Schmidt Syndrome: What It Is, Symptoms, And Treatment Options

The immune system plays a critical role in keeping the body healthy. Sometimes, however, the body’s defensive system goes awry.

In these cases, a person is at risk of what is called an autoimmune disorder. There are different types of autoimmune conditions that can affect the human body. Some of these conditions are relatively common, while others can be quite rare. 

Schmidt syndrome is one of the rarer autoimmune conditions. It is not a specific autoimmune condition but rather a syndrome that includes a collective number of disorders. The condition often results in a need for life-long treatment and maintenance. This post looks at what Schmidt syndrome is, what symptoms signal the condition, and how it is treated. 

What Is Schmidt Disease?

Schmidt syndrome is a condition also sometimes referred to as PAS II or APS-2. It is not a term that refers to a single condition but rather considered a collective name for multiple autoimmune conditions. These conditions may co-occur in the patient’s body. 

The primary disease that forms part of Schmidt syndrome is autoimmune primary adrenal insufficiency. This autoimmune condition is also known as Addison’s disease. In addition to adrenal insufficiency, the patient may also develop:

  • Autoimmune hypothyroidism

  • Type 1 diabetes mellitus

Researchers have classified Schmidt disease as part of autoimmune polyendocrine syndrome type 2, or APS-2. Sometimes, APS-2 is rather referred to as polyglandular autoimmune syndrome type II, or PAS II for short. This is why there is often an interchangeable use of Schmidt syndrome, APS-2, and PAS II. 

Schmidt M.B. identified Schmidt syndrome in 1926. It was only in 1964 that type 1 diabetes mellitus was considered part of the disease. Carpenter C.C made this identification. 

It is also important to note that additional disorders can be present too. A patient with Schmidt syndrome may experience additional autoimmune conditions associated with APS-2 or PAS II. 

Some of the possible co-occurring autoimmune conditions include:

  • Sjogren’s syndrome

  • Hypoparathyroidism

  • Hypopituitarism

  • Myasthenia gravis

  • Rheumatoid arthritis

  • Idiopathic thrombocytopenic purpura

  • Alopecia

  • Celiac disease

  • Pernicious anemia

Recent studies have also suggested that a further subdivision of the disorders is needed. Researchers suggest a subdivision of APS-2, in particular. The suggestions indicate that adding subtypes, such as APS-3 and APS-4, might be useful. 

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Risk Factors

Medical experts do not fully understand the precise cause of Schmidt syndrome. It is known that an autoimmune reaction is triggered. Various triggers may result in such a reaction. It has been suggested that a virus could cause an autoimmune reaction in some patients. Environmental antigens have also been suggested as potential triggers. 

In some studies, congenital rubella infection has been associated with hypothyroidism, as well as diabetes. These further suggest that certain microorganisms could lead to an autoimmune response in the human body. 

Researchers and scientists have also made other suggestions. For example, in some papers, researchers explain that dietary proteins might also be a potential risk factor. Certain proteins obtained from the diet may cause a stimulation on the immune system. 

In the major histocompatibility complex, a number of proteins have specific gene coding. This is where the potential connection comes into play. 

In patients with variants of DR4-DQ8 and DR3-DQ2, particularly those at risk of Celiac disease, there seems to be a higher likeliness of Schmidt syndrome too. Specifically, studies find that these risks may yield an indication for the possibility of the following autoimmune conditions:

  • Addison’s disease

  • Autoimmune thyroid disease

  • Type 1 diabetes

As we can see, these are also the three conditions that collectively form part of Schmidt syndrome. 

Other than these factors, a few more suggestions have been made in regards to risk factors:

  • Women seem to be more likely to develop Schmidt syndrome than men. The ratio has been reported as 3:1. For every four individuals who develop the syndrome, three would be female and one male. 

  • Age also seems to play a part. Studies show that the peak incidence of Schmidt syndrome occurs between the ages of 30 and 50. 

  • Genetics also comes into play when looking at the risk factors. Some studies show Schmidt syndrome runs in families. Thus, if the patient has relatives with Schmidt syndrome, their own risk may be elevated. 

Symptoms Of Schmidt Disease

Symptoms can differ from one patient to another. This is because Schmidt’s disease can include different conditions.

Primary adrenal deficiency concerning autoimmune activity is the main condition associated with Schmidt syndrome.

Patients also develop autoimmune hypothyroidism or type 1 diabetes mellitus with this syndrome. In some patients, only two of these conditions will be present. There are, however, cases where all three conditions are diagnosed in a patient. 

Adrenal insufficiency will result in additional symptoms developing. These symptoms will generally include:

  • Orthostasis

  • Weakness

  • Emesis

  • Cravings for salt

  • Patient may experience pain in the abdomen

  • Nausea

  • Dizziness

In some patients, adrenal insufficiency leads to the development of anorexia. 

The majority of patients will experience these symptoms, as adrenal insufficiency is the primary case with Schmidt syndrome. 

When the patient has type 1 diabetes mellitus, along with Addison’s disease, symptoms of Schmidt disease may include:

  • Fatigue

  • Hypoglycemia

  • Hypotension

  • Weight loss

  • Vitiligo

  • Hyperpigmentation

Some patients also have a reduced need for insulin treatment at this point. 

In cases where hypothyroidism and type 1 diabetes develop, symptoms may include:

  • A reduction in the requirement for insulin administration

  • Hypoglycemia – which leads to frequent dips in blood glucose levels

  • Persistent fatigue may be present.

On the other hand, in rare cases, hyperthyroidism develops instead. This is an increased activity of the thyroid gland. The opposite effects are generally experienced with hyperthyroidism and type 1 diabetes. Fatigue still remains present, but the patient experienced hyperglycemia. This means there may be frequent spikes in the patient’s blood sugar levels

There are also laboratory testing procedures that may help identify the presence of Schmidt syndrome. Blood tests will generally reveal the following signs:

Additional symptoms associated with co-occurring autoimmune conditions can also develop in these patients. The specific symptoms depend on the situation.

Doctors will generally discuss the symptoms experienced with the patient. This allows the physician to determine which tests need to be done. By understanding symptoms, the physician also gets a better idea of which co-occurring disorders to look out for. 


Doctors have no specialty test used to diagnose Schmidt syndrome or the associated conditions, including APS-2. This makes the diagnosis process more difficult for the physician. The idea behind diagnosis is to identify the “component” disorders associated with APS-2 and Schmidt syndrome. By identifying these conditions’ presence, doctors have a better chance of providing an accurate diagnosis to the patient. 

The first step is for the doctor to take a closer look at the patient’s medical history. This allows the doctor to check for risk factors, such as age, gender, and a family history of autoimmune conditions.

The doctor will ask the patient about the symptoms experienced. The patient needs to provide a full overview of the symptoms. During the diagnosis process, the doctor needs to identify all autoimmune conditions affecting the patient. 

Laboratory testing plays an integral part in understanding how Schmidt disease is affecting the patient’s body. 

Blood tests are usually done by testing serum cortisol levels. Early morning testing is important. Doctors will also perform tests for specific antibodies. The detection of certain antibodies can indicate the presence of an autoimmune reaction in the patient’s body. 

Tests for TSH, T3, T4, and related hormones also play an important role in the diagnosis of Schmidt syndrome. These are the primary hormones of the thyroid gland. The hormones affect the functionality of this gland. An elevated level of thyroid hormones can signal hyperthyroidism. When there is a low level of these hormones, the doctor may find that the patient has hypothyroidism instead. 

Additional tests may be done to rule out other autoimmune disorders commonly associated with Schmidt syndrome. 


Treatment can only be provided once the patient has been diagnosed. The physician needs to understand all aspects of the patient’s condition, including the specific autoimmune conditions affecting their body. 

Individual treatments are usually prescribed for each of the autoimmune diseases identified during the diagnosis process. 

Levothyroxine will generally be used on patients with hypothyroidism. This is a form of thyroid hormone replacement therapy. Hydrocortisone may also be provided in cases where the thyroid gland is affected by an autoimmune reaction. 

Glucocorticoid therapy is often utilized in patients with Addison’s disease. The specific dose depends on several factors, including stress levels. An emergency kit is often provided to the patient, which contains a hydrocortisone self-injection system. Most patients with Schmidt syndrome are provided with a medical alert bracelet too. 

Regular follow-up appointments should be scheduled for the patient. During these appointments, new blood tests are taken. Antibody screening plays a vital role during follow-up sessions in patients with Schmidt syndrome. These tests allow the physician to determine the effectiveness of the prescribed treatment protocol. The results of the tests ensure appropriate modifications can be made to the current treatment plan if needed. 


Schmidt syndrome is a rare collection of autoimmune conditions. Adrenal sufficiency is the primary autoimmune condition that forms part of the syndrome.

Additional autoimmune conditions also affect the patient when they are diagnosed with Schmidt syndrome. There are treatment options that may assist in reducing the symptoms.

Some medicines may provide a reduced progression of the autoimmune syndrome too. Patients with Schmidt syndrome should prioritize frequent follow-ups with their physician. Following protocols provided in terms of treatment is essential, as these can help to prevent further complications in the future. 

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  1. Johns Hopkins Medicine. Schmidt Syndrome and Autoimmune Polyendocrine Syndrome Type 2. [online] Available at:,autoimmune%20syndrome%20type%20II%20(PAS
  2. NIH. (1964) Schmidt’s Syndrome (Thyroid and Adrenal Insufficiency). A Review Of The Literature And A Report Of Fifteen Cases Including Ten Instances Of Coexisting Diabetes Mellitus. [online] Available at:
  3. Deutsche Medizinische Wochenschrift. (1999) Polyglandular autoimmune syndrome type II: epidemiology and forms of manifestation. [online] Available at:
  4. New England Journal of Medicine. (2018) Autoimmune Polyendocrine Syndromes. [online] Available at:
  5. The Lancet. Diabetes & Endocrinology. (2015) Diagnosis and management of adrenal insufficiency. [online] Available at:

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