The authors faced a very challenging patient, whose imaging and laboratory results suggested the presence of an ACTH-secreting tumor. Several laboratory findings could have been erroneously attributed to 2 phenomena, “big ACTH” and complexes of ACTH with immunoglobulin, that occur in patients with ACTH-secreting tumors and affect measurement of ACTH.
In the normal pituitary, ACTH is made by proteolytic processing of the precursor molecule proopiomelanocortin. When processing is faulty, as occurs in some cases of ectopic production of ACTH by tumors, a big form of ACTH is formed. This form is often inactive, and thus the presence of inactive, tumor-associated ACTH could easily have been postulated to explain the discrepancy between the high ACTH result and the normal electrolyte results and normal skin pigmentation seen in this patient. Moreover, “big ACTH” is measured by some assays (notably RIAs) and not by others (1). This latter fact, too, could have been wrongly used to explain the discrepant results of the 2 assays in this case, further leading the diagnostician toward an erroneous conclusion.
ACTH–immunoglobulin complexes occur in patients with malignancies. In one study, such complexes led to increased circulating concentrations of ACTH, as measured by RIA, in 4 of 7 patients with small-cell carcinoma of the lung (2). Only 1 patient had evidence of ACTH excess (Cushing syndrome). Thus, ACTH–immunoglobulin complexes offer another explanation for the discrepant clinical and laboratory findings in the patient and would have reinforced the conclusion that the patient had an ACTH-secreting tumor. Moreover, the stability of the immunoreactive ACTH could have been attributed to formation of the immune complexes, which often stabilize the structure of the complexed antigen.
The authors are to be congratulated for carrying out the extensive testing that was required to document the presence of the heterophile antibodies that explained the findings in this patient.
Author Contributions: All authors confirmed they have contributed to the intellectual content of this paper and have met the following 3 requirements: (a) significant contributions to the conception and design, acquisition of data, or analysis and interpretation of data; (b) drafting or revising the article for intellectual content; and (c) final approval of the published article.
Authors' Disclosures or Potential Conflicts of Interest: Upon manuscript submission, all authors completed the author disclosure form. Disclosures and/or potential conflicts of interest:
Employment or Leadership: D.E. Bruns, AACC.
Consultant or Advisory Role: None declared.
Stock Ownership: None declared.
Honoraria: None declared.
Research Funding: None declared.
Expert Testimony: None declared.
- Received for publication July 16, 2011.
- Accepted for publication July 22, 2011.
- © 2012 The American Association for Clinical Chemistry