. Healthdirect Australia — Adrenal insufficiency
10. Better Health Channel — Addison’s disease
11. TGA — hydrocortisone and fludrocortisone product information
12. Hahner S et al. — Incidence of adrenal crisis (JCEM 2015)