Polyglandular autoimmune syndrome

Polyglandular autoimmune syndrome
Synonyms	Autoimmune polyglandular syndrome
Pronounce	N/A
Specialty	N/A
Symptoms	Varies depending on the type, may include fatigue, weight loss, hypoglycemia, vitiligo, hypothyroidism, Addison's disease
Complications	N/A
Onset	Varies
Duration	Chronic
Types	N/A
Causes	Autoimmune disease
Risks	Genetic predisposition, environmental factors
Diagnosis	Clinical evaluation, laboratory tests
Differential diagnosis	N/A
Prevention	N/A
Treatment	Hormone replacement therapy, immunosuppressive therapy
Medication	N/A
Prognosis	Varies
Frequency	Rare
Deaths	N/A

Polyglandular autoimmune syndrome (PAS), also known as autoimmune polyglandular syndrome, is a group of rare autoimmune disorders characterized by the dysfunction of multiple endocrine glands. These syndromes result from the immune system mistakenly attacking the body's own tissues, leading to the failure of various endocrine organs.

Classification

Polyglandular autoimmune syndromes are classified into three main types:

Type 1

Polyglandular autoimmune syndrome type 1 (PAS type 1), also known as autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), is a rare genetic disorder. It is caused by mutations in the AIRE gene and is inherited in an autosomal recessive manner. PAS type 1 typically presents in childhood and is characterized by the triad of:

• Chronic mucocutaneous candidiasis
• Hypoparathyroidism
• Adrenal insufficiency (Addison's disease)

Type 2

Polyglandular autoimmune syndrome type 2 (PAS type 2) is more common than type 1 and usually presents in adulthood. It is characterized by the presence of:

• Adrenal insufficiency
• Autoimmune thyroid disease (such as Hashimoto's thyroiditis or Graves' disease)
• Type 1 diabetes mellitus

PAS type 2 is associated with the presence of certain HLA genotypes, indicating a genetic predisposition.

Type 3

Polyglandular autoimmune syndrome type 3 (PAS type 3) involves autoimmune thyroid disease in combination with other autoimmune conditions, excluding adrenal insufficiency. It is further subdivided into:

• Type 3A: Autoimmune thyroid disease with pernicious anemia
• Type 3B: Autoimmune thyroid disease with type 1 diabetes mellitus
• Type 3C: Autoimmune thyroid disease with vitiligo and/or alopecia areata

Pathophysiology

The pathophysiology of polyglandular autoimmune syndromes involves a complex interplay between genetic and environmental factors. The immune system fails to recognize self-antigens, leading to the production of autoantibodies and autoreactive T cells that target endocrine tissues. This results in the progressive destruction and dysfunction of affected glands.

Clinical Features

The clinical presentation of polyglandular autoimmune syndromes varies depending on the type and the specific glands involved. Common symptoms include:

• Fatigue
• Weight loss
• Hypoglycemia
• Hyperpigmentation (in cases of adrenal insufficiency)
• Hypothyroidism or hyperthyroidism
• Hypocalcemia (in cases of hypoparathyroidism)

Diagnosis

Diagnosis of polyglandular autoimmune syndromes is based on clinical evaluation and laboratory tests. Key diagnostic steps include:

• Measurement of hormone levels (e.g., cortisol, thyroid hormones, parathyroid hormone)
• Detection of specific autoantibodies (e.g., anti-thyroid antibodies, anti-adrenal antibodies)
• Genetic testing for mutations in the AIRE gene (for PAS type 1)

Treatment

Management of polyglandular autoimmune syndromes involves hormone replacement therapy to address deficiencies and immunosuppressive therapy to modulate the immune response. Treatment strategies include:

• Glucocorticoid and mineralocorticoid replacement for adrenal insufficiency
• Levothyroxine for hypothyroidism
• Insulin therapy for type 1 diabetes mellitus
• Calcium and vitamin D supplementation for hypoparathyroidism

Prognosis

The prognosis of polyglandular autoimmune syndromes varies depending on the type and the effectiveness of treatment. Early diagnosis and appropriate management can improve outcomes and quality of life for affected individuals.

See Also

• Autoimmune disease
• Endocrine system
• Genetic disorders