Adrenal insufficiency (Addison's disease)
Definition | Aetiology | Pathophysiology | Risk Factors | Signs and Symptoms | Investigations | Management
Definition
Adrenal insufficiency (Addison’s disease) is a disorder characterised by inadequate production of adrenal hormones, primarily cortisol and aldosterone, due to adrenal gland dysfunction.
Aetiology
- Primary adrenal insufficiency: autoimmune adrenalitis (most common cause), infections (e.g., tuberculosis, HIV), adrenal haemorrhage, metastatic disease.
- Secondary adrenal insufficiency: pituitary dysfunction leading to reduced ACTH production, often due to pituitary tumours, surgery, or exogenous steroid use.
- Tertiary adrenal insufficiency: prolonged exogenous corticosteroid use leading to suppression of hypothalamic CRH release.
Pathophysiology
- Cortisol deficiency impairs gluconeogenesis, leading to hypoglycaemia and fatigue.
- Aldosterone deficiency results in sodium loss, hyperkalaemia, and hypotension.
- Loss of adrenal androgen production contributes to reduced secondary sexual characteristics (more evident in women).
- In secondary adrenal insufficiency, aldosterone production remains intact as it is regulated by the renin-angiotensin system.
Risk Factors
- Autoimmune diseases (e.g., type 1 diabetes, autoimmune thyroiditis).
- History of tuberculosis or chronic infections.
- Long-term corticosteroid therapy with abrupt withdrawal.
- Adrenal surgery or pituitary pathology.
- Genetic conditions (e.g., congenital adrenal hyperplasia).
Signs and Symptoms
- General: fatigue, weakness, weight loss.
- Gastrointestinal: nausea, vomiting, abdominal pain.
- Cardiovascular: postural hypotension, dizziness.
- Skin: hyperpigmentation (only in primary adrenal insufficiency due to excess ACTH stimulation of melanocytes).
- Metabolic: hyponatraemia, hyperkalaemia, hypoglycaemia.
Investigations
- Serum cortisol (before 9:30am): low levels confirm adrenal insufficiency. If corticol levels <100 nanomol/L admit to hospital, if betwee 100-500 refer to endocrine. Blood test can be repeated if results are uncertain. Urgency of referral depends on symptoms.
- ACTH levels (secondary care investigation): elevated in primary adrenal insufficiency, low in secondary causes.
- Short Synacthen test (secondary care investigation): assesses adrenal response to synthetic ACTH; failure to stimulate cortisol confirms primary adrenal insufficiency.
- Renin and aldosterone levels (secondary care investigation): elevated renin with low aldosterone supports primary adrenal insufficiency.
- Autoimmune screening: adrenal antibodies (e.g., anti-21-hydroxylase antibodies) in autoimmune adrenalitis.
- Electrolytes: check for hyponatraemia, hyperkalaemia, and hypoglycaemia.
Management (treatment is started by a specialist endo physician)
1. Hormone Replacement Therapy:
- Hydrocortisone: first-line corticosteroid replacement (given in divided doses).
- Fludrocortisone: required for primary adrenal insufficiency to replace aldosterone.
2. Emergency Management (Adrenal Crisis):
- IV hydrocortisone: immediate administration in suspected adrenal crisis.
- IV fluids: normal saline to manage hypotension and electrolyte imbalances.
- Glucose: to correct hypoglycaemia.
3. Patient Education:
- Advise patients on the importance of medication adherence.
- Provide an emergency steroid card and medical alert bracelet.
- Educate on the need for increased steroid doses during illness or stress.
4. Referral:
- Endocrinology: all patients with confirmed adrenal insufficiency for long-term management.
- Acute medical team: if presenting with adrenal crisis.