WBR0886

Author	[[PageAuthor::Serge Korjian M.D. (Reviewed by Serge Korjian)]]
Exam Type	ExamType::USMLE Step 1
Main Category	MainCategory::Pharmacology, MainCategory::Physiology
Sub Category	SubCategory::Endocrine
Prompt	[[Prompt::A 53-year-old man presents to the endocrinology clinic after his primary care physician documented new-onset diabetes mellitus poorly responding to oral antidiabetics with an HbA1C of 9.3%. The patient reports adhering to a strict diet but despite this feels like he has gained much weight in the past 3 months. He also reports significant lower extremity weakness and fatigue recently. His physical exam is notable for a blood pressure of 174/89 mmHg, significant abdominal obesity, proximal muscle weakness, and fat collection at the base of neck. After a series of tests, the physician diagnoses Cushing's disease and decides to start the patient on metyrapone therapy. What would you expect to increase after the initiation of therapy?]]
Answer A	AnswerA::11-deoxycortisol
Answer A Explanation	AnswerAExp::11-deoxycortisol the substrate of 11β-hydroxylase inhibited by metyrapone accumulates after initiation of therapy.
Answer B	AnswerB::Corticosterone
Answer B Explanation	AnswerBExp::Corticosterone is one of the products of 11β-hydroxylase and would decrease rather than increase with metyrapone therapy.
Answer C	AnswerC::Aldosterone
Answer C Explanation	AnswerCExp::Aldosterone is one of the products of 11β-hydroxylase and would decrease rather than increase with metyrapone therapy.
Answer D	AnswerD::17-hydroxypregnenolone
Answer D Explanation	AnswerDExp::17-hydroxypregnenolone is unaffected by inhibition of 11β-hydroxylase.
Answer E	AnswerE::Pregnenolone
Answer E Explanation	AnswerEExp::Pregnenolone is unaffected by inhibition of 11β-hydroxylase.
Right Answer	RightAnswer::A
Explanation	[[Explanation::Metyrapone is an agent used mainly for diagnosing adrenal insufficiency via blocking steroid synthesis and monitoring the hypothalamic-pituitary-adrenal axis for increase in steroidogenesis. Failure of detecting an increase in ACTH or 11-deoxycortisol levels support the diagnosis of adrenal insufficiency. Metyrapone acts by inhibiting the last step in cortisol synthesis by blocking the enzyme 11β-hydroxylase. It is also used in the treatment of Cushing's disease (not very common practice) to decrease the corticoid load. Typically, if 11β-hydroxylase is inhibited, it's substrate would accumulate. After initiation of therapy, serum levels of 11-deoxycortisol would be expected to increase. Urine levels of 17-hydroxysteroids, the breakdown products of 11β-hydroxylase are also expected to increase. Educational Objective: Metyrapone inhibits the last step in cortisol synthesis by blocking the enzyme 11β-hydroxylase. References: Avgerinos PC, Yanovski JA, Oldfield EH, Nieman LK, Cutler GB. The metyrapone and dexamethasone suppression tests for the differential diagnosis of the adrenocorticotropin-dependent Cushing syndrome: a comparison. Ann Intern Med. 1994;121(5):318-27. First Aid 2014 page 317]]
Approved	Approved::Yes
Keyword	WBRKeyword::Metyrapone, WBRKeyword::Cushing's disease, WBRKeyword::Cortisol, WBRKeyword::Diabetes, WBRKeyword::Adrenal insufficiency
Linked Question	Linked::
Order in Linked Questions	LinkedOrder::