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Adrenal Gland: Chemically Induced Structural and Functional Changes in the Cortex

Chemical Pathology Research Division, Departments of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115

I. Th. Lippe

Chemical Pathology Research Division, Departments of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115

The adrenal cortex is the target of a surprisingly large number of exogenous chemicals. Until recently, the toxic action of these chemicals was discovered serendipitously. Following our observations that acrylonitrile, cysteamine or pyrazole induces hemorrhagic adrenocortical necrosis in the rat, we recently recognized a structure-activity correlation which predicts the adrenocorticolytic property of alkyl chemicals, i.e., 2–3 carbons with double or triple bonds and with nucleophilic terminal radicals (e.g., -CN, -SH, -NH2). On the basis of our results obtained with electron microscopic, histochemical and biochemical studies as well as those of others, we propose the following sequence of events in the pathogenesis of chemically induced adrenocortical necrosis: 1) Depletion of glutathione and increased dopamine concentration in the adrenals; 2) Endothelial damage and rupture of capillary walls in the adrenal cortex due to either direct attack by the chemicals (metabolites) and/or released monoamines; 3) Retrograde embolization of medullary tissue fragments into the cortical capillaries; 4) Enhanced destruction of cortical vascular walls with subsequent platelet aggregation, fibrin deposition which is of ten associated with a systemic drop in platelet counts, and changes in blood coagulation; 5) Escape of plasma and cellular elements of blood into extravascular spaces and damage of adrenocortical parenchymal cells; and 6) Hemorrhage and necrosis in the adrenal cortex. This pathogenetic sequence was investigated in detail with acrylonitrile, and studied in various aspects with thioguanine, cysteamine and pyrazole.

Key Words: Adrenal necrosis • acrylonitrile • cysteamine • pyrazole • drugs • structure-activity

Toxicologic Pathology, Vol. 17, No. 2, 317-329 (1989)
DOI: 10.1177/019262338901700208


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