Julie Ray (Presenter)
Bio: Julie A Ray works as an R&D Investigator at ARUP laboratories. Her interest lies in developing high sensitivity and selectivity LC-MS/MS assays for small molecules, especially steroids. This includes extensive validation of new methods for quantitative analysis. Exploring sample preparation procedures for simplifying an assay in a high throughput production set-up, derivatization procedures and the use of ion mobility spectrometry in enhancing specificity of assays are also a focus of her work.
Authorship: Julie A. Ray1, Mark M Kushnir1, A. Wayne Meikle2, 3, Frederick G. Strathmann1, 2
(1)ARUP Institute for Clinical and Experimental Pathology, Salt Lake City, UT, (2)Department of Pathology, University of Utah, (3) Department of Medicine, University of Utah
Chronic use of opiates leads to adrenal and pituitary dysfunction and altered sexual function. Positivity of the drugs hydrocodone, oxycodone, morphine, methadone and gabapentin in 100 residual samples from adult men and women were evaluated for association with endocrine function. Concentrations of free testosterone, free estradiol, free thyroxine, free cortisol, triiodothyronine and reverse triiodothyronine in blood measured by LC-MS/MS methods were significantly impacted by the presence of these opiates. A gender based difference in metabolism of certain drugs was also noticed. Given the lack of clinical information regarding changes in levels of free hormones in opiate users, this could be important in determining the association of painkiller treatments with endocrine disorders.
Opiates are known to effect hormone biosynthesis. Chronic use of opiates leads to hypogonadism, adrenal and pituitary dysfunction, reduced bone mineral density and abnormalities of glucose and lipid metabolism. Reduced testosterone and estrogen concentrations have been reported to be associated with osteoporosis and altered sexual function. These conditions are often observed in heroin addicts and oxycodone (prescription pain killer) users. Majority of publications in this area of research have focused on measurement of total hormone concentrations in chronic opiate users. The “free” hormone approach could provide a more accurate representation of the biologically active hormone concentrations. Limited information is available on the effect of opiates on free hormone concentrations [free testosterone (fTe), free cortisol (fC), free estrogen (fE2) and free thyroxine (fT4)] and alterations of thyroid hormones [total triiodothyronine (T3) and reverse T3 (rT3)] in chronic opiate users, hence representing an important area of investigation.
Conventional and off-label analgesics of interest such as hydrocodone, oxycodone, morphine, methadone and gabapentin were evaluated on their effect on free hormone concentrations. In the study we used 100 residual serum samples from adult men (n=50, mean age 51.2) and women (n=50, mean age 52.3). The samples were parsed based on drug concentration (using cutoffs accepted for confirmatory drug testing) and gender. The samples were assayed for fC, fT4, T3, rT3, fTe (men only) and fE2 (women only), using validated LC-MS/MS methods. Positivity of the drugs in blood samples was evaluated for impact on the free hormone concentrations. Considering the mode of drug action and for the purpose of data analysis, data corresponding to the prescription pain killers (hydrocodone, oxycodone and morphine (HOM)) were combined into a single group while methadone and gabapentin were evaluated separately.
In samples testing positive for opiates, the between-groups comparison for the hormone concentration was performed using Mann-Whitney test. Men with elevated concentrations of HOM showed statistically lowered concentrations of serum fTe (p = 0.0253, mean = 39.96 pg/mL, SD = 29.93) as compared to controls (mean = 88.56 pg/mL, SD = 66.20). In samples of men and women positive for HOM we observed higher concentrations of fT4 (p = 0.0038; mean = 5.79 ng/dL, SD = 15.64) compared to controls (mean = 1.47 ng/dL, SD = 0.47). Among the samples positive for HOM, samples tested positive for morphine had higher concentrations of rT3 and fT4 (p = 0.0007, 0.0002 respectively). In samples tested positive and negative for methadone significant increase was observed in the concentrations of serum T3 (p = <0.0001) while gabapentin showed a significant decrease in concentration of T3 (p= 0.0076). Samples positive for gabapentin also showed a decrease in concentration of serum fE2 (p = 0.0039). When samples from males and females of the groups positive and negative for HOM were compared, statistically significantly higher concentrations of T3 and fC were observed (p = 0.0046 and 0.0437 respectively) in men. In samples from women tested positive for HOM (aged 45 years and above) fC was found to be reduced (p=0.0310). When associations for the individual opioids were evaluated, samples of the oxycodone group showed significantly higher concentrations of T3 in men (p = 0.0190), while the gabapentin group showed significantly higher concentrations of fT4 in women (p = 0.0464). Distribution of the steroid concentrations in the methadone group did not show gender-specific associations.
Concentrations of fTe, fT4, fC, T3 and rT3 in blood are significantly impacted by presence of opiates. The significant effect of morphine on fC, rT3 and fT4 concentrations in men vs. gabapentin on rT3 and oxycodone on fT4 concentrations in women requires further investigation on the gender based difference in metabolism of these drugs. Our data suggests that increased use of opioid drugs could lead to endocrinopathy. Given the lack of clinical information regarding changes in the levels of free hormones in opiate users, this could be an important area of investigation for determining association of the painkiller treatments with endocrine disorders.
References & Acknowledgements:
We thank ARUP Institute for Clinical and Experimental Pathology® for supporting this project.
IP Royalty: no
|Planning to mention or discuss specific products or technology of the company(ies) listed above:||