JPC SYSTEMIC PATHOLOGY
Signalment (JPC #2677977): 4-year-old castrated male German shorthair pointer dog
HISTORY: Tissue from a dog with chronic weight loss, azotemia, and hyperkalemia.
HISTOPATHOLOGIC DESCRIPTION: Adrenal gland: Diffusely, the cortex is reduced to a thin rim of tissue with loss of the distinct radial arrangement of cells within all zones, and retention of remnants of stromal elements including thin strands of supporting fibrous connective tissue and blood vessels. The capsule is thickened up to 2-3x normal by fibrous connective tissue that is accentuated by subjacent cortical stromal collapse. The cortex is infiltrated by moderate numbers of lymphocytes, plasma cells, macrophages, and fewer eosinophils admixed with hemorrhage, fibrin, and edema. Macrophages often have microvacuolated cytoplasm and intracytoplasmic golden brown, granular pigment (hemosiderin). There are multifocal clusters of remaining zona reticularis cells with foamy, vacuolated cytoplasm (lipoidal degeneration).
MORPHOLOGIC DIAGNOSIS: Adrenal gland, cortex: Atrophy and loss, diffuse, severe, with lymphoplasmacytic and histiocytic adrenalitis, German shorthair pointer, canine.
CONDITION: Primary hypoadrenocorticism (Addison’s disease)
- Uncommon syndrome in animals, most often seen in dogs; characterized by loss of the adrenal glands capacity to secrete glucocorticoids and mineralocorticoids
- Most frequent lesion in dogs is bilateral adrenocortical atrophy involving all three layers of the cortex
- Zona glomerulosa: Secretes mineralocorticoids (aldosterone); secretion independent of ACTH
- Zona fasciculata: Secretes glucocorticoids (cortisol) and small amounts of androgens; secretion controlled by hypothalamic-pituitary axis
- Zona reticularis: Secretes androgens and glucocorticoids
- Loss of 85-90% of adrenocortical cells must occur before clinical signs are obvious
- Occurs more frequently in young adult dogs, predilection for females
- Risk of disease significantly higher in the Portuguese water dog, standard poodle, bearded collie, Cairn terrier, and Cocker spaniel
- Primary hypoadrenocorticism (adrenal-dependent hypoadrenocorticism/Addison’s disease)
- Idiopathic: Unknown pathogenesis; likely immune mediated destruction of cortex (see E-M04)
- Granulomatous disease: Destruction of adrenal cortex with histoplasmosis, blastomycosis, coccidiomycosis, or tuberculosis
- Other: Amyloidosis; infarction secondary to coagulopathy; cancer metastasis and subsequent destruction of adrenal cortex; hemorrhage and necrosis with replacement by fibrous connective tissue
- Secondary hypoadrenocorticism
- Naturally occurring disease (pituitary dependent hypoadrenocorticism); reduced secretion of ACTH by pituitary (i.e. due to neoplasia) resulting in decreased synthesis of adrenocortical hormones
- Iatrogenic: Acute discontinuation of chronic corticosteroid administration, or overdosage with o,p"-DDD (mitotane) for treatment of hyperadrenocorticism
TYPICAL CLINICAL FINDINGS:
- Chronic, insidious illness; initially episodic (waxing-waning) and only manifested in times of stress
- Weakness, low blood pressure/weak pulse, vomiting, diarrhea, dehydration, weight loss, shock
- Hyperpigmentation of the skin secondary to lack of negative feedback on pituitary and increased release of ACTH and also, possibly, melanocyte-stimulating hormone
- Cardiovascular disturbances secondary to hyperkalemia
- Hyponatremia and hyperkalemia
- Sodium/potassium ratio less than 23:1 is highly suggestive of adrenal insufficiency (normal range 27:1 to 40:1)
- Aldosterone deficiency results in renal loss of sodium and retention of potassium
- Cortisol deficiency > loss of gradient across cell membrane > shift of K+ from intracellular to extracellular compartment > hyperkalemia
- Less sodium and chloride are reabsorbed from the renal tubules, leading to various degrees of hypernatruria and hyperchloruria
- Sodium excretion is accompanied by water excretion, resulting in dehydration
- Hypochloridemia: Failure of resorption from renal tubules
- Hypoglycemia: A failure in gluconeogenesis and increased sensitivity to insulin contributes to the development of moderate hypoglycemia
- No response to ACTH stimulation
- Baseline plasma cortisol may be within reference interval or decreased
- Azotemia secondary to decreased renal perfusion or chronic urinary sodium loss
- Hypercalcemia occurs in approximately 33% of dogs with Addison"s syndrome; unknown pathogenesis, although several mechanisms have been postulated to be important: (1) decreased glomerular filtration rate and/or increased tubular calcium resorption (2) excessive intestinal absorption of calcium (3) increased bone resorption
- Mild metabolic acidosis from impaired renal tubular hydrogen secretion
- Atypical cases may present without electrolyte abnormalities
- Absence of a stress leukogram in stressful situations with lymphocytosis
TYPICAL GROSS FINDINGS:
- Bilateral adrenal cortical atrophy
- Compensatory pituitary hyperplasia
TYPICAL LIGHT MICROSCOPIC FINDINGS:
- Adrenal cortex is reduced to 1/10 or less of its normal thickness with marked atrophy of all three zones
- Adrenal medulla and capsule become relatively more prominent
- Multiple foci of lymphocytes and plasma cells early in disease giving way to atrophy and fibrosis and condition progresses (see E-M04)
- Thickened capsule from collapse of cortex and fibroblast proliferation
ADDITIONAL DIAGNOSTIC TESTS:
- Clinical signs, clinical-pathologic abnormalities
- ACTH stimulation test is test of choice, with no cortisol produced following ACTH administration
- The zones of adrenal cortex appear to become damaged at the same rate, so ACTH stimulation is used to directly assess cortisol synthesis and indirectly assess aldosterone synthesis
- Does not distinguish primary from secondary adrenocortical insufficiency
- Plasma ACTH concentration (although of limited use) is decreased in pituitary dependent hypoadrenocorticism, and increased in dogs with adrenal-dependent hypoadrenocorticism
- Acute renal failure: Important differential diagnosis for clinical signs and clinical pathology of Addison"s disease in general
- Urinary outflow obstruction
- Severe metabolic acidosis
- Chylous pleural effusion
- Pseudohyperkalemia: Akita (large concentration of potassium in RBCs); hemolyzed blood sample
- May be heritable in standard poodles
- Feline: Rare; may be primary (idiopathic) or secondary (administration of exogenous steroids or megestrol acetate)
- Bovine: Congenital hypoplasia of adrenal cortex inherited in Holstein and Ayrshire > prolonged gestation (2 months longer than normal) > nonviable large calf > dystocia
- Rabbits: Hereditary in IIIVO/ahJ strain
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