Cui Dongmei. Atlas of Histology: with functional and clinical correlations. 1st ed

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nuclei, and the arcuate nuclei. The hypothalamus itself receives

signals from many areas of the brain, including the amygdala,

hippocampus, brainstem tegmentum, and the infralimbic and

cingulate cortices. The hypothalamus maintains body homoeo-

stasis by regulating production of the hypothalamic hormones,

which, in turn, control the secretion of the pituitary hormones

from the pituitary gland.

THE ADENOHYPOPHYSIS, also called the anterior pitu-

itary, is the anterior division of the gland and is derived

from the ectoderm of the roof of the developing oral cav-

ity (Rathke pouch). It is composed of glandular tissue. The

adenohypophysis can be divided into three regions based on

their anatomic positions: the pars distalis, pars tuberalis, and

pars intermedia.

1. The pars distalis is the main body of the adenohypophysis,

containing blood vessels, a capillary network, and two main

types of secretory cells supported by a network of reticu-

lar connective tissues. These secretory cells are classiﬁ ed as

chromophobes and chromophils. The chromophobes do not

effectively take a stain, so they appear clear in the Mallory

trichrome stain. These cells are undifferentiated cells but are

capable of differentiating into chromophils. The chromophils

include basophils and acidophils (Fig. 17-4A).

Basophils appear blue in Mallory stain and include three

subtypes of hormone secretory cells: corticotrophs, thyrotrophs,

and gonadotrophs. Various hormones are produced by these

cells, including ACTH, TSH, FSH, and luteinizing hormone

(LH). These hormones stimulate various target organs includ-

ing the cortex of the adrenal glands, the thyroid, the testes, and

the ovaries (see Fig. 17-2 for details). The secretion of hormones

by cells in the adenohypophysis is controlled by hypothalamic

releasing hormones and inhibitory hormones. Corticotrophs

are stimulated by corticotropin-releasing hormone (CRH)

from the hypothalamus. Thyrotrophs are stimulated by thy-

rotropin-releasing hormone. Gonadotrophs are stimulated by

gonadotropin-releasing hormone.

Acidophils appear red in Mallory stain and contain two sub-

types of hormone secretory cells: somatotrophs and mammotro-

phs. Somatotrophs secrete somatotropin (growth hormone),

which stimulates the liver to produce the insulin-like growth

factor (IGF-1) that promotes cartilage and bone growth, pro-

tein deposition, and cell reproduction. Mammotrophs secrete

prolactin, which increases mammary gland size and promotes

milk production.

2. The pars tuberalis is the neck of the adenohypophysis; it wraps

around the infundibular stalk of the pituitary gland (Fig. 17-3A).

It contains a rich capillary network and some low columnar

basophilic cells that are commonly arranged in cords.

3. The pars intermedia is located between the pars distalis and

pars nervosa (Figs. 17-3A and 17-5A). It contains cuboidal

follicular cells and colloid cysts called Rathke cysts

, which

are lined by follicular cells. Rathke cysts are derived from

the ectoderm of the dorsal portion of the Rathke pouch;

these cysts are considered to be the remnants of the Rathke

pouch that was present during development. The secretory

cells may be involved in producing melanocyte-stimulating

hormone (MSH). These cells are usually lightly stained by

basophilic dye.

THE NEUROHYPOPHYSIS is derived from the inferior sur

face of the developing diencephalon. It is considered to be ner-

vous tissue. It can be divided into the infundibular stalk, the

median eminence, and the pars nervosa.

1. The infundibular stalk connects the median eminence to the

pars nervosa (Fig. 17-3A,B).

2. The median eminence connects the inferior portion of the hypo-

thalamus to the infundibular stalk of the neurohypophysis

(Fig. 17-3B). It contains long axons that carry antidiuretic

hormone (ADH) and oxytocin hormone produced by nuclei

in the hypothalamus. These axons pass through the median

eminence and terminate in the pars nervosa. The median emi-

nence also contains short axons and axon terminal endings

from the hypothalamus that release neurosecretory hormones

(hypothalamic releasing and inhibiting hormones). These

hormones are transported through the hypophyseal portal

system from the primary capillary plexus to the secondary

capillary plexus, thereby regulating the secretion of the secre-

tory cells in the adenohypophysis.

3. The pars nervosa is the main body of the neurohypophysis

(Figs. 17-3A and 17-6A,B). It contains a fenestrated capil-

lary plexus, pituicytes (glial cells), and axons and axon ter-

minal endings from neuron cell bodies in the hypothalamus.

Pituicytes provide support and nutrition to the axons of

the neurons. The enlarged axon terminal endings are ﬁ lled

with neurosecretory granules that are called Herring bod-

ies. The neurosecretory hormones released in the pars ner-

vosa include ADH or vasopressin, oxytocin hormone, and

neurophysins.

Thyroid Gland

The thyroid gland has two lobes that are located inferior to the

thyroid cartilage and anterior to the trachea. It contains thyroid

follicles that produce T

and T

, which regulate body metabo-

lism (Fig. 17-8A,B). The parafollicular cells located between the

follicles are known as clear cells (C cells) and produce calcitonin

hormone. This hormone is released in response to high blood

calcium and inhibits the activity of the osteoclasts. Calcitonin

is involved in calcium and phosphorus metabolism. It decreases

blood calcium levels and has opposing effects to the parathor-

mone or PTH.

Parathyroid Glands

There are typically four small parathyroid glands, most com-

monly lying posterior to the thyroid gland. They consist of chief

cells and oxyphil cells (Fig. 17-9A,B). Chief cells are hormone-

producing cells that secrete parathormone, also called PTH.

PTH is released in response to low blood calcium levels and

indirectly promotes the proliferation and activity of osteoclasts,

which remove bone. PTH also inhibits the activity of osteo-

blasts, which help to build up new bone.

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PTH indirectly promotes osteoclasts by stimulating

osteoblasts to produce osteoclast differentiation factor, also

known as RANKL, which stimulates precursors (monocytes)

to differentiate and fuse to become multinuclear osteoclasts.

Increased numbers of osteoclasts cause active bone resorption,

which results in more Ca

being released into the blood. PTH

also affects the distal tubules of the kidney to increase blood cal-

cium levels by enhancing the reabsorption of calcium from distal

tubules.

Adrenal Glands

The adrenal glands lie on the superior tips of the kidneys, in the

posterior portion of the abdominal cavity. The adrenal glands can

be divided into the cortex and the medulla (Fig. 17-10A). The cor-

tex has three zones: (moving from external to internal) the zona

glomerulosa, zona fasciculata, and zona reticularis (Fig. 17-10B).

Cells in the cortex produce various corticosteroid hormones

including mineralocorticoids, glucocorticoids, and weak andro-

gens (see Table 17-1). The medulla contains ganglion neurons and

chromafﬁ n cells. The chromafﬁ n cells produce adrenaline (epi-

nephrine) and noradrenaline (norepinephrine). These hormones

are known as sympathomimetic hormones (Fig. 17-12A,B).

Pineal Gland

The pineal gland is located inside the skull and lies above the

superior colliculi of the midbrain. It is considered part of the

epithalamus of the brain. It contains pinealocytes, neuroglial

cells, and calciﬁ ed structures called brain sand (corpora

arenacea). The corpora arenacea are derived from the organic

matter in the pineal gland and are rich in calcium and phos-

phate. The pineal gland has a rich blood supply. Pinealocytes,

modiﬁ ed neurons that produce melatonin, are the predominant

cells in the pineal gland. Melatonin is an important hormone

in the regulation of the day and night cycle called the circadian

rhythm (Fig. 17-13A,B).

Endocrine Pancreas (Islets of Langerhans)

There are many islets of Langerhans interspersed in the exocrine

portion of the pancreas (Figs. 17-14A to 17-15B). The islets of

Langerhans contain alpha cells, beta cells, delta cells, and pancre-

atic polypeptide (PP) cells. These hormone secretory cells produce

glucagon, insulin, somatostatin, and PP, important hormones in

regulating blood glucose levels.

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Figure 17-1. Overview and orientation of detailed endocrine organ illustrations.

The illustration on the left shows the location of the endocrine organs, which include the pituitary gland, pineal gland, thyroid gland,

parathyroid glands, adrenal glands, endocrine pancreas (islet of Langerhans), testes (see Chapter 18, “Male Reproductive System”),

and ovaries (see Chapter 19, “Female Reproductive System”). The pituitary and pineal glands are neuroendocrine organs; they are

located inside the skull and are considered part of the brain. The thyroid gland has two lobes and is located inferior to the thyroid

cartilage and anterior to the trachea. There are four parathyroid glands located behind (posterior to) the thyroid gland. The adrenal

glands and pancreas are located in the abdominal cavity. The islet of Langerhans is the endocrine portion of the pancreas. The ovaries

and testes produce sex-related hormones and also are part of the reproductive system; the details are discussed in Chapters 18 and 19.

The illustration on the right shows the orientation of detailed endocrine organ illustrations presented in different ﬁ gures.

Hypothalamus

Pituitary

gland

Thyroid

gland

Adrenal

gland

Testis

Parathyroid

gland

(behind thyroid)

Pancreas

Ovary

Pineal

gland

Pineal

gland

Fig. 17-13A,B

Fig. 17-14A to

Fig. 17-15B

Fig. 17-10A to

Fig. 17-12B

Fig. 17-3B to

Fig. 17-6B

Fig. 17-8A,B

Fig. 17-9A,B

Endocrine Organs with Figure Numbers

Pituitary glands

Figure 17-2

Figure 17-3A

Figure 17-3B

Figure 17-3C

Figure 17-4A

Figure 17-4B

Figure 17-5A

Figure 17-5B

Figure 17-6A

Figure 17-6B

Figure 17-7A–C

Thyroid glands

Figure 17-8A

Figure 17-8B

Figure 17-8C

Parathyroid glands

Figure 17-9A

Figure 17-9B

Figure 17-9C

Adrenal glands

Figure 17-10A

Figure 17-10B

Figure 17-11A

Figure 17-11B

Figure 17-12A

Figure 17-12B

Pineal glands

Figure 17-13A

Figure 17-13B

Figure 17-13C

Endocrine pancreas (islet of Langerhans)

Figure 17-14A

Figure 17-14B

Figure 17-15A

Figure 17-15B

Figure 17-16

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Pituitary Gland

Kidney

Water absorption

(collecting tubules)

Uterus

Contraction

(smooth muscle of

myometrium)

Mammary gland

Milk secretion

(secretory cells)

Muscle

Growth

(skeletal muscle)

Adipose tissue

Utilization for energy

(adipose cells)

Mammary gland

Contraction

(myoepithelial cells)

Adrenal cortex

Corticosteroids

secretion

(salt, sugar, sex)

Thyroid

T and T secretion

(metabolic activity)

Ovary

Progesterone

secretion

(ovulation)

Liver

Secretion of IGF-1

(somatomedins)

(hepatocytes)

Ovary

Estrogen

secretion

(follicle growth)

Testis

Secretion of testosterone

by Leydig cells

(sex characteristics)

Testis

Secretion by Sertoli cells

(spermatogenesis)

ACTH (+)

(corticotrophs)

TSH (+)

(thyrotrophs)

Oxytocin (+)

(from supraoptic and

paraventricular nuclei)

Prolactin (+)

(mammotrophs)

Growth hormone/

somatotrophin (+)

(somatotrophs)

ADH/vasopressin (+)

(from supraoptic nucleus)

LH (+)

(gonadotrophs)

FSH (+)

(gonadotrophs)

Bone

Growth

(epiphyseal plate)

Hypothalamus

(–)

Releasing hormones

Figure 17-2. Overview of hormone regulation by the pituitary gland.

The hormones released by the basophils in the adenohypophysis of the pituitary gland include ACTH, TSH, FSH, and LH. ACTH is syn-

thesized by corticotrophs, which are stimulated by CRH from the hypothalamus. ACTH is synthesized by thyrotrophs, which stimulates

the adrenal cortex to produce corticosteroids (glucocorticoids, androgens) and indirectly inﬂ uences aldosterone. TSH is also synthesized

by thyrotrophs; it stimulates production of T

and T

by the thyroid. FSH and LH are secreted by gonadotrophs; these hormones promote

secondary sex characteristics and stimulate the development of ovarian follicles (ovary) and spermatogonia (testis). The hormones released

by acidophils include prolactin and growth hormone. Prolactin is secreted by mammotrophs (lactotrophs) and stimulates the mammary

glands to produce milk. The growth hormone (somatotropin) is secreted by somatotrophs; it stimulates the liver to produce IGF-1, also

known as somatomedins, which promotes protein deposition, cell reproduction, and cartilage and bone growth and enhances fat utiliza-

tion for energy by increasing fatty acids in the bloodstream. The hormones released by the neurohypophysis include ADH (or vasopressin)

and oxytocin, which are produced by neurons whose cell bodies lie in the hypothalamus. ADH promotes water absorption by collecting

tubules and ducts. Oxytocin stimulates contraction of smooth muscle ﬁ bers in the myometrium of the uterus.

Pituitary Gland

I. Adenohypophysis (anterior pituitary gland)

A. Pars distalis

1. Chromophobes

2. Chromophils

a. Acidophils: Somatotrophs (secrete growth hormone),

mammotrophs/lactotrophs (secrete prolactin)

b. Basophils: Corticotrophs (secrete ACTH), thyrotrophs

(secrete TSH), gonadotrophs (secrete FSH and LH)

B. Pars/tuberalis: Gonadotrophs (secrete FSH and LH)

C. Pars intermedia

1. Rathke cysts (colloid-containing cysts)

2. Basophilic cells/melanotrophs (secrete MSH)

II. Neurohypophysis (posterior pituitary gland)

A. Neural (infundibular) stalk

B. Median eminence

C. Pars nervosa

1. Herring bodies (contain neurosecretory granules)

2. Neurohypophyseal hormones: ADH (secreted by neu-

rons whose cell bodies are in the supraoptic nucleus),

oxytocin (secreted by neurons whose cell bodies are in

both supraoptic and paraventricular nuclei)

Abbreviations

ACTH: Adrenocorticotropic hormone

TSH: Thyroid-stimulating hormone

FSH: Follicle-stimulating hormone

LH: Luteinizing hormone

MSH: Melanocyte-stimulating hormone

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Pars

distalis

Pars

distalis

Pars

Intermedia

Pars

Intermedia

Pars

nervosa

Pars

nervosa

Capsule

Hypothalamus

Optic

chiasm

Optic

chiasm

Optic chiasm

Pituitary

gland

Pituitary

gland

Infundibula

stalk

Pituitary

gland

Pituitary

gland

Pineal

gland

Pineal

gland

Figure 17-3A. Overview of the pituitary gland.

The pituitary gland is a small, bean-shaped gland,

about 1 cm in diameter, located inferior to the hypothal-

amus and separated from it by the diaphragma sellae

through which the infundibular stalk (infundibulum)

passes. The pituitary gland lies within the sella turcica.

Various important surrounding structures are visible

in the photograph and inset. The pituitary gland is

located inferior, and slightly caudal, to the optic chi-

asm; this is a particularly important anatomical rela-

tionship that is applicable to clinical medicine.

A pituitary tumor, as it enlarges, may impinge on

the crossing ﬁ bers within the optic chiasm, causing

visual ﬁ eld deﬁ cits. This most commonly results in

bitemporal hemianopia, a loss of the temporal visual

ﬁ elds of both eyes. Other visual ﬁ eld deﬁ cits can also

result from pituitary tumors.

Mammillary

body

Pars

nervosa

Pars

intermedia

Infundibular

stalk

Arcuate

nucleus

Optic

chiasm

Median

eminence

Basophils

Acidophils

Pars

tuberalis

Pars

distalis

Supraoptic

nucleus

Anterior lobe

Posterior lobe

Paraventricular

nucleus

Hypothalamus

Infundibular

stalk

Hypothalamus

Pars

tuberalis

Pars

nervosa

Pars

distalis

Pars

tuberalis

Figure 17-3B. Pituitary gland. Mallory trichrome and H&E, 10

The pituitary gland is closely associated with the hypothalamus; it can be divided into two regions based on embryonic origins: the

adenohypophysis (anterior pituitary gland) and the neurohypophysis (posterior pituitary gland). The adenohypophysis arises from

the ectoderm of the Rathke pouch (roof of the developing oral cavity). It includes the pars distalis, pars tuberalis, and pars intermedia.

The neurohypophysis is differentiated from the neural ectoderm of the inferior surface of the developing diencephalon. It includes the

median eminence, infundibular stalk, and pars nervosa and contains axons whose cell bodies are located in the hypothalamus.

Figure 17-3C. Pituitary gland. Mallory trichrome and H&E, 31

The adenohypophysis (anterior pituitary gland) with its connective tissue

capsule is shown on the left of the microphotograph. It stains red-blue

because it contains chromophils (acidophils and basophils) and chromo-

phobes. The pars nervosa of the neurohypophysis (posterior pituitary

gland) is nervous tissue; it is shown on the right. It contains axons,

pituicytes, and capillaries. It stains much lighter than the adenohypo-

physis. The cell bodies of these axons are located in the supraoptic and

paraventricular nuclei of the hypothalamus. These neurons have long

axons that extend from the hypothalamus into the neurohypophysis of

the pituitary gland. The axons contain neurosecretory granules consist-

ing of two types of hormones: oxytocin (supraoptic and paraventricular

nuclei) and ADH (supraoptic nucleus). Enlarged axon terminal endings

are known as Herring bodies (Fig. 17-6A,B).

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Acidophils

Chromophobes

Basophils

Blood

vessel

Blood

vessel

Figure 17-4A. Pars distalis, adenohypophysis (anterior pitu-

itary gland). Mallory trichrome and H&E, 281

The pars distalis, the largest part of the adenohypophysis, contains

two major types of cells: chromophobes and chromophils. Chro-

mophobes are so named because the cytoplasm does not absorb

chromium salt stains, whereas the cytoplasm of chromophils does

absorb chromium salts. In a Mallory trichrome–stained specimen,

the chromophils can be divided into acidophils and basophils accord-

ing to the staining (red or blue, respectively) of the granules in the

cytoplasm. Overall cell composition is about 50% chromophobes,

15% basophils, and 35% acidophils. Acidophilic granules are char-

acteristic of cells that secrete polypeptide hormones, such as growth

hormone (somatotrophs) or prolactin (mammotrophs), and baso-

philic granules are characteristic of cells that secrete glycoprotein

hormones such as TSH (thyrotrophs), LH, and FSH (gonadotrophs).

Corticotrophs, which secrete molecules of the proopiomelanocortin

family, also have basophilic granules. In this photomicrograph, chro-

mophobes have pale cytoplasm, basophils have blue-staining gran-

ules in their cytoplasm, and acidophils have red-staining granules.

Chromophobes

Basophil

Acidophil

Golgi complex

Chromophobe

Chromophil (possible mammotroph)

Chromophil (possible corticotroph)

Chromophil (possible somatotroph)

Figure 17-4B. Cells in the pars distalis, anterior pituitary gland. EM, ×7,700; inset (color) Mallory trichrome and H&E, 423

The ﬁ ve types of hormone-secreting (chromophil) cells in the anterior pituitary are most reliably identiﬁ ed by immunocytochemistry

using antibodies against the speciﬁ c hormone or hormones that each cell type secretes. However, an expert can also identify cell types

on the basis of the size, density, and distribution of secretory granules in transmission electron micrographs. This image has an appar-

ent chromophobe and at least three different types of chromophils. Note the differences in the features of the granules in the three

chromophils that have been labeled. Note also that the nuclei of the chromophils have nucleoli and substantial euchromatin, features

of cells that are actively synthesizing polypeptides. A moderate amount of rough endoplasmic reticulum (RER) and prominent Golgi

complexes can also be seen in the chromophils. The rich capillary bed in the adenohypophysis consists of capillaries that are fenes-

trated, a feature that allows ready movement of both releasing factors and hormones between the blood plasma and the endocrine

cells. The relative proportions of the speciﬁ c cell types vary signiﬁ cantly according to speciﬁ c location within the anterior lobe.

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Blood vessel

Colloid

Rathke

cysts

Rathke

cysts

Follicular cells

Pars

distalis

Pars

distalis

Blood cells

Pars

nervosa

Pars

nervosa

Figure 17-5A. Pars intermedia, anterior pituitary gland.

Mallory trichrome and H&E, 127

The pars intermedia originates from the ectoderm of the Rathke

pouch and is part of the adenohypophysis. This bandlike struc-

ture lies between the pars distalis and pars nervosa. It is of the

same embryonic origin as the pars distalis. The pars intermedia

contains colloid cysts called Rathke cysts, which are lined by

cuboidal to columnar follicular cells. These cells are associated

with the formation of MSH in the fetus. This photomicrograph

shows several colloid-ﬁ lled cysts (Rathke cysts). Most cells in

the pars intermedia resemble basophilic cells (melanotrophs). A

blood vessel separates the pars intermedia and the pars distalis.

Branch of

internal

carotid artery

Hypophyseal

vein

Trabecular

artery

Superior

hypophyseal

arteries

Inferior hypophyseal

artery

Median

eminence

Hypothalamus

Secondary

capillary

plexus

Primary

capillary

plexus

Hypophyseal

veins

Median

eminence

Hypophyseal

portal veins

Anterior lobe

Posterior lobe

Figure 17-5B. Blood supply of the pituitary gland.

The superior hypophyseal arteries, which arise from the internal carotid artery and posterior communicating artery of the circle of

Willis, supply the pars tuberalis, the infundibular (neural) stalk, and the median eminence. The darker shaded area indicates the

primary capillary plexus, which receives blood from the superior hypophyseal arteries, drains blood into the hypophyseal portal

veins supplying the secondary capillary plexus (white shaded area), and, ﬁ nally, drains into the hypophyseal veins. Both primary and

secondary capillary plexuses contain fenestrated capillaries. The portal blood circulation (from primary to secondary capillary plex-

uses) carries neurosecretory hormones from the median eminence into the pars distalis where they stimulate or inhibit basophils and

acidophils to produce hormones. The pars nervosa receives blood mainly from the inferior hypophyseal arteries, which arise from the

internal carotid artery. This artery also receives blood from the trabecular artery, which arises from the superior hypophyseal artery.

The hormones released by Herring bodies enter the blood circulation through the capillary plexuses of the inferior hypophyseal

and trabecular arteries.

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Lumen of

small vein

Lumen of

small vein

Herring

bodies

Herring

bodies

Capillary

Pituicytes

Figure 17-6A. Pars nervosa, neurohypophysis (posterior

pituitary gland). Masson trichrome stain, 281

The neurohypophysis is an outgrowth of the diencephalon

and includes the median eminence, the infundibular stalk,

and the pars nervosa. The median eminence is the termina-

tion site of short axons carrying factors from the arcuate

nuclei that regulate activity of cells in the adenohypophysis.

Long axons from the supraoptic and paraventricular nuclei of

the hypothalamus pass through the infundibular stalk and termi-

nate in the pars nervosa (Fig. 17-3A). The pars nervosa contains

unmyelinated axons, axon terminals, pituicytes, and capillaries.

Precursors of hormones (ADH/vasopressin and oxytocin) and

carrier proteins (neurophysins) are synthesized in the cell bodies

of neurons in the two hypothalamic nuclei and are transported

through the axons in the infundibular stalk to the axon terminal

endings in the pars nervosa, where processing is completed and

secretion occurs adjacent to fenestrated capillaries. Herring bod-

ies are large dilated axon terminal endings that are ﬁ lled with

accumulated neurosecretory granules. Pituicytes are glial cells

that provide support and nutrition to the axons of the neurons.

Herring

body

Pituicyte

Fenestrated capillary

Axon terminals

Pituicyte

Figure 17-6B. Pars nervosa, posterior pituitary gland. EM, 30,000; inset (color) Masson trichrome stain, 791

Major components of the posterior lobe can be seen in this electron micrograph. Terminals of hormone secreting neurons are seen

as vesicle-ﬁ lled, membrane-bounded proﬁ les of widely varying shapes and sizes. The largest, most distended proﬁ les appear as

Herring bodies in ordinary sections for light microscopy. The vesicles have been transported in unmyelinated axons to this site from

the supraoptic and paraventricular nuclei of the hypothalamus, where they were constructed in the cell bodies of the neurons. ADH

or oxytocin is released when action potentials are conducted from the hypothalamus in response to neural signals acting on the cell

bodies and dendrites in the hypothalamus. The two secreted hormones have only a short distance to diffuse to reach the wall of a

fenestrated capillary. There are no neuronal cell bodies in the posterior lobe, so any nuclei seen in the posterior lobe most likely will

belong either to endothelial cells of capillaries or to pituicytes, as is the case with the nucleus in this view. Like astrocytes in other

parts of the central nervous system, pituicytes have processes that contact nerve processes and the walls of capillaries.

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Acidophils

Pleomorphic

nucleus

Interstitial

blood

Tumor cells

Normal

Prolactinoma—H&E

Figure 17-7A,B. Pituitary Adenoma. A:

H&E, (left)213; (right)154. B: Immuno-

cytochemistry, (left)213; (right)154

Pituitary adenomas are benign tumors of the

anterior pituitary gland. Clinically, they can be

divided into nonsecreting and secreting forms.

Historically, adenomas were classiﬁ ed by their

staining properties, the degree to which they

took up the stains hematoxylin and eosin. They

were classiﬁ ed as basophilic, acidophilic, or

chromophobic adenomas. With modern immu-

nocytochemical techniques, however, tumor

cells can be classiﬁ ed by the type of hormone

they produce. Some cells do not mark with any

antibody, and their tumors are called null-cell

adenomas. Pituitary tumors may compress the

hypothalamus, cranial nerves, or the optic chi-

asm. A bitemporal hemianopia is commonly

seen in patients suffering from compression of

the optic nerve. Mutations are believed to play

a role in the development of the tumors. Patho-

logically, the tumors are composed of uniform,

polygonal cells arrayed in sheets or cords. They

lack a reticular network of supporting connec-

tive tissue and show monomorphism. Treatment

includes drug therapy and surgery, depending

on the type and the size of the tumors. A: The

prolactinoma lacks acidophils and has tumor

cells with pleomorphic nuclei (variable size

nuclei). The normal tissue of the pars distalis of

the pituitary gland shows individual or clusters

of acidophils interspersed among basophils and

chromophobes (right). B: The cell membranes

of prolactin-producing tumor cells have been

stained brown using an immunocytochemical

reaction. The majority of the cells in this sample

are tumor cells. By contrast, in the normal tissue

sample shown on the right, only a small number

of prolactin-producing cells are stained.

Figure 17-7C. Pituitary Adenoma in Magnetic Resonance

Imaging.

Pituitary tumors, called adenomas, can be classiﬁ ed accord-

ing to their size, secretory status, histology, and general

clinical picture of the patient. Regarding size, they can be

microadenomas, which are less than 1 cm in size (about 50%

of all tumors at diagnosis) and may be difﬁ cult to remove,

and macroadenomas, which are greater than 1.0 cm in

diameter, and may cause deﬁ cits related to hormone imbal-

ance or compression of adjacent structures. Classiﬁ cation

by secretory status may reﬂ ect, for example, excess cortisol

(Cushing disease) or prolactin (prolactinoma) or the over-

production of growth hormone (gigantism or acromegaly).

The MRI may reﬂ ect damage to the hypothalamus; the optic

chiasm, nerve, or tracts; or increased intracranial pressure.

Histologic classiﬁ cation relies on demonstrating particular

abnormal cell types in biopsy samples.

CLINICAL CORRELATIONS

Tumor

Normal

Tumor cells

Prolactin-producing

cells

Prolactinoma—immunocytochemistry

CUI_Chap17.indd 333 6/2/2010 8:18:43 PM

334

UNIT 3

■

Organ Systems

Thyroid Gland

Follicle

Colloid

Septum

Connective

tissue septum

Connective

tissue septum

Figure 17-8A. Thyroid follicles, thyroid gland. H&E, 70

The thyroid gland is derived from the developing endoderm of the

foramen cecum of the tongue; it has two lobes and is one of the

largest endocrine glands. Connective tissue septa divide the thyroid

gland into lobules. Each lobule consists of numerous thyroid fol-

licles. The thyroid follicles are the main functional components of

the gland; they synthesize and release T

and T

. Each follicle is ﬁ lled

with colloid, which is a gelatinous substance containing the stored

form of T

and T

. The follicular cells are usually simple cuboidal

cells but may change to simple squamous (inactive) or columnar

cells (active) depending on their states of secretion (Fig. 17-8B).

The thyroid hormones play an important role in regulating the

basal metabolic activity of the body. Iodine is required for for-

mation of thyroxine; iodine deﬁ ciency can lead to the develop-

ment of thyroid goiters (nodules).

CLINICAL CORRELATION

Figure 17-8C.

Hashimoto Thyroiditis. H&E, 55

Hashimoto thyroiditis is a chronic autoimmune disease, char

acterized by enlargement of the thyroid gland (goiter) and

gradual failure of thyroid function. Hashimoto thyroiditis is

the most common cause of hypothyroidism in the United States

and primarily affects women. Autoantibodies against thyroid

antigens, genetic susceptibility, and environmental factors are

believed to play a role in the development of the disease. The

signs and symptoms related to hypothyroidism include fatigue,

increased sensitivity to cold, pale skin, constipation, muscle

pain and weakness, and weight gain. Histologically, inﬁ ltrating

lymphocytes form lymphoid follicles (lymphatic nodules) with

germinal centers within the thyroid parenchyma. Some thyroid

follicle cells show Hurthle cell change with abundant eosino-

philic cytoplasm. Thyroid hormone replacement therapy is the

treatment for the disease. Surgery may be indicated if enlarge-

ment of the thyroid gland causes compression of the airway.

Follicular

(cuboidal)

cells

Follicular

(cuboidal)

cells

Colloid

Parafollicular

cells

Parafollicular

cells

Follicular

(squamous)

cells

Follicular

(squamous)

cells

Figure 17-8B. Parafollicular cells, thyroid gland. H&E, 702

Another type of endocrine cell located between the follicules of

the thyroid gland is called a parafollicular cell. These cells are also

called clear cells or C cells and are commonly located within the

interstitial connective tissue septa. Parafollicular cells produce calci-

tonin, which inhibits osteoclasts from resorbing bone tissue, thereby

decreasing blood calcium levels. High blood calcium levels stimulate

parafollicular cells to secrete calcitonin. Parafollicular cells are rela-

tively large cells with round nuclei and pale cytoplasm. They can be

found scattered beneath the follicular cells or in small groups in the

interstitial connective tissue between the follicles, as shown here.

Graves disease is an example of hyperthyroidism in which exces-

sive amounts of thyroid hormones are secreted by follicular cells

(see Fig. 3-5C). In hypothyroidism, thyroid glands produce

abnormally low levels of thyroid hormones, such as in Hashim-

oto thyroiditis.

Thyroid

follicle

Hurthle cell

change

Lymphocytes

in germinal

center

CUI_Chap17.indd 334 6/2/2010 8:18:48 PM