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Polyglandular autoimmune (PGA) syndromes(otherwise known as polyglandular failure

syndromes) are constellations of multiple

endocrine gland insufficiencies.Other descriptive terminologies, such as

autoimmune polyendocrine syndrome (APS)

PGA-I, also known as autoimmunepolyendocrinopathy-candidiasis-ectodermaldystrophy (APECED) or as Whitaker syndrome

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presence of chronic inflammatory infiltratescomposed mainly of lymphocytes in the

affected organs and on the presence ofautoantibodies reacting to target tissue

specific antigens.

PGA-I is unique among autoimmuneendocrine disorders, because it has no HLAantigen association.

A monogenic mutation ofAIRE (autoimmuneregulator), which codes for a putative

transcription factor featuring 2 zinc motifs,is believed to be the likely pathogenic

paradigm for PGA-I.

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extremely rareMortality/Morbidity: equivalent to the

individual components of the syndrome

Race: certain ethnic populationsSex: female-to-male ratio ranges from 0.8:1

to 1.5:1

Age: usually occurs in children aged 3-5 yearsor in early adolescence, but it always occursby the early part of the third decade of life

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(1) chronic mucocutaneous candidiasis(2) hypoparathyroidism(3) autoimmune adrenal insufficiency

(Addison disease )Additional manifestations type 1A diabetes (documented autoimmune

etiology)

Hypogonadism pernicious anemia malabsorption, alopecia vitiligo

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earliest and is the most common of the 3main diseases

most often presenting in people younger than5 years

Most of the lesions are limited to the skin(usually < 5% of surface area), nails, and oraland anal mucosa

possible state of T-cell deficiency ; noincreased frequency of other opportunistic

infectionsnormal B-cell response to candidal antigens,

they are spared from developingdisseminated candidiasis

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usually developing after candidiasis and beforeAddison disease, usually in people younger than10 years(More than 75% of patients )

must be differentiated from: neonatalhypocalcemia (DiGeorge syndrome or congenitalabsence or malformation of the parathyroid) ,notinvolve the adrenal glands

Clinical features (1) tetanic clinical symptoms, such as carpopedal

spasm and paresthesias of the lips, fingers, and feet;

(2) seizures (3) laryngospasm (4) leg cramps (5) diffuse mild encephalopathy (6) cataracts (7) papilledema Electrocardiography may show a prolonged QT

interval.

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typically occurs in people aged 10-30 years(mean, 12-13 y)

Mineralocorticoid and glucocorticoiddeficiencies

CYP21 appears to be the major autoantigen inisolated Addison disease and Addison disease

associated with PGA-II. Autoantibodies to CYP17

and a side-chain cleavage enzyme (CYP11A1)have been associated with Addison disease inPGA-I.

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Early symptoms include weakness, fatigue,and orthostatic hypotension

Pigmentation usually is increased and may serveas a differentiating point from secondaryhypoadrenalism (primary pituitary failure)

Anorexia, nausea, vomiting, diarrhea, and coldintolerance often occur

Late symptoms include weight loss, dehydration,hypotension, and a small-sized heart

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Hypergonadotropic hypogonadism Type 1 diabetes mellitus Autoimmune thyroid disease (not including Graves disease) Pernicious anemia Chronic atrophic gastritis Chronic active hepatitis Enamel hypoplasia, which occasionally precedes the onset

of hypoparathyroidism

Asplenia Keratoconjunctivitis Cholelithiasis Malabsorption Alopecia Vitiligo Interstitial nephritis

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DiGeorge SyndromeHemochromatosisPolyglandular Autoimmune Syndrome, Type IIPolyglandular Autoimmune Syndrome, Type IIISeptic ShockThymoma

WDHA Syndrome

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clinical history and examination that suggestevidence of more than 1 endocrinedeficiency should prompt the use of the

following tests:

Serum endocrine autoantibody screen autoantibodies to 21-hydroxylase, 17-hydroxylase thyroid peroxidase (TPO) and thyroid-stimulating

immunoglobulins (TSI)

glutamic acid decarboxylase and islet cellantibodies

parietal cell enzyme (H+/K+ -ATPase) antibodiesthe absence of these antibodies does not

exclude PGA-I

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End-organ function tests are necessary toconfirm 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 isnecessary. If menses are irregular or absent,obtain estradiol, FSH, LH, and prolactin levels

TSH and, if necessary, free thyroxine (T4) andfree triiodothyronine (T3)

Adrenocorticotropic hormone (ACTH) andcosyntropin (Cortrosyn) stimulation test

Plasma renin activity

Electrolytes Fungal skin scrapings Complete blood count (CBC) with mean cell

volume (MCV) and vitamin B-12 levels

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computed tomography (CT) scan of theadrenal glands to exclude hemorrhage and

fungal infections

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The patient's diet should be high in calcium,fresh fruits, and vegetables and low in simple

carbohydrates

In addition to any other stress managementtechniques, encourage moderate exercise.This is mainly relevant for patients with

adrenal insufficiency

Patients may need a dual-energyradiographic absorptiometry (DEXA) scan to

assess any degree of osteoporosis due to

long-term steroid use

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Inform patients about the symptoms of an acuteexacerbation, such as dizziness, lightheadedness,abdominal pain, and nausea and vomiting

In addition, make patients aware of the signs andsymptoms of hypoparathyroidism, includingmuscle cramps or spasms

If evidence of hypothyroidism exists, perform anadrenal evaluation before any thyroidreplacement. If replacement of thyroidhormones is urgent or emergent, draw blood forlater adrenal evaluation, and administer steroidsbefore starting thyroid replacement dosing

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Hypoparathyroidism Cataract Laryngospasm Basal ganglial calcification Ventricular arrhythmias Renal stones may arise from vitamin D use due to possible

excessive urine Ca++ excretion. Urine calcium excretion may bemonitored in these patients

Addison disease Arrhythmias secondary to electrolyte imbalance Loss of libido Psychotic illnesses Hypoglycemic spells

Gastrointestinal complaints Complications from treatment, such as osteoporosis or

gastrointestinal ulceration with concurrent use of nonsteroidalanti-inflammatory drugs (NSAIDs)

Other complications include the following Neuropathies and anemia (pernicious anemia) Malabsorption (celiac disease)

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