Schmidts syndrome
🧬 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
