Toxic Effects on the Adrenals

Example compounds affecting the adrenal cortex include acrylonitrile, amino-gluthemide, amytriptyline, aniline, carbon tetrachloride (Colby et al. 1994), chloroform, cimetidine, etomidate, domperidone, fluphenazine, glycyrrhizin, ketoconazole (Loose et al. 1983), methanol, parathion, pentabarbitone, phencyclidine, pyra-zole, spironolactone, tamoxifen, and urethane (Colby and Longhurst 1992 Szabo and Sandoz 1997). Amytriptyline and cimetidine reduce corticosterone secretion, whereas pentobarbitone and phencyclidine increase its secretion. Etomidate inhibits 11(3- and 17a-hydroxylating reactions. Spironolactone affects cytochrome P450 enzymes (Kossor et al. 1991), and domperidone blocks cortisol secretion. Some ACAT inhibitors cause adrenal cytotoxicity (Wolfgang et al. 1995). 

Example compounds affecting the adrenal medulla include acrylonitrile, cysteam-ine, dichloromethane, malathion, estrogens, and thiouracil. 

Urinary corticoid measurements (in 17-24 h, but not short-term samples) can be used to assess adrenocortical function as alternatives to blood sampling techniques (Hilfenhaus 1977). The use of urinary measurements over a timed period may provide a better indication of corticosteroid metabolism in contrast to the fluctuations observed in plasma measurements. Although some reports in the literature use randomly collected urine for veterinary clinical diagnosis, these measurements are not suitable for toxicological studies. Older methods for urinary 17-hydroxycorticoster-oids have been replaced by cortisol or corticosterone measurements. 

For ACTH measurements, although there are small differences in amino acid sequences, most antibodies appear to react across several species, and several immunoassays have been used and reported in the literature. Plasma ACTH assays are problematic because the samples need to be carefully collected, separated promptly, and stored at low temperatures using ice. The proteinase inhibitor aprotinin has been used to reduce sample degradation (Kemppainen, Clark, and Peterson 1994 Scott-Moncrieff et al. 2003). 

There are functional tests in which ACTH or glucocorticoid measurements can be made following the administration of metyrapone, which inhibits adrenal llp-hydroxylase activity and causes a transient reduction in cortisol synthesis and increased secretion of 11-deoxycortisol (Orth et al. 1988), or dexamethasone suppression tests. However, these are not commonly employed in toxicological studies. 

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