Biopsy is the only means of accurate diagnosis as no autoantigen has been discovered. Biopsy of the pituitary gland is not easily performed with safety as it sits under the brain, however, a test does exist to detect antibodies to the pituitary without biopsy: autoantibodies to M(r) 49,000 pituitary cytosolic protein may represent markers for an immunological process affecting the pituitary gland. Tests for normal pituitary gland hormone production tend to be expensive and in some cases difficult to administer. In addition, certain hormone levels vary largely throughout the day and in response to metabolic factors, making abnormal levels difficult to calibrate—further hampering diagnosis.

Various tests can be chosen depending on the presenting symptoms. Doctors may search for Thyroid peroxidase Antibodies (TPOAb) when a person has symptoms of hypothyroidism, or when a person will be started on a drug therapy associated with risks of developing hypothyroidism, such as lithium or Interferon alfa. This antibody is related to Hashimoto's thyroiditis and Graves' disease. If the person presents symptoms of hyperthyroidism, doctors are more likely to test for Thyroid stimulating hormone receptor Antibodies (TRAb), and monitor the effects of anti-thyroid therapy, also associated with Graves' disease.

Doctors may check Thyroglobulin Antibodies (TgAb) also, whenever a thyroglobulin test is performed to see if the antibody is interfering. TgAb may also be ordered in regular intervals after a person has been diagnosed with thyroid cancer, and just like TPOAb, it can be associated with Hashimoto’s thyroiditis.

80% of patients with pituitary antibodies also have antibodies to thyroid gland or its hormones. Likewise, 20% of autoimmune thyroid patients also have pituitary antibodies. It follows that a subset of thyroid patients may have a disease related to autoimmune hypophysitis. Recent research has focused on a defect at the CTLA-4 gene which, coupled with other factors, may result in autoimmunity primarily focusing on certain endocrine glands including the pituitary and thyroid.

Mainly, the diagnosis of hypophysitis is through exclusion – patients often undergo surgery because they are suspected of having a pituitary adenoma. But, the most accurate diagnosis is using Magnetic Resonance Imaging (MRI) to find any mass or lesions on the Sella Turcica.

Pregnant women who are positive for Hashimoto's thyroiditis may have decreased thyroid function or the gland may fail entirely. If a woman is TPOAb-positive, clinicians can inform her of the risks for themselves and their infants if they go untreated. "Thyroid peroxidase antibodies (TPOAb) are detected in 10% of pregnant women," which presents risks to those pregnancies. Women who have low thyroid function that has not been stabilized are at greater risk of having an infant with: low birth weight, neonatal respiratory distress, hydrocephalus, hypospadias, miscarriage, and preterm delivery. The embryo transplantion rate and successful pregnancy outcomes are improved when Hashimoto's is treated. Recommendations are to only treat pregnant women who are TPOAb-positive throughout the entirety of their pregnancies and to screen all pregnant women for thyroid levels. Close cooperation between the endocrinologist and obstetrician benefits the woman and the infant. The Endocrine Society recommends screening in pregnant women who are considered high-risk for thyroid autoimmune disease.

Thyroid peroxides antibodies testing is recommended for women who have ever been pregnant regardless of pregnancy outcome. "...[P]revious pregnancy plays a major role in development of autoimmune overt hypothyroidism in premenopausal women, and the number of previous pregnancies should be taken into account when evaluating the risk of hypothyroidism in a young women ["sic"]."

Diagnosis is usually made by detecting elevated levels of anti-thyroid peroxidase antibodies (TPOAb) in the serum, but seronegative (without circulating autoantibodies) thyroiditis is also possible.

Given the relatively non-specific symptoms of initial hypothyroidism, Hashimoto's thyroiditis is often misdiagnosed as depression, cyclothymia, PMS, chronic fatigue syndrome, fibromyalgia and, less frequently, as erectile dysfunction or an anxiety disorder. On gross examination, there is often presentation of a hard goiter that is not painful to the touch; other symptoms seen with hypothyroidism, such as periorbital myxedema, depend on the current state of progression of the response, especially given the usually gradual development of clinically relevant hypothyroidism. Testing for thyroid-stimulating hormone (TSH), free T3, free T4, and the anti-thyroglobulin antibodies (anti-Tg), anti-thyroid peroxidase antibodies (anti-TPO, or TPOAb) and anti-microsomal antibodies can help obtain an accurate diagnosis. Earlier assessment of the person may present with elevated levels of thyroglobulin owing to transient thyrotoxicosis, as inflammation within the thyroid causes damage to the integrity of thyroid follicle storage of thyroglobulin; TSH secretion from the anterior pituitary increases in response to a decrease in negative feedback inhibition secondary to decreased serum thyroid hormones. Typically T4 is the preferred thyroid hormone test for hypothyroidism. This exposure of the body to substantial amounts of previously isolated thyroid enzymes is thought to contribute to the exacerbation of tolerance breakdown, giving rise to the more pronounced symptoms seen later in the disease. Lymphocytic infiltration of the thyrocyte-associated tissues often leads to the histologically significant finding of germinal center development within the thyroid gland.

Hashimoto's when presenting as mania is known as Prasad's syndrome after Ashok Prasad, the psychiatrist who first described it.

The prognosis for hypophysitis was variable for each individual. The depending factors for hypophysitis included the advancement of the mass on the Sella Turcica, percentage of fibrosis, and the body's response to corticosteroids. Through the use of Corticosteroids, the vision defects tend to recover when the gland size began to decrease. The prognoses of the limited number of reported cases were usually good.

Diagnosing SS is complicated by the range of symptoms a patient may manifest, and the similarity between symptoms of SS and those of other conditions. Also, patients who have symptoms of SS approach different specialities regarding their symptoms which make the diagnosis difficult. Since the symptoms of this autoimmune disorder such as dry eyes and dry mouth are very common among people, and mostly observed from the age of 40 and above, it is often mistaken as age-related, thus ignored. However, some medications can also cause symptoms that are similar to those of SS. The combination of several tests, which can be done in a series, can eventually lead to the diagnosis of SS.

SS is usually classified as either 'primary' or 'secondary'. Primary Sjögren syndrome occurs by itself and secondary Sjögren syndrome occurs when another connective tissue disease is present.

Blood tests can be done to determine if a patient has high levels of antibodies that are indicative of the condition, such as antinuclear antibody (ANA) and rheumatoid factor (because SS frequently occurs secondary to rheumatoid arthritis), which are associated with autoimmune diseases. Typical SS ANA patterns are SSA/Ro and SSB/La, of which Anti-SSB/La is far more specific; Anti-SSA/Ro is associated with numerous other autoimmune conditions, but are often present in SS. However, Anti-SSA and Anti-SSB tests are frequently not positive in SS.

The rose bengal test uses a stain that measures state and function of the lacrimal glands. This test involves placing the non-toxic dye rose bengal on the eyes. The dye’s distinctive colour helps in determining the state and functioning of tear film and the rate of tear evaporation. Any distinctive colour change observed will be indicative of SS, but many related diagnostic tools will be used to confirm the condition of SS.

Schirmer's test measures the production of tears: a strip of filter paper is held inside the lower eyelid for five minutes, and its wetness is then measured with a ruler. Producing less than of liquid is usually indicative of SS. This measurement analysis varies among people depending on other eye-related conditions and medications in use when the test is taken. A slit-lamp examination can reveal dryness on the surface of the eye.

Symptoms of dry mouth and dryness in the oral cavity are caused by the reduced production of saliva from the salivary glands (parotid gland, submandibular gland, and sublingual gland). To check the status of salivary glands and the production of saliva, a salivary flow-rate test is performed, in which the person is asked to spit as much as they can into a cup, and the resulting saliva sample is collected and weighed. This test's results can determine whether the salivary glands are functioning adequately. Not enough saliva produced could mean the person has SS. An alternative test is non-stimulated whole saliva flow collection, in which the person spits into a test tube every minute for 15 minutes. A resultant collection of less than is considered a positive result.

A lip/salivary gland biopsy takes a tissue sample that can reveal lymphocytes clustered around salivary glands, and damage to these glands due to inflammation. This test involves removing a sample of tissue from a person’s inner lip/salivary gland and examining it under a microscope. In addition, a sialogram, a special X-ray test, is performed to see if any blockage is present in the salivary gland ducts (i.e. parotid duct) and the amount of saliva that flows into the mouth.

Also, a radiological procedure is available as a reliable and accurate test for SS. A contrast agent is injected into the parotid duct, which opens from the cheek into the vestibule of the mouth opposite the neck of the upper second molar tooth. Histopathology studies should show focal lymphocytic sialadenitis. Objective evidence of salivary gland involvement is tested through ultrasound examinations, the level of unstimulated whole salivary flow, a parotid sialography or salivary scintigraphy, and autoantibodies against Ro (SSA) and/or La (SSB) antigens.

SS can be excluded from people with past head and neck radiation therapy, acquired immunodeficiency syndrome (AIDS), pre-existing lymphoma, sarcoidosis, graft-versus-host disease, and use of anticholinergic drugs.

In terms of diagnosis for this condition, the following methods/tests are available:

- Endoscopic

- CT scan

- Serum endocrine autoantibody screen

- Histologic test

The best diagnostic tool to confirm adrenal insufficiency is the ACTH stimulation test; however, if a patient is suspected to be suffering from an acute adrenal crisis, immediate treatment with IV corticosteroids is imperative and should not be delayed for any testing, as the patient's health can deteriorate rapidly and result in death without replacing the corticosteroids.

Dexamethasone should be used as the corticosteroid if the plan is to do the ACTH stimulation test at a later time as it is the only corticosteroid that will not affect the test results.

If not performed during crisis, then labs to be run should include: random cortisol, serum ACTH, aldosterone, renin, potassium and sodium. A CT of the adrenal glands can be used to check for structural abnormalities of the adrenal glands. An MRI of the pituitary can be used to check for structural abnormalities of the pituitary. However, in order to check the functionality of the Hypothalamic Pituitary Adrenal (HPA) Axis the entire axis must be tested by way of ACTH stimulation test, CRH stimulation test and perhaps an Insulin Tolerance Test (ITT). In order to check for Addison’s Disease, the auto-immune type of primary adrenal insufficiency, labs should be drawn to check 21-hydroxylase autoantibodies.

There is no prevention mechanism for SS due to its complexity as an autoimmune disorder. However, lifestyle changes can reduce the risk factors of getting SS or reduce the severity of the condition with patients who have already been diagnosed. Diet is strongly associated with inflammation that is mostly seen in many autoimmune related diseases including SS. An experimental study concludes that SS patients show high sensitivity to gluten that directly relates to inflammation. Moderate exercise is also found to be helpful in SS patients mainly reducing the effect of lung inflammation.

Thyroid autoantibodies appear mostly with the presence of lymphocytes in the targeted organ. Lymphocytes produce antibodies targeting three different thyroid proteins: Thyroid peroxidase Antibodies (TPOAb), Thyroglobulin Antibodies (TgAb), and Thyroid stimulating hormone receptor Antibodies (TRAb). Some patients who are healthy may be positive for more than one of these antibodies. Doctors who attend to such patients will most likely do routine follow-ups on the patient’s health since, even though it is highly unlikely that they will present any thyroid problems, there is still a chance that they will develop some type of dysfunction with time.

Diagnosis of autoimmune disorders largely rests on accurate history and physical examination of the patient, and high index of suspicion against a backdrop of certain abnormalities in routine laboratory tests (example, elevated C-reactive protein). In several systemic disorders, serological assays which can detect specific autoantibodies can be employed. Localised disorders are best diagnosed by immunofluorescence of biopsy specimens. Autoantibodies are used to diagnose many autoimmune diseases. The levels of autoantibodies are measured to determine the progress of the disease.

Treatment is as with hypothyroidism, daily thyroxine(T4) and/or triiodothyronine(T3).

Autoimmune polyendocrine syndrome type 1 treatment is based on the symptoms that are presented by the affected individual, additionally there is:

- Hormone replacement

- Systemic antifungal treatment

- Immunosuppressive treatment

Immunosuppressive therapy may be used in "type I" of this condition, ketoconazole can be used for "autoimmune polyendocrine syndrome type I" under certain conditions The component diseases are managed as usual, the challenge is to detect the possibility of any of the syndromes, and to anticipate other manifestations. For example, in a person with known Type 2 autoimmune polyendocrine syndrome but no features of Addison's disease, regular screening for antibodies against 21-hydroxylase may prompt early intervention and hydrocortisone replacement to prevent characteristic crises

Computed tomography (CT) findings in AIP include a "diffusely enlarged hypodense" pancreas or a focal mass that may be mistaken for a pancreatic malignancy. A low-density, "capsule-like rim on CT" (possibly corresponding to an inflammatory process involving peripancreatic tissues) is thought to be an additional characteristic feature (thus the mnemonic: "sausage-shaped"). Magnetic resonance imaging (MRI) reveals a diffusely decreased signal intensity and delayed enhancement on dynamic scanning. The characteristic ERCP finding is segmental or diffuse irregular narrowing of the main pancreatic duct, usually accompanied by an extrinsic-appearing stricture of the distal bile duct. Changes in the extrapancreatic bile duct similar to those of primary sclerosing cholangitis (PSC) have been reported.

The role of endoscopic ultrasound (EUS) and EUS-guided fine-needle aspiration (EUS-FNA) in the diagnosis of AIP is not well described, and EUS findings have been described in only a small number of patients. In one study, EUS revealed a diffusely swollen and hypoechoic pancreas in 8 of the 14 (57%) patients, and a solitary, focal, irregular mass was observed in 6 (46%) patients. Whereas EUS-FNA is sensitive and specific for the diagnosis of pancreatic malignancy, its role in the diagnosis of AIP remains unclear.

Most patients will maintain a diagnosis of undifferentiated connective tissue disease. However, about one third of UCTD patients will differentiate to a specific autoimmune disease, like rheumatoid arthritis or systemic sclerosis. About 12 percent of patients will go into remission.

Severe vitamin D deficiency has been associated with the progression of UCTD into defined connective tissue diseases. The presence of the autoantibodies anti-dsDNA, anti-Sm, and anti-cardiolipin has been shown to correlate with the development of systemic lupus erythematosus, specifically.

There is no official diagnostic criteria for UCTD. Diagnostic testing generally aims to determine whether a patient has a "definite" or "undifferentiated" connective tissue disease.

Most recently the fourteenth Congress of the International Association of Pancreatology developed the International Consensus Diagnostic Criteria (ICDC) for AIP. The ICDC emphasizes five cardinal features of AIP which includes the imaging appearance of pancreatic parenchyma and the pancreatic duct, serum IgG4 level, other organ involvement with IgG4-related disease, pancreatic histology and response to steroid therapy.

In 2002, the Japanese Pancreas Society proposed the following diagnostic criteria for autoimmune pancreatitis:

For diagnosis, criterion I (pancreatic imaging) must be present with criterion II (laboratory data) and/or III (histopathologic findings).

Mayo Clinic has come up with five diagnostic criteria called HISORt criteria which stands for histology, imaging, serology, other organ involvement, and response to steroid therapy.

Although GH can be readily measured in a blood sample, testing for GH deficiency is constrained by the fact that levels are nearly undetectable for most of the day. This makes simple measurement of GH in a single blood sample useless for detecting deficiency. Physicians therefore use a combination of indirect and direct criteria in assessing GHD, including:

- Auxologic criteria (defined by body measurements)

- Indirect hormonal criteria (IGF levels from a single blood sample)

- Direct hormonal criteria (measurement of GH in multiple blood samples to determine secretory patterns or responses to provocative testing), in particular:

- Subnormal frequency and amplitude of GH secretory peaks when sampled over several hours

- Subnormal GH secretion in response to at least two provocative stimuli

- Increased IGF1 levels after a few days of GH treatment

- Response to GH treatment

- Corroborative evidence of pituitary dysfunction

"Provocative tests" involve giving a dose of an agent that will normally provoke a pituitary to release a burst of growth hormone. An intravenous line is established, the agent is given, and small amounts of blood are drawn at 15 minute intervals over the next hour to determine if a rise of GH was provoked. Agents which have been used clinically to stimulate and assess GH secretion are arginine, levodopa, clonidine, epinephrine and propranolol, glucagon and insulin. An insulin tolerance test has been shown to be reproducible, age-independent, and able to distinguish between GHD and normal adults, and so is the test of choice.

Severe GH deficiency in childhood additionally has the following measurable characteristics:

- Proportional stature well below that expected for family heights, although this characteristic may not be present in the case of familial-linked GH deficiency

- Below-normal velocity of growth

- Delayed physical maturation

- Delayed bone age

- Low levels of IGF1, IGF2, IGF binding protein 3

- Increased growth velocity after a few months of GH treatment

In childhood and adulthood, the diagnosing doctor will look for these features accompanied by corroboratory evidence of hypopituitarism such as deficiency of other pituitary hormones, a structurally abnormal pituitary, or a history of damage to the pituitary. This would confirm the diagnosis; in the absence of pituitary pathology, further testing would be required.

The differential diagnosis of Kikuchi disease includes systemic lupus erythematosus (SLE), disseminated tuberculosis, lymphoma, sarcoidosis, and viral lymphadenitis. Clinical findings sometimes may include positive results for IgM/IgG/IgA antibodies.

For other causes of lymph node enlargement, see lymphadenopathy.

Patient should seek a physician for skin tests. Typically, after a consultation with rheumatologist, the disease will be diagnosed. A dermatologist is also another specialist that can diagnose.

Blood studies and numerous other specialized tests depending upon which organs are affected.

In terms of genetic testing, while it is done for "type 1" of this condition, "type 2" will only render (or identify) those genes which place the individual at higher risk. Other methods/exam to ascertain if an individual has autoimmune polyendocrine syndrome type 2 are:

- CT scan

- MRI

- Ultrasound

Diagnosis for "type 1" of this condition for example, sees that the following methods/tests are available:

- Endoscopic

- CT scan

- Histologic test