Close
New

Medscape is available in 5 Language Editions – Choose your Edition here.

 

Type I Polyglandular Autoimmune Syndrome Workup

  • Author: Saleh A Aldasouqi, MD, FACE, ECNU; Chief Editor: Romesh Khardori, MD, PhD, FACP  more...
 
Updated: Aug 28, 2014
 

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 screen[14, 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.
  • 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.

Next

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.

Previous
Next

Other Tests

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

Previous
Next

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.

Previous
Next

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
Previous
 
 
Contributor Information and Disclosures
Author

Saleh A Aldasouqi, MD, FACE, ECNU Associate Professor of Medicine, Vice Chief of Endocrinology Division, Department of Medicine, Michigan State University College of Human Medicine

Saleh A Aldasouqi, MD, FACE, ECNU is a member of the following medical societies: American Association of Clinical Endocrinologists, American College of Physicians

Disclosure: Received honoraria from Takeda for speaking and teaching; Received honoraria from Janssen for speaking and teaching; Received honoraria from Invokana for speaking and teaching.

Coauthor(s)

Olakunle P A Akinsoto, MD, MB, BCh Consulting Staff, Family Health Center

Olakunle P A Akinsoto, MD, MB, BCh is a member of the following medical societies: American College of Physicians-American Society of Internal Medicine, American Medical Association

Disclosure: Nothing to disclose.

Serge A Jabbour, MD, FACP, FACE Professor of Medicine, Division of Endocrinology, Diabetes and Metabolic Diseases, Jefferson Medical College of Thomas Jefferson University

Serge A Jabbour, MD, FACP, FACE 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, Pennsylvania Medical Society

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

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 Nutrition, American Society for Bone and Mineral Research, International Society for Clinical Densitometry, American College of Endocrinology, American College of Physicians, American College of Physicians-American Society of Internal Medicine, American Medical Informatics Association, Endocrine Society

Disclosure: Nothing to disclose.

Chief Editor

Romesh Khardori, MD, PhD, FACP Professor of Endocrinology, Director of Training Program, Division of Endocrinology, Diabetes and Metabolism, Strelitz Diabetes and Endocrine Disorders Institute, Department of Internal Medicine, Eastern Virginia Medical School

Romesh Khardori, MD, PhD, FACP is a member of the following medical societies: American Association of Clinical Endocrinologists, American College of Physicians, American Diabetes Association, Endocrine Society

Disclosure: Nothing to disclose.

Acknowledgements

I would like to thank Jinie Shirey at the Department of Medicine, College of Human Medicine, Michigan State University, East Lansing for manuscript assistance and preparation, and Laura Smith at the Medical Library, Sparrow Hospital, Lansing, Michigan, for assistance in reference retrieval.

References
  1. Garcia-Hernandez FJ, Ocana-Medina C, Gonzalez-Leon R, et al. Autoimmune polyglandular syndrome and pulmonary arterial hypertension. Eur Respir J. 2006 Mar. 27(3):657-8. [Medline]. [Full Text].

  2. Neufeld M, Maclaren NK, Blizzard RM. Two types of autoimmune Addison's disease associated with different polyglandular autoimmune (PGA) syndromes. Medicine (Baltimore). 1981 Sep. 60(5):355-62. [Medline].

  3. Eisenbarth GS, Gottlieb PA. Autoimmune polyendocrine syndromes. N Engl J Med. 2004 May 13. 350(20):2068-79. [Medline].

  4. Alimohammadi M, Bjorklund P, Hallgren A, et al. Autoimmune polyendocrine syndrome type 1 and NALP5, a parathyroid autoantigen. N Engl J Med. 2008 Mar 6. 358(10):1018-28. [Medline]. [Full Text].

  5. Bhansali A, Kotwal N, Suresh V, et al. Polyglandular autoimmune syndrome type 1 without chronic mucocutaneous candidiasis in a 16 year-old male. J Pediatr Endocrinol Metab. 2003 Jan. 16(1):103-5. [Medline].

  6. Bjorses P, Halonen M, Palvimo JJ, et al. Mutations in the AIRE gene: effects on subcellular location and transactivation function of the autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy protein. Am J Hum Genet. 2000 Feb. 66(2):378-92. [Medline]. [Full Text].

  7. Org T, Chignola F, Hetenyi C, et al. The autoimmune regulator PHD finger binds to non-methylated histone H3K4 to activate gene expression. EMBO Rep. 2008 Apr. 9(4):370-6. [Medline]. [Full Text].

  8. Heino M, Scott HS, Chen Q, et al. Mutation analyses of North American APS-1 patients. Hum Mutat. 1999. 13(1):69-74. [Medline].

  9. Rosatelli MC, Meloni A, Meloni A, et al. A common mutation in Sardinian autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy patients. Hum Genet. 1998 Oct. 103(4):428-34. [Medline].

  10. Zlotogora J, Shapiro MS. Polyglandular autoimmune syndrome type I among Iranian Jews. J Med Genet. 1992 Nov. 29(11):824-6. [Medline]. [Full Text].

  11. Dittmar M, Kahaly GJ. Polyglandular autoimmune syndromes: immunogenetics and long-term follow-up. J Clin Endocrinol Metab. 2003 Jul. 88(7):2983-92. [Medline]. [Full Text].

  12. Iannello S, Campanile E, Cipolli D, et al. [A rare case of juvenile diabetes mellitus associated with APECED (autoimmune poly-endocrinopathy, candidiasis and ectodermal dystrophy) with strong X-linked familial inheritance]. Minerva Endocrinol. 1997 Jun. 22(2):51-9. [Medline].

  13. LeBoeuf N, Garg A, Worobec S. The autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome. Pediatr Dermatol. 2007 Sep-Oct. 24(5):529-33. [Medline].

  14. Meloni A, Furcas M, Cetani F, et al. Autoantibodies against type I interferons as an additional diagnostic criterion for autoimmune polyendocrine syndrome type I. J Clin Endocrinol Metab. 2008 Nov. 93(11):4389-97. [Medline].

  15. Oftedal BE, Wolff AS, Bratland E, et al. Radioimmunoassay for autoantibodies against interferon omega; its use in the diagnosis of autoimmune polyendocrine syndrome type I. Clin Immunol. 2008 Oct. 129(1):163-9. [Medline].

  16. Ahonen P, Myllarniemi S, Sipila I, et al. Clinical variation of autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) in a series of 68 patients. N Engl J Med. 1990 Jun 28. 322(26):1829-36. [Medline].

  17. An autoimmune disease, APECED, caused by mutations in a novel gene featuring two PHD-type zinc-finger domains. Nat Genet. 1997 Dec. 17(4):399-403. [Medline].

  18. Katzung BG, ed. Basic and Clinical Pharmacology. 7th ed. Stamford, Conn: Appleton & Lange; 1998. 635-52, 706-22.

  19. Betterle C, Greggio NA, Volpato M. Clinical review 93: autoimmune polyglandular syndrome type 1. J Clin Endocrinol Metab. 1998 Apr. 83(4):1049-55. [Medline]. [Full Text].

  20. Eisenbarth GS, Gottlieb PA. The immunoendocrinopathy syndromes. Larsen PR, Kronenberg HM, Melmed S, et al, eds. Williams Textbook of Endocrinology. 10th ed. Philadelphia, Pa: Saunders; 2003. 1763-76.

  21. Halonen M, Eskelin P, Myhre AG, et al. AIRE mutations and human leukocyte antigen genotypes as determinants of the autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy phenotype. J Clin Endocrinol Metab. 2002 Jun. 87(6):2568-74. [Medline]. [Full Text].

  22. Hannigan NR, Jabs K, Perez-Atayde AR, et al. Autoimmune interstitial nephritis and hepatitis in polyglandular autoimmune syndrome. Pediatr Nephrol. 1996 Aug. 10(4):511-4. [Medline].

  23. Hogenauer C, Meyer RL, Netto GJ, et al. Malabsorption due to cholecystokinin deficiency in a patient with autoimmune polyglandular syndrome type I. N Engl J Med. 2001 Jan 25. 344(4):270-4. [Medline].

  24. Muir A, Schatz DA, Maclaren NK. Polyglandular failure syndromes. DeGroot LJ, et al, eds. Endocrinology. 3rd ed. Philadelphia, Pa: Saunders; 1995. 3013-22.

  25. Myhre AG, Halonen M, Eskelin P, et al. Autoimmune polyendocrine syndrome type 1 (APS I) in Norway. Clin Endocrinol (Oxf). 2001 Feb. 54(2):211-7. [Medline].

  26. Nieman LK. Causes of primary adrenal insufficiency (Addison's disease). www.uptodate.com. Available at http://www.utdol.com/utd/content/topic.do?topicKey=adrenal/7188&view. Accessed: May, 10, 2006.

  27. Obermayer-Straub P, Manns MP. Autoimmune polyglandular syndromes. Baillieres Clin Gastroenterol. 1998 Jun. 12(2):293-315. [Medline].

  28. Rybojad M, Abimelec P, Feuilhade M, et al. [Familial chronic mucocutaneous candidiasis associated with autoimmune polyendocrinopathy. Treatment with fluconazole: 3 cases]. Ann Dermatol Venereol. 1999 Jan. 126(1):54-6. [Medline].

  29. Soderbergh A, Myhre AG, Ekwall O, et al. Prevalence and clinical associations of 10 defined autoantibodies in autoimmune polyendocrine syndrome type I. J Clin Endocrinol Metab. 2004 Feb. 89(2):557-62. [Medline]. [Full Text].

  30. Beers MH, Berkow R, eds. The Merck Manual of Diagnosis and Therapy. 17th ed. Whitehouse Station, NJ: Merck; 1999. 119-20.

  31. Toonkel R, Levine M, Gardner L. Erythropoietin-deficient anemia associated with autoimmune polyglandular syndrome type I. Am J Hematol. 2004 Feb. 75(2):84-8. [Medline].

Previous
Next
 
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2016 by WebMD LLC. This website also contains material copyrighted by 3rd parties.