Detection of clenbuterol in heroin users in twelve postmortem cases at the Philadelphia medical examiner's office.

The presence of clenbuterol, a beta2-adrenergic agonist banned for human use in the United States because of its serious side effects, is reported in a series of 12 postmortem cases in which the cause of death was attributed to illicit drug use. During the first three months of 2007, postmortem specimens from cases previously screening positive for opiates or fentanyl were screened specifically for clenbuterol using enzyme-linked immunosorbent assay. Confirmation of clenbuterol was performed using solid-phase extraction, derivatization with trimethylboroxine, and analysis utilizing a gas chromatograph-mass spectrometer (GC-MS) operated in the full-scan mode. The limits of detection and quantitation in blood were 2.5 and 5 ng/mL, respectively. Linearity was from 5 to 100 ng/mL. Clenbuterol was positive in 12/106 (11%) drug-related cases and in 12/575 (2.1%) of the total cases tested. In each of the 12 cases positive for clenbuterol, heroin use was either confirmed by the presence of 6-acetylmorphine or strongly suspected by the presence of morphine with a history of heroin abuse. Because the use of clenbuterol in the United States is restricted to veterinary medicine, its detection is an unexpected finding. Its presence in these cases serves as a caution to emergency room physicians and toxicologists to consider and test for clenbuterol when treating a suspected heroin user who presents atypically. This is the first known series of clenbuterol-positive cases of illicit drug users to be reported from a medical examiner's toxicology laboratory.

Hypothalamic-pituitary-adrenal axis and interleukin-6 activity in children with head trauma and syndrome of inappropriate secretion of antidiuretic hormone.

OBJECTIVE: Arginine vasopressin (AVP; anti-diuretic hormone) and corticotropin-releasing hormone are the two major secretagogues of hypophyseal adrenocorticotropin (ACTH). Interleukin-6 (IL-6) is a potent stimulator of the human hypothalamic-pituitary-adrenal axis (HPA) and a secretagogue of both parvocellular and magnocelullar AVP. We have previously suggested that IL-6-stimulated AVP secretion may be the origin of the syndrome of inappropriate antidiuretic hormone secretion (SIADH) in inflammatory conditions. STUDY DESIGN: To further elucidate the relationship between IL-6 and SIADH as well as IL-6 and HPA axis activity, we studied eight previously healthy children (age 6.3 +/- 4.8 [mean +/- SD] years, weight 23.8 +/- 10.5 kg) who--after sustaining head trauma--presented SIADH during hospitalization (for 7.1 +/- 3.8 days) in the pediatric intensive care unit (P-ICU). Routine blood samples were taken twice daily at 08:00 and 20:00 hours. All children but one survived. Measurements included blood and urine osmolality (BlOsm and UrOsm, respectively), serum cortisol (F) and IL-6, plasma ACTH and AVP. Correlations were assessed with linear regression among the areas under the curve (AUC) of BlOsm, UrOsm, ACTH, F, IL-6 and AVP, separately for BlOsm values <280 mOsm (SIADH phase) and > or = 280 mOsm (non-SIADH phase). RESULTS: During the SIADH phase AVP-AUC correlated positively with IL-6-AUC (r = +0.96, p<0.05), BlOsm-AUC correlated positively with AVP-AUC and F-AUC (r = +0.95 and +0.98, p<0.05, respectively) and F-AUC correlated positively with ACTH-AUC (r = +0.99, p<0.05). During the non-SIADH phase ACTH-AUC correlated positively with BlOsm-AUC (r = +0.96, p<0.05). CONCLUSION: IL-6 secreted during an aseptic inflammatory state, such as sustaining head trauma with SIADH, is quantitatively correlated to AVP, indicating that this cytokine is directly and/or indirectly involved in the pathogenesis of SIADH.