eMedicine Specialties > Endocrinology > Multiple Endocrine Disease and Miscellaneous Endocrine Disease

Polyglandular Autoimmune Syndrome, Type I: Treatment & Medication

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

Treatment

Medical Care

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.

• Mucocutaneous candidiasis
  • 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.
• Hypoparathyroidism
  • 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.
  • The hypocalcemia seen in PGA-I also has been reported to result from pancreatic insufficiency, giardiasis (which occurs with increased frequency in PGA-I), and lymphangiectasia. Each of these requires specific therapy.
• 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.

Surgical Care

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.

Consultations

• 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.

Diet

• A high-salt diet is beneficial to patients with adrenal insufficiency.
• If coexisting diabetes is present, institute a diabetic diet.

Activity

As tolerated

Medication

The drugs listed here are used primarily for the replacement of deficient hormones and electrolytes (except for ketoconazole). The medications detailed in this list are the major, well-established drugs available for each category. However, newer agents, especially in the antifungal category, have been introduced; these may be administered by qualified physicians, especially to critically ill patients in the ICU.

Corticosteroids

These are used for adrenocortical insufficiency replacement. Corticosteroids have anti-inflammatory properties and cause profound and varied metabolic effects. They modify the body's immune response to diverse stimuli.

Hydrocortisone (Cortef, Hydrocortone, Hydrocort, Hydro-Tex)

DOC because of mineralocorticoid activity and glucocorticoid effects. Useful for treatment of many diseases, especially autoimmune and inflammatory diseases. Used in PGA-I for primary adrenal failure.

Fludrocortisone (Florinef)

Partial replacement therapy for primary and secondary adrenocortical insufficiency. Most commonly prescribed synthetic mineralocorticoid. Possesses glucocorticoid qualities. Encourages sodium reabsorption at distal renal tubules, GI mucosa, and the sweat and salivary glands.

Antifungals

These drugs treat mucocutaneous candidiasis. Their mechanism of action may involve an alteration of ribonucleic acid (RNA) and deoxyribonucleic acid (DNA) metabolism or an intracellular accumulation of peroxide that is toxic to the fungal cell.

Ketoconazole (Nizoral)

First azole used in clinical practice. Imidazole broad-spectrum antifungal agent that inhibits synthesis of ergosterol, causing cellular components to leak, resulting in fungal cell death. Also acts on several P450 enzymes including the first step in cortisol synthesis, cholesterol side-chain cleavage, and conversion of 11-deoxycortisol to cortisol. May inhibit ACTH secretion when used at therapeutic doses. Possess narrow therapeutic index.

Fluconazole (Diflucan)

Fungistatic activity. Synthetic oral antifungal (broad-spectrum bis-triazole) that selectively inhibits fungal cytochrome P-450 and sterol C-14 alpha-demethylation, which prevents conversion of lanosterol to ergosterol, thereby disrupting cellular membranes.

Vitamins and mineral salts

These are used as nutritional supplements.

Calcitriol (Calcijex, Rocaltrol)

Active metabolite of vitamin D synthesized from precursor in the kidney under influence of PTH. Increases calcium levels by promoting absorption of calcium in intestines and retention in kidneys. Low in absence of PTH or hypoparathyroidism.

Ergocalciferol (Calciferol, Drisdol)

Stimulates absorption of calcium and phosphate from small intestine and promotes release of calcium from bone into blood. Precursor of active form of vitamin D (calcitriol). Because it is a precursor, a significant delay between dose administration and effect exists. Liver must be intact for intermediate to be formed (calcidiol, 25-hydroxy vitamin D). Many drugs may affect this step. Has lipid storage, so overdoses may cause prolonged hypercalcemia.
Measure of efficacy is serum calcium concentration.

Calcium carbonate (Oystercal, Caltrate)

Calcium moderates nerve and muscle performance by regulating action potential excitation threshold. For hypoparathyroidism, use a supplementation of at least 2 g of elemental calcium/d.

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