Cushing’s Syndrome Britni Hebert PGY 2 4/9/10 Notes located in presenter note section below each slide.

Outline Presentation Diagnosis Diagnose Hypercortisolism Isolate source Therapy

Normal HPA Physiology

Presentation Weight Gain Glucose Intolerance HTN Hypokalemia Proximal Muscle Weakness Infections

Phenotype

Diagnosing Cushings

Step 1: Diagnosing Hypercortisolism 3 first line tests Low Dose Dexamethasone Suppression Test Late Night Salivary Cortisol Urinary Cortisol

Step 2: Isolate Source ACTH level < 5 = ACTH Independent >20 = ACTH Dependent

in ACTH Dependent Cushings (like our patient) Isolate Source... of ACTH ie High Dose Dexamethasone Confirm Image

EAS by Source

Treating Cushings

Therapy Surgery by source when possible Adrenalectomy Transphenoidal resection Tumor Resection

Therapy Adrenal Enzyme Inhibitors Ketoconazole – first line Aminoglutethimide Metyrapone Etomidate

Therapy Medical Adrenalectomy - Mitotane Glucocorticoid Antagonists - Mifepristone Somatostatin Analogues - Octreotide

Summary

Marked HTN and Hypokalemia are typical of ectopic ACTH secretion. First Line therapy in unresectable disease = Ketoconazole CV, HTN, VTE and infection commonly lead to death in the untreated Cushingoid patient. The former does not improve with therapy.

Resources Up To Date Clinical Manifestations of Cushing’s Syndrome Establishing the Diagnosis of Cushing’s Syndrome Establishing the Cause of Cushing’s Syndrome Overview of the Treatment of Cushing’s Syndrome Diminishing Adrenal Cortisol Synthesis Ectopic ACTH syndrome. Andrea M. Isidori; Andrea Lenzi, DFM – Department of Pathophysiology, "Sapienza" University of Rome, Italy