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Master Professor Rounds

Master Professor Rounds. Master Professor: Madup Naim , MD Division of Endocrinology Presenter: S. Marty Pantz , MD Date. Case Presentation. ID/CC: HPI:. Case Presentation (cont’d). PMH: HTN x 25 yrs Depression DM x 18 yrs Dyslipidemia Hypothyroidism x 18 yrs Arthritis

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Master Professor Rounds

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  1. Master Professor Rounds Master Professor: MadupNaim, MD Division of Endocrinology Presenter: S. Marty Pantz, MD Date

  2. Case Presentation ID/CC: HPI:

  3. Case Presentation (cont’d) PMH: HTN x 25 yrs Depression DM x 18 yrs Dyslipidemia Hypothyroidism x 18 yrs Arthritis Hospitalizations x 2 • January 2006—nausea/vomiting, given IVF and discharged later that day • January 2006—atypical chest pain, scheduled for outpatient ischemic work-up h/o L CVA in January, with residual R-sided facial paresthesias Menstrual/OB Hx: postmenopausal x 9 yrs, not on HRT h/o regular menses, G1P1 Allergies: NKDA

  4. Case Presentation (cont’d) Meds: Lexapro 10 mcg daily Spironolactone 25 mg daily Norvasc 10 mg daily Metoprolol 50 mg BID Synthroid 75 mcg daily Benazepril 40 mg daily Metformin 500 mg BID Zocor 40 mg qHS ASA 81 mg daily Family Hx: mother deceased from heart disease (+) DM Social Hx: (+) tobacco use — 5 cigarettes/day x 10 yrs denies EtOH, IVDA from Mexico

  5. Physical Exam Vital Signs: T 98.2 BP 139/74 HR 78 RR 20 0/10 pain General: WDWN, dark in appearance, (+) truncal obesity, NAD, AAO x 3, slow to respond to questions, at times inattentive HEENT: NC/AT, (+) moon facies, (+) hirsutism, PERRL, EOMI, mmm, no thyromegaly, no LAD, (+) dorsal fat pad Chest: CTAB, no c/w/r CV: RRR, nl S1S2, no S3/S4, no m/c/r/g Ab: (+) BS, S/NT/ND, no HSM GU: no clitoromegaly Skin/Extremities: (+) abdominal striae, (+) ecchymotic areas over abdomen and antecubital fossa, (+) thinning of skin, decreased subcutaneous fat, (+) bilateral muscle wasting, 1+ edema BLE Neuro: AAO x 3, proximal muscle weakness, 2+ DTR

  6. Differential Diagnosis

  7. Differential Diagnosis • Cushing’s Syndrome • ACTH-dependent vs. ACTH-independent • Pseudo-Cushing’s Syndrome • PCOS • Uncontrolled Hypothyroidism • Rheumatoid Arthritis • Polymyalgia Rheumatica • Myopathy

  8. How would you approach this patient?

  9. Studies Labs: • BMP • CBC w/diff • TSH/free T4 • Additional Tests • Screening Tests I • Screening Tests II Imaging studies: • CXR • MRI brain Next

  10. Basic Metabolic Panel 135 101 17 236 4.0 22 0.6 Return to Menu

  11. CBC w/differential 12.7 322 7.7 37.5 N80 L14 M6 Return to Menu

  12. TSH/Free T4 TSH 1.81 uIU/ml Free T4 1.34 ng/dl Return to Menu

  13. Additional Tests • random cortisol 37.8 mcg/dl (10:40) 26.5 mcg/dl (21:20)(normal AM: 5-25 mcg/dl, normal PM: 3-13 mcg/dl) • ACTH 69 pg/ml (21:20)(normal 5-27 pg/ml) • Estradiol 25 pg/ml • DHEA-S 227 μg/dl • FSH 1.0 U/L • Testosterone 47 pg/dl • LH < 1.0 U/L • Prolactin 15.8 ng/ml Return to Menu

  14. Initial Screening Tests 24 hour urinary free cortisol457 μg (4-50 μg) Low dose Dexamethasone Suppression Test Return to Menu

  15. High Dose DexamethasoneSuppression Test Return to Menu

  16. CXR atherosclerotic vascular disease Return to Menu

  17. MRI Brain MRI

  18. MRI Brain MRI no identifiable masses chronic non-specific white matter changes Return to Menu

  19. Working Diagnosis Cushing’s Syndrome ACTH-dependent most likely pituitary in origin

  20. A Quick Synopsis on Cushing’s Syndrome • rare condition that results from chronic exposure to glucocorticoids, characterized by abnormally high levels of cortisol • more common in females than male, although ectopic causes occur more frequently in males • two broad categories • ACTH-dependent (includes Cushing’s disease, ectopic ACTH syndrome, and ectopic CRH syndrome) • ACTH-independent(adrenal adenoma, adrenal carcinoma, micronodular hyperplasia, macronodular hyperplasia)

  21. ACTH-Dependent Cushing’s Syndrome • characterized by high cortisol associated with normal/high ACTH levels with dexamethasone suppression • Cushing’s disease(70% of cases) • pituitary source of excess ACTH production • females > males • Ectopic ACTH syndrome(15%) • usually from small cell cancer or other ACTH-producing tumors • males > females • Ectopic CRH syndrome • very rare

  22. ACTH-IndependentCushing’s Syndrome • high cortisol, with low ACTH levels on dexamethasone suppression testing • ~15% of cases • usually adrenal in origin

  23. Physiologic and Pathophysiologic Features of the Hypothalamic-Pituitary-Adrenal Axis in Normal Subjects and Patients with Cushing's Syndrome (Top Panels) and the Effect of Dexamethasone (Bottom Panels) * ACTH-independent Cushing’s Syndrome ACTH-dependent Cushing’s Syndrome Orth D. N Engl J Med 1995;332:791-803 *Erratum: thick purple lines should be dotted purple lines (denoting suppressed secretion)

  24. Clinical Manifestations of Cushing’s Syndrome • central obesity (>80%) • facial plethora (>50%) • glucose intolerance (>40%) • weakness/proximal myopathy* (>75%) • hypertension • psychological changes • easy bruisability* • hirsutism • oligomenorrhea/amenorrhea • impotence • acne, oily skin • abdominal striae • moon facies • ankle edema • backache, vertebral collapse, fracture • polydipsia, polyuria • renal calculi • hyperpigmentation • headache • exophthalmos • fungal infection • abdominal pain • thinning of skin* • weight gain • dorsal/supraclavicular fat pad *features that distinguish Cushing’s syndrome from Pseudo-Cushing’s syndrome

  25. An Algorithmic Approach to the Patient with Cushing’s Syndrome

  26. Tests Used for Work-Up • 24 hour urine cortisol • used as initial screening to confirm diagnosis of Cushing’s syndrome • most direct way of measuring cortisol secretion • must correlate with urine creatinine levels to confirm adequate sample collection • preferably, should have 2 or 3 elevated values to confirm dx • Low-dose dexamethasone suppression test • helps distinguish ACTH-dependent vs. ACTH-independent • check evening ACTH/cortisol, give 1 mg dexamethasone between 11pm-MN, check ACTH/cortisol at 8am • standard 2-day, 2 mg suppression test is used as initial screening or if overnight test equivocal

  27. Tests Used for Work-Up (II) • High-dose dexamethasone suppression test • delineates pituitary vs ectopic sources of ACTH production • same process as for low-dose suppression testing, but 8mg dexamethasone used • alternative test is total 48 mg given over 8 doses (2 mg every 6 hrs), checking ACTH/cortisol 6 hrs after last dose • Octreotide Scan • useful in identifying ectopic ACTH production in tumors with somatostatin receptors • Inferior Petrosal Sinus Sampling (IPSS) • most direct way to identify excess pituitary ACTH production • simultaneous bilateral sinus & venous samples to measure ACTH • CRH or DDAVP given peripherally, with additional samples drawn at 2-3 minutes & at 5-6 minutes • central:peripheral ratio before/after is compared; if >2-3pituitary • gold standard for detecting Cushing’s disease • $$$, invasive

  28. Management of Cushing’s Syndrome • depends on source, but surgery is usually first-line tx • Cushing’s disease • transsphenoidal surgery (70-80% cure rate) • pituitary irradiation as second line • consider total bilateral adrenalectomy as last resort • Ectopic ACTH/CRH syndrome • surgical resection of underlying tumor (poor cure rate in malignancy) • adrenal enzyme inhibitors (i.e. ketoconazole) • medical/surgical adrenalectomy • Adrenal tumors • surgical resection if deemed operable (usually bilateral adrenalectomy) • mitotane as a palliative measure for recurrent/residual disease • surgical resection of recurrent disease • adrenal enzyme inhibitors • Exogenous glucocorticoid use • wean off offending agent slowly

  29. Summary • 2 elevated random cortisol levels  get an ACTH level • if cortisol + ACTH are high and s/sx consistent with possible Cushing’s  initial screening tests to confirm dx and distinguish etiology (24 hr urine cortisol & low-dose dexamethasone suppression test) • depending on the ACTH level, work-up accordingly • if low ACTH on suppression  think adrenal causes and get a CT A/P • if high/normal ACTH  high-dose dexamethasone suppression test to delineate pituitary (suppressed ACTH) & ectopic sources, followed by appropriate imaging studies • surgery is usually first-line therapy, if resectable

  30. References

  31. Special ThankstoChief Holmanfor his invaluable resources and insight during the preparation of this case!

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