Predicting the development of Cushing's syndrome in medullary thyroid cancer: Utility of proopiomelanocortin messenger ribonucleic acid in situ hybridization

Objective: To determine the ability to predict the development of Cushing's syndrome (CS) by immunostaining prior to its clinical recognition. Design: In the current report, we demonstrated that a medullary thyroid carcinoma (MTC) patient had the ability to develop CS several years before its clinical recognition. Special stains on tumor tissue confirmed the presence of ectopic adrenocorticotropic hormone (ACTH) 3 years before his clinical presentation of CS. Subsequently, we identified eight MTC patients and reviewed their records to determine whether there was clinical or laboratory evidence of CS. Tissue blocks were obtained from the primary tumor and metastasic lesions for ACTH staining and for proopiomelanocortin messenger ribonucleic acid (POMC mRNA) in situ hybridization. Chromogranin A staining was also performed. Main outcome: ACTH staining did not detect ectopic ACTH. However, measuring ACTH precursor (POMC mRNA) by in situ hybridization confirmed the diagnosis, which preceded the patient's clinical presentation by 3 years. We also found that in a small series of eight MTC patients, most with metastatic disease, there was no histologic evidence of ACTH or POMC production. Conclusion: Our current report demonstrates that ACTH staining may not detect ACTH, but measuring POMC mRNA by in situ hybridization is very helpful in confirming the source of ectopic ACTH production.