AUTOSOMAL DOMINANT DISEASE. SCREENING F FAMILY MEMBERS SHOULD BE DONE TO IDENTIFY EARLY DISEASE.
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
o Approximately 90% of hypothyroidism cases are due to Hashimoto disease.
o Treatment of hypothyroidism remains independent of its cause. The aim is to achieve euthyroidism.
o Comorbidity (cardiac disease and advanced age) necessitates initial smaller doses, usually 12.5-25 mcg/d.
o States, such as pregnancy, or younger healthy people require maintenance doses, approximately 75-125 mcg/d (1.6 mcg/kg/d).
o 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.
o 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
o It requires lifelong treatment with exogenous insulin.
o A roughly estimated dose for otherwise healthy individuals is approximately 0.6-1.2 U/kg/d (35-50 U/d in adults).
o 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.
o Various dosage regimens and types of insulin exist. The ultimate goal of treatment is to achieve persistent normoglycemia with a minimum of hypoglycemic complications.
o The most important aspect of management is educating the patient with diabetes. Without this, the goals can never be achieved.
" Pernicious anemia
o Replacement with cyanocobalamin is the goal of therapy.
o 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.
o Symptomatic hypokalemia may occur within 48 hours of initiating therapy, and supplemental potassium may be needed.
o 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
o 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.
o 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.
o 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.
o 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
o Adrenal insufficiency requires replacement therapy with both hydrocortisone and fludrocortisone.
o 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.
o In case of concurrent illness, increase the doses of hydrocortisone.
o 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.
o Adrenal gland transplants have been successful in experimental rodents and humans.
o In addition to these, vitamin and mineral replacement occasionally is needed to compliment hormonal replacement.
" Celiac disease
o Place patients on a gluten-free diet.
o Depending on the degree of malabsorption, they also may require iron, folate, calcium, or vitamin supplementation.
o In patients whose conditions are severe or refractory, a trial of prednisone (10-20 mg) may be effective.
o If symptoms persist despite this therapy, consider dietary indiscretion or the possibility of small bowel lymphoma, and perform the appropriate radiological examination.
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.
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" 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.
DRUG TREATMENT : WITH THE EXCEPTION OF ANTITHYROID DRUGS FOR GRAVES DISEASE, MOST MEDICATIONS LISTED HERE ARE ESSENTIALLY FOR REPLACEMENT THERAPY.
1. CORTICOSTEROIDS :
- HYDROCORTISONE
2. THYROID HORMONES :
- LEVOTHYROXINE
3. ANTITHYROID AGENTS :
- PROPYLTHIOURACIL
- METHIMAZOLE
4. ANTIDIABETIC AGENTS :
- INSULINS
5. MINERALOCORTICOIDS :
- FLUDROCORTISONE
6. VITAMINS
- VIT B12 - IN PERNICIOUS ANEMIA