Type I Polyglandular Autoimmune Syndrome Workup

Updated: Nov 11, 2021
  • Author: Saleh A Aldasouqi, MD, FACE, ECNU; Chief Editor: Romesh Khardori, MD, PhD, FACP  more...
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Workup

Laboratory Studies

The diagnosis of polyglandular autoimmune (PGA) syndrome, type I is usually made with two or three of the following conditions: mucocutaneous candidiasis, hypoparathyroidism and/or adrenal insufficiency. In diagnosing PGA-1, a clinical history and examination that suggest evidence of more than 1 endocrine deficiency should prompt the use of the following tests:

Serum endocrine autoantibody screen [7, 17]

  • This helps to verify the autoimmune etiology of the disease and to identify patients who may later develop multi-endocrine deficiency.

  • It is useful for screening family members who may develop autoimmune endocrine disease in the future.

  • The screening panel may include autoantibodies to 21-hydroxylase, CYP450c21, 17-hydroxylase, thyroid peroxidase (TPO) and thyroid-stimulating immunoglobulins (TSI), glutamic acid decarboxylase and islet cell antibodies, and parietal cell enzyme (H+/K+ -ATPase) antibodies.

  • Not all patients have positive antibodies; therefore, the absence of these antibodies does not exclude PGA-I.

Since the different components of this disease develop over years to decades, once there is clinical suspicion, surveillance is essential for other associated autoimmune disorders.

End-organ function tests are necessary to confirm the diagnosis.

  • Test testosterone, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) in males.

  • In females who have regular menses, no laboratory assessment of the gonadotropin axis is necessary. If menses are irregular or absent, obtain estradiol, FSH, LH, and prolactin levels.

  • Thyroid-stimulating hormone (TSH) and, if necessary, free thyroxine (T4) and free triiodothyronine (T3) - TSH may be elevated, and free T4 and T3 may be low.

  • Adrenocorticotropic hormone (ACTH) and cosyntropin (Cortrosyn) stimulation test - ACTH may be elevated with an abnormal Cortrosyn test, which consists of a low cortisol level found 30 minutes after administering Cortrosyn.

  • Plasma renin activity - High renin activity may be noted.

  • Electrolytes; calcium, phosphorus, magnesium, and albumin; and fasting blood glucose: Hyponatremia, hyperkalemia, mild metabolic acidosis, and azotemia may occur with dehydration. The values for calcium, phosphorus, and magnesium vary, depending on the extravascular status of the patient and the severity and duration of illness. These also depend on the severity of hypoparathyroidism, which causes low calcium, an elevated phosphorus, and low magnesium.

  • Fungal skin scrapings - These may be positive for candidiasis (see Fungal Culture).

  • Complete blood count (CBC) with mean cell volume (MCV) and vitamin B-12 levels - These may show lymphocytosis, neutropenia, and anemia. If coexisting pernicious anemia exists, the MCV is elevated and the vitamin B-12 levels are low.

  • CD4 counts and possibly human immunodeficiency virus (HIV) testing - Both of these are performed to exclude the differential diagnosis of HIV.

  • Some authorities have recommended that some of these tests be performed on an annual basis, because not all diseases manifest at the time of the initial diagnosis.

Depending on the presentation, liver function tests along with antibodies to the liver, kidney, and spleen (autoimmune hepatitis) may be considered because of their occasional association with PGA-I.

Malabsorption and atrophic gastritis occasionally are associated with PGA-I, and patients with suggestive clinical features may require endoscopic biopsies to prove the diagnosis.

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Imaging Studies

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

Other imaging studies depend on the syndrome components or other associated disorders present at the time of the evaluation.

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Other Tests

Other tests depend on the syndrome components or other associated disorders present at the time of the evaluation.

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Procedures

Endoscopies with biopsies of the stomach and small bowel are used to rule out atrophic gastritis and celiac disease.

Other procedures depend on the syndrome components or other associated disorders present at the time of the evaluation.

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Histologic Findings

Histology depends on the organ that has been affected. There usually is chronic inflammatory cell infiltration of the affected organs. Examples are as follows:

  • Adrenal gland - May be anything ranging from cellular infiltration (lymphocytic and plasma cells) to extensive fibrosis of the adrenal cortex

  • Gastric atrophy - Lymphocytic/plasma cell infiltration of the lamina propria, with a progression of parietal cells and eventual atrophy with only mucous glands

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