WBR0493

Author	[[PageAuthor::Rim Halaby, M.D. [1] (Reviewed by Alison Leibowitz) (Reviewed by Serge Korjian)]]
Exam Type	ExamType::USMLE Step 1
Main Category	MainCategory::Immunology
Sub Category	SubCategory::Endocrine
Prompt	[[Prompt::A 33-year-old woman presents to the physician's office for complaints of chronic fatigue. She explains that she was highly active until a few months ago when she began to get excessively tired and sleepy. The patient reports that she is also sad that she has been gaining weight. Review of systems reveals chronic constipation and cold intolerance. Which of the following mechanisms is most likely involved in the patient’s condition?]]
Answer A	AnswerA::Hypersensitivity type I
Answer A Explanation	[[AnswerAExp::Type I hypersensitivity disorders include anaphylaxis, atopy, and allergy. Hashimoto's disease is not a type I hypersensitivity disorder.]]
Answer B	AnswerB::Hypersensitivity type II
Answer B Explanation	AnswerBExp::Hashimoto's disease is a type IV hypersensitivity disorder. Grave's disease is considered a form of type II hypersensitivity, because the pathophysiology of Grave's disease involves an antibody against a specific antigen.
Answer C	AnswerC::Hypersensitivity type III
Answer C Explanation	AnswerCExp::Hypersensitivity type III disorders include conditions where an antigen-antibody complex forms and activates the complement system. Hashimoto's disease is not a type III hypersensitivity disorder.
Answer D	AnswerD::Hypersensitivity type IV
Answer D Explanation	[[AnswerDExp::Hypersensitivity type IV disorders include conditions characterized by delayed T-cell mediated immune reactions such as contact dermatitis, tuberculosis testing, delayed transplant rejection, and Hashimoto's disease.]]
Answer E	AnswerE::Not a hypersensitivity disorder
Answer E Explanation	AnswerEExp::Hashimoto's disease is a type IV hypersensitivity disorder.
Right Answer	RightAnswer::D
Explanation	[[Explanation::The patient's symptoms of fatigue, weight gain, chronic constipation, and cold intolerance are suggestive of hypothyroidism most commonly caused by Hashimoto's disease particularly in young aged women. The highest incidence of Hashimoto's thyroiditis occurs in middle aged women. Other classical symptoms include depression, hair loss, periorbital edema, abnormal menstrual cycles, and galactorrhea. Hashimoto's disease is associated with the presence of anti-thyroid peroxidase (anti-TPO; 95% at diagnosis) or anti-thyroglobulin antibodies. While these antibodies may contribute to disease pathogenesis and they recognize a specific antigen, Hashimoto's disease is not considered a Type II hypersensitivity disorder because the main immunologic dysfunction is a cell-mediated immune response. Because it is a cell-mediated immune response, Hasimoto's disease is considered a form of type IV hypersensitivity. Risk factors include a family history and positivity for either HLADR3 or DR5 serotypes. Patients are at increased risk for thyroid nodules, and non-Hodgkin's lymphoma. Treatment is usually with levothyroxine replacement therapy. Educational Objective: Hashimoto's disease, a major cause of hypothyroidism in middle aged women, is caused by T-cell mediated destruction of the thyroid. It is considered a type IV hypersensitivity. References: Pearce EN, Farwell AP, Braverman LE. Thyroiditis. N Engl J Med. 2003;348(26):2646-2655. First Aid 2014 page 320]]
Approved	Approved::Yes
Keyword	WBRKeyword::Hypersensitivity, WBRKeyword::Hypothyroidism, WBRKeyword::Hashimoto, WBRKeyword::Immune system, WBRKeyword::Anti-TPO, WBRKeyword::Antithyroglobulin, WBRKeyword::Type III Hypersensitivity, WBRKeyword::Hypersensitivities, WBRKeyword::Antibodies, WBRKeyword::Hashimoto's thyroiditis
Linked Question	Linked::
Order in Linked Questions	LinkedOrder::