AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

Polyglandular autoimmune (PGA) syndrome type II is the most common of the immunoendocrinopathy syndromes. It is characterized by the obligatory occurrence of autoimmune Addison's disease in combination with thyroid autoimmune diseases and/or type 1 diabetes mellitus. Primary hypogonadism, myasthenia gravis, and celiac disease also are commonly observed in this syndrome. The definition of the syndrome depends on the fact that if one of the component disorders is present, an associated disorder occurs more commonly than in the general population. The most frequent clinical combination association is Addison disease and Hashimoto thyroiditis, while the least frequent clinical combination is Addison disease, Graves disease, and type 1 diabetes mellitus. The complete triglandular syndrome is sometimes referred to as Carpenter syndrome.

PGA type II (PGA-II) occurs primarily in adulthood, usually around the third and fourth decades of life. Middle-age women have shown an increased prevalence of PGA-II. It is associated with HLA-DR3 and/or HLA-DR4 haplotypes, and the pattern of inheritance is autosomal dominant with variable expressivity.

Two other related autoimmune endocrinopathies exist, namely type I and type III. The former is rare and presents in childhood. It usually is comprised of mucocutaneous candidiasis, hypoparathyroidism, and primary adrenal insufficiency (presenting in that order). Type III, though ill defined, is the co-occurrence of autoimmune thyroid disease with 2 other autoimmune disorders, including insulin-dependent diabetes mellitus (type 1); pernicious anemia; or a nonendocrine, organ-specific, autoimmune disorder in the absence of Addison disease.

Pathophysiology

The pathogenesis of PGA-II is poorly understood. The following steps have been postulated:

• Some degree of genetic susceptibility must exist in the individual.

• The individual is then exposed to the autoimmune trigger, which could be an environmental or intrinsic factor. The trigger mimics the molecular structure of a self-antigen. An alternative explanation is that a breakdown in normal immunological tolerogenesis occurs.

• Then, a subclinical phase of active production of organ-specific autoantibodies occurs.

• This phase is followed by autoimmune activity in the respective organ, in which there is progressive glandular destruction. The individual is still asymptomatic.

• Then, overt clinical disease occurs when extensive organ damage has occurred, caused by the aforementioned autoimmune activity. Evidence of this autoimmune phenomenon that may be responsible for this syndrome is based on whether the affected organs demonstrate a chronic inflammatory infiltrate composed of lymphocytes (mainly).

Some of the component diseases are associated with immune-response genes encoded by the class II HLA complex. The syndrome is replete with autoantibodies reacting to target tissue-specific antigens.

Frequency

United States

Approximately 14-20 people per million population are affected. Recent observations have revealed, however, that the disease is much more prevalent if subclinical forms are included.

Mortality/Morbidity

To date, the mortality and morbidity rates of PGA-II have not been clinically estimated. The mortality and morbidity of PGA-II are believed to equal the mortality and morbidity of the individual component disorders.

Sex

The female-to-male ratio of PGA-II is 3-4:1.

Age

PGA-II occurs in the third or fourth decade of life.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

PGA-II consists of Addison disease plus either an autoimmune thyroid disease or type 1 diabetes mellitus associated with hypogonadism, pernicious anemia, celiac disease, and recent primary biliary cirrhosis. The clinical features consist of a constellation of the individual endocrinopathies.

• Type 1 diabetes mellitus
• • Symptoms - Polyuria, polydipsia, polyphagia, unexplained weight loss, intermittent blurred vision, and lethargy (may present initially with diabetic ketoacidosis and coma)
  
  
  
  • Signs - Depend on the severity and are poor skin turgor, orthostasis, and hypotension
  
  
  
  • Some of these clinical features closely mimic those of primary adrenal insufficiency. 
     
• Hashimoto thyroiditis (chronic lymphocytic thyroiditis)
• • Symptoms - Usually nonspecific and include cold intolerance, fatigue, somnolence, poor memory, constipation, menorrhagia, myalgias, and hoarseness
  
  
  
  • Signs - Slow tendon reflexes, bradycardia, facial and periorbital edema, dry skin and nonpitting edema, carpal tunnel syndromes, deafness, and pericardial or pleural effusions 
     
• Grave disease
• • Symptoms - Heat intolerance, weight loss, weakness, palpitations, oligomenorrhea, and anxiety
  
  
  
  • Signs - Brisk tendon reflexes, fine tremor, proximal weakness, stare and eyelid lag, exophthalmos, atrial fibrillation, and sinus tachycardia 
     
• Addison disease (primary adrenal insufficiency)
• • Symptoms - Anorexia, nausea, vomiting, weight loss, weakness, and fatigue
  
  
  
  • Signs - Chronic hyperpigmentation of creases and scars and orthostatic hypotension 
     
• Celiac disease - Weight loss, steatorrhea, bloating, cramping, and malnutrition



• Pernicious anemia - Pallor, jaundice, ataxia, glossitis, impaired cognition, impaired vibratory and position sense, and impaired cognition



• Other disorders associated with this syndrome include the following:
• • Hypogonadism (usually autoimmune oophoritis) and hypopituitarism
  
  
  
  • Idiopathic thrombocytopenic purpura
  
  
  
  • Myasthenia gravis
  
  
  
  • Parkinson disease
  
  
  
  • Vitiligo
  
  
  
  • Alopecia
  
  
  
  • Seronegative arthritis

Physical

See History.

Causes

The etiology is very poorly understood.

• Some association has been seen between diabetes or hypothyroidism and congenital rubella infection.



• Immune stimulation by certain dietary proteins is a possible etiological factor.



• Additional possibilities include genetic susceptibility and idiopathic immunopathological dysfunction. 



• Animal models have demonstrated that cytomegalovirus infected mice may give rise to type 2 PGA with lymphocytic infiltration of the adrenals, pancreatic islets, thyroid, liver, myocardium, and salivary glands. At this time, however, no infectious agents or noticeable immunodeficiency states have been demonstrated in human type 2 PGA.

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

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
Endocrine deficiency
Thyrogastric autoimmunity

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• 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.



• 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 as follows:



• Serum autoantibodies screen: This helps verify the autoimmune etiology of the disease and identify those who may develop multi-endocrine deficiency later. 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) 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 Grave's disease.
  
  
  
  • Glutamic acid decarboxylase and islet cell antibodies are used to screen for type 1 diabetes mellitus.
  
  
  
  • Antitissue transglutaminase antibodies are used because 2-3% of patients with type 1 diabetes mellitus have celiac disease. Other antibodies for celiac disease include IgA endomysial antibodies and antigliadin antibodies.
  
  
  
  • Parietal cell and anti-intrinsic factor antibodies 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 is recommended as follows:
• • Test 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) level and Cortrosyn-stimulation test
  
  
  
  • Plasma renin activity and serum electrolytes
  
  
  
  • Calcium, phosphorus, magnesium, and albumin
  
  
  
  • Fasting blood glucose
  
  
  
  • Complete blood count with mean cell volume (MCV) and vitamin B-12 levels
  
  
  
  • Some authorities recommend that some of these tests be performed annually because not all diseases manifest at the time of the initial diagnosis.

Imaging Studies

• Perform a CT scan of the adrenal glands to exclude hemorrhage and fungal infections as the cause of primary adrenal insufficiency.
• Perform a MRI 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.

Procedures

Perform a small bowel biopsy, if antitissue transglutaminase antibodies are present, 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.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical Care

Currently, the treatment of the polyendocrine autoimmune syndromes is dictated by the individual disorders. With the exception of celiac disease and Graves disease, the mainstay of treatment is primarily hormonal replacement therapy. Succinct organ-specific therapies exist to treat the associated diseases, but general therapeutic considerations specifically for PGA-II must be addressed as well.

Most of the component disorders of this syndrome have long prodromal phases that express organ-specific autoantibodies before overt disease develops. Considering this, several experimental attempts have been made to intervene during this prodromal phase in an effort to forestall overt disease. Studies evaluating the use of cyclosporin A for immunosuppression in new onset type 1 diabetes mellitus have shown preservation of some residual insulin secretion. Unfortunately, the extent of beta-cell damage at diagnosis precluded long-term remission of diabetes, not to mention the multiple adverse effects of the long-term use of the drug.

Another approach currently under investigation is isohormonal therapy, a form of immunomodulatory therapy that uses the hormonal product of the affected organ to influence autoimmune activity. Such therapies are believed to cause a bystander suppression of the prevailing autoimmune activity and/or induction of immunologic tolerance to the relevant hormone, while simultaneous negative feedback of the target organ occurs.

T4 therapy can precipitate life-threatening adrenal insufficiency. However, before thyroid replacement therapy can be instituted in patients who are hypothyroid, assess adrenal function. This situation arises due to the action of thyroxine in enhancing hepatic corticosteroid metabolism. If immediate thyroid replacement is indicated, coverage with glucocorticoids can be provided and the status assessed later. A patient with both deficiencies who has glucocorticoid replacement initially may see an improvement in their thyroid function.

A decreasing insulin requirement in patients with type 1 diabetes mellitus can be one the earliest indications of adrenal insufficiency or renal dysfunction. This can occur before the development of hyperpigmentation or electrolytes abnormalities.

The organ-specific therapies used to treat the associated diseases are as follows:

• Hashimoto thyroiditis
  
  
  • Approximately 90% of hypothyroidism cases are due to Hashimoto disease.
  
  
  
  • Treatment of hypothyroidism remains independent of its cause. The aim is to achieve euthyroidism.
  
  
  
  • Comorbidity (cardiac disease and advanced age) necessitates initial smaller doses, usually 12.5-25 mcg/d.
  
  
  
  • States, such as pregnancy, or younger healthy people require maintenance doses, approximately 75-125 mcg/d (1.6 mcg/kg/d).
  
  
  
  • Much higher doses are required in patients who are on drugs that increase the metabolism of T4 and in those who have undergone thyroidectomy secondary to thyroid cancer in an attempt to reduce potential tumorigenesis.
  
  
  
  • Thyroid-stimulating hormone (TSH) is used to assess the level of euthyroidism. After 6 weeks of therapy, measure plasma TSH. Adjust the dose in increments of 12-25 mcg at intervals of 6-8 weeks until TSH is normal. Thereafter, annual measurements can be taken to ensure compliance and prevent overtreatment.
     
• Type 1 diabetes mellitus (see Diabetes Mellitus, Type 1)
  
  
  • It requires lifelong treatment with exogenous insulin.
  
  
  
  • A roughly estimated dose for otherwise healthy individuals is approximately 0.6-1.2 U/kg/d (35-50 U/d in adults).
  
  
  
  • Basal needs (insulin needed to maintain glycemic control between meals and during sleep) are estimated at around 40-50% of the dosage figure. The dietary requirement is devoted to controlling glucose after meals and accounts for the remaining percentage.
  
  
  
  • Various dosage regimens and types of insulin exist. The ultimate goal of treatment is to achieve persistent normoglycemia with a minimum of hypoglycemic complications.
  
  
  
  • The most important aspect of management is educating the patient with diabetes. Without this, the goals can never be achieved.
     
• Pernicious anemia
  
  
  • Replacement with cyanocobalamin is the goal of therapy.
  
  
  
  • A typical schedule is 1 mg IM once a day for 7 days, then weekly for 1-2 months or until the hemoglobin is normalized. Long-term therapy is 1 mg/mo.
  
  
  
  • Symptomatic hypokalemia may occur within 48 hours of initiating therapy, and supplemental potassium may be needed.
  
  
  
  • With therapy, the reticulocytosis should rise and peak in 1 week, followed by a rising hemoglobin level in the next 6-8 weeks.
     
• Graves disease
  
  
  • Antithyroid medications usually are the first line of treatment in older patients (>60 y) or in those with underlying heart disease. When euthyroidism is achieved, radioactive iodine is then administered.
  
  
  
  • Ablation by radioactive iodine administration is the therapy of choice by most patients (young and healthy). It is simple, highly effective, and causes no life-threatening complications.
  
  
  
  • Thyroidectomy is less common and has uncommon but possible complications, which include recurrent laryngeal nerve damage or hypoparathyroidism. In addition, the intrinsic risks of general anesthesia and surgery exist.
  
  
  
  • The restoration of euthyroidism using antithyroid drugs takes several months. Patients are evaluated at 6-week intervals by assessing the clinical findings and serum free T4 and free T3. There is no agreement on the optimal duration of therapy, but 1-2 years is the common range.
     
• Addison disease
  
  
  • Adrenal insufficiency requires replacement therapy with both hydrocortisone and fludrocortisone.
  
  
  
  • Adjust the hydrocortisone dose depending on patient's symptoms. Monitor the activity levels of plasma renin to assess the efficacy of treatment with fludrocortisone and serum electrolytes.
  
  
  
  • In case of concurrent illness, increase the doses of hydrocortisone.
  
  
  
  • In the presence of coexisting diabetes occasionally seen in PGA-I, the daily dose usually should not exceed 30 mg/d because this necessitates higher doses of insulin, and on many occasions, there is difficulty in controlling glucose levels.
  
  
  
  • Adrenal gland transplants have been successful in experimental rodents and humans.
  
  
  
  • In addition to these, vitamin and mineral replacement occasionally is needed to compliment hormonal replacement.
     
• Celiac disease
  
  
  • Place patients on a gluten-free diet.
  
  
  
  • Depending on the degree of malabsorption, they also may require iron, folate, calcium, or vitamin supplementation.
  
  
  
  • In patients whose conditions are severe or refractory, a trial of prednisone (10-20 mg) may be effective.
  
  
  
  • If symptoms persist despite this therapy, consider dietary indiscretion or the possibility of small bowel lymphoma, and perform the appropriate radiological examination.

Consultations

• Endocrinologist
• Hematologist - Pernicious anemia
• Gastroenterologist - Celiac disease

Diet

• Dietary guidelines depend on the presentation.



• If the patient is diabetic and underweight, institute a 2000-calorie (minimum) diabetic diet.



• If the patient is overweight, institute an 1800-calorie diabetic diet, preferably with low salt, low cholesterol, and low saturated fat.



• If Addison disease is present, institute a high-sodium low-potassium diet until electrolytes are controlled with mineralocorticoid therapy.



• If the patient has Celiac disease, consult a dietician for a gluten-free diet.

Activity

• Patients can participate in all of their regular activities. However, inform patients that their disease could unpredictably alter their lives, depending on the severity of the presentation.
• In type 1 diabetes mellitus, muscular exertion reduces the requirement for insulin, and either a snack must be provided or less insulin taken before the exercise. Where possible, consistency of diet and exercise will make control more consistent.

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

With the exception of antithyroid drugs for Graves disease, most medications listed here are essentially for replacement therapy.

Drug Category: Glucocorticoids

Replacement therapy in adrenal failure. Significant trauma can increase the need for glucocorticoids acutely.

Drug Category: Thyroid hormones

Thyroid replacement in hypothyroidism.

Drug Category: Antithyroid agents

Act by inhibiting TPO-catalyzed reactions to block iodine organification and by inhibiting peripheral deiodination of T4/T3 (the last effect is seen only by PTU).

Drug Name	Methimazole (Tapazole)
Description	Inhibits thyroid hormone by blocking oxidation of iodine in thyroid gland. However, not known to inhibit peripheral conversion of thyroid hormone. Taper gradually to the minimum dose required to keep the patient clinically euthyroid and to avoid fetal hypothyroidism. Cases of fetal aplasia cutis are reported.
Adult Dose	Initial: 15-60 mg PO divided tid (can also be administered as 20-30 mg qd), depending on severity Maintenance: 5-15 mg PO qd
Pediatric Dose	Initial: 0.4 mg/kg/d PO divided tid Maintenance: 0.2 mg/kg/d PO divided tid, not to exceed 30 mg/d
Contraindications	Documented hypersensitivity; breastfeeding
Interactions	Inhibits vitamin K activity and may potentiate activity of oral anticoagulants; toxicity increased with coadministration of lithium and potassium iodide
Pregnancy	D - Unsafe in pregnancy
Precautions	Monitor PT during therapy; may cause hypoprothrombinemia and bleeding; once symptoms of hyperthyroidism have resolved, the presence of elevated serum TSH suggests a lower maintenance dose of methimazole should be used; during pregnancy, goal of therapy is to keep TSH in lower range of normal and free T4/FTI at upper range of normal

Drug Category: Antidiabetic agents

Type 1 diabetes mellitus replacement.

Drug Category: Mineralocorticoids

Partial replacement therapy for primary and secondary adrenocortical insufficiency.

Drug Category: Vitamins

Vitamin B-12 replacement in pernicious anemia. Megaloblastic anemia must be further evaluated to differentiate folate and vitamin B-12 deficiency due to the latter requiring life-long treatment. Cyanocobalamin deficiency mainly due to malabsorption must be replaced via NG route. Hydroxocobalamin is the more potent vitamin B-12 variant because it forms a tight bond with plasma proteins and stays in circulation longer. Hydroxocobalamin may be a good complexing agent for cyanide poisoning. Possible effective antidote.

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Further Inpatient Care

• Continuously screen patients who have had fewer than all 3 diseases every 1-2 years until they are aged 50 years. This detects new disorders before overt clinical features develop.
• • Screening should include an assessment of autoantibodies, electrolytes, thyroid function tests, liver function tests, vitamin B-12 levels, Cortrosyn-stimulation test, fasting blood glucose, plasma renin activity, complete blood counts, gonadotropins, and testosterone/estradiol.

  • In females who have regular menses, gonadotropins and estradiol are not necessary.

• Evaluate patients for asplenia, and administer pneumococcal and flu vaccinations.
• Family members should be strongly considered for genetic counseling and undergo necessary screening for autoimmune diseases.
• All patients with adrenal insufficiency should wear emergency identification bracelets because adrenal crises are a significant cause of preventable mortality in these patients. Bracelets should indicate if the patient also has diabetes because the coexistence of adrenal failure increases the risk of hypoglycemia.
• Patients committed to the lifelong use of minerals, vitamins, blood work, and hormonal replacement therapy require psychosocial support.
• The mortality and morbidity rates associated with PGA-II are assumed to be identical to those of the component diseases when they occur in isolation.

In/Out Patient Meds

• Administer specific hormone replacement as necessary (eg, T4, corticosteroids, sex steroids, insulin), depending on which endocrine end-organ failures have occurred.

Complications

• Complications are related to the underlying endocrine organ failure, ie, complications of diabetes in autoimmune insulitis/diabetes.

Prognosis

• See Further Inpatient Care.

Patient Education

• Provide extensive education for the patient about diabetes if autoimmune destruction of pancreas occurs. The same is true for the thyroid and other aspects.
• The genetic predisposition of PGA-II requires educating other family members regarding testing.
• For excellent patient education resources, visit eMedicine's Endocrine System Center; Diabetes Center; Esophagus, Stomach, and Intestine Center; and Blood and Lymphatic System Center. Also, see eMedicine's patient education articles Thyroid Problems, Diabetes, Celiac Sprue, and Anemia.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• Failure to provide detailed information to the patient about the unpredictable outcome and variety of disorders, ranging from diabetes to intestinal lymphoma, that are associated with this syndrome
• Failure to closely monitor the patient in the face of the constellation of chronic diseases associated with this syndrome
• Failure to recommend that patients who are diabetic or have Addison disease wear medical alert bracelets to protect them in an emergency
• Failure to offer genetic and family counseling in the face of the unpredictable nature of the inheritance of this disease

Special Concerns

• When evidence of a second autoimmunity is present, consider if the patient has PGA-I or PGA-II because of the different prognoses of the syndromes.

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

• Baker JR Jr. Autoimmune endocrine disease. JAMA. Dec 10 1997;278(22):1931-7. [Medline].
• Betterle C, Lazzarotto F, Presotto F. Autoimmune polyglandular syndrome Type 2: the tip of an iceberg?. Clin Exp Immunol. Aug 2004;137(2):225-33. [Medline].
• Borgaonkar MR, Morgan DG. Primary biliary cirrhosis and type II autoimmune polyglandular syndrome. Can J Gastroenterol. Nov 1999;13(9):767-70. [Medline].
• Cooper GS, Stroehla BC. The epidemiology of autoimmune diseases. Autoimmun Rev. May 2003;2(3):119-25. [Medline].
• Eisenbarth G, Verge C. Immunoendocrinopathy syndromes. In: Williams Textbook of Endocrinology. 9th ed. 1998;1651-59.
• Eisenbarth GS, Gottlieb PA. Autoimmune polyendocrine syndromes. N Engl J Med. May 13 2004;350(20):2068-79. [Medline].
• Forster G, Krummenauer F, Kuhn I, Beyer J, Kahaly G. [Polyglandular autoimmune syndrome type II: epidemiology and forms of manifestation]. Dtsch Med Wochenschr. Dec 10 1999;124(49):1476-81. [Medline].
• Lachman P, Rosen F. Autoimmune endocrine disease. In: Clinical Aspects of Immunology. 5th ed. 1993;2001-2.
• Muir A, Katz D, McClaren N. Polyglandular failure syndromes. In: DeGroot's Endrocrinology. 3rd ed. 1995;3013-22.
• Obermayer-Straub P, Manns MP. Autoimmune polyglandular syndromes. Baillieres Clin Gastroenterol. Jun 1998;12(2):293-315. [Medline].
• Rakel. In: Conn's Current Therapy. 1999;630-54.

Article Last Updated: Jun 2, 2006