Autoimmune polyendocrine syndrome type 2

Overview

Autoimmune Polyendocrine Syndrome Type 2 (APS-2), also known as Schmidt’s syndrome, is a chronic autoimmune disorder in which two or more endocrine glands are damaged by the body’s immune system. It is characterized by the presence of primary adrenal insufficiency (Addison’s disease) along with either autoimmune thyroid disease or type 1 diabetes mellitus.

APS-2 is more common than APS-1 and typically presents in adulthood, especially between the ages of 20 and 40. It affects women more often than men and is often associated with other autoimmune disorders.

Causes

APS-2 is caused by an autoimmune response in which the immune system produces antibodies that attack the body’s own endocrine glands. Unlike APS-1, which is monogenic and linked to mutations in the AIRE gene, APS-2 is a polygenic disorder with a complex genetic background.

Known contributing factors include:

• Genetics: Strongly associated with certain HLA class II genes (e.g., HLA-DR3, DR4)

• Family history: Increases the risk of autoimmune diseases

• Environmental triggers: Infections, stress, or other immune challenges may trigger disease onset

Symptoms

Symptoms depend on which endocrine glands are affected, but typically include:

Primary Adrenal Insufficiency (Addison’s disease):

• Fatigue and weakness

• Weight loss

• Hyperpigmentation (darkening of the skin)

• Hypotension (low blood pressure)

• Salt craving

• Nausea, vomiting, abdominal pain

Autoimmune Thyroid Disease:

• Hypothyroidism (Hashimoto’s thyroiditis): Fatigue, weight gain, cold intolerance, constipation

• Hyperthyroidism (Graves’ disease, less common): Weight loss, anxiety, palpitations, heat intolerance

Type 1 Diabetes Mellitus:

• Increased thirst and urination

• Unexplained weight loss

• Blurred vision

• Fatigue

Other associated autoimmune conditions may include celiac disease, vitiligo, pernicious anemia, and alopecia.

Diagnosis

APS-2 is diagnosed based on clinical presentation and confirmed through laboratory testing:

Hormonal evaluations:

• Cortisol and ACTH levels: Low cortisol with high ACTH confirms adrenal insufficiency

• TSH and free T4: To assess thyroid function

• Blood glucose or HbA1c: To diagnose diabetes mellitus

Autoantibody testing:

• Anti-21-hydroxylase antibodies (Addison’s)

• Anti-thyroid peroxidase (TPO) and anti-thyroglobulin antibodies (thyroiditis)

• Islet cell and GAD antibodies (type 1 diabetes)

Additional evaluations:

• Electrolyte testing (low sodium, high potassium in Addison’s)

• ACTH stimulation test for adrenal reserve

• Family history and HLA typing (optional)

Treatment

There is no cure for APS-2, but lifelong hormone replacement therapy and management of each affected gland can allow individuals to lead relatively normal lives.

Endocrine replacement therapies include:

• Hydrocortisone or fludrocortisone: For adrenal insufficiency

• Levothyroxine: For hypothyroidism

• Insulin therapy: For type 1 diabetes

Additional management:

• Monitoring for new autoimmune conditions

• Patient education on adrenal crisis and emergency hydrocortisone use

• Regular follow-up with endocrinology

Prognosis

The prognosis for individuals with APS-2 is generally good with proper treatment and follow-up. However, several factors can influence long-term outcomes:

• Risk of adrenal crisis: A life-threatening condition requiring emergency care

• Management complexity: Patients require lifelong medications and regular monitoring

• Quality of life: Can be maintained with adherence to therapy and preventive care

With awareness, early detection, and multidisciplinary care, most patients with APS-2 can live healthy, productive lives.