Endocrine System

Adrenal Gland, Cortex - Vacuolization, Cytoplasmic

Narrative
Comment:
Adrenal cortical vacuolization in rats and mice is characterized by the accumulation of usually clear vacuoles within cortical cells, mainly in the zona fasciculata, although the zonae reticularis and glomerulosa are also often affected. The vacuolization can be focal (Figure 1 and Figure 2) or diffuse (Figure 3 and Figure 4). Even large focal lesions generally cause little to no compression. The vacuoles can range from a single to a few large vacuoles to multiple smaller ones. In many cases, the vacuoles have been shown to represent accumulations of various lipids or cholesterol.

Cortical vacuolization can occur as a spontaneous, age-related change (especially in rats); secondary to stress from various causes; and from administration of many exogenous drugs and toxins, especially those that interfere with normal steroidogenesis in the adrenal cortex and/or perturb the hypothalamic-pituitary-adrenal hormonal axis (including normal secretion and metabolism of adrenocorticotropic hormone [ACTH]). Cortical vacuolization can also result from experimental administration of excess ACTH or corticosterone.
Recommendations:
Adrenal cortical cytoplasmic vacuolization should be diagnosed and assigned a severity grade. An appropriate distribution modifier (i.e., focal or diffuse) should also be included in the diagnosis. If localized to a particular zone of the cortex, this should be noted in the pathology narrative. In cases of adrenal cortical hyperplasia or hypertrophy with some constituent vacuolated cells, the vacuolization should not be diagnosed separately, though it should be described in the narrative as a feature of the hyperplasia or hypertrophy. If vacuolization is seen in both adrenal glands, the modifier "bilateral" should be added to the diagnosis (lesions are assumed to be unilateral unless otherwise indicated).
References:

Burkhardt WA, Guscetti F, Boretti FS, Todesco AI, Aldajarov N, Lutz TA, Reusch CE, Sieber-Ruckstuhl NS. 2011. Adrenocorticotropic hormone, but not trilostane, causes severe adrenal hemorrhage, vacuolization, and apoptosis in rats. Dom Anim Endocrinol 40:155-164.

Abstract: https://www.ncbi.nlm.nih.gov/pubmed/21194873

Cassano AE, White JR, Penraat KA, Wilson CD, Rasmussen S, Karatsorenos. 2012. Anatomic, hematologic, and biochemical features of C57BL/6NCrl mice maintained on chronic oral corticosterone. Comp Med 62:348-360.

Abstract: https://www.ncbi.nlm.nih.gov/pubmed/23114038

Frith CH, Botts S, Jokinen MP, Eighmy JJ, Hailey JR, Morgan SJ, Chandra M. 2000. Non-proliferative lesions of the endocrine system in rats, E-1. In: Guides for Toxicologic Pathology. STP/ARP/AFIP, Washington, DC.

Full Text: https://www.toxpath.org/docs/SSNDC/EndocrineNonprolifRat.pdf

Hamlin MH, Banas DA. 1990. Adrenal gland. In: Pathology of the Fischer Rat: Reference and Atlas (Boorman GA, Eustis SL, Elwell MR, Montgomery CA, MacKenzie WF, eds). Academic Press, San Diego, 501-518.

Abstract: https://www.ncbi.nlm.nih.gov/nlmcatalog/9002563

Harvey PW, Everett DJ, Springhall CJ. 2007. Adrenal toxicology: A strategy for assessment of functional toxicity to the adrenal cortex and steroidogenesis. J Appl Toxicol 27:103-115.

Abstract: https://www.ncbi.nlm.nih.gov/pubmed/17265431

Matsuura I, Saitoh T, Ashina M, Wako Y, Iwata H, Toyota N, Ishizuka Y, Namiki M, Hoshino N, Tsuchitani M, Ikeda Y. 2005. Evaluation of a two-generation reproduction toxicity adding endpoints to endocrine disrupting activity using vinclozolin. J Toxicol Sci 30:163-188.

Abstract: https://www.ncbi.nlm.nih.gov/pubmed/16641540

National Toxicology Program. 1990. NTP TR-378. Toxicology and Carcinogenesis Studies of Benzaldehyde (CAS No. 100-52-7) in F344/N Rats and B6C3F1 Mice (Gavage Studies). NTP, Research Triangle Park, NC.

Abstract: https://ntp.niehs.nih.gov/go/11295

National Toxicology Program. 1994. NTP TR-433. Toxicology and Carcinogenesis Studies of Tricresyl Phosphate (CAS No. 1330-78-5) in F344/N Rats and B6C3F1 Mice (Gavage and Feed Studies). NTP, Research Triangle Park, NC.

Abstract: https://ntp.niehs.nih.gov/go/6010

Nyska A, Maronpot RR. 1990. Adrenal gland. In: Pathology of the Mouse: Reference and Atlas (Maronpot RR, Boorman GA, Gaul BW, eds). Cache River Press, Vienna, IL, 509-536.

Abstract: http://www.cacheriverpress.com/books/pathmouse.htm

Rosol TJ, Yarrington JT, Latendresse J, Capen CC. 2001. Adrenal gland: Structure, function, and mechanisms of toxicity. Toxicol Pathol 29:41-48.

Abstract: https://www.ncbi.nlm.nih.gov/pubmed/11215683
  • Image of vacuolization, cytoplasmic in the adrenal gland cortex from a female F344/N rat in a chronic study

    Adrenal gland, Cortex - Vacuolization, Cytoplasmic in a female F344/N rat from a chronic study. A large focus of vacuolated cells (CV) in the zona fasciculata causes little if any compression of the adjacent cortex.

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<p>Adrenal gland, Cortex - Vacuolization, Cytoplasmic in a female F344/N rat from a chronic study. A large focus of vacuolated cells (CV) in the zona fasciculata causes little if any compression of the adjacent cortex.</p>

Adrenal gland, Cortex - Vacuolization, Cytoplasmic in a female F344/N rat from a chronic study. A large focus of vacuolated cells (CV) in the zona fasciculata causes little if any compression of the adjacent cortex.
<p>Adrenal gland, Cortex - Vacuolization, Cytoplasmic in a female F344/N rat from a chronic study (higher magnification of Figure 1). A large focus of cells (CV) in the zona fasciculata with variably sized vacuoles.</p>

Adrenal gland, Cortex - Vacuolization, Cytoplasmic in a female F344/N rat from a chronic study (higher magnification of Figure 1). A large focus of cells (CV) in the zona fasciculata with variably sized vacuoles.
<p>Adrenal gland, Cortex - Vacuolization, Cytoplasmic in a male F344/N rat from a subchronic study. Diffuse cytoplasmic vacuolization is present predominantly in the zonae fasciculata and glomerulosa.</p>

Adrenal gland, Cortex - Vacuolization, Cytoplasmic in a male F344/N rat from a subchronic study. Diffuse cytoplasmic vacuolization is present predominantly in the zonae fasciculata and glomerulosa.
<p>Adrenal gland, Cortex - Vacuolization, Cytoplasmic in a male F344/N rat from a subchronic study (higher magnification of Figure 3). The cells of the zonae fasciculata and glomerulosa contain variably sized vacuoles.</p>

Adrenal gland, Cortex - Vacuolization, Cytoplasmic in a male F344/N rat from a subchronic study (higher magnification of Figure 3). The cells of the zonae fasciculata and glomerulosa contain variably sized vacuoles.

Authors

Mark J. Hoenerhoff, DVM, PhD, DACVP
Associate Professor
Veterinary Pathologist, In Vivo Animal Core
Unit for Laboratory Animal Medicine
University of Michigan
Ann Arbor, MI

Georgette D. Hill, D.V.M., Ph.D.
Toxicologic Pathologist/Assistant Pathology Program Manager
Comparative Molecular Pathology Division
Integrated Laboratory Systems, Inc.
Research Triangle Park, NC

Margarita M. Gruebbel, DVM, PhD, DACVP
Senior Pathologist
Experimental Pathology Laboratories, Inc.
Research Triangle Park, NC

Reviewers

Thomas J. Rosol, DVM, PhD, DACVP
Professor of Veterinary Biosciences
Senior Advisor, Life Sciences, Technology Commercialization and Knowledge Transfer
The Ohio State University
Columbus, OH

Gordon Flake, MD
Staff Scientist
NTP Pathologist
Cellular and Molecular Pathology Branch
National Institute of Environmental Health Sciences
Research Triangle Park, NC