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Anti-21-hydroxylase (adrenal)
Anti-TPO or anti-thyroglobulin (thyroid)
Anti-GAD or anti-islet cell (pancreas)
Adrenal glands
Thyroid gland
Pancreas (in some cases)
May also affect skin, stomach, reproductive organs, or intestines
Autoimmune Polyendocrine Syndrome Type 2 (APS-2) is a chronic autoimmune disorder in which the immune system attacks multiple endocrine glands, especially the adrenal glands, thyroid gland, and pancreas. It most often includes:
Addison’s disease (adrenal insufficiency)
Autoimmune thyroid disease (like Hashimoto’s or Graves’)
Type 1 diabetes
Unlike APS-1 (which is rare and genetic), APS-2 is more common, usually develops in adulthood, and is not linked to a single gene mutation.
Fatigue, dizziness, salt craving (Addison’s)
Weight gain, cold intolerance, constipation (hypothyroidism)
Weight loss, thirst, frequent urination (if type 1 diabetes is present)
Low blood pressure or fainting
Skin darkening (from adrenal hormone deficiency)
Other autoimmune diseases may appear (e.g., vitiligo, celiac disease)
APS-2 is an autoimmune disorder, not inherited in a simple genetic pattern. It’s believed to be triggered by a combination of:
Genetic susceptibility (e.g., certain HLA genes)
Environmental factors (infections, stress)
Immune system dysregulation, leading to attacks on hormone-producing glands
It’s more common in women and often appears between ages 30 and 50.
Blood tests:
Low cortisol and high ACTH (Addison’s)
High TSH and low T4 (hypothyroidism)
Blood sugar and HbA1c (diabetes)
Electrolyte imbalances (sodium, potassium)
Autoantibody tests:
Anti-TPO (thyroid)
Anti-21-hydroxylase (adrenal)
Anti-GAD (diabetes)
Diagnosis is based on the presence of two or more autoimmune endocrine disorders
Hormone replacement therapy:
Cortisol (hydrocortisone) and sometimes fludrocortisone for adrenal support
Thyroid hormone (levothyroxine)
Insulin (if type 1 diabetes is present)
Electrolyte and blood sugar monitoring
Regular screening for additional autoimmune conditions
Lifelong follow-up with an endocrinologist
Manageable with consistent treatment
Requires lifelong hormone replacement and routine monitoring
Missing an Addison’s diagnosis can be life-threatening—early diagnosis is crucial
Quality of life is generally good with appropriate care
Estimated at 1 in 20,000 people
More common in women (3:1 ratio)
Onset typically in adulthood
Betterle C, et al. (2004). Autoimmune polyglandular syndrome type 2: the tip of the iceberg? Clin Exp Immunol.
NIH GARD. (2023). Autoimmune polyglandular syndrome type 2.
https://rarediseases.info.nih.gov/diseases/7408/autoimmune-polyendocrine-syndrome-type-2
Michels AW, Eisenbarth GS. (2010). Polyglandular autoimmune syndromes. Nat Rev Endocrinol.
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