Type II Polyglandular Autoimmune Syndrome Workup

The time course of the development of organ-specific autoimmunity makes it necessary to repeatedly reevaluate patients and their families over time. Provocative and suppressive testing frequently is necessary. ^{[12, 13]}

Among patients with type 1 diabetes mellitus, thyroid autoimmunity and celiac disease coexist with sufficient frequency to justify screening. Measuring annual thyrotropin levels in individuals with type 1 diabetes mellitus is recommended as cost-effective.

Clinical history and examination suggesting evidence of more than 1 endocrine deficiency should prompt testing, to include serum autoantibody screening and an evaluation of end-organ function.

Serum autoantibodies screen - This helps to verify the autoimmune etiology of the disease and to identify persons who may later develop multi-endocrine deficiency. This test also is useful in screening asymptomatic family members who may develop autoimmune endocrine disease in the future. The screening panel includes autoantibodies to the following:

• 21-hydroxylase

• 17-hydroxylase

• Thyroid peroxidase (TPO) - The antibodies may be present without the progression to overt disease. If they are positive in a patient who is hypothyroid, they are diagnostic of Hashimoto's thyroiditis. Thyroid-stimulating immunoglobulins (TSI) in patients with signs of hyperthyroidism are diagnostic of Graves disease.

• Glutamic acid decarboxylase-65 and islet cells - The antibodies are used to screen for type 1 diabetes mellitus.

• Antitissue transglutaminase antibodies - These are used because 2-3% of patients with type 1 diabetes mellitus have celiac disease. Other antibodies for celiac disease include immunoglobulin-A (IgA) endomysial antibodies and antigliadin antibodies.

• Parietal cell and anti-intrinsic factor antibodies - These are used to screen for pernicious anemia.

Evaluation of end-organ function is necessary to confirm the diagnosis in patients with positive autoantibodies. Even if these antibodies are negative, still perform testing if clinical suspicion is high, because the sensitivity of these assays is not perfect. Testing—some of which certain authorities advocate be performed annually, because not all diseases manifest at the time of the initial diagnosis—is recommended as follows:

• Gonadotropins (follicle-stimulating hormone [FSH], luteinizing hormone [LH]), and appropriate sex hormones (testosterone, estradiol) (In females who have regular menses, gonadotropins and estradiol are not necessary.)

• TSH, free thyroxine (T4), and free triiodothyronine (T3) if necessary

• Adrenocorticotropic hormone (ACTH) plasma cortisol level and Cortrosyn-stimulation test

• Plasma renin activity and serum electrolytes

• Calcium, phosphorus, magnesium, and albumin

• Fasting blood glucose

• Complete blood count (CBC) with mean cell volume (MCV) and vitamin B-12 levels

Perform a computed tomography (CT) scan of the adrenal glands to exclude hemorrhage and fungal infections as the cause of primary adrenal insufficiency. ^[8]

Perform a magnetic resonance imaging (MRI) scan of the pituitary if hypopituitarism (autoimmune hypophysitis vs other causes) is a possibility (rare).

Perform thyroid imaging (uptake and/or scan) only in patients who are hyperthyroid; in Graves disease, it shows uniform distribution and high uptake.

If antitissue transglutaminase antibodies are present, perform a small-bowel biopsy to rule out celiac disease. The majority of patients with high levels of antitissue transglutaminase are asymptomatic.

Histologic findings

The biopsy findings range from villi atrophy (with numerous plasma cells within the lamina propria) to almost complete disappearance of villi. These findings are not specific, but they are suggestive of celiac disease.