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Addison's Disease (Primary Adrenal Insufficiency)

Table of Contents

  • Introduction
  • Aetiology
  • Pathophysiology
  • Risk Factors
  • Clinical Features
  • Diagnosis
  • Investigations
  • Management
  • Complications
  • References
  • Related Notes
  • Test Yourself

Introduction

  • Addison’s disease is primary adrenal insufficiency caused by failure of adrenal cortex resulting in glucocorticoid and mineralocorticoid deficiency.
  • Prevalence: ~100 per million, >90% female.
  • Can present insidiously or acutely (Addisonian crisis).

Aetiology

  • 75-90% autoimmune (antibodies against 21-hydroxylase).
  • Other causes: infections (TB, CMV), vascular (adrenal haemorrhage, VTE), trauma, short-term steroid use, adrenal tumors, surgery, congenital adrenal hyperplasia (CAH), drugs (ketoconazole, rifampicin, phenytoin).

Pathophysiology

  • Deficiency of adrenal cortex hormones: glucocorticoids, mineralocorticoids, and androgens.
  • Loss of negative feedback → increased ACTH release.
  • Impaired electrolyte and energy homeostasis leads to symptoms and risk of Addisonian crisis.

Risk Factors

  • Female sex (90% cases).
  • Autoimmune polyglandular syndromes.
  • Other autoimmune endocrine diseases: thyroid disease, type 1 diabetes, coeliac disease, vitiligo.
  • Presence of adrenocortical antibodies.
  • Thromboembolic/hypercoagulable states.

Clinical Features

Symptoms

  • Due to hypocortisolism: fatigue (worse during day), muscle weakness, weight loss, anorexia.
  • Due to hypoandrogenism: loss of libido, sexual dysfunction.
  • Due to hypoaldosteronism: nausea, vomiting, salt craving, dizziness, abdominal pain.

Signs

  • Mucosal and cutaneous hyperpigmentation (due to high ACTH).
  • Low BMI.
  • Orthostatic hypotension, tachycardia.
  • Loss of axillary and pubic hair in women.
  • Associated autoimmune signs: goitre, vitiligo, dermatitis herpetiformis.

Addisonian Crisis

  • Acute severe presentation with weakness, syncope, severe abdominal/back pain, vomiting, confusion, hypotension, reduced consciousness.
  • Medical emergency.

Diagnosis and Investigations

Bedside

  • Blood glucose (hypoglycemia).
  • ECG (signs of hyperkalemia: peaked T waves, widened QRS).
  • Venous blood gas (metabolic acidosis).

Laboratory

  • Full blood count (anemia, eosinophilia, lymphocytosis).
  • Urea & electrolytes (hyponatremia, hyperkalemia, sometimes hypercalcemia).
  • Morning serum cortisol (low in Addison’s).
  • Plasma ACTH (high in primary AI).
  • ACTH stimulation test (Synacthen): failure to increase cortisol confirms diagnosis.
  • Aldosterone & renin: low aldosterone, raised renin in Addison’s.
  • Autoimmune antibodies (anti-21 hydroxylase).

Imaging

  • Adrenal CT/MRI: atrophy in autoimmune Addison’s; enlargement in infection, hemorrhage, malignancy.

Management

Long-Term

  • Lifelong hormone replacement:
  • Hydrocortisone (glucocorticoid)
  • Fludrocortisone (mineralocorticoid)
  • “Sick day rules”: increase glucocorticoid doses during illness/stress.
  • Medical alert bracelet.
  • Education on emergency hydrocortisone injection.

Acute (Addisonian Crisis)

  • Immediate IV hydrocortisone.
  • Fluid resuscitation with normal saline ± 5% dextrose (beware hyponatremia).
  • Correct electrolyte imbalances.
  • Monitor and treat precipitating cause.

Special Situations

  • Pregnancy: adjust glucocorticoid doses; extra doses during labour.

Complications

  • Cushing’s syndrome from glucocorticoid overreplacement (CUSHINGOID mnemonic).
  • Hypertension, hypokalemia from mineralocorticoid excess.
  • Associated autoimmune diseases (thyroid disease, type 1 diabetes in autoimmune polyglandular syndrome type II).

References

  • Barthel A et al. An Update on Addison's Disease. 2019.
  • Betterle C et al. Epidemiology, Pathogenesis and Diagnosis of Addison's Disease.
  • Hahner S et al. Adrenal Insufficiency.
  • Charmandari E et al. Adrenal Insufficiency Clinical Guidelines.
  • BMJ Best Practice. Primary Adrenal Insufficiency.
  • UpToDate. Diagnosis of Adrenal Insufficiency.
  • Nieman LK et al. Addison’s Disease.
  • Arlt W et al. Emergency Management of Adrenal Crisis.
  • Acromegaly
  • Cushing’s Syndrome
  • Diabetes Insipidus
  • Growth Hormone Deficiency
  • Hyperparathyroidism

Test Yourself

  • [Link to Addison’s Disease MCQs and flashcards]

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