Autoimmune polyendocrine syndrome type II, also known as Schmidt syndrome, is a rare autoimmune disorder in which there is a steep drop in production of several essential hormones by the glands that secrete these hormones. When first described, this disorder was thought to involve only adrenal insufficiency (Addison’s disease) and thyroid insufficiency (Hashimoto’s thyroiditis). However, over time, as more patients were studied, the scope of the disorder was expanded to include disorders of other underperforming endocrine glands. These include the gonads, which secrete sex hormones; the pancreas which secretes insulin and is intimately tied up with diabetes mellitus; and sometimes the parathyroid glands. Failure of the endocrine glands to function is usually accompanied by signs of malnutrition because the ability of the intestinal tract to absorb nutrients is reduced dramatically. Since the combination of affected glands differs from patient to patient, the signs of this disorder are diverse.
Most cases of this disorder are sporadic although some clinical researchers believe that there is a familial or hereditary trait associated with AIPS-II. If so, it may involve a complex interaction among many genes.
Many conditions and symptoms are associated with this disorder. The symptoms may vary greatly among affected individuals.
Addison’s disease is a rare disorder characterized by chronic and insufficient functioning of the outer layer of the adrenal gland (adrenal cortex). Patients with Addison’s disease have a deficiency in the production of glucocorticoid hormones which are manufactured by the adrenal gland. These hormones (especially cortisol and aldosterone) are involved in carbohydrates, fat and protein metabolism, carbohydrate and blood sugar storage, and they fight inflammation and suppress the immune response. The deficiency in glucocorticoid causes an increased release of sodium and decreased release of potassium in the urine, sweat, saliva, stomach and intestines. These changes can cause low blood pressure and increased water excretion that can lead to severe dehydration. (For more information on this disorder choose “Addison’s Disease” as your search term in the Rare Disease Database).
Hypothyroidism (underactive thyroid) is a disorder that can be genetic or acquired and may occur alone or as a symptom of another illness. Major symptoms may include the development of an enlarged thyroid gland in the neck, a dull facial expression, puffiness and swelling around the eyes, drooping eyelids, thinning hair which is coarse and dry, and poor memory. Hypothyroidism can be caused by disorders of the hypothalamus or pituitary centers in the brain, disorders that affect control of the thyroid hormone, blockage in the metabolic process of transporting thyroid or iodine in the thyroid gland itself, or the result of a hereditary disorder called Hashimoto’s thyroiditis. Hashimoto’s thyroiditis is an autoimmune disorder in which the body’s natural defenses against invading organisms (i.e., antibodies, lymphocytes etc.) suddenly begin to attack healthy tissue. (For more information on these disorders choose “Hypothyroidism” and “Hashimoto” as your search terms in the Rare Disease Database).
Some (but not all) of the following additional findings may be present in patients with autoimmune polyendocrine type II :
Diabetes mellitus: This type of diabetes generally starts during childhood or adolescence. The starches and sugars (carbohydrates) in the foods we eat are normally processed by digestive juices into glucose. The glucose circulates in the blood as a major energy source for body functions. A hormone produced by the pancreas (insulin) regulates the body’s use of glucose. In diabetes mellitus, the pancreas does not manufacture the correct amount of insulin needed to metabolize sugar. As a result, the patient needs daily injections of insulin to regulate blood sugar levels. Symptoms of this disorder may be frequent urination, extreme thirst, constant hunger, weight loss, itching of the skin, changes in vision, slow healing of cuts and bruises, and in children there is a failure to grow and develop normally. (For more information on this disorder choose “Insulin-Dependent Diabetes” as your search term in the Rare Disease Database).
Hypoparathyroidism: This disorder causes lower than normal levels of calcium in the blood due to insufficient levels of parathyroid hormones. This condition can be inherited, associated with other disorders, or the result of a neck injury. Symptoms of hypoparathyroidism may be weakness, muscle cramps, abnormal sensations of the hands such as burning and numbness, excessive nervousness, loss of memory, headaches, cramping of wrists and feet, and spasms in facial muscles. (For more information on this disorder choose “Hypoparathyroidism” as your search term in the Rare Disease Database).
Gonadal failure: This refers to the failure of the organ that produces sex cells (gonads-or testes in the male, and ovaries in the female) to function properly causing an absence of secondary sex characteristics.
Pernicious anemia: This is a blood disorder resulting from an impaired absorption of vitamin B-12. This vitamin is used in the production of red blood cells. Healthy individuals absorb sufficient amounts of vitamin B-12 in their normal diet with the help of a substance secreted by the stomach called intrinsic factor. Patients with pernicious anemia generally lack intrinsic factor and can not absorb sufficient amounts of vitamin B-12. Symptoms of vitamin B-12 deficiency usually appear years after absorption of the vitamin ceases because B-12 is stored in large quantities in the liver. Symptoms of this disorder may be shortness of breath, fatigue, weakness, rapid heartbeat, angina, anorexia, abdominal pain, indigestion, and possibly intermittent constipation and diarrhea. (For more information on this disorder choose “Pernicious Anemia” as your search term in the Rare Disease Database).
Vitiligo: This is a skin condition in which there is an absence of pigment producing cells (melanocytes) causing decreased pigmentation of the skin. These “white spots” on the skin appear most often on the face, neck, hands, abdomen, and thighs although they may appear on all parts of the skin. Vitiligo is sometimes familial, but the exact mode of heredity is not yet understood. (For more information on this disorder choose “Vitiligo” as your search term in the Rare Disease Database).
Celiac sprue: This chronic hereditary intestinal malabsorption disorder is caused by intolerance to gluten. The most common symptoms of this disorder are weight loss, chronic diarrhea, abdominal cramping and bloating, intestinal gas and abdominal distention and muscle wasting. Celiac sprue is a hereditary congenital disorder. Gluten is a protein that is present in wheat, oats, barley, rye and probably millet. Patients with celiac sprue cannot properly absorb a part of gluten called gliadin. This causes intestinal abnormalities as well as physiological deficiencies. Although the disorder begins in infancy, it is sometimes not diagnosed until the patient reaches adulthood. (For more information on this disorder choose “Celiac Sprue” as your search term in the Rare Disease Database).
Myasthenia gravis: Sometimes this disorder can be associated with autoimmune polyendocrine syndrome type II. Myasthenia gravis is a chronic neuromuscular disease characterized by weakness and abnormally rapid fatigue of the voluntary muscles, with improvement following rest. Any group of muscles may be affected, but those around the eyes and the muscles used for swallowing are the most commonly involved. (For more information on this disorder choose “Myasthenia Gravis” as your search term in the Rare Disease Database).
Grave’s disease: This is a disorder that affects the thyroid gland. It is thought to occur as a result of an imbalance in the immune system. This disorder causes increased thyroid secretion (hyperthyroidism), enlargement of the thyroid gland and protrusion of the eyeballs. The exact cause of this disorder is not known. It is thought to be inherited as an autosomal recessive trait. (For more information on this disorder choose “Graves Disease as your search term in the Rare Disease Database).
The exact cause of AIPS-II is not known, but it is thought to result from one or more abnormal immune responses. Autoimmune reactions occur when, for reasons not quite clear, the body mistakenly reacts to a normal antibody as if it were a foreign one.
Report suggest that the prevalence of AIPS-II is about 14 to 20 cases per million of population and that it affects females 3 to 4 times as often as it does males. AIPS-II usually strikes in the third or fourth decade of life.
Each disorder in a case of autoimmune polyendocrine type II is treated separately. For many of the specific disorders, treatment is focused on hormone replacement therapy.
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Beers MH, Berkow R, eds. The Merck Manual, 17th ed. Whitehouse Station, NJ: Merck Research Laboratories; 1999:119-20.
Berkow R., ed. The Merck Manual-Home Edition.2nd ed. Whitehouse Station, NJ: Merck Research Laboratories; 2003:943.
Fauci AS, Braunwald E, Isselbacher KJ, et al., eds. Harrison’s Principles of Internal Medicine. 14th ed.McGraw-Hill Companies. New York, NY; 1998:2135-36.
Wilson JD, Foster DW, eds. Textbook of Endocrinology. 8th ed. W.B. Saunders Company. Philadelphia, PA; 1992:1555-61.
Sperling MA, ed. Pediatric Endocrinology. 1st ed. W.B. Saunders Company. Philadelphia, PA; 1996:509-22.
Betterle C, Lazzarotto F, Presotto F. Autoimmune polyglandular syndrome Type 2: the tip of an iceberg? Clin Exp Immunol. 2004;137:225-33.
Eisenbarth GS, Gottlieb PA. Autoimmune polyendocrine syndromes. N Engl J Med. 2004;350:2068-79.
Urbanek-Ruiz I, Ruiz PJ, Steinman L, et al. Immunomodulatory vaccination in autoimmune disease. Endocrinol Metab Clin North Am. 2002;31:441-56.
Falorni A, Laureti S, Santeusanio F. Autoantibodies in autoimmune polyendocrine syndrome type II. Endocrinol Metab Clin North Am. 2002;31:369-89.
Robles DT, Fain PR, Gottlieb PA, et al. The genetics of autoimmune polyendocrine syndrome type II. Endocrinol Metab Clin North Am. 2002;31:353-68.
Schatz DA, Winter WE. Autoimmune polyglandular syndrome. II: Clinical syndrome and treatment. Endocrinol Metab Clin North Am. 2002;31:339-52.
FROM THE INTERNET
McKusick VA, ed. Online Mendelian Inheritance In Man (OMIM). The Johns Hopkins University. Schmidt Syndrome. Entry Number; 269200: Last Edit Date; 5/19/2004.
McKusick VA, ed. Online Mendelian Inheritance In Man (OMIM). The Johns Hopkins University. Major Histocompatability Complex, ClassI, B; HLA-B. Entry Number; 142830: Last Edit Date; 5/5/2004.
Akinsoto OPA, Jabbour SA. Polyglandular Autoimmune Syndrome, Type II. emedicine. Last Updated: December 9, 2004. 17pp.
Dacic S. Final Diagnosis/Case 239. Final Diagnosis — Polyglandular Autoimmune Syndrome Type II. nd. 2pp.
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