Autoimmune Polyendocrine Syndrome (APS)

What APS is

Autoimmune disease of one endocrine gland, such as Hashimoto's thyroiditis or type 1 diabetes, is common. In APS, the immune system targets several glands, either at once or over many years. Each gland is gradually destroyed by immune cells and autoantibodies, so hormone levels fall. Having one autoimmune endocrine disease raises the chance of developing another, which is why doctors screen for related conditions.

Types of autoimmune polyendocrine syndrome

A related, very rare condition is IPEX syndrome, caused by a FOXP3 gene mutation in boys, with severe diarrhea, early diabetes and eczema in infancy.

APS type 1

Also called APECED (autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy). It typically starts with chronic candidiasis of the mouth, nails or skin in early childhood, followed by hypoparathyroidism and then Addison's disease. Other features include ovarian or testicular failure, dental enamel defects, nail changes, hair loss, vitiligo, hepatitis, malabsorption and keratitis (eye surface inflammation).

APS type 2

Addison's disease with Hashimoto's thyroiditis, Graves' disease and/or type 1 diabetes. Associated conditions include celiac disease, vitiligo, pernicious anemia, alopecia areata, early ovarian failure and myasthenia gravis.

Symptoms

Symptoms depend on which glands fail:

• Adrenal (Addison's disease): fatigue, weight loss, dizziness on standing, salt craving, nausea, belly pain and darkening of the skin and gums.
• Thyroid: underactive (tiredness, weight gain, feeling cold) or overactive (weight loss, heat intolerance, palpitations).
• Pancreas (type 1 diabetes): thirst, frequent urination, weight loss.
• Parathyroid: low calcium causing tingling, muscle cramps, spasms and seizures.
• Ovaries or testes: missed periods, early menopause, infertility, low libido.
• Skin and other: pale patches (vitiligo), hair loss, persistent thrush.

Diagnosis

1. Hormone tests: morning cortisol and ACTH, TSH and free T4, blood glucose and HbA1c, calcium, phosphate and parathyroid hormone, FSH and LH.
2. Autoantibodies: 21-hydroxylase antibodies (adrenal), thyroid peroxidase antibodies, diabetes antibodies (GAD, IA-2, ZnT8), celiac antibodies, and interferon antibodies, which are very characteristic of APS-1.
3. Stimulation tests: an ACTH (Synacthen) stimulation test confirms adrenal insufficiency.
4. Genetic testing: AIRE gene testing confirms APS-1 and allows family screening.

Screening

People with one autoimmune endocrine disease, particularly Addison's disease or type 1 diabetes, are usually screened periodically for thyroid disease, celiac disease and B12 deficiency, and sometimes adrenal antibodies. People with APS-1 need lifelong regular checks for new components.

Treatment

Treatment replaces each missing hormone:

• Addison's disease: hydrocortisone (or another glucocorticoid) plus fludrocortisone, with sick-day rules to increase the dose during illness and an emergency injection kit.
• Hypothyroidism: levothyroxine.
• Hyperthyroidism: antithyroid medicines, radioactive iodine or surgery.
• Type 1 diabetes: insulin.
• Hypoparathyroidism: calcium and active vitamin D, or parathyroid hormone replacement.
• Gonadal failure: sex hormone replacement.
• Chronic candidiasis: antifungal medicines.
• Celiac disease: a strict gluten-free diet.

Living with APS

• Carry a steroid emergency card or wear a medical alert bracelet if you have Addison's disease.
• Learn sick-day rules and how to give an emergency hydrocortisone injection.
• Keep regular follow-up with an endocrinologist.
• Report new symptoms early; another gland may be failing.
• Tell relatives: family members may benefit from screening.

Outlook

With hormone replacement, most people with APS-2 and APS-3 live normal, active lives. APS-1 is more complex and needs specialist care because of its many components, but outcomes have improved. The main risks come from unrecognized adrenal crisis and severe low calcium, which are preventable with education and monitoring.

Frequently asked questions

What is autoimmune polyendocrine syndrome?

It is a condition in which the immune system attacks two or more hormone-producing glands, causing them to fail. Common combinations include Addison's disease with autoimmune thyroid disease or type 1 diabetes. It is treated by replacing the missing hormones.

What is the difference between APS type 1 and type 2?

APS-1 is a rare inherited condition caused by AIRE gene mutations. It starts in childhood with chronic thrush, low parathyroid function and Addison's disease. APS-2 is more common, begins in adulthood, and combines Addison's disease with thyroid disease or type 1 diabetes.

Is autoimmune polyendocrine syndrome hereditary?

APS-1 is inherited in an autosomal recessive pattern, so both parents must carry a faulty AIRE gene. APS-2 and APS-3 run in families through a combination of genes, so relatives have a higher risk of autoimmune conditions but no single gene causes it.

Can autoimmune polyendocrine syndrome be cured?

There is no cure for the underlying autoimmunity, and gland damage is usually permanent. However, hormone replacement effectively treats each component, and most people lead normal lives with regular monitoring.

Why is screening important in APS?

New gland failures can develop years after the first diagnosis, and some, such as Addison's disease and low calcium, can become life-threatening if missed. Regular blood tests catch problems early, before they cause a crisis.