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{{WBRQuestion | {{WBRQuestion | ||
|QuestionAuthor={{ | |QuestionAuthor={{SSK}} (Reviewed by Serge Korjian) | ||
|ExamType=USMLE Step 1 | |ExamType=USMLE Step 1 | ||
|MainCategory=Pharmacology, Physiology | |MainCategory=Pharmacology, Physiology | ||
| Line 21: | Line 21: | ||
|MainCategory=Pharmacology, Physiology | |MainCategory=Pharmacology, Physiology | ||
|SubCategory=Endocrine | |SubCategory=Endocrine | ||
|Prompt=A 53 year old man presents to the endocrinology clinic after his primary care physician documented new onset diabetes mellitus | |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? | ||
|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. | |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. | ||
|AnswerA=11-deoxycortisol | |AnswerA=11-deoxycortisol | ||
|AnswerAExp=11-deoxycortisol the substrate of 11β-hydroxylase inhibited by metyrapone accumulates after initiation of therapy. | |AnswerAExp=11-deoxycortisol the substrate of 11β-hydroxylase inhibited by metyrapone accumulates after initiation of therapy. | ||
| Line 34: | Line 34: | ||
|AnswerEExp=Pregnenolone is unaffected by inhibition of 11β-hydroxylase. | |AnswerEExp=Pregnenolone is unaffected by inhibition of 11β-hydroxylase. | ||
|EducationalObjectives=Metyrapone inhibits the last step in cortisol synthesis by blocking the enzyme 11β-hydroxylase. | |EducationalObjectives=Metyrapone inhibits the last step in cortisol synthesis by blocking the enzyme 11β-hydroxylase. | ||
|References= | |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.<br> | ||
First Aid 2014 page 317 | |||
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. | |||
|RightAnswer=A | |RightAnswer=A | ||
|WBRKeyword=Metyrapone, | |WBRKeyword=Metyrapone, Cushing's disease, Cortisol, Diabetes, Adrenal insufficiency | ||
|Approved= | |Approved=Yes | ||
}} | }} | ||
Revision as of 17:42, 9 March 2015
| 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. |
| 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:: |