Type II Polyglandular Autoimmune Syndrome Treatment & Management

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. ^[8] Succinct organ-specific therapies exist to treat the associated diseases, but general therapeutic considerations that are specifically related to polyglandular autoimmune syndrome type II (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. ^[14] 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 his/her thyroid function.

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

For Hashimoto thyroiditis (Hashimoto disease), note the following:

• 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 smaller initial doses, usually 12.5-25 mcg/d. This view has been questioned by some.

• States such as pregnancy and younger healthy people require maintenance doses, approximately 75-125 mcg/d (1.6 mcg/kg/d). Thyroid hormone requirement increases during pregnancy by about 30% from prepregnancy replacement dose.

• 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.

For type 1 diabetes mellitus (see Diabetes Mellitus, Type 1), note the following:

• 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.

For pernicious anemia, note the following:

• Replacement with cyanocobalamin is the goal of therapy.

• A typical schedule is 1 mg IM once a day for 7 days, and 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.

For Graves disease, note the following:

• 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 can occasionally cause complications, including recurrent laryngeal nerve damage and hypoparathyroidism. In addition, the intrinsic risks of general anesthesia and surgery exist. Surgery is much safer in experienced hands.

• 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.

For Addison disease, note the following:

• Adrenal insufficiency requires replacement therapy with hydrocortisone and fludrocortisone. ^[15]

• 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 polyglandular autoimmune syndrome type 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 complement hormonal replacement.

For celiac disease, note the following:

• Place patients on a gluten-free diet.

• Depending on the degree of malabsorption, patients 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 radiologic examination.

The following consultations may be helpful:

• Endocrinologist

• Hematologist - Pernicious anemia

• Gastroenterologist - Celiac disease

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, CBCs, 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 should 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 individuals. Bracelets should indicate whether the patient also has diabetes, because the coexistence of adrenal failure increases the risk of hypoglycemia.

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

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 polyglandular autoimmune syndrome type II (PGA-II) are assumed to be identical to those of the component diseases when these disorders occur in isolation.

Dietary guidelines for polyglandular autoimmune syndrome type II depend on its presentation. Such guidelines include the following:

• 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.

Patients with polyglandular autoimmune syndrome type II can participate in all of their regular activities. However, inform patients that their disease could unpredictably alter their life, 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.