Adrenocortical hypertrophy: establishing cause and toxicological significance

Journal of Applied Toxicology - Tập 30 Số 7 - Trang 617-626 - 2010
Philip W. Harvey1, Catherine G. Sutcliffe2
1Toxicology Department, Covance Laboratories, Otley Road, Harrogate, North Yorkshire HG3 1PY, UK
2Pathology Department Covance Laboratories, Otley Road, Harrogate, North Yorkshire HG3 1PY, UK

Tóm tắt

AbstractThe primary cause of adrenocortical hypertrophy is increased adrenocorticotrophic hormone (ACTH) stimulation. In toxicology studies, such a condition can arise as a result of the stress response, but it may also occur due to deficient glucocorticoid feedback regulation of ACTH due to toxicity to the adrenal cortex. This latter condition is defined as adrenocortical insufficiency and represents a serious adverse toxic effect on the function of the adrenal cortex. Adrenocortical hypertrophy may occur in the absence of other adrenocortical lesions such that a toxicopathological mechanism is not obvious, for example by pharmacological inhibition of steroidogenesis at the biochemical level. This review discusses the different aetiological factors and mechanisms producing adrenocortical hypertrophy. The need for further evidence in ascribing findings to stress is discussed, as is a protocol for establishing differential diagnoses between stress‐induced and toxicity‐induced adrenocortical hypertrophy, which is useful in cases where there are no other histopathological lesions in the adrenal cortex. It is concluded that all cases of adrenocortical hypertrophy require further investigation or evidence to ascribe such findings to either stress or adrenocortical inhibition/insufficiency, and that all cases of adrenocortical insufficiency (whether due to a histopathological lesion or reversible pharmacological enzyme inhibition) represent a serious adverse effect that must be properly considered in toxicological risk assessment. Copyright © 2010 John Wiley & Sons, Ltd.

Từ khóa


Tài liệu tham khảo

10.1210/endo-113-6-2232

10.1210/endo-113-6-2226

10.1056/NEJMra0804635

Buckingham JC, 2002, Encyclopaedia of Stress, 261

Buckingham JC, 2008, Adrenal Toxicology, 77

Buckingham JC, 1992, The Adrenal Gland, 131

Camacho AM, 1967, Inhibition of adrenal steroidogenesis by aminoglutethimide and the mechanism of action, J. Am. Chem. Soc., 202, 114

Colagiovanni DB, 2008, Adrenal Toxicology, 161

10.1080/10915810600605898

Colby HD, 1996, The Adrenal in Toxicology: Target Organ and Modulator of Toxicity, 131

10.1210/er.2009-0002

10.1080/01926230600964722

10.1677/joe.0.1590035

Goldberg A, 1983, Etomidate, Lancet., 60

Greaves P, 2007, Histopathology of Preclinical Toxicity Studies: Interpretation and Relevance in Drug Safety Evaluation

Gumbleton M, 1996, The Adrenal in Toxicology: Target Organ and Modulator of Toxicity, 81

Hadley AJ, 1990, Modulation of corticotrophin release in vitro by methylxanthines and adenosine analogues, Br. J. Pharmacol., 100, 337

Harvey PW, 1996, The Adrenal in Toxicology: Target Organ and Modulator of Toxicity, 10.3109/9780203482674

10.1016/B978-0-08-046884-6.01115-5

10.1002/jat.896

10.1177/096032719201100611

10.1002/jat.1221

Harvey PW, 2008, Adrenal Toxicology, 3, 10.3109/9781420061307

Harvey PW, 2008, Adrenal Toxicology, 10.3109/9781420061307

10.1007/s00216-007-1657-5

10.1065/espr2007.03.402

Hinson JP, 1996, The Adrenal in toxicology: Target Organ and Modulator of Toxicity, 23

Hinson JP, 1999, Endocrine and Hormonal Toxicology, 67

10.1016/j.beem.2005.09.006

Holt RIG, 2008, Adrenal Toxicology, 39

10.1016/S0887-2333(01)00111-4

10.1210/endo-121-2-561

Kaspareit J, 2008, Adrenal Toxicology, 139

10.1038/sj.bjp.0701158

10.1016/S0140-6736(83)92712-5

10.1016/S0140-6736(83)92373-5

10.1177/0885066606298140

10.1016/0303-7207(92)90091-J

10.1210/edrv-5-1-25

10.1002/jat.1166

Parmar J, 2008, Adrenal Toxicology, 183

10.1210/jc.2008-0903

10.1080/01926230600978458

Philip JG, 1999, Endocrine and Hormonal Toxicology, 171

10.1002/ar.1092100408

Raven PW, 1996, The Adrenal in Toxicology: Target Organ and Modulator of Toxicity, 53

10.1016/0272-0590(84)90224-0

10.1080/019262301301418847

10.1093/toxsci/kfl051

Sanderson T, 2008, Adrenal Toxicology, 175

10.1080/01926230701595300

Stefanski SA, 1990, Pathology of the Fischer Rat: Reference and Atlas, 389

10.1177/019262338901700208

Tringali G, 2004, Valproic acid inhibits corticotropin‐releasing factor synthesis and release from the rat hypothalamus in vitro: evidence for the involvement of GABAergic neurotransmission, J. Psychiatry Neurosci., 29, 459

10.1152/ajpendo.00070.2006

10.1111/j.1365-2265.1983.tb00044.x

Yarrington JT, 1997, Comprehensive Toxicology, 637

Thông tin
Thông tin xuất bản

Journal of Applied Toxicology

Tập 30 Số 7

617-626

Thông tin tác giả