January 2019
E-M04 (NP)

Slide A:  Signalment (JPC #2028971):  12-year-old German shepherd dog

HISTORY:  Tissue from a dog intermittently treated with prednisolone for skin allergies.

HISTOPATHOLOGIC DESCRIPTION:  Adrenal gland, adrenal cortex:  Diffusely, the zona fasciculata and zona reticularis are severely atrophied, reduced to approximately one-third normal thickness.  Multifocally, cortical cells near the corticomedullary junction have abundant vacuolated cytoplasm (degenerate) that contains small amounts of yellow-gold granular pigment (lipofuscin).  Multifocally, there are intracapsular nests of cortical cells, and the capsule and connective tissue septa are diffusely moderately expanded by fibrous connective tissue.  Vessels are mildly congested.

MORPHOLOGIC DIAGNOSIS:  Adrenal gland, zonae fasciculata and reticularis:  Atrophy, diffuse, moderate, German shepherd dog, canine.

ETIOLOGY:  Exogenous corticosteroid administration

ETIOLOGIC DIAGNOSIS:  Iatrogenic adrenocortical atrophy

Slide B:  SIGNALMENT (JPC #1669572):  10-year-old, male German shepherd dog

HISTORY:  Incidental finding

HISTOPATHOLOGIC DESCRIPTION:  Adrenal gland:  Diffusely all three cortical zones (zonae glomerulosa, fasciculata, and reticularis) are severely atrophic, and there is stromal collapse. Often, the few remaining cortical cells contain abundant vacuolated cytoplasm (degeneration) with small amounts of yellow-gold granular pigment (lipofuscin).  Multifocally within the cortex, medulla, and capsule, there are low to moderate numbers of infiltrating plasma cells and lymphocytes.

Heart, ventricle with AV valve: The free margin of the valve is mildly thickened by clusters of spindle cells on a loosely arranged myxomatous matrix (fibromyxomatous degeneration).  Multifocally, the walls of several arterioles within the myocardium are mildly expanded by an acellular, eosinophilic, waxy material (hyalinosis).


  1. Adrenal gland, cortex:  Pancortical atrophy, diffuse, severe, German shepherd dog, canine.
  2. Heart, valve: Fibromyxomatous degeneration (valvular endocardiosis). 

ETIOLOGY:  Immune-mediated

ETIOLOGIC DIAGNOSIS:  Idiopathic adrenocortical atrophy

CONDITION SYNONYMS:  Hypoadrenocorticism (HA), adrenocortical insufficiency, Addison’s disease


Adrenal Cortex:

  1. Zona glomerulosa (outermost): 15% of the cortex, produces mineralocorticoids (e.g. aldosterone)
    1. Principal effects of mineralocorticoids are on ion transport by epithelial cells (especially the renal tubular epithelium) -> maintenance of sodium and potassium concentrations and extracellular fluid volume
    2. Increased aldosterone -> increased sodium and chloride retention and increased potassium excretion by renal tubular epithelium (especially distal convoluted tubules via Na/K cation exchange)
    3. Amount of aldosterone released is controlled by the renin-angiotensin-aldosterone system (see below)
    4. In the ABSENCE of aldosterone, sodium and chloride with be lost and potassium retained (hyponatremia, hypochloremia, hyperkalemia); potentially lethal hyperkalemia in dogs
  2. Zona fasciculata (middle layer): 70% of the cortex; primary site of glucocorticoid production:  Cortisol, corticosterone, and cortisone
    1. Glucocorticoids antagonize the effects of insulin: they promote gluconeogenesis and glycogenesis and decrease glucose uptake by insulin-sensitive tissues -> net increase in serum glucose concentration, increased tissue catabolism
    2. Glucocorticoids cause decreased lipogenesis and increased lipolysis
    3. Glucocorticoids suppress inflammatory and immunologic responses and wound healing
  3. Zona reticularis (inner layer): 15% of the cortex; produces sex steroids (progesterone, estrogens, and androgens) in minute amounts normally, and some glucocorticoids

Hypoadrenocorticism (HA):









  1. Ferguson DC, Hoenig M. Endocrine system. In: Latimer KS, ed. Duncan & Prasse’s Veterinary Laboratory Medicine: Clinical Pathology. 5th Ames, IA: Wiley-Blackwell; 2011:317-323.
  2. Friedenberg SG, Brown DL, Meurs KM, Law JM. Lymphocyte subsets in the adrenal glands of dogs with primary hypoadrenocorticism.  Vet Pathol.  2018;55(1):177-181.
  3. Miller MA. Endocrine system. In: Zachary JF, McGavin MD, ed. Pathologic Basis of Veterinary Disease. 6th St. Louis, MO: Elsevier; 2017:708.
  4. Rosol TJ, Gröne Endocrine glands. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. 6th ed. St. Louis, MO: Elsevier; 2016:336-338, 341-343.

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