Type I Polyglandular Autoimmune Syndrome Treatment & Management
- Author: Saleh A Aldasouqi, MD, FACE, ECNU; Chief Editor: Romesh Khardori, MD, PhD, FACP more...
The treatment for polyglandular autoimmune (PGA) syndrome, type I, is targeted at whatever organ is affected. It is always best to identify and treat the respective autoimmunity before any significant morbidity can develop.
For the most part, replacement therapy and patient education about the chronic diseases are integral to treatment success. The educational aspect is extremely important, because it helps the patient with the early detection of any new autoimmune states and aids in the adequate treatment of this chronic syndrome.
- This condition is treated with oral fluconazole and ketoconazole.
- Absorption of ketoconazole may be compromised if coexistent atrophic gastritis exists. Ketoconazole may also inhibit adrenal and gonadal synthesis, which could worsen the coexistent Addison disease and cause hepatitis.
- Fluconazole is preferred, because it does not inhibit steroidogenesis and is less frequently associated with the development of hepatitis. It is, however, an expensive medication.
- This disorder usually is gradual and permanent, and oral calcium and vitamin D usually are adequate therapy. Doses of vitamin D range from 50,000-100,000 U/d. Calcitriol (1,25-dihydroxy D) is a better choice physiologically, but it is more expensive. Other vitamin D synthetic analogues also are suitable for replacement, but cost again must be considered.
- In cases in which there is coexisting malabsorption, tetany may occur and IV calcium gluconate and magnesium may be necessary.
Adrenal insufficiency (Addison disease)
- The treatment of adrenal failure depends mainly on 2 factors.
- Treatment is influenced by the question of whether or not the patient is in crisis with hypotension and consequently requires IV fluids and IV steroids. Otherwise, treatment is influenced by the question of whether or not chronic and otherwise stable oral steroids, eg, prednisone, can be used with or without fludrocortisone.
- Another factor influencing treatment is whether or not a confident diagnosis of adrenal failure can be made based on the information at hand when the patient is seen. This may determine what kind of IV steroid is used. If the diagnosis is not clear, then the physician may opt to use dexamethasone IV, because it does not interfere with subsequent cortisol measurements required for the diagnosis of Addison disease. However, if sufficient clinical evidence exists in favor of Addison disease, then using hydrocortisone is better because of its additional mineralocorticoid benefit, as an aldosterone defect also is seen. Most of the time, a mineralocorticoid (eg, fludrocortisone) also is added to the regimen.
- The glucocorticoid dose is changed according to the patient's symptoms. Monitor electrolytes and the activity levels of plasma renin to assess the efficacy of treatment with fludrocortisone.
- In cases of intercurrent illness, increase the doses of hydrocortisone.
- In the presence of coexisting diabetes, which is occasionally seen with PGA-I, the daily dose usually should not exceed 30 mg/d, unless the need for a larger dosage is confirmed. This necessitates higher doses of insulin; on many occasions, this results in difficulty controlling glucose levels.
- Other deficiencies seen in association with diabetes and pernicious anemia, eg, hypothyroidism, can be corrected by replacement therapy.
- Adrenal gland transplants have been successful in experimental rodents and in humans.
- Vitamin and mineral replacement occasionally is needed to complement hormonal replacement.
No specific surgical interventions exist that are unique to the management of polyglandular autoimmune (PGA) syndrome, type I. However, complications from a component of the syndrome may require therapeutic procedures or surgical interventions, as for example, in the case of a patient requiring intubation and other critical care therapeutic interventions after going into adrenal crisis culminating in septic/hypovolemic shock.
See the list below:
- Endocrinology - Complex interactions exist that may affect the replacement of adrenal, thyroid, and parathyroid hormones; these are best handled by an endocrinologist.
- Infectious diseases - To help with recurrent candidiasis
- Gastroenterology - If bowel or hepatic involvement is noted
- Rheumatology - If necessary because of the autoimmune nature of the disease, especially when considering immunosuppressive therapy
- Other consultations may be needed according to the clinical situation.
A high-salt diet is beneficial to patients with adrenal insufficiency.
If coexisting diabetes is present, institute a diabetic diet.
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].
Eisenbarth GS, Gottlieb PA. Autoimmune polyendocrine syndromes. N Engl J Med. 2004 May 13. 350(20):2068-79. [Medline].
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].
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].
Heino M, Scott HS, Chen Q, et al. Mutation analyses of North American APS-1 patients. Hum Mutat. 1999. 13(1):69-74. [Medline].
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].
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].
LeBoeuf N, Garg A, Worobec S. The autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome. Pediatr Dermatol. 2007 Sep-Oct. 24(5):529-33. [Medline].
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].
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].
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].
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].
Katzung BG, ed. Basic and Clinical Pharmacology. 7th ed. Stamford, Conn: Appleton & Lange; 1998. 635-52, 706-22.
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.
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].
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].
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].
Muir A, Schatz DA, Maclaren NK. Polyglandular failure syndromes. DeGroot LJ, et al, eds. Endocrinology. 3rd ed. Philadelphia, Pa: Saunders; 1995. 3013-22.
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].
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.
Obermayer-Straub P, Manns MP. Autoimmune polyglandular syndromes. Baillieres Clin Gastroenterol. 1998 Jun. 12(2):293-315. [Medline].
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].
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].
Beers MH, Berkow R, eds. The Merck Manual of Diagnosis and Therapy. 17th ed. Whitehouse Station, NJ: Merck; 1999. 119-20.
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].