What is Polyglandular Autoimmune Syndrome Type II?
Polyglandular autoimmune syndrome (PAS) is a condition where a patient has at least two or more diseases involving their glands coming together. Some common types of this syndrome are called PAS-1, PAS-2, and X-linked immune dysregulation polyendocrinopathy and enteropathy (IPEX). Recently, a new type has been discovered which can occur from using certain drugs on cancer patients.
For example, a drug called Ipilimumab used to treat advanced cancer can cause hypophysitis, an inflammation of the pituitary gland. PAS-2 is an autoimmune disease, which is a condition where your immune system accidentally attacks your own body. PAS-2 affects more than one gene and it’s also known as Schmidt syndrome and Carpenter syndrome.
The idea of multiple gland-related diseases occurring in one person was noted well before the term PAS was used. In 1926, Schmidt reported two cases of Addison disease, a condition where the adrenal glands don’t produce enough hormones, and chronic lymphocytic thyroiditis, an inflammation of the thyroid gland known as Schmidt syndrome. A few years later, in 1931, the first case of Addison disease with hyperthyroidism and Type 1 Diabetes was reported.
A review of previous cases showed that most of these patients had lymphocytic infiltration, or lymphocytes (a type of white blood cell) collecting in the glands, which confirmed it was an autoimmune disease. It was Carpenter’s review that associated diabetes with Schmidt syndrome, where he introduced Carpenter syndrome, which is a combination of Addison disease, autoimmune thyroid disease, and Type 1 Diabetes. This article will concentrate on understanding and managing PAS-2, which is recognized by a combination of Type 1 Diabetes, autoimmune thyroid disease, and Addison disease.
What Causes Polyglandular Autoimmune Syndrome Type II?
PAS-2 is a disease where the body’s immune system mistakenly targets several of the body’s hormone-producing organs. The causes of PAS-2 are complex and can be influenced by both genetic and environmental factors.
The genetic elements of PAS-2 are related to a group of genes known as the Major Histocompatibility Complex (MHC). MHC helps your immune system recognize and attack foreign substances in the body. However, in people with PAS-2, it’s believed that certain types of these MHC genes – HLA-DR3, HLA-DR4, DQ2, and DQ8 – might trigger the immune system to damage the body’s organs specifically.
There are also non-MHC genes that could make a person more likely to develop PAS-2. These include the CD25 (a receiver for a signal protein called interleukin-2), CTLA-4 (a protein that helps control the immune system’s response), and PTPN22 (a protein that assists in immune system signaling).
It’s important to note that whilst genetics play an important part, environmental factors also contribute to the development of PAS-2. We’re still trying to understand fully the relationship between these different causes, and ongoing research continues to shed light on these complex connections.
Risk Factors and Frequency for Polyglandular Autoimmune Syndrome Type II
PAS-2 is the most common type of PAS. There is a broad range in how often PAS-2 is found, with estimates between 1 in 1,000 people to 1 in 20,000 people. PAS-2 is generally three times more common in women. The typical age when people first start experiencing PAS-2 symptoms is between 20 to 40 years old.
Signs and Symptoms of Polyglandular Autoimmune Syndrome Type II
PAS-2 is a condition that can take a while to diagnose, leading to potential complications. People with PAS-2 usually first experience problems with their endocrine system, which regulates hormones. Over time, they may also develop problems in other areas of the body.
A study that tracked 151 PAS-2 patients over 13 years found that the most common condition was autoimmune thyroid disease, affecting about 66% of patients. Within this group, just over half had Graves’ disease and the rest had Hashimoto’s thyroiditis. Type 1 diabetes was present in 61% of patients, and 18.5% had Addison’s disease. Typically, type 1 diabetes developed first around the age of 27.5, with other conditions appearing between the ages of 36.5 and 40. It was most common for patients to have both type 1 diabetes and thyroid disease.
- Weight loss
- Fatigue
- Nausea
- Vomiting
- Feeling generally weak
- Loss of appetite
- Abdominal pain
- Diarrhea
- Increase urination
- Excessive thirst
Some physical signs could include changes in skin and mouth color, low blood sugar levels, and feeling faint when standing up (especially if Addison’s disease is present). If type 1 diabetes is present, there may also be increased urination and thirst, along with high blood sugar levels. Possible signs of hypothyroidism include a slow heart rate and delayed physical response times.
People with Addison’s disease may experience more severe symptoms like low blood pressure, fast heart rate, and confused thinking, which can indicate a life-threatening adrenal crisis. In fact, patients with Addison’s disease who also have PAS-2 are 2.5 times as likely to experience an adrenal crisis.
Testing for Polyglandular Autoimmune Syndrome Type II
Polyglandular Autoimmune Syndrome Type 2 (PAS-2) is a condition that affects various organs within the body. It is diagnosed when at least two out of three health issues are found in the same person: these problems include primary adrenal insufficiency (aka, Addison’s disease), autoimmune thyroid diseases which may result in conditions like hyperthyroidism or hypothyroidism, and type 1 diabetes (T1DM). Some other health problems that can occur due to PAS-2 are primary hypogonadism, myasthenia gravis, celiac disease, and conditions like alopecia, vitiligo, pernicious anemia, Parkinson disease and hypophysitis.
To determine if Addison’s disease is present, a series of tests is conducted, including measuring morning serum cortisol levels. If these levels are lower than expected, it would suggest the person has Addison’s disease. Additionally, the presence of specific autoantibodies can confirm whether the adrenal gland is affected by an autoimmune response.
Meanwhile, the diagnosis of thyroid problems, such as Hashimoto’s thyroiditis (a form of hypothyroidism) or Graves’ disease (a form of hyperthyroidism), is confirmed by measuring the levels of hormones produced by the thyroid (TSH and T4/T3). Thyroid-specific antibodies can help identify patients who may be at risk of thyroid disease.
To diagnose T1DM, doctors will look for symptoms like excessive urination, excessive thirst, and extreme hunger, in combination with high levels of sugar in the blood or an excess of HbA1c, a type of hemoglobin associated with diabetes.
Correctly diagnosing PAS-2 can be challenging, due to the wide range of symptoms and the fact that all three major endocrine glands (the adrenal gland, thyroid, and pancreas) are not typically affected simultaneously. Patients with PAS-2 and their unaffected family members should be monitored on a regular basis. This is because of the potential for harm if detection of the disease is delayed, such as severe underactive thyroid, adrenal crisis, and diabetic ketoacidosis.
Some additional tests checking for antibodies of specific organs can assist in diagnosing the diseases associated with PAS-2. However, it is important to bear in mind that having these antibodies does not necessarily predict if a failure of the organ will occur.
PAS-2 can be differentiated from PAS-1 due to its usual appearance after the age of 20, different patterns of disease combination, and its polygenic inheritance (where the trait is controlled by two or more genes), whereas PAS-1 is monogenic (the trait is controlled by one gene).
To evaluate thyroid disease, doctors may use an ultrasound, which is a noninvasive tool. However, imaging of the adrenal gland or the pancreas does not consistently show clear signs of these diseases.
Treatment Options for Polyglandular Autoimmune Syndrome Type II
Patients with hormone deficiencies will require hormone replacement therapy. These individuals should have regular check-ups, preferably every six months, with a medical team led by a specialist known as an endocrinologist. These check-ups will include blood tests to ensure the hormone replacement is working correctly and to safeguard against over or under-medication.
These patients could potentially experience conditions like adrenal crisis, low blood sugar, diabetic ketoacidosis, and various other health problems. Diabetic ketoacidosis is a serious diabetes complication where the body starts breaking down fat too quickly. Adrenal crisis, or Addisonian crisis, is a life-threatening situation that results in low cortisol levels in the body. Your treating doctor should look out for these possible conditions and symptoms to catch them early and prevent further complications.
Patients with low thyroid hormones, or hypothyroidism, are often treated with a medication called levothyroxine. However, in patients with an undiagnosed condition known as adrenal insufficiency, this medication may trigger a severe, life-threatening health crisis. So, before treating hypothyroidism with levothyroxine, it’s important to test for adrenal insufficiency. If adrenal insufficiency is confirmed, a medication called hydrocortisone is typically given before starting the thyroid medication.
For those individuals who have family members with a condition known as Polyglandular Autoimmune Syndrome Type II (PAS-2), they can get checked for antibodies that target certain organs to see if they’re at risk for developing the condition.
This is an autoimmune disease, which means that the body’s immune system mistakenly attacks healthy cells. Therefore, several drugs that suppress or modulate the immune system have been tested for treating this condition. However, none are regularly used due to potential side effect risks.
What else can Polyglandular Autoimmune Syndrome Type II be?
The following conditions might be responsible for certain medical symptoms:
- Adrenal crisis, which is a life-threatening situation related to the adrenal glands
- Celiac disease, a digestive disorder that damage the small intestine
- Chronic pancreatitis, a long-lasting inflammation of the pancreas
- DiGeorge syndrome, a disorder caused by a defect in chromosome 22
- Hemochromatosis, a condition causing the body to absorb too much iron
- Hypoglycemia, or low blood sugar
- Hyponatremia, or low salt levels in the blood
- Hypothyroidism, an underactive thyroid condition
- Macrocytosis, where red blood cells are larger than normal
- Septic shock, a severe infection that causes a dramatic drop in blood pressure
