Paraneoplastic Cushing Syndrome

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Paraneoplastic Cushing Syndrome

• Wael Batobara

2
History

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

3
History

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

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Examination

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

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Investigations

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

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Investigations

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

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The Story is not done Yet !!!

• Chest Medicine Has Not Been Involved Yet

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This Should Have Been Picked Up Earlier

• R3 Medical Resident

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New Complaint

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

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Any Suggestions?!
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Sequence Of Events

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

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Investigation

• CBC Coagulation N
• Na 150 Co2 40 Cl ,BUN , Creat N
• K 2.2 in spite of gt300 meq daily supplement
• FBS 8.1 Mg N
• ABG PH 7.51 PAO2 65
• PCO2 48 HCO3 41
• Metabolic abnormalities persists after stopping
  the diuretics

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Investigation

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

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Investigation

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

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24Hour Urine Cortisol 5250!!!

• Normal lt 250

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Hospital Course

• Overnight Dexamethasone suppression test
• -ve Serum Cortisol 1750?1400
• ACTH pending
• Oncology Consult ? Medical Resident Input
• Cis platinum Etoposide
• Endocrinology ? Ketoconazole

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Investigation

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

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Paraneoplastic Cushing Syndrome

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

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Incidence

• 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
• immunoreactive not necessarily biologically
  active
• Up to 50 of Lung Ca will have High ACTH
• though 2-10 will have clinically significant
  disease

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Incidence

• 3 Retrospective studies ? SCLC had Cushing Synd
• 14/840 1.6 Vs 5/157 3.2 Vs 10/126 2.6
• Dx clinical High serum/urine cortisol
• Majority Had extensive disease 60-90
• Cushing synd. Was diagnosed either with Ca Dx or
  shortly after
• Cancer Sept 81
  Mar 94 Arch Int Med Mar 93

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Clinical Presentation

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

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Treatment

• Majority required additional Rx to control
  hypercortosilemia
• 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
• Rx used Ketoconazole , Metyrapone
• ,Aminoglutethimide Bilateral
  Adrenalectomy

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Prognosis

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