Autoimmune adrenalitis (most common in developed countries)
TB, fungal infections, CMV
Metastatic cancer, adrenal haemorrhage
Congenital adrenal hyperplasia (e.g., 21-hydroxylase deficiency), adrenoleukodystrophy

Secondary Causes:

Presentation

Cortisol deficiency - weakness (99%), weight loss (98%), N/V/D, hypoglycaemia
Aldosterone Deficiency - Postural hypotension, tachycardia, hyponatraemia, hyperkalaemia
ACTH Excess - Hyperpigmentation (sun-exposed, palmar creases), vitiligo.

Diagnosis

Initial Tests:
- Morning cortisol, ACTH, renin, aldosterone.
Short Synacthen Test:
- Administer synthetic ACTH (tetracosactide)
- Cortisol fails to rise significantly in Addison’s
Autoimmune Workup:
- Check anti-adrenal antibodies if autoimmune cause suspected

Management

Acute Management (Adrenal Crisis):
- Hydrocortisone: 100 mg IV initially, then 50 mg IV q6h until stable
- Can also give IM however eTG states give 40 mg oral pred if IV access impossible
- Rehydration: IV 0.9% saline +/- dextrose for hypoglycaemia
- Correct hyperkalaemia (usually resolves with fluids and steroids)
Chronic Replacement Therapy: In Addison’s, the adrenal cortex is damaged, leading to deficiencies in both cortisol and aldosterone. Replace both with:
- Hydrocortisone 15–25 mg daily (split doses, e.g., 2/3 in the morning, 1/3 in the afternoon) AND
- Fludrocortisone 100 mcg daily (adjust based on renin, potassium, and blood pressure)
- Patient education: Wear a medical alert bracelet and have a "sick day" glucocorticoid plan
- If sx persist despite optimised therapy, consider DHEA
Stress Dose Adjustments:
- Double or triple hydrocortisone dose during intercurrent illness or surgery

Note

21-Hydroxylase deficiency: Common cause of CAH, causing cortisol and aldosterone deficiency with androgen excess due to shunting of 17-hydroxyprogesterone.

Long-term Management

Managed by endocrinologist; adjust glucocorticoids during illness/surgery.
Replacement Therapy:
- Glucocorticoids: Oral hydrocortisone split into 2–3 daily doses (e.g., 2/3 AM, 1/3 PM)
- Mineralocorticoids: Fludrocortisone 50–300 mcg/day (adjust by BP, renin, K).
Annual check: Na, K, renin. BMD every 2 years.
Education on Associated Risks:
- Co-existing autoimmune conditions: Hashimoto’s thyroiditis, coeliac disease, T1DM
- Sx and signs of excess or insufficient glucocorticoid or mineralocorticoid replacement

Self-Care Counselling

Sick Day Rules:
- Increase glucocorticoid dose during acute illness (typically 2–3x usual dose for 2–3 days)
Adrenal Crisis Preparedness:
- Recognise early signs: N/V, hypotension, dehydration
- Carry injectable hydrocortisone for emergencies
- Wear medical alert bracelet or necklace
Lifestyle Adjustments:
- Regular follow-ups to reinforce self-care education
- Carry wallet card with treatment details (template available from Hormones Australia)

Notes:

Excess Glucocorticoid Replacement: Monitor for signs of Cushing’s syndrome (e.g., weight gain, elevated blood pressure)
Plasma ACTH levels are unreliable for assessing glucocorticoid dosing adequacy

Primary Adrenal Insufficiency (Addison's Disease)

Aetiology:

Primary Causes: Autoimmune adrenalitis is the most common cause, leading to gradual adrenal cortex destruction. Globally, infectious causes like tuberculosis, fungal infections, and cytomegalovirus (CMV) can also lead to adrenal insufficiency.
Paediatric Cases: Congenital adrenal hyperplasia (e.g., 21-hydroxylase deficiency) is a frequent cause in children, where enzyme deficiencies affect cortisol synthesis.
Secondary Causes: Long-term corticosteroid use suppresses adrenal function. Pituitary adenomas can also decrease adrenocorticotropic hormone (ACTH) production, leading to adrenal atrophy.

Symptoms (Clinical Features):

Cortisol Deficiency: Weakness (common in 99% of cases), weight loss (98%), nausea, vomiting, diarrhoea, and hypoglycaemia.
Aldosterone Deficiency: Postural hypotension, tachycardia, hyponatraemia, and hyperkalaemia.
Excess ACTH: Hyperpigmentation (characteristic of Addison's disease), particularly in sun-exposed areas and skin creases, and potentially vitiligo.

Differential Diagnosis:

Other causes of chronic fatigue and weight loss i.e., hypothyroidism, chronic infections.
Conditions associated with skin pigmentation changes i.e., haemochromatosis.

Investigations:

Cortisol Levels: Measured in serum and 24-hour urine samples; low cortisol confirms adrenal insufficiency.
Plasma ACTH: Elevated ACTH supports primary adrenal insufficiency (Addison’s), while low ACTH suggests secondary causes.
Short Synacthen Test: Assesses adrenal function by administering synthetic ACTH; minimal cortisol response indicates Addison's disease.
Plasma Renin Activity: Increased renin due to aldosterone deficiency.
Autoantibodies: Positive anti-adrenal antibodies suggest autoimmune adrenalitis.

Management:

Immediate Management (Crisis):

IV hydrocortisone 100 mg initially, followed by 50 mg every 6 hours.
Intramuscular (IM) hydrocortisone if IV access is not available; alternatively, oral prednisolone 40 mg if IM access is also challenging.
IV 0.9% saline bolus (10–20 mL/kg) for dehydration, alongside 5–10% dextrose to prevent hypoglycaemia.
Hyperkalaemia usually resolves with fluid therapy.

Long-term Management:

Referral to an endocrinologist for specialist management.
Lifelong glucocorticoid (e.g., hydrocortisone) and mineralocorticoid (e.g., fludrocortisone) replacement.
Bone mineral density (BMD) assessment at diagnosis and every two years to monitor for osteoporosis.
Annual biochemical and clinical evaluations (including Na, K, renin levels) to monitor response and adjust hormone replacement.
Patient education on recognising signs of insufficient or excessive hormone replacement.

Self-Care Counselling:

Sick Day Management: Increase glucocorticoid dose (usually 3x normal dose for 2–3 days) during illness or stress.
Emergency Preparedness: Carry an emergency injectable form of hydrocortisone for acute adrenal crisis.
Symptom Awareness: Educate on signs of deterioration i.e., nausea, vomiting, dehydration.
Medical Identification: Advise wearing a medical alert bracelet indicating adrenal insufficiency.

Notes:

Congenital adrenal hyperplasia (CAH): In cases of 21-hydroxylase deficiency, there is a buildup of 17-hydroxyprogesterone, leading to shunting of steroid synthesis toward androgen production due to impaired cortisol/aldosterone synthesis.
Excess glucocorticoid replacement can lead to Cushingoid symptoms. Plasma ACTH may not be a reliable marker for assessing the adequacy of glucocorticoid replacement in such cases.

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