View source for WBR0734

 {{WBRQuestion
|QuestionAuthor= {{YD}} (Reviewed by  {{YD}})
|ExamType=USMLE Step 1
|MainCategory=Immunology
|SubCategory=Endocrine
|MainCategory=Immunology
|SubCategory=Endocrine
|MainCategory=Immunology
|SubCategory=Endocrine
|MainCategory=Immunology
|MainCategory=Immunology
|MainCategory=Immunology
|SubCategory=Endocrine
|MainCategory=Immunology
|SubCategory=Endocrine
|MainCategory=Immunology
|SubCategory=Endocrine
|MainCategory=Immunology
|SubCategory=Endocrine
|MainCategory=Immunology
|MainCategory=Immunology
|SubCategory=Endocrine
|Prompt=An 22-year-old female medical student presents to the physician's office for fatigue. She explains that she has recently been unable to continue daily chores and feels unmotivated all the time. She also states that she has recently gained weight despite normal appetite, and has been losing her hair. Physical examination is remarkable for a palpable midline neck mass. Initial work-up reveals elevated TSH levels. Following further investigation, the physician explains to the patient that her condition is best described as an abnormal presence of lymphocytic infiltrates with germinal center formation in the thyroid gland. Which of the following diseases is also associated with the same HLA subtype as that responsible for the patient's condition?
|Explanation=The patient has Hashimoto's thyroiditis, an autoimmune thyroid disease that causes hypothyroidism due to the presence of anti-thyroid peroxidase and antithyroglobulin antibodies. It is characterized on histopathological analysis by lymphocytic infiltrates with germinal center formation, along with the presence of Hurthle cells. Hurthle cells are frequently described as large well-defined epithelial cells with eosinophilic granular cytoplasm. The patient has typical features of hypothyroidism, including fatigue, weight gain, and hair loss. Her laboratory work-up is remarkable for elevated TSH, which is consistent with the disease. TSH is produced by the anterior pituitary gland to stimulate the production of thyroid hormones T3 and T4. In primary hypothyroidism (disease intrinsic to the thyroid gland), T3 and T4 levels are low, and TSH levels are elevated due to loss of feedback inhibition. In contrast, T3, T4, and TSH levels are all low in secondary hypothyroidism (disease of the pituitary gland), whereby deficient TSH is unable to stimulate thyroid hormone production. Hashimoto's thyroiditis is the most common cause of primary hypothyroidism. It frequently presents among young women with a personal or family history of autoimmune diseases. Various clinical entities are now included under Hashimoto's thyroiditis: classic form, fibrous variant, IgG4-related variant, juvenile form, Hashitoxicosis, sporadic painless thyroiditis, and post-partum painless thyroiditis.

Hashimoto's thyroiditis is associated with HLA-DR5 subtype. Similarly, pernicious anemia, an autoimmune disease that causes vitamin B12 deficiency due to the presence of auto-antibodies against gastric parietal cells, is also associated with HLA-DR5 subtype.

Common HLA subtypes and their associated diseases are shown in the table below.<br>
[[Image:HLA subtypes and associated diseases.jpg|600px]]
|AnswerA=Autoimmune disease characterized by auto-antibodies against gastric parietal cells
|AnswerAExp=Pernicious anemia is an autoimmune disease characterized by the presence of auto-antibodies against gastric parietal cells. It causes vitamin B12 deficiency. It is also associated with HLA-DR5 subtype.
|AnswerB=Autoimmune disease characterized by inflammation and demyelination of the brain and the spinal cord
|AnswerBExp=Multiple sclerosis is an autoimmune disease characterized by inflammation and demyelination of the brain and the spinal cord. It is associated with HLA-DR2 subtype, along with hay fever, systemic lupus erythematosus, and Goodpasture's syndrome.
|AnswerC=Autoimmune disease characterized by inflammatory destruction of synovial joints
|AnswerCExp=Rheumatoid arthritis is associated with HLA-DR4 subtype, along with diabetes mellitus type 1.
|AnswerD=Autoimmune disease characterized by IgG antibodies that stimulate TSH receptors on the thyroid gland
|AnswerDExp=Graves' disease is characterized by IgG antibodies that stimulate TSH receptors on the thyroid gland. It is associated with HLA DR3 subtype, along with diabetes mellitus type 1.
|AnswerE=Autoimmune disease characterized by intolerance to gliadin in wheat
|AnswerEExp=Celiac disease is an autoimmune disease characterized by intolerance to gliadin in wheat. It is is associated with HLA DQ2/DQ8 subtypes.
|EducationalObjectives=Hashimoto's thyroiditis and pernicious anemia are both associated with HLA-DR5 subtype.
|References=Caturegli P, De Remigis A, Rose NR. Hashimoto thyroiditis: clinical and diagnostic criteria. Autoimmune Rev. 2014;13(4-5):391-7.<br>
Gough SCL, Simmonds MJ. The HLA region and autoimmune disease: associations and mechanisms of action. Curr Genomics. 2007;8(7):453-65.<br>
First Aid 2014 page 199
|RightAnswer=A
|WBRKeyword=Pernicious, Anemia, Pernicious anemia, Vitamin, B12, Hashimoto, Hashimoto's, Hashimoto thyroiditis, Hashimoto's thyroiditis, Hypothyroidism, Hair loss, Weight gain, Autoimmune, HLA DR5, HLA-DR5, HLA, HLA subtype, DR5
|Approved=Yes
}}