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

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 SyndromePCS • 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 1.6 - 3.2% • PCS Dx was either concurrent with SCLC Dx or shortly after SCLC Dx • 60 - 90% 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 withPCS had shorter survival 4-6 months • Possible explanations • Larger tumor burden • Relative lack of responsiveness to Chemo • Tendency to develop serious infections Cancer. 1992 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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SCLC , Hypertension & Hypokalemia . Is there any correlation?!