Paradoxical Results after Inadvertent Use of Cosyntropin [Adrenocorticotropin Hormone (1-24)] Rather than Acthrel (Ovine Corticotropin Releasing Hormone) during Inferior Petrosal Sinus Sampling.
OBJECTIVE
The use of ovine corticotropin releasing hormone (oCRH) maximizes the diagnostic accuracy of inferior petrosal sinus sampling (IPSS) in patients with adrenocorticotropin hormone (ACTH)-dependent Cushing's syndrome (CS). oCRH is marketed as ACTHrel and, understandably, may be confused with cosyntropin [ACTH (1-24)]. The inadvertent substitution of synthetic ACTH(1-24) for oCRH (ACTHrel) during IPSS may cause unexpected and misleading results. The aim of this report is to raise awareness of the potential confounding results created when synthetic ACTH(1-24) is mistakenly used during IPSS.


METHODS
We present 3 patients treated at 3 different centers with ACTH-dependent CS in whom ACTH(1-24) was mistakenly substituted for oCRH (ACTHrel) during IPSS.


RESULTS
In all patients, there was an abrupt and unexpected decrease in plasma ACTH in the inferior petrosal sinus (IPS) samples after presumptive stimulation with oCRH. Re-evaluation of the patients' pharmacy records confirmed that synthetic ACTH(1-24) had been used rather than oCRH during each procedure. Because "sandwich" immunometric assays for ACTH measure the entire pool of endogenous ACTH, the administration of synthetic ACTH(1-24) artifactually decreases the endogenous plasma ACTH(1-39) measurement by binding only to the N-terminal antibody raised against ACTH(1-17) and not to the C-terminal antibody raised against ACTH(34-39). This results in a lack of a detectable sandwich complex and explains the apparent reduction in ACTH concentration.


CONCLUSIONS
An abrupt decrease in ACTH during IPSS suggests that synthetic ACTH(1-24) rather than oCRH (ACTHrel) has been administered. The labeling of oCRH as ACTHrel poses a potential patient safety problem about which endocrinologists, interventional radiologists, and pharmacists should be aware.
Endocrinology Center and Clinics, Medical College of Wisconsin, Milwaukee, Wisconsin.
Ty B
TB
Carroll
Division of Endocrinology, Metabolism, and Clinical Nutrition, Medical College of Wisconsin, Milwaukee, Wisconsin Division of Endocrinology, Diabetes and Metabolism, Wheaton Franciscan Medical Group, Racine, Wisconsin.
Amy J H
AJ
Fisco
University of Texas Southwestern Medical School, Dallas, Texas Division of Metabolism, Endocrinology, and Diabetes, University of Michigan, Ann Arbor, Michigan.
Richard J
RJ
Auchus
Department of Endocrinology, Diabetes, and Metabolism, Cleveland Clinic, Cleveland, Ohio.
Laurence
L
Kennedy
Endocrinology Center and Clinics, Medical College of Wisconsin, Milwaukee, Wisconsin.
James W
JW
Findling
D000324:Adrenocorticotropic Hormone / Q000097:blood*; D000328:Adult; D003346:Corticotropin-Releasing Hormone / Q000008:administration & dosage / Q000031:analogs & derivatives*; D003366:Cosyntropin / Q000009:adverse effects*; D003480:Cushing Syndrome / Q000175:diagnosis*; D005260:Female; D006801:Humans; D008508:Medication Errors; D017591:Petrosal Sinus Sampling
C085671:corticorelin ovine; D003366:Cosyntropin; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone