Corticotropin-releasing hormone production by a small cell carcinoma in a patient with ACTH-dependent Cushing's syndrome.

We describe a patient with Cushing's syndrome and metastatic small cell lung cancer. The plasma ACTH concentrations were markedly elevated (91.6 pmol/L), and the AM cortisol did not suppress by > 50% overnight after administration of 8 mg dexamethasone, both consistent with the ectopic ACTH syndrome. Immunohistochemical studies of a single metastatic tumor specimen, however, demonstrated an absence of ACTH and yet an abundance of corticotropin-releasing hormone (CRH). In addition, radioimmunoassay of the patient's plasma demonstrated persistently elevated CRH concentrations. The majority of the plasma CRH immunoreactivity exhibited the same chromatographic mobility as synthetic r/h CRH (1-41) on HPLC. Failure to evaluate the tumor tissue for the presence of ACTH and/or CRH would have led to the erroneous conclusion that this patient's Cushing's syndrome resulted from paraneoplastic ACTH production. We conclude that immunoassay of plasma for both ACTH and CRH and, perhaps, immunostaining of tumor samples are required to distinguish between the ectopic ACTH and CRH syndromes.