WBR0886

Author	[[PageAuthor::Rim Halaby, M.D. [1]]]
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 that is responding very poorly 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 fact 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 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. Reference: 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. Educational Objective: References: ]]
Approved	Approved::No
Keyword	WBRKeyword::Metyrapone, WBRKeyword::cushing's disease, WBRKeyword::cortisol
Linked Question	Linked::
Order in Linked Questions	LinkedOrder::