Makindo Medical Notes

🧬 Schmidt's Syndrome (Autoimmune Polyglandular Syndrome Type 2, APS-2) is a rare autoimmune disorder involving multiple endocrine glands. It classically combines Addison’s disease with autoimmune thyroid disease and/or type 1 diabetes.

📖 About

• First described in 1926, it is the most common of the polyglandular autoimmune syndromes.
• Characterised by coexistence of primary adrenal insufficiency with autoimmune thyroid disease (Hashimoto’s or Graves’) and/or type 1 diabetes mellitus.
• Prevalence: ~1.4–2 per 100,000; more frequent in women (3:1), typically aged 20–60 years.
• Patients often present with one autoimmune disease first, followed by others over months to years.

🧪 Aetiology & Pathogenesis

• Inherited in an autosomal dominant pattern with incomplete penetrance and variable expression.
• Linked to HLA haplotypes (esp. HLA-DR3, DR4, DQ2, DQ8).
• Autoantibodies directed against steroid-producing and thyroid tissues cause progressive gland failure.
• Environmental triggers (viral infections, stress) may accelerate onset.

⚡ Associated Autoimmune Conditions

• 🌑 Addison's disease (primary adrenal insufficiency) – always present by definition.
• 🦋 Autoimmune thyroid disease – Hashimoto’s thyroiditis or Graves’ disease.
• 💉 Type 1 diabetes mellitus.
• Other associations:
  • Pernicious anaemia (vitamin B12 deficiency).
  • Primary hypogonadism.
  • Vitiligo & alopecia areata.
  • Coeliac disease.
  • Myasthenia gravis.

🩺 Clinical Features

• Features vary depending on which glands are involved and may evolve over years.
• Addison’s: fatigue, hypotension, weight loss, hyperpigmentation, salt craving.
• Hypothyroidism: lethargy, cold intolerance, dry skin.
• Graves’ disease: weight loss, tremor, palpitations.
• Type 1 diabetes: polyuria, polydipsia, unexplained weight loss.
• Associated autoimmune features: anaemia, vitiligo, malabsorption (coeliac), neuromuscular weakness (myasthenia gravis).

🔬 Investigations

• Biochemical evidence of adrenal insufficiency (↓ cortisol, ↑ ACTH, failed Synacthen test).
• Thyroid function tests (TSH, T4/T3) and thyroid autoantibodies (anti-TPO, anti-TSH receptor).
• HbA1c, fasting glucose, GAD antibodies for diabetes.
• Vitamin B12, coeliac serology (anti-tTG/EMA), sex hormone profile if hypogonadism suspected.
• Pituitary/adrenal imaging rarely required unless atypical presentation.

💊 Management

• Treatment is condition-specific:
  • 💊 Addison’s: lifelong glucocorticoid (hydrocortisone) + mineralocorticoid (fludrocortisone) replacement.
  • 🦋 Hypothyroidism: levothyroxine replacement (NB: replace cortisol before thyroid hormone to avoid precipitating adrenal crisis).
  • Graves’: carbimazole, radioiodine, or surgery if indicated.
  • Type 1 diabetes: insulin therapy.
  • Other autoimmune diseases: managed per condition (e.g., pernicious anaemia ➝ IM B12 injections).
• ⚠️ Important: Always replace cortisol before thyroxine to avoid triggering Addisonian crisis.
• 🏥 Regular endocrine follow-up: lifelong risk of developing new autoimmune conditions.
• 👨‍👩‍👧 Genetic counselling for families.

📚 References

• Betterle C, et al. Autoimmune Polyglandular Syndrome Type 2: Clinical features and management. Endocrinol Metab Clin North Am. 2002.
• Royal College of Physicians. Polyglandular autoimmune syndromes