cosyntropin and corticorelin-ovine

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.. 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.. 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.. 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.

Topics: Adrenocorticotropic Hormone; Adult; Corticotropin-Releasing Hormone; Cosyntropin; Cushing Syndrome; Female; Humans; Medication Errors; Petrosal Sinus Sampling

Hyperactivity of the pituitary-adrenocortical axis is the most prominent neuroendocrine abnormality in major depression. It is state-related, returning to normal with resolution of the depressive episode. Adrenal gland enlargement also has been reported in patients with major depression and has been hypothesized as an index of cumulative lifetime depression. However, whether or not adrenal enlargement decreases with successful treatment of depression has not yet been studied, to our knowledge. We, therefore, determined adrenal gland volume in patients with major depression before and after treatment and in matched normal controls, and compared adrenal size with functional indexes of pituitary-adrenocortical activity.. Adrenal volumes were measured by magnetic resonance imaging in nine adult and two adolescent patients with major depression during their illness and during full remission when medication had been stopped for at least 1 month, and in nine adult and two adolescent normal control subjects individually matched to the patients. Basal, 4 to 7 PM plasma corticotropin 1-39 and cortisol levels, and corticotropin 1-39 and cortisol responses to administration of ovine corticorelin and lowdose cosyntropin also were measured.. Mean adrenal gland volume was significantly larger, by about 70% in the patients while depressed than after successful treatment, and it also was significantly larger, again by about 70%, than the mean adrenal gland volume of their matched controls. After treatment, the mean adrenal volume of the patients decreased and was no longer significantly different from that of their controls at baseline. The magnitude of the decrease was significantly positively correlated with the duration of the depressive episode. Basal, late-afternoon plasma corticotropin 1-39 levels were significantly lower in the patients while depressed than in their matched controls, but basal plasma cortisol levels did not differ significantly among the three groups, nor did the corticotropin 1-39 and cortisol responses to corticorelin or the cortisol response to cosyntropin. Correlations between adrenal gland volume and basal corticotropin and cortisol levels, and the corticotropin and cortisol responses to hormone challenge, were not consistently in the expected direction in any of the three groups of subjects.. Adrenal gland enlargement occurring during an episode of major depression appears to be state-dependent, in that it reverts to the normal size range during remission after treatment. It thus does not appear to be an index of cumulative lifetime depression. The lack of a discernible relationship between adrenal volume and pituitary-adrenocortical activity remains to be explained and might be related to noncorticotropin influences on the adrenal gland, including other tropic hormones and/or neural mechanisms.

Topics: Adolescent; Adrenal Glands; Adrenocorticotropic Hormone; Adult; Ambulatory Care; Antidepressive Agents; Circadian Rhythm; Corticotropin-Releasing Hormone; Cosyntropin; Depressive Disorder; Female; Humans; Hydrocortisone; Magnetic Resonance Imaging; Male; Middle Aged; Treatment Outcome