SYSTEMIC PATHOLOGY I - VPM 221

Pathology of the
Endocrine System

Lecture 2
Adrenal & Thyroid Glands
(Web review)

Paul Hanna

Fall 2012

Adrenal Gland

[Anatomy of the Dog, Miller et al]

Adrenal Cortex
STRUCTURE AND FUNCTION
cortex ~75% of adrenal

produces over 50 different steroids

Figure 2014 (Mesher) Adrenal gland. Inside the capsule of each adrenal gland is an adrenal cortex, formed from embryonic
mesodermal cells, which completely surrounds an innermost adrenal medulla derived embryologically from neural crest cells.
Both regions are very well vascularized with fenestrated sinusoidal capillaries. Cortical cells are arranged as three layers: the
zona glomerulosa near the capsule, the zona fasciculata (the thickest layer), and the zona reticularis.

Adrenal Cortex

Zona glomerulosa - 15% (SALT)

Basic Histology

Figure 12-06 (Zachary). Aldosterone secreted by the zona glomerulosa of the adrenal cortex acts on the distal portions of
the nephron to increase tubular excretion of potassium and increase resorption of sodium (and secondarily of chloride).
The resulting osmotic gradient facilitates movement of water from the glomerular filtrate into the extracellular fluid (ECF).

Zona fasciculata - 70% (SUGAR)

Basic Histology

Glucocorticoids

CHO ( use of glucose in muscle /fat & gluconeogenesis, esp liver)

protein catabolic
lipolytic

cause hyperglycemia

increase glucose production // antagonistic to action of insulin

suppress inflammation, healing and immune response

Zona reticularis - 15% (SEX)

Basic Histology

Developmental Anomalies & Miscellaneous Lesions

1) Agenesis, unilateral or total
2) Hypoplasia 2o to maldevelopment of pituitary gland
3) Accessory adrenal cortical tissue
4) Mineralization
5) Amyloid deposition
6) Capsular sclerosis
7) Telangiectasis
8) Hemorrhages - sepsis / toxemia; severe stress or trauma in newborn

Diffuse hemorrhage of the inner region of the adrenal cortical ; gross (left) and histo (right)

Inflammation (Adrenalitis)
1) Viruses

herpesvirus

2) Bacteria
3) Fungi

gram negatives & mycobacteria

dimorphic fungi

4) Parasites

Toxoplasma

Multifocal necrosuppurative
adrenalitis in a foal with
sepsis due to A. equuli

Cornell - CVM

Hypoadrenocorticism (Addisons disease)

1) 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

Figure 12-59 (Zachary). 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.

Hypoadrenocorticism (Addisons disease)

a) Bilateral idiopathic adrenal cortical atrophy (contd)

Normal

Bilateral adrenal
cortical atrophy

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)

Hypoadrenocorticism (Addisons disease)

1) Primary Hypoadrenocorticism
b) Bilateral destruction of adrenal glands
due to inflammation, infarction, hemorrhage, tumor

2) 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

Hypoadrenocorticism (Addisons disease)

Clinical Signs / Lesions

primarily dogs
lethargy, stress intolerance, bradycardia, anorexia, vomiting & diarrhea

dehydration /
emaciation

possible acute circulatory failure, ie cardiogenic / hypovolemic shock

electrolyte imbalance (hyponatremia & hyperkalemia)

hallmark of Addisons

hypoglycemia, hemoconcentration & low plasma cortisol (no response to ACTH when 1o)

Adrenal Cortical Hyperplasia / Neoplasia

1) Diffuse hyperplasia:

ACTH (pit. adenoma or idiopathic)

excess glucocorticoids

cortex uniformly enlarged (inner 2 zones)

Cushings

Fig. 12-17 (Zachary) Secondary

hyperfunction of adrenal glands, brain,
pituitary gland and left and right adrenal
glands, dog. Corticotroph
(adrenocorticotropic hormone [ACTH]secreting) chromophobe adenoma (A) in
the pituitary gland and bilateral
(symmetrical) enlargement of the adrenal
glands. The chronic secretion of ACTH
has resulted in bilateral (symmetrical)
hypertrophy and hyperplasia of secretory
cells of the zona fasciculata and zona
reticularis in the adrenal cortex (arrows)
and excessive secretion of cortisol.

Adrenal Cortical Hyperplasia / Neoplasia

2) 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.

Adrenal Cortical Hyperplasia / Neoplasia

3) 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

Adrenal Cortical Hyperplasia / Neoplasia

4) Cortical carcinoma:
old dogs (may be functional)
often bilateral and may invade vena cava

Figure 12-28 (Zachary). 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.

Hypercortisolism (Cushings Disease)

a) Primary hyperadrenocorticism (10-15%): functional cortical neoplasm, esp adenoma
b) Secondary hyperadrenocorticism (80%): PDH or idiopathic (altered -ve set-point?)
c) Iatrogenic (pharmacological) hyperadrenocorticism (5-10%): overmedication

this type
occasionally
seen in humans;
very rare in nonhuman animals
Meuten: Tumors of Domestic Animals

Hypercortisolism (Cushings Disease)

Clinical Signs / Lesions
due to combined gluconeogenic, lipolytic, protein catabolic & anti-inflammatory /
immunosuppressive effects.

polyuria / polydipsia
polyphagia
hepatomegaly

direct affect on satiety center

steroid (glycogen) hepatopathy

pendulous abdomen
skin lesions

GFR &/or interfer with ADH

muscle atrophy/weakness from protein catabolism & hepatomegaly

dermal atrophy, bilateral symmetric alopecia, delayed wound healing

dystrophic mineralization

esp skin; +/- lung, etc (catabolism alters collagen / elastin)

susceptibility to bacterial infections

others:

due to immunosuppressive effects

hypercoagulability

eosinopenia
lymphopenia / lymphoid involution

Bristol

Fig. 8-73 (Zachary)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.

Figure 12-07 (Zachary). Dehiscence of surgical

wound, skin, dog. Wounds heal slowly in dogs with
cortisol excess because of an inhibition of fibroblastic
proliferation.

Adrenal Medulla

STRUCTURE AND FUNCTION

derived from neuroectoderm / neural crest

25% of adrenal gland

composed of pheochromocytes and a few ganglion cells

catecholamines derived from tyrosine

norepinephrine to epinephrine

Figure 2016. (Mescher) Adrenal medulla. The hormonesecreting cells of the adrenal medulla are chromaffin cells, which resemble
sympathetic neurons. (a): The micrograph shows they are large palestaining cells, arranged in cords interspersed with wide capillaries. Faintly
stained cytoplasmic granules can be seen in most chromaffin cells. X200. H&E. (b): TEM reveals that the granules of norepinephrinesecreting
cells (NE) are more electrondense than those of cells secreting epinephrine (E), which is a function of the chromogranins to which the
catecholamines are bound in the granules. Most of the hormone produced is epinephrine, which is only made in the adrenal medulla. X33,000.

Adrenal Medullary Hyperplasia / Neoplasia

Pheochromocytoma:
mainly in dogs & cattle
tumor is often large and encapsulated
rarely functional

may invade the vena cava and metastasize

tachycardia, edema and cardiac hypertrophy

K2Cr2O7 or KI on cut surface

dark-brown coloration in 5-20 min

Figure 12-36 (McGavin). Pheochromocytoma, adrenal gland, horse. A pheochromocytoma

compressing the adjacent unaffected adrenal cortex.

Figure 12-31 (Zachary). 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).

Pheochromocytoma, kidney, adrenal gland, caudal vena cava, dog. Opened caudal
vena cava showing invasion of a pheochromocytoma into the lumen (arrow).

Thyroid Gland
THYROID FOLLICULAR CELLS

THYROID C (PARAFOLLICULAR)
CELLS

[Anatomy of the Dog, Miller et al]

Thyroid Gland

Normal thyroids and parathyroids

Basic Histology

Thyroid Follicular Cells

STRUCTURE AND FUNCTION

largest endocrine organ and secretion controlled by TSH & TRH
T4 and T3 act like steroid hormones, but act on virtually all cells
regulate growth / differentiation / rate of metabolism

increase BMR

evaluate via serum cholesterol, T4 & T3, TSH Stimulation Test, biopsy

thyroid follicles containing colloid

TSH

TSH
Figure 2021 (Mescher) Thyroid follicular cell functions. The diagram shows the multistep process by which thyroid hormones are produced via the stored
thyroglobulin intermediate. In an exocrine phase of the process, the glycoprotein thyroglobulin is made and secreted into the follicular lumen and iodide is
pumped across the cells into the lumen. In the lumen tyrosine residues of thyroglobulin are iodinated and then covalently coupled to form T3 and T4 still within
the glycoprotein. The iodinated thyroglobulin is then endocytosed by the follicular cells and degraded by lysosomes, releasing free active T3 and T4 to the
adjacent capillaries in an endocrine manner. Both phases are promoted by TSH and may occur simultaneously in the same cell.

Developmental Anomalies

1) Aplasia and Hypoplasia

2) Accessory Thyroid Tissue
3) Thyroglossal duct cysts

Degenerative and Inflammatory Changes

1) Lymphocytic (Immune-mediated) Thyroiditis:
esp dogs,

develop clinical hypothyroidism

due to autoantibodies to thyroglobulin and other colloid Ags

multifocal to diffuse infiltrate of lymphocytes, plasma cells and macrophages

later fibrosis

vacuolated colloid which may contain inflammatory cells / cellular debris

note: severe lymphoid infiltration with destruction / effacement of normal thyroid architecture

Degenerative and Inflammatory Changes

2) Idiopathic Follicular Atrophy ("Collapse"):
cause of hypothyroidism in dogs
progressive loss of follicular epithelium & replacement by adipose tissue

Thyroid atrophy, note apparent (not real)

enlargement parathyroids because of reduced
size of thyroid gland.

FIG 51-2 (Small Animal Internal Medicine, 4th

Edition) .Histologic section of a thyroid gland
from a dog with idiopathic atrophy of the thyroid
gland and hypothyroidism. Note the small size
of the gland, decrease in follicular size and
colloid content, and lack of a cellular infiltration.

Hypothyroidism
mostly dogs
esp due to: idiopathic follicular collapse or lymphocytic thyroiditis
[rarely bilateral nonfunctional tumors, chronic pituitary lesions or severe I2 deficiency]

Clinical Signs / Lesions

reduced BMR
skin

lethargy, weight gain, muscular weakness & slow reflexes

bilaterally symmetric alopecia, hyperpigmentation,

reproductive abnormalities
joint pain & effusion

Clin Path

myxedema

lack of libido, infertility, etc

? pathogenesis?

low T4 & T3, normocytic normochromic anemia & high serum cholesterol

hypercholesterolemia

atherosclerosis & hepatic / glomerular / corneal lipidosis

Hypothyroidism

note: symmetric alopecia (above)

and obesity and myxedema (right)

www.cvm.okstate.edu

Hypothyroidism

Web Figure 12-5 (Zachary). Atherosclerosis, hypothyroidism with marked

hyperlipidemia, heart, coronary arteries, dog. Note the atherosclerosis (arrows) of the
coronary arteries which are thickened, firm, yellow-white, and often beaded.

Thyroid Hyperplasia (Goiter)

nonneoplastic, noninflammatory enlargement due to increased TSH secretion
results from inadequate thyroxine synthesis and decreased T4 & T3 blood levels
the four major pathogenetic mechanisms include:
a) iodine deficient diet

b) excess dietary iodine

c) goitrogenic compounds interfering with thyroxinogenesis
d) genetic enzyme defects in hormone synthesis

Thyroid Hyperplasia (Goiter)

1) Diffuse Hyperplastic Goiter:
in young of dams on I2 deficient / excess I2 diets or fed goitrogenic substances
marked enlargement

irregular hyperplastic follicles with pale & vacuolated colloid

Figure 12-38 (Zachary). Hyperplastic goiter, thyroid gland, dog.

Hyperplastic follicular epithelium forms a papillary projection (arrow), which
extends into the follicular lumen devoid of colloid. Note that the majority of
follicular lumens are small and collapsed. Periodic acidSchiff reaction.

Thyroid Hyperplasia (Goiter)

2) Colloid goiter:
represents involutionary phase of hyperplastic goiter
see large follicles with densely eosinophilic colloid & less vascularization

Figure 12-10 (McGavin) Colloid

goiter, thyroid gland, dog. Thyroid
follicular are progressively distended
with densely eosinophilic colloid. This
occurs for a period after the
correction of the inciting cause of the
hyperplastic goiter as the hyperplastic
follicular cells have in the short-term
produced more colloid than is
needed. Over time the gland can
eventually return to normal.

Thyroid Hyperplasia (Goiter)

3) Congenital dyshormonogenetic goiter (inherited goiter):
AR in some breeds of sheep, goats and cattle
genetic impairment of thyroglobulin synthesis
T4 & T3 levels are low even though I2 uptake / turnover are increased
see subnormal growth rate, sparse haircoat, myxedema, weakness & sluggish behaviour
thyroid lobes are symmetrically enlarged at birth

Neonatal goat kid with congenital

dyshormongenetic goiter

Thyroid Hyperplasia / Neoplasia

1) Multifocal Nodular Hyperplasia:
idiopathic
usually incidental in old animals; except cats where it may be functional

thyroids moderately enlarged with multiple, irregular, non-encapsulated nodules

Nodular hyperplasia, thyroid glands,

cat. Note the multiple hyperplastic
nodules in thyroid glands

Thyroid Hyperplasia / Neoplasia

2) Follicular Cell Adenoma

may be functional; cats > dogs & horses
adenomas usually single, encapsulated nodular or cystic masses

Follicular cell adenoma, thyroid gland,

horse. Note compression of adjacent
thyroid tissue on histology (right).

Thyroid Hyperplasia / Neoplasia

3) Follicular Cell Carcinoma:

carcinomas are more common in dogs (+/- functional)
typically multinodular, invade local tissues & often metastasize early to the lungs
may arise from accessory thyroids (ie mediastinum or heart base regions)

Thyroid carcinoma (arrows),

dog. Note, this poorly
circumscribed and wellvascularized thyroid carcinoma
(arrows) is locally invasive and
has extended into the wall of
the esophagus.

Hyperthyroidism
esp aged cats with nodular hyperplasia or functional adenomas / carcinomas

Clinical Signs / Lesions

PU / PD, restlessness, increased activity and weight loss in spite of polyphagia
may be cervical swelling, coughing and dyspnea, left ventricular hypertrophy

Note the obvious weight

loss in this cat with
hyperthyroidism.