Solution to "A 41-Year-Old Woman With Back Pain"

Robert M. Centor, MD; Christy Collier; Elisa Haley, MD; David McMillion, MD


June 07, 2006

This is the solution to a case we presented recently. You may review the case here.

1. The patient has a severe hypokalemic metabolic alkalosis. Here is the differential diagnosis:

  1. The most common causes of hypokalemic metabolic alkalosis are protracted vomiting and excess diuresis. With both of these common presentations, the patient has a low urine chloride (generally < 10 mEq/L). Such patients improve with volume expansion and potassium replacement.

  2. Any excess of mineralocorticoid activity can lead to hypokalemic metabolic alkalosis. Examples include hyperaldosteronism, oral mineralocorticoids, and Bartter's syndrome.

  3. Mineralocorticoid-like activity can occur with licorice ingestion. The active ingredient is glycyrrhetinic acid; European licorice contains this steroid (most US licorice is not true licorice). We have seen this syndrome secondary to chewing tobacco (which sometimes contains licorice flavoring).

  4. Rare inherited disorders are Liddle's syndrome and Gitelman's syndrome.

  5. Adrenocorticotropic hormone (ACTH)-secreting tumors can result in excess mineralocorticoid activity.

2. We suggest a chest x-ray, spine films, and urine chloride as the initial tests. Results:

  1. A chest x-ray done in the emergency department revealed a shadow in the apex of the right lung, possibly due to a mass.

  2. The patient was admitted and correction of her hypokalemia was initiated. X-rays of her thoracic spine were ordered to evaluate her back pain, and a chest CT was ordered to evaluate the possible mass.

  3. A nurse noted that the patient looked "a little yellow." Liver function tests revealed:

    • Alkaline phosphatase (ALP) 324 U/L

    • Aspartate aminotransferase (AST) 347 U/L

    • Alanine aminotransferase (ALT) 928 U/L

    • Total bilirubin 3.0 mg/dL

    • Direct bilirubin 1.4 mg/dL

    • Total protein 5.6 g/dL

    • Albumin 3.1 g/dL

    • Prothrombin time (PT) 15.1 sec

    • International normalized ratio (INR) 1.1

  4. Other lab tests revealed:

    • Cortisol (am) 142.5 UG/dL (normal, 8.0-25.0)

    • Urine chloride 44 mEq/L

    • Lipase 48 U/L

    • HgA1C 5.8%

    • BetaHCG negative

    • Hepatitis profile nonreactive (HBsAg, HBcore Ab IgM, HAV Ab IgM, HC Ab)

3. Now we have a patient with a lung mass and a markedly elevated cortisol level. The urine chloride level gives evidence against vomiting or diuretic excess. We suspect an ACTH-secreting lung tumor and proceed with further evaluation, which confirmed our suspicions.

4. Further imaging revealed:

  1. Thoracic x-ray: vertebral compression fractures of T5 and T9; degenerative changes noted throughout spine

  2. CT angio chest: no evidence of pulmonary embolus; evidence of bulky right paratracheal lymphadenopathy; lymph node mass (3.8 cm × 3.2 cm) and right hilar mass (5 cm × 4.2 cm). Also, lymph node to the left of the aortic arch is seen, as well as subcarinal lymphadenopathy. Patchy areas of pneumonitis on both lungs. Some atelectasis of right upper lobe apparently due to the large tumor. Impressions: (1) large amount of tumor burden involving right lung and mediastinum; (2) patchy areas of pneumonitis bilaterally; cannot exclude acute overlying inflammatory process.

  3. CT pelvis: no acute pelvic pathology

  4. CT abdomen: innumerable low-density masses compatible with metastatic disease (the largest one measured 3.6 cm × 3.9 cm). Both adrenal glands are somewhat prominent in size, but no discrete adrenal mass is seen.

  5. CT head: negative for any signs of metastasis

5. Upon receiving the results of the chest CT, Pulmonology was consulted for bronchoscopy to biopsy the lung mass. The pathology report is as follows:

Endobronchial biopsy of right upper lobe: extensive infiltration by a malignant neoplasm that displays extensive crush artifact. The intact neoplastic cells are small, with little cytoplasm, a fine chromatin pattern, and indistinct nucleoli. Occasional mitotic figures and apoptotic bodies are seen. Immunohistochemical stains: cytokeratin -- positive, in a dot-like pattern; CAM5.2 -- positive, in a dot-like pattern; synaptophysin -- faintly positive; chromogranin -- negative; staining and morphologic appearance are diagnostic of small-cell carcinoma.

The patient was diagnosed with small-cell carcinoma of the lung with an associated paraneoplastic syndrome of secreted ACTH as well as metastatic lesions to the liver. Her ACTH level was 1056 pg/mL (normal, 0-46).

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