1. ADDIS ABABA UNIVERSITY COLLEGE OF VETERINARY MEDICINE AND
AGRICULTURE
INDIVIDUAL PRESENTATION ON ADRENAL GLAND PATHOLOGY
BY:
Akinaw Wagari
Instructor: Tilaye D. (DVM, MSc, Assistant Prof.) (Pathologist)
April, 20/2015
Bishoftu, Ethiopia
3. 1. INTRODUCTION
• The adrenal glands (suprarenal glands) are endocrine glands that produce a wide
variety of hormones.
• They are found on the top of the kidneys and consist of a number of different
layers that directly influence the structure and function of the glands.
• Each gland has an outer cortex made of steroid-producing cells surrounding a
core of medulla, formed by chromaffin cells in direct relationship with the
sympathetic nervous system.
4. Cont…
• Mineralocorticoids, produced in the zona glomerulosa, help in the regulation of
blood pressure and electrolyte balance.
• Glucocorticoids such as cortisol, are synthesized in the zona fasciculata and
their functions include regulation of glycogen and lipid metabolism and immune
system suppression.
• The innermost layer of the cortex produces androgens (steroid hormones) that are
converted to fully functional sex hormones in the gonads and other target organs.
6. Cont…
• Regulation of synthesis and secretion of adrenal hormones is equally varied.
• Mineralocorticoid production is mainly under influence of the renin–
angiotensin–aldosterone system, in which specialized juxtaglomerular cells of
the kidneys monitor blood volume and start a cascade of reactions that leads to
the stimulation of aldosterone synthesis in the zona glomerulosa.
7. Cont…
• Cortisol and androgen synthesis are under control of the hypothalamic-pituitary-
adrenal (HPA) axis in a classic example of a negative feedback loop, in which
the hypothalamus and pituitary gland release stimulating hormones whenever
cortisol levels are low.
• In contrast, release of medullary catecholamine's is regulated by direct innervation
from the sympathetic nervous system.
9. Cont…
• A number of endocrine diseases and disorders can affect the normal functioning of the
adrenal gland.
• Overproduction of corticosteroid Cushing's syndrome, whereas insufficiency is
commonly associated with Addison's disease.
• Congenital adrenal hyperplasia is a genetic disease produced by a dis-regulation of
endocrine control mechanisms.
• A variety of tumors can arise from adrenal tissue, and are commonly found in medical
imaging when searching for other diseases.
10. 2. STRUCTURE
• The adrenal glands are located bilaterally in the retro-peritoneum superior and slightly
medial to the kidneys.
• Histological section of adrenal gland from the surface to the center: zona glomerulosa,
zona fasciculata, zona reticularis, medulla. In the medulla, the central adrenomedullary
vein is visible.
• A weak septum of connective tissue separates the glands from the kidneys and
facilitates surgical removal of the kidneys without damage to the glands.
11. Cont…
• The adrenal glands are in-close relationship with the diaphragm and are attached
to diaphragm by means of the renal fascia.
• It has two anatomically and functionally distinct parts, the outer adrenal cortex
and the inner medulla, both of which produce hormones.
• The cortex mainly produces aldosterone, cortisol and androgens, while the
medulla produces adrenaline and noradrenaline.
15. Cont…
• The adrenal cortex exhibits functional zonation as well: by virtue of the
characteristic enzymes present in each zone, the zones produce and secrete distinct
hormones.
Zona glomerulosa
• The outermost layer of the adrenal cortex, the zona glomerulosa, lies immediately
under the fibrous capsule of the gland.
• This layer is the main site for production of aldosterone, a mineralocorticoid, by
the action of the enzyme aldosterone synthase.
17. Zona fasciculata
• Situated between the glomerulosa and reticularis, the zona fasciculata is
responsible for producing mainly glucocorticoids such as cortisol.
• It is the widest of the three layers as it composes nearly 80% of the cortical
volume.
• Abundant mitochondria and a complex smooth endoplasmic reticulum are also
present in the cells of this layer.
18. Zona reticularis
• It produces androgens, mainly dehydroepiandrosterone (DHEA), DHEA
sulfate (DHEA-S), and androstenedione (the precursor to testosterone) in
humans.
• Its small cells form irregular cords and clusters, separated by capillaries and
connective tissue.
• The cells contain relatively small quantities of cytoplasm and lipid droplets, and
sometimes display brown lipofuscin pigment.
19.
20. Medulla
• The adrenal medulla is the core of the adrenal gland, and is surrounded by the
adrenal cortex.
• The chromaffin cells of the medulla (named for their characteristic brown
staining with chromic acid salts) are the body's main source of the circulating
catecholamines (adrenaline and noradrenaline).
• Approximately 20% noradrenaline (norepinephrine) and 80% adrenaline
(epinephrine) are secreted.
21. Cont…
• To carry out its response, the adrenal medulla receives input from the sympathetic
nervous system through preganglionic fibers originating in the thoracic spinal
cord from T5–T11.
• Because it is innervated by preganglionic nerve fibers, the adrenal medulla can
be considered as a specialized sympathetic ganglion.
• Unlike other sympathetic ganglia, however, the adrenal medulla lacks distinct
synapses and releases its secretions directly into the blood.
22. Blood supply
• The adrenal glands (alongside the thyroid gland) have one of the greatest blood
supply per gram of tissue of any organ. Up to 60 arterioles may enter each
adrenal gland. This may be one of the reasons that lung cancer commonly
metastasizes to the adrenals.
• The central adrenomedullary vein in the adrenal medulla; is structurally different
from the other veins in that the smooth muscle in its tunica media is arranged in
conspicuous, longitudinally oriented bundles.
23. CLINICAL SIGNIFICANCE
Corticosteroid overproduction
• Cushing's syndrome is the manifestation of glucocorticoid excess.
• It can be the result of a prolonged treatment with glucocorticoids or be caused by an
underlying disease which produces alterations in the HPA axis or the production of
cortisol.
• It can be further classified into ACTH-dependent or ACTH-independent.
• The most common cause of endogenous Cushing's syndrome is a pituitary
adenoma which causes an excessive production of ACTH.
27. Cont…
Glucocorticoid-induced hepatopathy, liver, dog. In
dogs with glucocorticoid excess (Cushing's
disease) from endogenous or exogenous sources,
an extensive accumulation of glycogen in
hepatocytes results in an enlarged, pale-brown to
beige liver.
Dehiscence of surgical wound, skin, dog. Wounds
heal slowly in dogs with cortisol excess because of
an inhibition of fibroblastic proliferation.
28. Addison's disease (Primary Hypoadrenocorticism)
a) Bilateral idiopathic adrenal cortical atrophy:
• Esp. young to middle-aged female dogs; autoimmune / hereditary
• Destruction of all 3 layers deficient production of all cortical hormones
Adrenal cortical atrophy, brain stem and
pituitary gland, adrenal glands, dog.
Bilateral atrophy of all three cortical layers
(arrows) is characteristic of
hypoadrenocorticism. The pituitary gland
(arrowhead) was grossly normal with
microscopic evidence of corticotroph
hyperplasia.
29. Cont…
• An adrenal crisis is a medical emergency in which low glucocorticoid and
mineralocorticoid levels result in hypovolemic shock and an array of nonspecific
symptoms such as vomiting and fever.
• An adrenal crisis can progressively lead to stupor and coma.
30. Normal (above) Adrenal cortical atrophy – low
power (top right) and high power (bottom right)
Note: collapsed, thickened capsule (*) (top
right) and macrophages filled with yellow
ceroid / lipofuscin pigment (below right)
31. Secondary hypoadrenocorticism
• ACTH deficiency -> trophic atrophy of inner 2 zones (not mineralocorticoids)
a) Destructive pituitary lesions
• damage to the cells making ACTH
b) Iatrogenic
• following sudden withdrawal of glucocorticoid after prolonged usage
32. Tertiary adrenal insufficiency
• Tertiary adrenal insufficiency results from a deficiency in the production of CRH
(produced by the hypothalamus).
Clinical signs / lesions
•Primarily dogs: lethargy, stress intolerance, bradycardia, anorexia, vomiting &
diarrhea, dehydration / emaciation
•Possible acute circulatory failure, i.e., cardiogenic / hypovolemic shock
•Electrolyte imbalance (hyponatremia & hyperkalemia) hallmark of Addison’s
•Hypoglycemia, hemoconcentration & low plasma cortisol (no response to ACTH
when 1o)
33. Adrenal cortical hyperplasia / neoplasia
Diffuse hyperplasia:
• ACTH (pit. adenoma or idiopathic) cortex uniformly enlarged (inner 2 zones)
• excess glucocorticoids -> Cushings
Nodular hyperplasia:
• Seen in old horses, dogs & cats (+/- functional)
• Often multiple, bilateral and yellow
Multiple hyperplastic nodules of cortical scattered
throughout adrenal; note: minimal compression.
34. Cont…
Cortical adenomas:
• Especially old dogs (often functional)
• Nodular hyperplasia vs adenoma (generally larger, encapsulated and compressive)
Cortical adenoma note: single, larger mass
with some evidence of compressive atrophy
of adjacent adrenal tissue
35. Cont…
Cortical carcinoma: Old dogs (may be functional)
• Often bilateral and may invade vena cava
Adrenocortical carcinoma and contralateral cortical atrophy, adrenal glands, dog. The adrenal gland (right) has a large
adrenocortical carcinoma that is almost half the size of an adult kidney (left). Multifocal to coalescing areas of hemorrhage and
necrosis are apparent (arrowheads) in this tumor. The cortex of the contralateral adrenal gland (lower) is notably thinned (arrow)
because of severe trophic atrophy of the zona fasciculata and zona reticularis.
36. Adrenal medullary hyperplasia / neoplasia
Pheochromocytoma:
• Mainly in dogs & cattle
• Tumor is often large and encapsulated may invade the vena cava and metastasize
• Rarely functional tachycardia, edema and cardiac hypertrophy
• K2Cr2O7 or KI on cut surface dark-brown coloration in 5-20 min
38. Cont…
Pheochromocytoma, kidney, adrenal gland, caudal vena cava, dog. A large pheochromocytoma (P) has obliterated the
adrenal gland medial to the kidney (K) and has extensively invaded into the lumen of the caudal vena cava (arrow).
39. Cont…
Pheochromocytoma, kidney, adrenal gland, caudal vena cava, dog. Opened caudal vena cava showing invasion of a
pheochromocytoma into the lumen (arrow).
