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Polyglandular Autoimmune Syndrome, Type I: Differential Diagnoses & Workup

Author: Saleh A Aldasouqi, MD, FACP, FACE, Assistant Professor of Medicine, Associate Program Director, Department of Medicine, Division of Endocrinology, Michigan State University College of Human Medicine
Coauthor(s): Olakunle PA Akinsoto, MD, MB, BCh, Consulting Staff, Family Health Center, Jacksonville Medical Center; Serge A Jabbour, MD, Associate Professor, Department of Medicine, Division of Endocrinology, Thomas Jefferson University
Contributor Information and Disclosures

Updated: Jan 7, 2009

Differential Diagnoses

DiGeorge Syndrome
Thymoma
Hemochromatosis
WDHA Syndrome
Polyglandular Autoimmune Syndrome, Type II
Polyglandular Autoimmune Syndrome, Type III
Septic Shock

Other Problems to Be Considered

Chromosomal disorder (45,O; trisomy 21)
Congenital rubella
Hemochromatosis
Kearns-Sayre syndrome - Possibly occurring with myopathic disease with hypoparathyroidism, primary hypogonadism, type 1 diabetes mellitus, and hypopituitarism, with or without cardiac conduction defects
Myotonic dystrophy - Hypogonadism and occasionally diabetes
Plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes (POEMS) - Usually occurring in Japanese patients
Wolfram syndrome (diabetes insipidus, diabetes mellitus, optic atrophy, and deafness [DIDMOAD])
Thymoma - Malignant more frequently than benign and associated with myasthenia gravis; as many as 50% of cases occur in people older than 40 years; possibly associated with Cushing, Graves, or Addison disease

Other conditions that may give rise to any of the components of the syndrome if solely present

Workup

Laboratory Studies

In diagnosing polyglandular autoimmune (PGA) syndrome, type I, 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 screen14,15
    • 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, 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.
  • 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.
    • 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.
    • 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.

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.

Other Tests

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

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.

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

More on Polyglandular Autoimmune Syndrome, Type I

Overview: Polyglandular Autoimmune Syndrome, Type I
Differential Diagnoses & Workup: Polyglandular Autoimmune Syndrome, Type I
Treatment & Medication: Polyglandular Autoimmune Syndrome, Type I
Follow-up: Polyglandular Autoimmune Syndrome, Type I
References
Further Reading
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References

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Keywords

polyglandular autoimmune syndrome, autoimmune, adrenal, autoimmune diseases, adrenal glands, Addison's disease, autoimmune disorders, adrenal gland, autoimmune disease, autoimmune disorder, candidiasis, Addison disease, auto immune, polyglandular autoimmune syndrome type I, polyglandular autoimmune syndrome type 1, autoimmune polyendocrine syndromes, APS, autoimmune polyendocrinopathy, autoimmune polyglandular syndrome, candidiasis ectodermal dysplasia, immunoendocrinopathy syndromes, PGA syndromes, polyglandular failure syndromes, endocrine gland insufficiency, autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy, APECED, Whitaker syndrome, PGA syndrome type I, PGA-I

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Contributor Information and Disclosures

Author

Saleh A Aldasouqi, MD, FACP, FACE, Assistant Professor of Medicine, Associate Program Director, Department of Medicine, Division of Endocrinology, Michigan State University College of Human Medicine
Saleh A Aldasouqi, MD, FACP, FACE is a member of the following medical societies: American Association of Clinical Endocrinologists and American College of Physicians
Disclosure: Glaxo Smith Kline Honoraria Speaking and teaching; Pfizer Honoraria Speaking and teaching; Merck Honoraria Speaking and teaching; Takeda Honoraria Speaking and teaching; Amylin Grant/research funds Clinical Trial

Coauthor(s)

Olakunle PA Akinsoto, MD, MB, BCh, Consulting Staff, Family Health Center, Jacksonville Medical Center
Olakunle PA Akinsoto, MD, MB, BCh is a member of the following medical societies: American College of Physicians-American Society of Internal Medicine and American Medical Association
Disclosure: Nothing to disclose.

Serge A Jabbour, MD, Associate Professor, Department of Medicine, Division of Endocrinology, Thomas Jefferson University
Serge A Jabbour, MD is a member of the following medical societies: American Association of Clinical Endocrinologists, American College of Physicians-American Society of Internal Medicine, American Diabetes Association, American Medical Association, American Thyroid Association, Endocrine Society, and Pennsylvania Medical Society
Disclosure: Nothing to disclose.

Medical Editor

Ghassem Pourmotabbed, MD†, Former Associate Professor, Department of Internal Medicine, Division of Endocrinology and Metabolism, University of Tennessee School of Medicine and Health Science Center
Ghassem Pourmotabbed, MD† is a member of the following medical societies: American Diabetes Association, American Federation for Medical Research, and Endocrine Society
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Arthur B Chausmer, MD, PhD, FACP, FACE, FACN, CNS, Professor of Medicine (Endocrinology, Adj), Johns Hopkins School of Medicine; Affiliate Research Professor, Bioinformatics and Computational Biology Program, School of Computational Sciences, George Mason University; Principal, C/A Informatics, LLC
Arthur B Chausmer, MD, PhD, FACP, FACE, FACN, CNS is a member of the following medical societies: American Association of Clinical Endocrinologists, American College of Endocrinology, American College of Nutrition, American College of Physician Executives, American College of Physicians, American College of Physicians-American Society of Internal Medicine, American Medical Informatics Association, American Society for Bone and Mineral Research, American Society of Law Medicine and Ethics, Endocrine Society, and International Society for Clinical Densitometry
Disclosure: Nothing to disclose.

CME Editor

Mark Cooper, MBBS, PhD, FRACP, Head, Diabetes & Metabolism Division, Baker Heart Research Institute, Professor of Medicine, Monash University
Disclosure: Nothing to disclose.

Chief Editor

George T Griffing, MD, Professor of Medicine, St Louis University School of Medicine
George T Griffing, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Medical Practice Executives, American College of Physician Executives, American College of Physicians, American Diabetes Association, American Federation for Medical Research, American Heart Association, Central Society for Clinical Research, Endocrine Society, International Society for Clinical Densitometry, and Southern Society for Clinical Investigation
Disclosure: Nothing to disclose.

 
 
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