|
|
Amin Sabet, M.D.
02-04-2011
- Schmidt's syndrome refers to the combination of autoimmune adrenal insufficiency (Addison's disease) with autoimmune hypothyroidism and/or type 1 diabetes mellitus (T1DM), and is part of a larger syndrome known as autoimmune polyendocrine syndrome type II or polyglandular autoimmune syndrome type II (PAS II).
- The term Schmidt's syndrome is sometimes used interchangeably with PAS II.
- PAS II is a polygenic disorder which may include autoimmune thyroid disease (hypothyroidism or hyperthyroidism), T1DM, Addison's disease, primary hypogonadism, and less commonly hypoparathyroidism or hypopituitarism.
- Associated non-endocrine autoimmune conditions may be present including include vitiligo, celiac disease, alopecia, pernicious anemia, myasthenia gravis, idiopathic thrombocytopenic purpura, Sjogren's syndrome, and rheumatoid arthritis.
- Schmidt's Syndrome: 1:20,000 prevalence in general population with 3:1 ratio of females to males affected (Forster)
- Peak incidence: 3rd - 4th decade of life
- Familial clustering with multiple family members often affected
- Autosomal dominant inheritance with variable penetrance likely associated with certain HLA antigens (Eisenbarth).
- Among patients with T1DM, < 1% of patients have Addison's disease, whereas 2-5% have autoimmune thyroid disease (mainly hypothyroidism) and up to 5% have celiac disease (Forster).
- Type 1 diabetes patients who developed autoimmune thyroid disease had an interval of 13.3 +/- 11.8 years between first and second endocrinopathies (Dittmar).
- In a survey of patients with PAS II, 61% had type 1 diabetes, 49% had autoimmune thyroid disease, and 18.5% had Addison's disease (Forster).
- Diagnosis of component disorders of PAS II is the same as that of the individual disorders.
-
Diagnosis of T1DM and celiac disease are reviewed elsewhere.
- Diagnosis of Addison's disease (primary adrenal insufficiency due to autoimmune adrenalitis) is based on the following: 1) early morning (i.e. 7-9 am) serum cortisol < 3 mcg/dL or a serum cortisol less than 18 mcg/dL 30 or 60 minutes after a 1 mcg or 250 mcg IV bolus of cosyntropin (ACTH), respectively; 2) elevated basal serum ACTH level; 3) presence of other autoimmune disorders. Antibodies to 21-hydroxylase may aid in making the diagnosis if detectable, though abdominal CT to evaluate for other causes of adrenal insufficiency (infection, hemorrhage, metastases) is recommended.
- Diagnosis of primary hypothyroidism is based on an elevated serum TSH and low (or normal in subclinical disease) serum T4 level, whereas hyperthyroidism is diagnosed based on a low TSH with elevated (or normal in subclinical disease) serum T4 and/or T3. The presence of antithyroid antibodies (e.g. anti-thyroglobulin antibodies, anti-microsomal antibodies, thyroid stimulating immunoglobulins) can be useful for diagnosis (see thyroid function tests module).
- In a patient with T1DM, Addison's disease may present as intermittent, severe hypoglycemia and intermittent, severe fatigue. Decreased insulin requirements, hypotension, hyperpigmentation, and vitiligo may be present.
- Hypothyroidism may also present with fatigue, decreased insulin requirements, and hypoglycemia, whereas hyperthyroidism is associated with increased insulin requirements and hyperglycemia.
- Signs and symptoms of related autoimmune conditions (e.g. alopecia, celiac disease) may be present.
- Treatment of the component disorders of PAS II is the same as that of the individual disorders.
- Treatment of primary hypothyroidism: physiologic thyroid hormone replacement with levothyroxine. Typical initial dose is 1.6 mcg/kg per day (lower dose in elderly and those with cardiac disease) and adjusted every 4-6 weeks according to the serum T4 and TSH.
- Chronic treatment of Addison's disease: physiologic glucocorticoid and mineralocorticoid replacement. Initial glucocorticoid regimen can be hydrocortisone 15-25 mg per day given in 2-3 divided doses and adjusted to relieve symptoms of glucocorticoid deficiency and avoid manifestations of glucocorticoid excess. Usual initial mineralocorticoid regimen is fludorcortisone 0.1 mg/day, adjusted as needed to avoid postural hypotension and maintain normal serum potassium.
- Treatment of Addison's disease in acute illness or surgery requires increased dosing of glucocorticoid therapy according to the degree of physiologic stress.
-
Antibody screening may help identify patients at risk for developing autoimmune gland failure. For example, GAD65 antibodies in a patient with Addison's may indicate increased risk for development of T1DM, while 21-hydroxylase antibodies in a patient with T1DM likely indicates increased risk for Addison's. However, an evidence based approach to antibody screening is lacking.
- Recommend screening of people with T1DM for hypothyroidism (by measuring serum TSH) and celiac disease (by measuring tissue transglutaminase antibodies) especially whenever symptoms are present and/or every 1-2 years.
- In the absence of symptoms, routine screening for Addison's disease or other associated PAS II autoimmune conditions is not recommended.
- Caution: In a patient with coexisting hypothyroidism and Addison's disease, thyroid hormone therapy without replacement of glucocorticoids can precipitate acute adrenal insufficiency.
|
|
