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Friday, December 17, 2010

Clinical Case: Patient With Elevated Serum Cortisol level Not Suppressed With Dexamethasone

Clinical Vignette: A 57-year-old man complains of fatigue, weakness, and weight gain, particularly around the abdomen. On examination, he is found to have hypertension, fullness over the upper back, and abdominal striae. Laboratory studies include an elevated serum cortisol level that is not suppressed with dexamethasone. Imaging studies reveal no pituitary or adrenal masses, but a computed tomography (CT) scan of the chest shows a right lung mass arising near the hilum.

         ◆  What is the most likely diagnosis?
         ◆  What other disorders may cause similar clinical findings?
         ◆  What are the underlying mechanisms involved? 



Summary: A 57-year-old man complains of cushingoid features. Laboratory studies include an elevated cortisol level that is not suppressed with dexamethasone. A CT scan of the chest shows a right lung mass arising near the hilum.
Most likely diagnosis: Cushing syndrome caused by small cell carcinoma of lung through a paraneoplastic process.

Other disorders causing similar clinical findings: Cancers of various origins; commonly seen in pancreatic cancer, small cell carcinoma of lung, and thymoma.

Underlying mechanisms: The lung cancer cells probably are producing ectopic adrenocorticotropic hormone (ACTH), resulting in Cushing syndrome.

CLINICAL CORRELATION

Another great clinical vignette for USMLE... Grasp the concept in this Clinical Vignette for your USMLE.
The paraneoplastic syndromes are collections of symptoms that result from substances produced by a tumor, and they occur remotely from the tumor. Approximately 10 percent of malignancies manifest these syndromes. Small cell carcinoma is the most common type of cancer that causes clinical hormone syndromes, and it causes a number of paraneoplastic effects. These manifestations can result from immune reactivity to tumor and/or tissue antigens, metabolic disorders causing electrolyte abnormalities, and endocrine dysfunction. The tumor cells may produce ectopic ACTH, resulting in Cushing syndrome. The symptoms of Cushing syndrome are nonspecific and often are attributed to other factors. Another paraneoplastic hormone syndrome that commonly occurs in small cell carcinoma of lung is the syndrome of inappropriate antidiuretic hormone (SIADH), which is caused by the secretion of adrenocorticotropic hormone (ACTH) from the tumor. Symptoms are related to the plasma hypotonicity that is secondary to water retention.


CLINICAL
SYNDROMES

MECHANISM
OF ACTION

MAJOR FORMS OF CANCER

Cushing  syndrome

Adrenocorticotropic hormone (ACTH) or ACTH-like substance

Small cell carcinoma of lung,  pancreatic
cancer

Syndrome of  inappropriate
ADH secretion

Antidiuretic hormone  (ADH) or
atrial natriuretic  hormone

Small cell carcinoma of lung,
brain tumors

Hypoglycemia

Insulin or insulin like
substance

Fibrosarcoma,  hepatocellular
carcinoma

Hypercalcemia

Parathyroid
hormone-related protein

Breast cancer,  renal
carcinoma,
squamous cell carcinoma of the
lung

Carcinoid syndrome

Serotonin,  bradykinin

Bronchial adenoma,  pancreatic
Carcinoma,  gastric carcinoma


Polycythemia

Erythropoietin

Renal cell carcinoma,
Cerebellar hemangioma


Myasthenia (Eaton-Lamber
syndrome)

Immune-mediated
(autoantibodies)

Bronchogenic carcinoma,
breast cancer


Venous thrombosis

Tumor products that
induce thrombosis

Pancreatic cancer and others