Autoimmune polyglandular syndrome (APS) refers to a rare collection of disorders where the immune system mistakenly attacks and damages multiple hormone-producing glands. This complex condition can also affect other non-endocrine organs, leading to a variety of health issues.
What is Autoimmune Polyglandular Syndrome
APS involves the immune system attacking the body’s own tissues, specifically endocrine glands. The term “polyglandular” signifies that more than one hormone-producing gland is affected. This immune dysregulation results in hormone production deficiencies, which can occur simultaneously or sequentially.
There are several recognized types of APS, each characterized by specific combinations of conditions. Autoimmune Polyglandular Syndrome Type 1 (APS-1), also known as autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), is a rare, inherited disorder caused by mutations in the AIRE gene. This type often presents with a triad of chronic mucocutaneous candidiasis (persistent fungal infections of the skin and mucous membranes), hypoparathyroidism (underactive parathyroid glands), and primary adrenal insufficiency (Addison’s disease). Mutations in the AIRE gene explain the varied presentation of APS-1.
Autoimmune Polyglandular Syndrome Type 2 (APS-2), or Schmidt Syndrome, is the most common form and typically manifests in adulthood, often between 20 and 40 years of age. This type is defined by primary adrenal insufficiency (Addison’s disease) combined with autoimmune thyroid disease (such as Hashimoto’s thyroiditis or Graves’ disease) and/or Type 1 diabetes mellitus. Genetic factors, including certain HLA DQ/DR regions, are associated with APS-2.
Autoimmune Polyglandular Syndrome Type 3 (APS-3) involves autoimmune thyroid disease alongside other autoimmune conditions, but notably, it does not include Addison’s disease. These other conditions can include Type 1 diabetes mellitus, pernicious anemia, vitiligo, or alopecia areata.
How Autoimmune Polyglandular Syndrome Presents
The clinical presentation of APS varies depending on the affected glands and specific type. For individuals with primary adrenal insufficiency, a component of both APS-1 and APS-2, symptoms can include fatigue, muscle weakness, weight loss, low blood pressure, and changes in skin color, such as hyperpigmentation. Nausea, vomiting, and abdominal pain are common. In severe cases, an adrenal crisis can occur, leading to sudden weakness, dehydration, and fainting due to hypotension.
When hypoparathyroidism is present, as seen in APS-1, individuals may experience tingling in the lips, fingers, and toes, muscle cramps, and pain in the abdomen, face, legs, and feet. These symptoms arise from low calcium levels in the blood. For those with Type 1 diabetes mellitus, part of APS-2 and APS-3, common signs include increased thirst, frequent urination, constant hunger, and unexplained weight loss. Blurred vision and fatigue are common.
Autoimmune thyroid diseases, such as Hashimoto’s thyroiditis (hypothyroidism) or Graves’ disease (hyperthyroidism), contribute to diverse symptoms. Hypothyroidism can lead to cold intolerance, fatigue, poor memory, constipation, and weight changes, while hyperthyroidism may cause heat intolerance, weight loss, palpitations, and anxiety. Chronic mucocutaneous candidiasis, often the first manifestation of APS-1, appears in early childhood as recurrent fungal infections of the skin, nails, and mucous membranes.
Diagnosing Autoimmune Polyglandular Syndrome
Diagnosing APS involves a thorough clinical evaluation, including a review of symptoms, medical history, and a physical examination. Diagnosis can be challenging due to the varied and often sequential onset of conditions, requiring monitoring for additional autoimmune disorders over time.
Laboratory tests assess hormone levels and detect specific autoantibodies. Blood tests may measure hormone levels such as cortisol, thyroid hormones, parathyroid hormone, and glucose to identify deficiencies or excesses. Screening for autoantibodies against affected endocrine glands is common, including anti-adrenal antibodies like 21-hydroxylase antibodies, anti-thyroid antibodies such as thyroid peroxidase (TPO) antibodies, and anti-GAD antibodies for Type 1 diabetes.
For APS-1, a definite diagnosis often requires at least two of the three main components: chronic mucocutaneous candidiasis, hypoparathyroidism, or Addison’s disease. Genetic testing for mutations in the AIRE gene can also confirm an APS-1 diagnosis. While autoantibodies help confirm the autoimmune nature, their absence does not entirely rule out the diagnosis.
Managing the Conditions
Managing APS primarily focuses on treating each individual autoimmune condition that manifests, as there is no single cure for APS itself. Lifelong hormone replacement therapy is a common approach to address deficiencies caused by affected glands. For instance, individuals with adrenal insufficiency require corticosteroid replacement, often with hydrocortisone and fludrocortisone. The dosage of hydrocortisone may need adjustment during times of illness.
Hypothyroidism is managed with thyroid hormone replacement, while Type 1 diabetes necessitates insulin therapy to regulate blood glucose levels. For hypoparathyroidism, calcium and vitamin D supplementation are prescribed to maintain adequate calcium levels. Chronic mucocutaneous candidiasis, a common feature of APS-1, requires ongoing antifungal therapy, such as oral fluconazole.
Regular monitoring of hormone levels and symptom management are important. Individuals with APS often benefit from a multidisciplinary approach, involving various specialists such as endocrinologists, dermatologists, and gastroenterologists, depending on the specific organs affected. Patients are educated about their chronic conditions to help with early detection of new autoimmune states and to ensure appropriate ongoing treatment.