ParaneoplasticParaneoplastic Cushing SyndromeCushing Syndrome

Wael BatobaraWael Batobara

HistoryHistory

• 52 y Male Smoker 30 pack52 y Male Smoker 30 pack

• Seen in Thoracic Sx Clinic with 1/12 H/OSeen 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 exertionlower costal 4/10 not related to exertion No Fever ,Wt loss , Cough , HemoptysisNo Fever ,Wt loss , Cough , Hemoptysis No Leg pain , swellingNo Leg pain , swelling

• Trail Of Abx & NSAID Trail Of Abx & NSAID no effect no effect

HistoryHistory• No SOB , Orthopnea , PNDNo SOB , Orthopnea , PND

• Associated flank pain , No dysuria ,hematuriaAssociated flank pain , No dysuria ,hematuria

• PMH : -ve IHD risk factorPMH : -ve IHD risk factor

• Works as Plumber , +ve exposure to asbestosWorks as Plumber , +ve exposure to asbestos

• No Rx , travel No Rx , travel

ExaminationExamination• BP 150/80 HR 80 RR 18 Sat 93% AfebrileBP 150/80 HR 80 RR 18 Sat 93% Afebrile

• Overweight Overweight

• N JVP & cardiac examN JVP & cardiac exam

• Chest N except bilateral tenderness lower ribsChest N except bilateral tenderness lower ribs

• ABD N ?LL edemaABD N ?LL edema

InvestigationsInvestigations• CBC WBC 16 Neut.13 Hb .Coagulation NCBC WBC 16 Neut.13 Hb .Coagulation N

• Lytes , BUN & Creat. NLytes , BUN & Creat. N

• LFT Alk Phos 170 ALT 180 LDH 650LFT Alk Phos 170 ALT 180 LDH 650

• Cardiac Enzymes & EKG NCardiac Enzymes & EKG N

• CXR & Chest CT CXR & Chest CT

InvestigationsInvestigations• Brochoscopy Brochoscopy edema Lt main edema Lt main

Endobronchial lesion Sup.LLLEndobronchial lesion Sup.LLL

• Mediastinoscopy Mediastinoscopy Multiple LN Multiple LN

• BAL & LN BxBAL & LN Bx Metastatic Small Cell CA Metastatic Small Cell CA

• Bone Scan Bone Scan Diffuse skeletal Mets Diffuse skeletal Mets

The Story is not done Yet !!!The Story is not done Yet !!!

Chest Medicine Has Not Been Chest Medicine Has Not Been Involved YetInvolved Yet

This Should Have Been Picked This Should Have Been Picked Up EarlierUp Earlier

R3 Medical Resident R3 Medical Resident

New ComplaintNew Complaint• Referred for work up of 1/12 H/OReferred for work up of 1/12 H/O

Bilateral Leg swellingBilateral Leg swelling

Edema extending to Abdominal wallEdema extending to Abdominal wall

No New respiratory , cardiac symptomsNo New respiratory , cardiac symptoms

No facial swelling No facial swelling

NO decrease urine output , Leg PainNO decrease urine output , Leg Pain

• Trial of Diuretics Trial of Diuretics no improvementno improvement

Any Suggestions?!Any Suggestions?!

Sequence Of EventsSequence Of Events

• Patient was admitted to H6Patient was admitted to H6

• BP 150/85 BP 150/85

• Not In CHF , No Signs of SVC obstructionNot In CHF , No Signs of SVC obstruction

• Pitting edema upto Ant Abd wallPitting edema upto Ant Abd wall

• No Leg Size Difference No Leg Size Difference

InvestigationInvestigation

• CBC & Coagulation NCBC & 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 supplementK 2.2 in spite of >300 meq daily supplement

• FBS 8.1 Mg NFBS 8.1 Mg N

• ABG PH 7.51 PAO2 65ABG PH 7.51 PAO2 65

PCO2 48 HCO3 41PCO2 48 HCO3 41

• Metabolic abnormalities persists after stopping Metabolic abnormalities persists after stopping the diuretics the diuretics

InvestigationInvestigation

• CT Abd & Pelvis CT Abd & Pelvis Multiple MetsMultiple Mets

Liver , spleen , kidneysLiver , spleen , kidneys

Adrenal Looks Adrenal Looks Chubby Chubby

No IVC obstructionNo IVC obstruction

• 2DE 2DE N LV & RV function N LV & RV function

• 24 Urine Collection 24 Urine Collection High K High K

InvestigationInvestigation

• Persistent Hypokalemia 2.3 EKG only U wavePersistent 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 Next day while rounding we caught Nephrology Staff Nephrology Staff Interesting Case!!! Interesting Case!!!

24Hour Urine Cortisol 5250!!!24Hour Urine Cortisol 5250!!!

Normal < 250Normal < 250

Hospital CourseHospital Course• Overnight Dexamethasone suppression testOvernight Dexamethasone suppression test

-ve Serum Cortisol 1750-ve Serum Cortisol 175014001400

• ACTH pendingACTH pending

• Oncology Consult Oncology Consult Medical Resident Input Medical Resident Input

Cis platinum & EtoposideCis platinum & Etoposide

• Endocrinology Endocrinology Ketoconazole Ketoconazole

InvestigationInvestigation

• Patient tolerated ChemoPatient tolerated Chemo

• Minimal K supplements with decrease CO2Minimal K supplements with decrease CO2

• DM & HTN being treatedDM & HTN being treated

• Follow up in Cancer CareFollow up in Cancer Care

ParaneoplasticParaneoplastic Cushing SyndromeCushing Syndrome• IncidenceIncidence

• 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 syndromesOther Paraneoplastic syndromes

IncidenceIncidence• 20-30% of Cushing Synd. is 2ry to ectopic ACTH 20-30% of Cushing Synd. is 2ry to ectopic ACTH

Lung Ca is the cause in 50% casesLung Ca is the cause in 50% cases

• Normal lung tissue secretes minimal amount of Normal lung tissue secretes minimal amount of POMCPOMC proopiomelanocortin which is cleaved into proopiomelanocortin which is cleaved into different hormones including ACTdifferent hormones including ACT

{ immunoreactive & not necessarily biologically active} { 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 diseasethough 2-10% will have clinically significant disease

IncidenceIncidence• 3 Retrospective studies 3 Retrospective studies SCLC had Cushing Synd SCLC had Cushing Synd

• 14/840 1.6% Vs 5/157 3.2% Vs 10/126 2.6%14/840 1.6% Vs 5/157 3.2% Vs 10/126 2.6%

• 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 Cushing synd. Was diagnosed either with Ca Dx or shortly aftershortly after

Cancer Sept 81 & Mar 94 Arch Int Med Mar 93Cancer Sept 81 & Mar 94 Arch Int Med Mar 93

Clinical PresentationClinical Presentation

• Less prominent than Cushing DiseaseLess prominent than Cushing Disease shorter time of exposure to cortisolshorter time of exposure to cortisol & the aggressive nature of tumor& the aggressive nature of tumor

• Most common Most common LL edema ,Muscle weakness LL edema ,Muscle weakness & moon faces & moon faces 40-60%40-60%

• Most common lab finding Most common lab finding Hypokalemia ,Met.Alk Hypokalemia ,Met.Alk & Hyperglycemia & Hyperglycemia 100%100%

TreatmentTreatment• Majority required additional Rx to control Majority required additional Rx to control

hypercortosilemia hypercortosilemia

• Worse consequence of febrile neutropenia in Patients Worse consequence of febrile neutropenia in Patients whom hypercortisolemia was not controlled whom hypercortisolemia was not controlled

• Usual doses used to treat Cushing disease is not Usual doses used to treat Cushing disease is not sufficient in Paraneoplastic Cushingsufficient in Paraneoplastic Cushing

• Rx used : Ketoconazole , MetyraponeRx used : Ketoconazole , Metyrapone ,Aminoglutethimide & Bilateral Adrenalectomy ,Aminoglutethimide & Bilateral Adrenalectomy

PrognosisPrognosis• SCLC with Cushing Synd, have a shorter survival SCLC with Cushing Synd, have a shorter survival

rates than SCLC without the Synd.rates than SCLC without the Synd. 4-6 months Vs 8-11 months4-6 months Vs 8-11 months

• 3 reasons 3 reasons Larger tumor burden Larger tumor burden Relative lack of responsiveness to ChemoRelative lack of responsiveness to Chemo Tendency to develop serious infectionsTendency to develop serious infections • Infections Infections common in patients with higher cortisol common in patients with higher cortisol levels with different sites & pathogens levels with different sites & pathogens