Paraneoplastic Cushing Syndrome Wael Batobara

History 52 y Male Smoker 30 pack 52 y Male Smoker 30 pack Seen in Thoracic Sx Clinic with 1/12 H/O Seen in Thoracic Sx Clinic with 1/12 H/O Chest Pain bilateral non pleuritic Chest Pain bilateral non pleuritic lower costal 4/10 not related to exertion lower costal 4/10 not related to exertion No Fever,Wt loss, Cough, Hemoptysis No Fever,Wt loss, Cough, Hemoptysis No Leg pain, swelling No Leg pain, swelling Trail Of Abx & NSAID  no effect Trail Of Abx & NSAID  no effect

History No SOB, Orthopnea, PND No SOB, Orthopnea, PND Associated flank pain, No dysuria,hematuria Associated flank pain, No dysuria,hematuria PMH : -ve IHD risk factor PMH : -ve IHD risk factor Works as Plumber, +ve exposure to asbestos Works as Plumber, +ve exposure to asbestos No Rx, travel No Rx, travel

Examination BP 150/80 HR 80 RR 18 Sat 93% Afebrile BP 150/80 HR 80 RR 18 Sat 93% Afebrile Overweight Overweight N JVP & cardiac exam N JVP & cardiac exam Chest N except bilateral tenderness lower ribs Chest N except bilateral tenderness lower ribs ABD N ?LL edema ABD N ?LL edema

Investigations CBC WBC 16 Neut.13 Hb.Coagulation N CBC WBC 16 Neut.13 Hb.Coagulation N Lytes, BUN & Creat. N Lytes, BUN & Creat. N LFT Alk Phos 170 ALT 180 LDH 650 LFT Alk Phos 170 ALT 180 LDH 650 Cardiac Enzymes & EKG N Cardiac Enzymes & EKG N CXR & Chest CT CXR & Chest CT

Investigations Brochoscopy  edema Lt main Brochoscopy  edema Lt main Endobronchial lesion Sup.LLL Endobronchial lesion Sup.LLL Mediastinoscopy  Multiple LN Mediastinoscopy  Multiple LN BAL & LN Bx  Metastatic Small Cell CA BAL & LN Bx  Metastatic Small Cell CA Bone Scan  Diffuse skeletal Mets Bone Scan  Diffuse skeletal Mets

The Story is not done Yet !!! Chest Medicine Has Not Been Involved Yet

This Should Have Been Picked Up Earlier R3 Medical Resident

New Complaint Referred for work up of 1/12 H/O Referred for work up of 1/12 H/O Bilateral Leg swelling Bilateral Leg swelling Edema extending to Abdominal wall Edema extending to Abdominal wall No New respiratory, cardiac symptoms No New respiratory, cardiac symptoms No facial swelling No facial swelling NO decrease urine output, Leg Pain NO decrease urine output, Leg Pain Trial of Diuretics  no improvement Trial of Diuretics  no improvement

Any Suggestions?!

Sequence Of Events Patient was admitted to H6 Patient was admitted to H6 BP 150/85 BP 150/85 Not In CHF, No Signs of SVC obstruction Not In CHF, No Signs of SVC obstruction Pitting edema upto Ant Abd wall Pitting edema upto Ant Abd wall No Leg Size Difference No Leg Size Difference

Investigation CBC & Coagulation N CBC & Coagulation N Na 150 Co2 40 Cl,BUN, Creat N Na 150 Co2 40 Cl,BUN, Creat N K 2.2 in spite of >300 meq daily supplement K 2.2 in spite of >300 meq daily supplement FBS 8.1 Mg N FBS 8.1 Mg N ABG PH 7.51 PAO2 65 ABG PH 7.51 PAO2 65 PCO2 48 HCO3 41 PCO2 48 HCO3 41 Metabolic abnormalities persists after stopping the diuretics Metabolic abnormalities persists after stopping the diuretics

Investigation CT Abd & Pelvis  Multiple Mets CT Abd & Pelvis  Multiple Mets Liver, spleen, kidneys Liver, spleen, kidneys Adrenal Looks Chubby Adrenal Looks Chubby No IVC obstruction No IVC obstruction 2DE  N LV & RV function 2DE  N LV & RV function 24 Urine Collection  High K 24 Urine Collection  High K

Investigation Persistent Hypokalemia 2.3 EKG only U wave Persistent Hypokalemia 2.3 EKG only U wave Nephrology Consult Nephrology Consult {Please help it is your game} {Please help it is your game} Next day while rounding we caught Nephrology Staff  Interesting Case!!! Next day while rounding we caught Nephrology Staff  Interesting Case!!!

24Hour Urine Cortisol 5250!!! Normal < 250

Hospital Course Overnight Dexamethasone suppression test Overnight Dexamethasone suppression test -ve Serum Cortisol 1750  ve Serum Cortisol 1750  1400 ACTH pending ACTH pending Oncology Consult  Medical Resident Input Oncology Consult  Medical Resident Input Cis platinum & Etoposide Cis platinum & Etoposide Endocrinology  Ketoconazole Endocrinology  Ketoconazole

Investigation Patient tolerated Chemo Patient tolerated Chemo Minimal K supplements with decrease CO2 Minimal K supplements with decrease CO2 DM & HTN being treated DM & HTN being treated Follow up in Cancer Care Follow up in Cancer Care

Paraneoplastic Cushing Syndrome Incidence Incidence Is the presentation different from Cushing Dis. Is the presentation different from Cushing Dis. Would prognosis differ in SCLC with Cushing Would prognosis differ in SCLC with Cushing Is Chemothherapyis enough ? Is Chemothherapyis enough ? Other Paraneoplastic syndromes Other Paraneoplastic syndromes

Incidence 20-30% of Cushing Synd. is 2ry to ectopic ACTH  Lung Ca is the cause in 50% cases 20-30% of Cushing Synd. is 2ry to ectopic ACTH  Lung Ca is the cause in 50% cases Normal lung tissue secretes minimal amount of POMC proopiomelanocortin which is cleaved into different hormones including ACT Normal lung tissue secretes minimal amount of POMC proopiomelanocortin which is cleaved into different hormones including ACT { immunoreactive & not necessarily biologically active} Up to 50% of Lung Ca will have High ACTH Up to 50% of Lung Ca will have High ACTH though 2-10% will have clinically significant disease though 2-10% will have clinically significant disease

Incidence 3 Retrospective studies  SCLC had Cushing Synd 3 Retrospective studies  SCLC had Cushing Synd 14/ % Vs 5/ % Vs 10/ % 14/ % Vs 5/ % Vs 10/ % Dx clinical +High serum/urine cortisol Dx clinical +High serum/urine cortisol Majority Had extensive disease 60-90% Majority Had extensive disease 60-90% Cushing synd. Was diagnosed either with Ca Dx or shortly after Cushing synd. Was diagnosed either with Ca Dx or shortly after Cancer Sept 81 & Mar 94 Arch Int Med Mar 93 Cancer Sept 81 & Mar 94 Arch Int Med Mar 93

Clinical Presentation Less prominent than Cushing Disease Less prominent than Cushing Disease  shorter time of exposure to cortisol  shorter time of exposure to cortisol & the aggressive nature of tumor & the aggressive nature of tumor Most common  LL edema,Muscle weakness Most common  LL edema,Muscle weakness & moon faces 40-60% & moon faces 40-60% Most common lab finding  Hypokalemia,Met.Alk Most common lab finding  Hypokalemia,Met.Alk & Hyperglycemia 100% & Hyperglycemia 100%

Treatment Majority required additional Rx to control hypercortosilemia Majority required additional Rx to control hypercortosilemia Worse consequence of febrile neutropenia in Patients whom hypercortisolemia was not controlled Worse consequence of febrile neutropenia in Patients whom hypercortisolemia was not controlled Usual doses used to treat Cushing disease is not sufficient in Paraneoplastic Cushing Usual doses used to treat Cushing disease is not sufficient in Paraneoplastic Cushing Rx used : Ketoconazole, Metyrapone Rx used : Ketoconazole, Metyrapone,Aminoglutethimide & Bilateral Adrenalectomy,Aminoglutethimide & Bilateral Adrenalectomy

Prognosis SCLC with Cushing Synd, have a shorter survival rates than SCLC without the Synd. SCLC with Cushing Synd, have a shorter survival rates than SCLC without the Synd. 4-6 months Vs 8-11 months 4-6 months Vs 8-11 months 3 reasons  Larger tumor burden 3 reasons  Larger tumor burden  Relative lack of responsiveness to Chemo  Relative lack of responsiveness to Chemo  Tendency to develop serious infections  Tendency to develop serious infections Infections  common in patients with higher cortisol Infections  common in patients with higher cortisol levels with different sites & pathogens levels with different sites & pathogens