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

Presentation outline

Introduction Structure Function Clinical significance

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.

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.

Cont…

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.

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.

Cont…

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.

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.

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.

Cont…

Cortex

The adrenal cortex is devoted to production of corticosteroid (aldosterone, cortisol)

and androgen hormones.

Cont…

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.

Aldosterone Functions

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.

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.

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.

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.

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.

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.

Cont…

This type occasionally seen in humans; very rare in non-human animals.

Cont…

Clinical signs / lesions

Due to combined gluconeogenic, lipolytic, protein catabolic & anti-

inflammatory / immunosuppressive effects:

• Polyuria / polydipsia, ↑ GFR &/or interfere with ADH

• Polyphagia direct affect on satiety center

• Hepatomegaly ―>steroid (glycogen) hepatopathy‖

Cont…

• Pendulous abdomen muscle atrophy/weakness from protein catabolism &

hepatomegaly

• Skin lesions dermal atrophy, bilateral symmetric alopecia, delayed wound healing

• Dystrophic mineralization esp skin; +/- lung, etc (catabolism alters collagen /

elastin)

• Susceptibility to bacterial infections due to immunosuppressive effects

• Others: hypercoagulability, eosinopenia, lymphopenia / lymphoid involution

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.

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.

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.

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)

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

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)

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.

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

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.

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

Cont…

Pheochromocytoma, adrenal gland, horse. A pheochromocytoma compressing the adjacent unaffected adrenal cortex.

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).

Cont…

Pheochromocytoma, kidney, adrenal gland, caudal vena cava, dog. Opened caudal vena cava showing invasion of a

pheochromocytoma into the lumen (arrow).

Keep your adrenal gland carefully like

“TAKORACH CAKE”

I THANK YOU!