SCLC, Hypertension & Hypokalemia. Is there any correlation?! Wael Batobara

History 52 y Male smoker 30 pack Extensive SCLC {liver, spleen,renal & bony metastasis} Admitted with 1 month H/O: Progressive bilateral Lower limb edema

History No leg pain, SOB, orthopnea, PND Increase in abdominal girth without pain No facial swelling or decrease UOP Trial of diuretic Rx was not helpful PMH –ve for IHD,CRF or chronic liver disease

Hospital Course Patient was admitted to H6 Respiratory floor BP 150/85 Not In CHF, No Signs of SVC obstruction Pitting edema up to Ant Abd wall No Leg Size Difference

Investigation CBC & Coagulation N BUN, Creatinine & LFT N Na 150 Co2 40 Cl 93 K 2.2 persistent even with supplement of KCL >300 meq /day

Investigation ABG PH 7.51 PAO2 65 PCO2 48 HCO3 41 FBS 8.1 Mg N UA –ve for proteinuria 2D Echo  N

Investigation CT Abdomen & Pelvis  No IVC obstruction Multiple Mets Liver, spleen, kidneys Adrenal Looks Chubby HTN, Hypokalemia & metabolic alkalosis were persistent after diuretic withdrawal

24Hour Urine Cortisol 5250!!! Normal < 250

Investigation ACTH 35 High Low dose overnight dexamethasone Serum Cortisol 1750  1400 Paraneoplastic Cushing Syndrome

Paraneoplastic Cushing Syndrome PCS Incidence Is the presentation different from other etiology of Cushing syndrome ? Would SCLC prognosis differ in the presence of Cushing syndrome ? Can SCLC treatment achieve a control of hypercortisolemia?

Incidence Normal lung tissue contains APUD cells (amine precursor uptake decarboxylase ) APUD cells secrete minimal amount of POMC (proopiomelanocortin) which is cleaved into different hormones including ACTH POMC is immunoreactive & not necessarily biologically active

Incidence 20-30% of Cushing syndrome cases is paraneoplastic  50% is 2ry to Lung Ca Incidence % PCS Dx was either concurrent with SCLC Dx or shortly after SCLC Dx % Extensive SCLC Up to 50% of Lung Ca will have High ACTH though 2-10% will have clinical disease Cancer Sept 81 & Mar 94 Arch Int Med Mar 93

Clinical Presentation Typical Cushing Disease features are less prominent in SCLC related PCS  short exposure time to ACTH & catabolic nature of underlying cancer Clinically  LL edema,Muscle weakness & moon faces 40-60% Laboratory  Hypokalemia,Met.Alkalosis & Hyperglycemia 100%

Treatment In majority of cases additional Rx was required to control hypercortosilemia Rx used Medical  Ketoconazole, Metyrapone & Aminoglutethimide Surgical  Bilateral Adrenalectomy Usual doses used to treat Cushing disease is not sufficient in Paraneoplastic Cushing

Prognosis SCLC with PCS had shorter survival 4-6 months Possible explanations  Larger tumor burden  Relative lack of responsiveness to Chemo  Tendency to develop serious infections Cancer Jan 1;69(1):66-71.

Back to Our Patient Medical oncology consult  Cis Platinum & Etoposide Endocrinology Consult  Ketoconazole Follow up  resolution of metabolic abnormality & reduction in ACTH & cortisol level

Take Home Points SCLC related PCS is uncommon but well described entity SCLC related PCS have less obvious clinical presentation  it might be underdiagnosed SCLC related PCS have a worse prognosis than SCLC without PCS

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