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STRUCTURE OF THE BASIC ENDOCRINE GLANDS OF THE BODY

Structurally, the endocrine system consists of cells, tissues, and organs that secrete
hormones as a primary or secondary function. The endocrine gland is the major player in this
system. The primary function of these ductless glands is to secrete their hormones directly
into the surrounding fluid. The interstitial fluid and the blood vessels then transport the
hormones throughout the body.

TYPES OF GLANDS

The two types of glands in the human body are discussed below:

1 Exocrine Gland:

Exocrine glands are glands that produce and secrete substances onto an epithelial surface by
way of a duct. Examples of exocrine glands include sweat, salivary, mammary, ceruminous,
lacrimal, sebaceous, and mucous. The liver and pancreas are both exocrine and endocrine
glands; they are exocrine glands because they secrete products—bile and pancreatic juice—
into the gastrointestinal tract through a series of ducts, and endocrine because they secrete
other substances directly into the bloodstream.

2 Endocrine Glands:

As we said in our first class, Endocrine glands are glands of the endocrine system that secrete
their products, chemical messengers (hormones), directly into the blood rather than through a
duct. The major glands of the endocrine system include the pineal gland, pituitary gland,
pancreas, ovaries, testes, thyroid gland, parathyroid gland, hypothalamus and adrenal glands.
The hypothalamus and pituitary gland are neuroendocrine organs.

Basic glands of the endocrine system include:

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1. Hypothalamus. The hypothalamus is located at the base of the brain, near the optic
chiasm where the optic nerves behind each eye cross and meet. Nerve cells in the
hypothalamus make chemicals that control the release of hormones secreted from the
pituitary gland. The hypothalamus gathers information sensed by the brain and sends
it to the pituitary. The hypothalamus stimulates or suppresses the release of hormones
in the pituitary gland, in addition to controlling water balance, sleep-wake cycles,
body temperature, blood pressure and appetite. It can also regulate the function of
other endocrine glands.
The hypothalamus secretes the following hormones:
 Corticotropin-releasing hormone (CRH): stimulates synthesis and secretion of
corticotropin from the anterior pituitary gland
 Growth hormone-releasing hormone (GHRH): stimulates synthesis and secretion of
growth hormone from the anterior pituitary gland
 Thyrotropin-releasing hormone (TRH): stimulates and regulates secretion of
thyrotropin from the anterior pituitary gland and may modulate neuronal activity in
the brain and spinal cord
 Gonadotropin-releasing hormone (GnRH): stimulates synthesis and secretion of
follicle-stimulating hormone and luteinizing hormone from the anterior pituitary
gland
 Prolactin-inhibiting factor (PIF): inhibits secretion of prolactin from the anterior
pituitary gland
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 Somatostatin: inhibits secretion of growth hormone from the anterior pituitary gland,
inhibits secretion of insulin and glucagon in the pancreas, and inhibits secretion of
gastrointestinal hormones and secretion of acid in the stomach
 Gastrointestinal neuropeptides: hormones secreted from the stomach and pancreas
that stimulate hypothalamic secretion of neuropeptides, such as neuropeptide Y,
gastrin releasing peptide, and somatostatin, that regulate appetite, fat storage, and
metabolism

2. Pituitary. The pituitary gland is located below the hypothalamus. Usually no larger
than a pea, the hormones it produces affect growth and reproduction. The gland
controls many functions of the other endocrine glands. The pituitary is divided into;
the anterior and posterior pituitary glands as well as intermediate lobe. The anterior
pituitary gland makes the following hormones:

a) Growth Hormone - stimulates the growth of bone and other body tissues and plays a
role in the body's handling of nutrients and minerals
b) Thyroid Stimulating Hormones (TSH)/Thyrotropin, - stimulates secretion of thyroid
hormone and growth of thyroid cells
c) Adrenocorticotropic Hormone (ACTH) - stimulates growth and secretion of cells of
the adrenal cortex; increases skin pigmentation, it also stimulates the adrenal gland to
make certain hormones
d) Follicle Stimulating Hormone (FSH) - stimulates maturation of egg follicles in
females and development of spermatozoa in males
e) Luteinizing Hormone (LH) - stimulates rupture of mature egg follicles and production
of progesterone and androgens in females and secretion of androgens in males
f) Prolactin - stimulates and maintains lactation (activates milk production) in breast-
feeding

The posterior pituitary gland makes the following hormones:

 Antidiuretic hormone (ADH) - regulates fluid volume by increasing or decreasing
fluid excretion in response to changes in blood pressure through its effect on
the kidneys
 Oxytocin - stimulates milk ejection during breast-feeding and uterine muscle
contraction during childbirth
The intermediate lobe of the pituitary gland makes the following hormones:
 Melanocyte-stimulating hormones (MSH): stimulate melanin synthesis in skin cells to
increase skin pigmentation; may also suppress appetite

3. Pineal. small endocrine gland in the brain located near the center of the brain, between
the two hemispheres, tucked in a groove where the two rounded thalamic bodies join.
It produces the hormone Melatonin (it regulates circadian rhythm [primarily in
response to light and dark cycles] and release of gonadotropin-releasing hormone
from the hypothalamus and gonadotropins from the pituitary gland)
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4. Thyroid. endocrine gland that consists of two lateral masses that are attached to the
trachea of the neck below the larynx (voice box). It makes the thyroid hormones;
Thyroxine [T4] (stimulates cellular metabolism, lipid production, carbohydrate
utilization, and central and autonomic nervous system activation), Triiodothyronine
[T3] (stimulates cellular metabolism, lipid production, carbohydrate utilization, and
central and autonomic nervous system activation) and Calcitonin (decreases serum
calcium concentrations by promoting uptake of calcium into bone tissue and excretion
of calcium in the urine)

5. Parathyroid. Attached to the thyroid in the front of the neck are four tiny glands that
work together called the parathyroids. They release parathyroid hormone or
Parathormone (increases serum calcium concentrations by stimulating release of
calcium from bone tissue, reabsorption of calcium in the kidneys, and production of
vitamin D in the kidneys; inhibits reabsorption of phosphate in the kidneys),

6. Thymus. The thymus is located in the upper part of the chest behind the sternum.
The thymus is active until puberty and produces hormones important for the
development of a type of white blood cell called a T cell that fight infections and
destroy abnormal cells.

7. Adrenal. An adrenal gland is located on top of each kidney. Like many glands, the
adrenal glands work hand-in-hand with the hypothalamus and pituitary gland. These
glands produce hormones important for regulating functions such as blood pressure,
heart rate, stress response, and regulation of metabolism
 The outer part is the adrenal cortex. It makes hormones that help control salt and
water balance in the body, the body's response to stress, metabolism, the immune
system, and sexual development and function. Hormones produced by this cortex
include
-Mineralocorticoids: aldosterone (regulates balance of salt and water in the body) and
11-deoxycorticostrone
-Glucocorticoids: cortisol and corticosterone (activates physiological stress responses
to maintain blood glucose concentrations, augments constriction of blood vessels to
maintain blood pressure, and stimulates anti-inflammatory pathways)
-Sex hormones: androgens (contribute to growth and development of the male
reproductive system and serve as precursors to testosterone and estrogen), estrogen
and progesterone

 The inner part is the adrenal medulla. It makes catecholamines, such as epinephrine.
Also called Adrenaline, (stimulates "fight or flight" response, increases heart rate,
dilates blood vessels in skeletal muscles and liver, increases oxygen delivery to
muscle and brain tissues, increases blood glucose concentrations, and suppresses
digestion), Norepinephrine or Noradrenaline (stimulates "fight or flight" response,
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increases heart rate, constricts blood vessels, increases blood glucose concentrations,
and suppresses digestion) and dopamine

8. Pancreas. The pancreas is located across the back of the abdomen, behind the
stomach. The pancreas plays a role in digestion, as well as hormone production.
Hormones produced by the pancreatic Islet of Langerhans include; Insulin (stimulates
glucose uptake and storage in adipose, muscle, and liver tissues), Glucagon (maintains
blood glucose concentrations by stimulating release of glucose from the liver and
production of glucose from amino acids and glycerol), and Somatostatin (inhibits
glucagon and insulin secretion from the pancreas and inhibits secretion of
gastrointestinal hormones and secretion of acid in the stomach).
9. Ovary. A woman's ovaries are located on both sides of the uterus, below the opening
of the fallopian tubes (tubes that extend from the uterus to the ovaries). In addition to
containing the egg cells necessary for reproduction, the ovaries also produce Estrogen
(stimulate development of female sex organs and secondary sex characteristics,
maturation of ovarian follicles, formation and maintenance of bone tissue, and
contraction of the uterine muscles), Inhibin/Folliculostin (inhibits secretion of follicle-
stimulating hormone from the pituitary gland) and Progesterone (stimulates secretion
of substances from the lining of the uterus [endometrium] in preparation for egg
implantation in the uterine wall induces relaxation of pubic ligaments during
childbirth to facilitate infant delivery).
10. Testis. A man's testes are located in a pouch that hangs suspended outside the male
body. The testes produce sperm. Hormones secreted by the testis are; Testosterone
(stimulates development of male sex organs and secondary sex characteristics,
including facial hair growth and increased muscle mass), dihydrotestosterone and
androstenedion
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HORMONE ACTION

Introduction

Hormones does not act directly on cellular structures, they cause cellular changes by binding
to transmembrane receptors present in target cells to form a hormone receptor complex which
induces changes or reactions in the target cell. This implies that the ability of a target cell to
respond to a hormone depends on the presence of receptors, within the cell or on its plasma
membrane, to which the hormone can bind. The number of receptors on a target cell can
increase or decrease in response to hormone activity.

Hormone action

Most hormone production is managed by a negative feedback system. The nervous system
and certain endocrine tissues monitor various internal conditions of the body. If action is
required to maintain homeostasis, hormones are released, either directly by an endocrine
gland or indirectly through the action of the hypothalamus of the brain, which stimulates
other endocrine glands to release hormones.

The hormones activate target cells, which initiate physiological changes that adjust the body
conditions. When normal conditions have been recovered, the corrective action - the
production of hormones - is discontinued. Endocrine glands release hormones in response to
one or more of the following stimuli:

 Hormones from other endocrine glands.

 Chemical characteristics of the blood (other than hormones).

 Neural stimulation

Chemistry of Hormone

Hormones can be chemically classified into three groups:

 Amino acid-derived Hormones: There are 2 types of hormones that are modified amino acid
called tyrosine; the thyroid hormones and the adrenal medullary hormones.

 Protein Hormones: Hormones that are chains of amino acids of less than or more than about
100 amino acids, respectively. i.e they are large of small peptides. Some protein hormones
are actually glycoproteins, containing glucose or other carbohydrate groups. Protein
hormones are secreted by pituitary gland, parathyroid glands, pancreas and placenta

 Steroid Hormones: Hormones that are lipids synthesized from cholesterol or its derivatives.
Steroids are characterized by four interlocking carbohydrate rings. Steroid hormones are
secreted by adrenal cortex, gonads and placenta. Hormones can equally act as Eicosanoids:
which are lipids synthesized from the fatty acid chains of phospholipids found in plasma
membrane.

Assignments: In a Tabular form classify hormones based on the following:

a. Anterior pituitary
b. Posterior pituitary
c. Thyroid gland
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d. Parathyroid
e. Pancreas
f. Adrenal cortex
g. Adrenal medulla
h. Gonads
i. Testis
j. Ovary
k. Pineal gland
l. Heart
m. Kidney
n. Thymus
o. Placenta
p. Local hormones

Hormone receptors
Hormone receptors are dynamic structures and large proteins present in target cells. In every
cell there are thousands of receptors highly specific for one single hormone. The hormone
acts on a target cell only when it has receptor for that particular hormone present in it.
Changes in number and sensitivity of hormone receptors may occur in response to high or
low levels of stimulating hormones. Because of the specificity of hormone and target cell, the
effects produced by a single hormone may vary among different kinds of target cells

Blood levels of hormones reflect a balance between secretion and degradation/excretion. The
liver and kidneys are the major organs that degrade hormones; breakdown products are
excreted in urine and feces. Hormone half-life and duration of activity are limited and vary
from hormone to hormone.

Locations of Hormone receptors

In every cell, hormone receptors are located in three different regions as discussed below:

1. Cell membrane: the receptors of protein hormone types (eg FSH, LH, Insulin, Glucagon
etc) and adrenal medullary hormones (eg Catecholamines) are present in this region of the
cell

2. Cytoplasm: the receptors of steroid hormone types (eg Estrogen and Progesterone) are
present in the cytoplasm of target cells.

3. Nucleus: the receptors of thyroid hormone types (eg T3 and T4) are present in the nucleus
of target cells.
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Mechanism of Action

Recall: mechanism of hormonal action can be initiated in three ways; by altering cell
membrane permeability, by activating intracellular enzyme and by activating gene. These is
discussed in details

1. Altering the permeability of cell membrane:

The NT substances in the synapse or neuromuscular junction act by changing the

permeability of postsynaptic membrane. For instance, when an impulse (AP) reaches the
terminal ends of axon of motor nerve Ach is released from the vesicles within the
neuromuscular junctions following the following sequence

a. Ach moves through presynaptic membrane, synaptic cleft and reaches the
post-synaptic membrane
b. There, Ach combines with the receptor on the membrane and forms the
hormone –receptor complex
c. The hormone –receptor complex opens the ligand gated sodium channels
d. Sodium ions enters the neuromuscular junction from ECF through the
channels
e. Sodium ions alter the resting membrane potential so that endplate potential is
developed

2. Activating intracellular enzyme:

The mode of action of protein hormones and the catecholamine

3. Activating Gene expression:

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HYPOTHALAMUS AS AN ENDOCRINE GLAND

Are you hot right now? Cold? Maybe you're like Goldilocks and are just right. What about
your height? Are you tall? Average? Short? Maybe your metabolism is lightning fast and
you're always hungry, or maybe it's a bit slow and you stay full longer. All of these—
regardless of which one you identify with—are regulated by the endocrine system.

Overview

The hypothalamus is the link between the endocrine and nervous systems. The hypothalamus
produces releasing and inhibiting hormones, which stop and start the production of other
hormones throughout the body. The endocrine hypothalamus constitutes those cells which
project to the median eminence and secrete neurohormones into the hypophysial portal blood
to act on cells of the anterior pituitary gland.

The neuroendocrine cells are found in specific regions of the hypothalamus and are regulated
by afferents from higher brain centers. Integrated function is clearly complex and the
networks between and amongst the neuroendocrine cells allows fine control to achieve
homeostasis. The entry of hormones and other factors into the brain, either via the
cerebrospinal fluid or through fenestrated capillaries (in the basal hypothalamus) is important
because it influences the extent to which feedback regulation may be imposed. Recent
evidence of the passage of factors from the pars tuberalis and the median eminence casts a
new layer in our understanding of neuroendocrine regulation.

ANATOMY OF THE HYPOTHALAMUS

The hypothalamus is a small region of the brain. It’s located at the base of the brain. It is
located below the thalamus (a part of the brain that relays sensory information) and above
the pituitary gland and brain stem. It is about the size of an almond. The hypothalamus has
three main regions. Each one contains different nuclei. These are clusters of neurons that
perform vital functions, such as releasing hormones.
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1 Anterior region

This area is also called the supraoptic region. Its major nuclei include the supraoptic and
paraventricular nuclei. There are several other smaller nuclei in the anterior region as well.

The nuclei in the anterior region are largely involved in the secretion of various hormones.
Many of these hormones interact with the nearby pituitary gland to produce additional
hormones. Some of the most important hormones produced in the anterior region include:
Corticotropin-releasing hormone (CRH), Thyrotropin-releasing hormone (TRH),
Gonadotropin-releasing hormone (GnRH), Oxytocin, Vasopressin, Somatostatin.

The anterior region of the hypothalamus also helps regulate body temperature through sweat.
It also maintains circadian rhythms.

2 Middle region

This area is also called the tuberal region. Its major nuclei are the ventromedial and arcuate
nuclei.

The ventromedial nucleus helps control appetite, while the arcuate nucleus is involved in
releasing growth hormone-releasing hormone (GHRH). GHRH stimulates the pituitary gland
to produce growth hormone. This is responsible for the growth and development of the body.

3 Posterior region

This area is also called the mammillary region. The posterior hypothalamic nucleus and
mammillary nuclei are its main nuclei.

The posterior hypothalamic nucleus helps regulate body temperature by causing shivering
and blocking sweat production.

The role of the mammillary nuclei is less clear. Doctors believe it’s involved in memory
function

BLOOD SUPPLY OF THE HYPOTHALAMUS

Strokes of the hypothalamus are vanishingly rare, as the hypothalamus has the most luxuriant
blood supply in the brain, befitting a site that is absolutely critical to maintain life. The
hypothalamus is what the circle of Willis circles. It is literally surrounded by the internal
carotid and basilar arteries, and the blood vessels that connect them.
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FUNCTION OF THE HYPOTHALAMUS

The hypothalamus plays a significant role in the endocrine system. It is responsible for
maintaining your body’s internal balance, which is known as homeostasis. In general, the
hypothalamus acts as an integrator to regulate and coordinate basic functions necessary for
life, such as fluid and electrolyte balance; feeding and energy metabolism; wake-sleep cycles;
thermoregulation; stress responses; and sexual behavior and reproduction.

Homeostatic control system

The hypothalamus protects the vital capacity of the organism in three critical ways. First, it
must maintain a well regulated internal milieu of electrolyte concentrations and osmolality,
glucose and other fuels, and body temperature. The intracellular biochemical machinery of
the mammalian body is exquisitely adapted to this environment, and cannot tolerate even
small alterations in it. When exposed to levels of sodium, for example, that are 10-15% too
high or too low; to levels of glucose less than 50% of the optimum; or body temperatures 4-
50C above or below the normal, there is substantial degradation of brain function. Similar
alterations occur in other tissues, although perhaps with margins that are perhaps not quite so
narrow as for the brain.

The hypothalamus therefore normally maintains a homeostasis (Greek for “staying the
same”) with electrolytes such as sodium generally held within 5% of optimum; glucose above
levels that may cause impairment; and body temperature within a few tenths of degree of
optimum. The hypothalamus accomplishes this by having neurons that either receive inputs
from sensory systems that monitor these variables, or are themselves sensitive to them. These
neurons attempt to regulate these parameters against what amounts to a set point, just as the
thermostat in a home is adjusted to a set point.

Hypothalamus and Allostatic control system

In contrast to the homeostatic systems of the hypothalamus, other systems deal with large and
unpredictable perturbations of the environment that require a change in behavior and
physiology. These allostatic responses range from recognition of and appropriate adjustments
to the presence on the one hand of a mate, and on the other hand of a life threatening attack.
The responses can include resetting various set points (e.g., increase in body temperature and
blood pressure), as well as endocrine adjustments (such as cortisol and adrenaline release
when under threat), and of course include abrupt and dramatic alterations of behavior (from
mating to fight or flight).

Hypothalamic control of stress responses

When an animal is under attack, it must reach full arousal, mobilize its energy stores, and be
ready either for fight or flight. Reproductive behavior, food foraging, and other non-essential
tasks must be inhibited. The signals that regulate this response must come from cognitive and
limbic systems that are capable of assessing threats. The paraventricular nucleus plays a key
role in stress responses, as it contains most of the neurons that produce corticotropin releasing
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hormone, which causes release of ACTH and then adrenal steroids. The paraventricular
nucleus also contains many of the autonomic control neurons, necessary to cause adrenaline
release. However, lateral hypothalamic neurons must be engaged to bring the cortex to a full
state of alert wakefulness, as must medial hypothalamic neurons to mobilize energy stores.
Stress inhibits sexual behavior, and in some cases may even lead to interruption of
pregnancy. Because stress is inherently non-specific, i.e., it can include any stimulus that
threatens survival, it may inherently interact with any of the other hypothalamic regulatory
systems.

Hypothalamus and Circadian control system

In addition to making adjustments of the internal milieu that support homeostasis, and
responding to urgent external events, the hypothalamus also helps anticipate daily events that
are triggered by the external day-night cycle. Whether animals are diurnal (awake in the day)
or nocturnal (awake at night), they have predictable times for feeding, drinking, sleeping, and
sexual behavior. All of these are regulated by the circadian timing system in the brain, so that
the body anticipates its various demands and opportunities. For example, wakefulness and
cortisol levels peaks at the time of day necessary for an animal to forage for food, while the
set point for body temperature falls a full degree during the time of day when an animal
sleeps.

Hypothalamic control of sleep and wakefulness

Neurons in the posterior half of the lateral hypothalamus as well as in the tuberomammillary
nucleus, provide major inputs to the cerebral cortex and the basal forebrain that are concerned
with alerting and arousal responses, and are critical for producing a fully awake state. These
neurons, and others in the brainstem that promote wakefulness, are in turn under the influence
of a master switch, the ventrolateral preoptic nucleus, which inhibits the components of the
arousal system during sleep, and is necessary for normal sleep states to occur. The wake sleep
system, including neurons in the lateral hypothalamus containing the peptide orexin, is in turn
under the control of the circadian system. The dorsomedial nucleus, which receives circadian
timing signals from the suprachiasmatic nucleus, seems to play critical role in coordinating
the two. Sleep-wake regulation interacts with feeding, drinking, and sexual and defensive
behavior, all of which, of course, require a waking state. There is also a strong interaction
between sleep and thermoregulation.

Hypothalamic control of feeding and energy metabolism

The most common cause of death for most animals is starvation. To insure adequate energy
stores, the hypothalamus must drive feeding behavior, and regulate metabolic rate. The
conversion of fuel from sugars to fat during times of plenty, or of proteins to fuel in lean
times, are under the control of hypothalamic autonomic and endocrine regulation. The control
of feeding and energy metabolism is mainly accomplished by the arcuate nucleus, working
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with the ventromedial and dorsomedial nuclei, the paraventricular nucleus, and the lateral
hypothalamus. The regulation of energy metabolism interacts with reproduction (because
animals only can afford to reproduce when there is sufficient food to insure the survival of
the offspring), thermoregulation (in times of starvation metabolic rate drops and body
temperature is lower), and wake-sleep states (animals must be awake and alert to forage for
food and will completely invert their wake-sleep cycles if food is only available during their
normal sleep cycle).

Hypothalamic control of fluid and electrolyte balance

To maintain adequate tissue perfusion, the hypothalamus must regulate fluid acquisition
through drinking, and control the osmolality and electrolyte content of the blood, as well as
the overall blood volume. When there is excess fluid volume, it must regulate diuresis by the
kidney. These tasks are under the regulation of the preoptic area, in particular the median
preoptic nucleus and organum vasculosum of the lamina terminalis, along the anterior wall of
the third ventricle. Drinking behavior is tightly linked with feeding, and with
thermoregulation (as many of the cooling strategies used by the brain involve heat loss via
water evaporation).

Hypothalamic control of thermoregulation

Cellular biochemical reactions require that body temperature be tightly controlled. For
example, by raising body temperature by 20C during an infection, the activity of white blood
cells is increased, while most bacteria are less able to reproduce. This small advantage to the
host can spell the difference between survival and death. Thermoregulation is controlled
mainly by neurons in the median and medial preoptic nuclei, as well as the lateral preoptic
area. In general, these neurons tend to inhibit a thermogenic region in the dorsomedial
nucleus and paraventricular nucleus. The latter send excitatory inputs to brainstem cell
groups that increase body temperature. So, when the hypothalamus is warmed, inhibitory
neurons turn off this thermogenic system, and body temperature falls. Thermoregulation
interacts with feeding (as energy is required to produce heat and increase metabolic rate),
reproduction (as body temperature is affected by menstrual cycles), and wake-sleep cycles (as
body temperature falls during sleep). When food stores are low, animals may enter a state of
torpor, or hibernation, where their body temperature falls to about 30 degrees C, and the brain
enters a sleep-like state. On the other hand, body temperature increases during stress.

Hypothalamic control of reproduction

In mammalian females, the hypothalamus maintains cycles of reproductive readiness.

Animals do not enter this state (i.e., go through puberty) until they have achieved sufficient
body energy stores, and in many species the correct time of the year, for breeding.
Hypothalamic neurons in the periventricular region and arcuate nucleus produce reproductive
hormones, and sexual behavior is influenced by the medial preoptic, the ventromedial, and
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the ventral premammillary nuclei. The preoptic area also appears to regulate autonomic
control over the genitalia (penile erection, secretion of lubrication). Reproduction thus
interacts with systems controlling adequate energy stores, fluid balance to insure blood
supply to the developing fetus, and thermoregulation. It is also highly arousing.

Hypothalamic regulation of autonomic system

To exert its control over so many bodily functions, the hypothalamus uses three major
outputs: autonomic, endocrine, and behavioral systems. In autonomic control, the
hypothalamus contains neurons the send axons directly to the preganglionic neurons for both
the sympathetic and parasympathetic nervous systems. These autonomic control neurons are
in the paraventricular and arcuate nuclei, and the lateral hypothalamic area. In addition the
hypothalamus has extensive outputs to adjust brainstem circuits that regulate
autonomic reflexes. For example, hypothalamic control of autonomic responses may cause
signals (stomach grumbling when hungry; dry mouth when thirsty) that
reach conscious appreciation in higher cognitive systems as a need to engage in a behavior
(in this case, eat or drink).

Hypothalamic regulation of endocrine system

The hypothalamus controls the endocrine system in three ways. First, as described above,
neurons in the paraventricular and supraoptic nuclei send their axons to form the posterior
pituitary gland, where they secrete oxytocin and vasopressin. Second, neurons in the
periventricular, paraventricular, and arcuate nuclei send axons to the median eminence, to
secrete pituitary hormone releasing hormones, which regulate the anterior pituitary gland. In
other words, the hypothalamus controls autonomic outputs to many peripheral endocrine
tissues, which further regulate their secretion. Similarly, hypothalamic regulation of
endocrine systems may feedback on the brain. For example, many neurons in the brain have
receptors for steroid hormones involved in reproduction, stress responses, or salt depletion,
and changes in these hormones may alter the likelihood of various complex behaviors
regulated by those neuronal systems.

Hypothalamic regulation of behavioral functions

Hypothalamic control of behavior is mediated in several ways. First, the lateral hypothalamic
area and the histaminergic tuberomammillary nucleus play a major role in determining the
overall level of wakefulness or arousal. Second, hypothalamic inputs to various motor pattern
generators may increase the probability of specific behaviors. For example when hungry,
most animals need to forage for food, then explore it by licking and sniffing, and finally to
consume it. The hypothalamus may reduce the threshold for activating motor pattern
generators for locomotion, and for sniffing and oral behaviors that are involved in ingestion
of food. Thus animals are more likely to encounter food and more likely to explore and
consume it. Third, there are hypothalamic descending outputs to sensory systems that may
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sensitize them (e.g., when hungry, food tastes better) or desensitize them (e.g., when under
threat, pain is not perceived as readily).

DISORDERS OF HYPOTHALAMUS

A hypothalamic disease is any disorder that prevents the hypothalamus from functioning
correctly. A physical injury to the head that impacts the hypothalamus is one of the most
common causes of hypothalamic disease. Hypothalamic diseases can include appetite and
sleep disorders. Infact, these diseases are very hard to pinpoint and diagnose because the
hypothalamus has a wide range of roles in the endocrine system.

The hypothalamus also serves the vital purpose of signaling that the pituitary gland should
release hormones to the rest of the endocrine system. As it is difficult for doctors to diagnose
a specific, incorrectly functioning gland, these disorders are often called hypothalamic-
pituitary disorders.

In these cases, there are some hormone tests that doctors might prescribe to get to the root of
the disorder.

Causes and risk factors

The most common causes of hypothalamic diseases are injuries to the head that impact the
hypothalamus. Surgeries, radiation, and tumors can also cause disease in the hypothalamus.

Some hypothalamic diseases have a genetic link to hypothalamic disease. For instance,
Kallman syndrome causes hypothalamic problems in children, most noticeably delayed or
absent puberty, accompanied by an impaired sense of smell.

Hypothalamus problems also appear to have a genetic link in Prader-Willi Syndrome. This is
a condition in which a missing chromosome leads to short stature and hypothalamic
dysfunction.

Additional causes of hypothalamic disease can include:

 eating disorders, such as bulimia or anorexia

 genetic disorders that cause excess iron buildup in the body

 malnutrition
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 infections

 excessive bleeding

Symptoms of hypothalamus disorders

Symptoms of hypothalamus disorders vary depending on what hormones are in short supply.

Children might show signs of abnormal growth and abnormal puberty. Adults might show
symptoms linked to the various hormones their bodies cannot produce.

There is usually a traceable link between the absent hormones and the symptoms they
produce in the body. Tumor symptoms might include blurred vision, loss of vision,
and headaches.

Low adrenal function might produce symptoms such as weakness and dizziness.

Symptoms caused by an overactive thyroid gland include:

 sensitivity to heat

 anxiety

 feeling irritable

 mood swings

 tiredness and difficulty sleeping

 lack of sex drive

 diarrhea

 constant thirst

 itchiness
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An Overview of the Pituitary Gland

The pituitary is a pea-sized gland that lies at the sphenoid bone (sella turcica) at the base of
the brain. The sella turcica protects the pituitary but allows very little room for expansion.
It is a coordinating center for control of many downstream endocrine glands.

The pituitary gland also called hypophysis ductless gland of the endocrine system that
controls the function of most other endocrine glands and is therefore sometimes called the
master gland. The term hypophysis (from the Greek for “lying under”) refers to the gland’s
position on the underside of the brain.

In turn, the pituitary is controlled in large part by the hypothalamus, a region of the brain
that lies just above the pituitary. By detecting the levels of hormones produced by glands
under the pituitary's control (target glands), the hypothalamus or the pituitary can determine
how much stimulation the target glands need.

Fig 1: The Pituitary and Its Target Organs

Hormone Target Organ or Tissue

Adrenocorticotropic hormone( ACTH) Adrenal glands
Beta-melanocyte–stimulating hormone Skin
Endorphins Brain and immune system
Enkephalins Brain
Follicle-stimulating hormone Ovaries or testes
Growth hormone Muscles and bones
Luteinizing hormone Ovaries or testes
Oxytocin* Uterus and mammary glands
Prolactin Mammary glands
Thyroid-stimulating hormone Thyroid gland
Vasopressin (antidiuretic hormone)* Kidneys

Anatomy of the Pituitary Gland

 18

The pituitary gland lies at the middle of the base of the skull and is housed within a bony
structure called the sella turcica, which is behind the nose and immediately beneath
the hypothalamus.

The pituitary gland is attached to the hypothalamus by a stalk composed of

neuronal axons and the so-called hypophyseal-portal veins.

In most species the pituitary gland is divided into three lobes: the Front (anterior) lobe
(which accounts for 80% of the pituitary gland's weight), the intermediate lobe, and the
Back (posterior) lobe. The anterior lobe produces and releases hormones. In humans the
intermediate lobe does not exist as a distinct anatomic structure but rather remains only as
cells dispersed within the anterior lobe.

The lobes are connected to the hypothalamus by a stalk that contains blood vessels and
nerve cell projections (nerve fibers, or axons). The hypothalamus controls the anterior lobe
by releasing hormones through the connecting blood vessels. It controls the posterior lobe
through nerve impulses.

The hormones produced by the pituitary are not all produced continuously. Most are
released in bursts every 1 to 3 hours, with alternating periods of activity and inactivity.

The Anterior Pituitary Region

The cells of the anterior pituitary are embryologically derived from an out pouching of the
roof of the pharynx, known as Rathke’s pouch. Although, the cells appear to be
relatively homogeneous under a light microscope, there are in fact at least five different types
of cells, each of which secretes a different hormone or hormones.

Write on biosynthesis of proopiomelanocytes and its derivatives

 19

The Posterior Pituitary Region

The posterior lobe of the pituitary gland consists largely of extensions of processes (axons)
from two pairs of large clusters of nerve cell bodies (nuclei) in the hypothalamus. One of
those nuclei, known as the supraoptic nuclei, lies immediately above the optic tract, while the
other nuclei, known as the paraventricular nuclei, lies on each side of the third ventricle of
the brain. Those nuclei, the axons of the cell bodies of nerves that form the nuclei, and
the nerve endings in the posterior pituitary gland form the neurohypophyseal system. There
are neural connections that run from those nuclei to other regions of the brain, including to
regions that sense osmolality (solute concentrations) and regulate thirst.

Hormones of the Pituitary Gland

The hormones of the pituitary gland send signals to other endocrine glands to stimulate or
inhibit their own hormone production. For example, the anterior pituitary lobe will release
adrenocorticotropic hormone (ACTH) to stimulate cortisol production in the adrenal glands
when you’re stressed.

The anterior lobe releases hormones upon receiving releasing or inhibiting hormones from
the hypothalamus. These hypothalamic hormones tell the anterior lobe whether to release
more of a specific hormone or stop production of the hormone.

Anterior Lobe Hormones:

The hormones of the anterior pituitary are proteins that consist of one or two long
polypeptide chains. The production and secretion of each of the major anterior pituitary
hormones are regulated by peptides that are released from the median eminence neurons of
the hypothalamus into the hypophyseal-portal veins, which traverse a short distance to the
pituitary microvasculature. Feedback loops involving the pituitary hormones and their target
glands play an important role in pituitary-hormone signaling.
 Adrenocorticotropic hormone (ACTH): ACTH also called corticotropin stimulates the
adrenal glands to produce cortisol and other hormones.
 Follicle-stimulating hormone (FSH): FSH works with LH to ensure normal functioning of the
ovaries and testes.
 Growth hormone (GH): GH is essential in early years to maintaining a healthy body
composition and for growth in children. In adults, it aids healthy bone and muscle mass and
affects fat distribution.
 Luteinizing hormone (LH): LH works with FSH to ensure normal functioning of the ovaries
and testes.
 Prolactin: Prolactin stimulates the mammary glands of the breasts to produce milk
 Thyroid-stimulating hormone (TSH): TSH stimulates the thyroid gland to produce thyroid
hormones.
 20

The posterior lobe contains the ends of nerve cells coming from the hypothalamus. The
hypothalamus sends hormones directly to the posterior lobe via these nerves, and then the
pituitary gland releases them.

Posterior Lobe Hormones:

The hormones are released into the circulation in response to nerve signals that originate in
the hypothalamus and are transmitted to the posterior pituitary lobe. The hormones of this
lobe are synthesized and incorporated into neurosecretory granules in the cell bodies of the
nuclei. Those hormones are synthesized as part of a precursor protein that includes one of the
hormones and a protein called neurophysin. The major neurohypophyseal hormones are:
 Vasopressin (also called antidiuretic hormone -ADH): This hormone prompts the kidneys to
regulate the amount of water excreted by the kidneys and is therefore important in
maintaining water balance in the body
Oxytocin: This hormone causes the uterus to contract during childbirth and immediately
after delivery to prevent excessive bleeding. Oxytocin also stimulates contractions of the
milk ducts in the breast, which move milk to the nipple (the let-down) in lactating
women. Oxytocin has some additional roles in both men and women.

Pituitary gland conditions

Several conditions can affect your pituitary gland. Most are caused by a tumor in or around
the pituitary gland. This can impact the release of hormones. Examples of pituitary gland
disorders include:

 Galactorrhea: The most common cause of galactorrhea is a tumor in the pituitary

gland. In both sexes, the most common cause of galactorrhea is a prolactin-secreting
tumor (prolactinoma) in the pituitary gland. Prolactin is a hormone that stimulates the
breasts to produce milk. Galactorrhea can cause unexpected milk production and
infertility in both men and women. The diagnosis is based on measuring the blood
levels of the hormone prolactin. Imaging tests may be done to look for a cause. When
drugs alone do not stop prolactin production or shrink the tumor, surgery or
sometimes radiation therapy may be done.
 21

 Erectile Dysfunction (ED)

Erectile dysfunction (ED) is the inability to attain or sustain an erection satisfactory for
sexual intercourse. Every man occasionally has a problem achieving an erection, and such
occurrences are considered normal. Erectile dysfunction (ED) occurs when a man is never
able to achieve an erection, achieves erection briefly but not long enough for intercourse
and achieves effective erection inconsistently

ED is called primary if the man has never been able to attain or sustain an erection. ED is
called secondary if it is acquired later in life by a man who was previously able to attain
erections. Secondary ED is much more common than primary ED.

To achieve an erection, the penis needs an adequate amount of blood flowing in, a slowing
of blood flowing out, proper function of nerves leading to and from the penis, adequate
amounts of the male sex hormone testosterone, and sufficient sex drive (libido), so a
disorder of any of these systems may lead to erectile dysfunction (ED).

 Acromegaly or Gigantism. In this condition, whereby the pituitary gland produces too
much growth hormone. Children develop great stature, and adults develop deformed
bones but do not grow taller. This can lead to excessive growth, especially of your
hands and feet. It’s often associated with pituitary tumors. Heart failure, weakness, and
vision problems are common. The diagnosis is based on blood tests and imaging of
the skull and hands. Computed tomography (CT) or magnetic resonance imaging
(MRI) of the head are done to look for the cause. A combination of surgery, radiation
therapy, and drug therapy is used to treat the overproduction of growth hormone.
 22

This photo shows a person who has The woman on the right was
an enlarged forehead and nose, diagnosed with gigantism as an infant.
protruding jaw, and thickened skin. She is several feet taller than her
mother on the left.

 Cushing’s disease. The pituitary gland releases too much adrenocorticotropic hormone
in people with this condition or may usually results from taking corticosteroids to treat
a medical disorder or from a tumor in the pituitary or adrenal gland that causes the
adrenal glands to produce excessive corticosteroids. Cushing syndrome can also
result from tumors in other locations (such as the lungs). People with Cushing
syndrome usually develop excessive fat throughout the torso and have a large, round
face and thin skin. This can lead to easy bruising, high blood pressure, weakness, and
weight gain. Doctors measure the level of cortisol and do other tests to detect Cushing
syndrome. Surgery or radiation therapy is often needed to remove a tumor
 23

 Diabetes insipidus. This can be caused by a problem with the release of vasopressin.
Central diabetes insipidus has several causes, including a brain tumor, a brain
injury, brain surgery, tuberculosis, and some forms of other diseases. As a result,
people with this condition pass large amounts of heavily diluted urine. The deficiency
may be Inherited, Caused by another disorder or Of unknown cause They may also
feel like they need to drink a lot of water or other fluids. The diagnosis is based on
urine tests, blood tests, and a water deprivation test. People with central diabetes
insipidus usually are given the drugs vasopressin or desmopressin.
 Hypopituitarism. Hypopituitarism is an underactive pituitary gland that results in
deficiency of one or more pituitary hormones. This condition causes the pituitary gland
to produce very little or none of one or more of its hormones. This can affect things
like growth or reproductive system function. Symptoms of hypopituitarism depend on
what hormone is deficient and may include short height, infertility, intolerance to
cold, fatigue, and an inability to produce breast milk. The diagnosis is based on
measuring the blood levels of hormones produced by the pituitary gland and on
imaging tests done on the pituitary gland. Treatment focuses on replacing deficient
hormones with synthetic ones but sometimes includes surgical removal or irradiation
of any pituitary tumors.

 Hyperprolactinemia. In this condition, your blood contains an unusually high amount

of prolactin. This can lead to infertility and a decreased sex drive.

 Traumatic brain injury. This involves a sudden blow to your brain. Depending on the
injury, it can sometimes damage your pituitary gland and cause problems with
memory, communication, or behavior.
 24

GROWTH HORMONE
Introduction
Growth hormone is a peptide hormone produced by the pituitary gland. That is, growth
hormone is released into the bloodstream from somatotroph cells in the anterior pituitary. The
portion of the pituitary gland also produces other hormones that have different functions from
growth hormone.
Harvey Cushing proposed in 1912 in his monograph "The Pituitary Gland" the existence of a
"hormone of growth", and was thereby among the first to indicate that the primary action of
growth hormone (GH) was to control and promote skeletal growth. The multiple and
complex actions of human GH were, however, acknowledged shortly after the advent of a
pituitary-derived preparation of the hormone in the late fifties

Growth Hormone is a powerful metabolic hormone that has many functions including
maintaining normal body structure and metabolism. Growth hormone acts on many parts of
the body to promote growth in children.

Biosynthesis & Chemistry of GH

GH is a single chain protein with 191 amino-acids and two disulfide bonds. The human GH is
located on the long arm of human chromosome 17 as part of a locus th at comprises five
genes; the first is hGH-N (codes for the most abundant normal form of GH) i.e main adult
growth hormone produced in the somatotrophic cells found in the anterior pituitary gland, the
second is hGH-V (codes for the variant form of GH), meanwhile two genes code for human
chorionic somatomammotropin (hCS) and the fifth is probably a hCS pseudogene.
 25

Physiological Regulation of GH Secretion

The morphological characteristics and number of somatotrophs are remarkably constant
throughout life, while their secretion pattern changes.
Pituitary synthesis and secretion of GH is stimulated by pulsatile or episodic hypothalamic
secretion of Growth Hormone Releasing Hormone (GHRH) and in a circadian rhythm with a
maximal release in the second half of the night. So, sleep is an important physiological factor
that increases the GH release. Growth hormone release is not continuous; it is released in a
number of ‘bursts’ or pulses every three to five hours while somatostatin (SST) inhibits GH
production and release.
Interestingly, GH secretion is also gender-, pubertal status- and age- dependent. Integrated
24h GH concentration is significantly greater in women than in men and greater in the young
than in older adults. During puberty, a 3-fold increase in pulsatile GH secretion occurs that
peaks around the age of 15 years in girls and 1 year later in boys. The maximum GH levels
occur within minutes of the onset of slow wave sleep and there is marked sexual dimorphism
of the nocturnal GH increase in humans, constituting only a fraction of the total daily GH
release in women, but the bulk of GH output in men
Growth hormone levels are increased by sleep, stress, exercise and low glucose levels in the
blood. They also increase around the time of puberty. Growth hormone release is lowered in
pregnancy and if the brain senses high levels of growth hormone or insulin-like growth
factors already in the blood.
GH acts both directly through its own receptors and indirectly through the induced
production of Insulin-like Growth Factor I (IGF-I) which inhibits GH secretion by a negative
loop at both hypothalamic and pituitary levels. Their effects may be synergistic (stimulate
growth) or antagonistic, as for the effect on glucose metabolism: GH stimulates lipolysis and
promotes insulin resistance, whereas IGF-I acts as an insulin agonist.
 26

Fig 1: Factors that stimulate and suppress GH secretion under physiological conditions.

GROWTH HORMONE RELEASING HORMONE

GHRH is a 44 amino-acid polypeptide produced in the arcuate nucleus of the hypothalamus.
These neuronal terminals secrete GHRH to reach the anterior pituitary somatotrophs via the
portal venous system, which leads to GH transcription and secretion. In addition, GHRH up-
regulates GH gene expression and stimulates GH release

The secretion of GHRH is stimulated by several factors including depolarization, α2-

adrenergic stimulation, hypophysectomy, thyroidectomy and hypoglycemia, and it is
inhibited by SST, IGF-I, and activation of GABAergic neurons.

GHRH acts on the somatotrophs via a seven trans-membrane G protein-coupled stimulatory

cell-surface receptor.

SOMATOSTATIN (SST)
SST is a cyclic peptide, encoded by a single gene in humans, which mostly exerts inhibitory
effects on endocrine and exocrine secretions. Many cells in the body, including specialized
cells in the anterior paraventricular nucleus and arcuate nucleus, produce SST. These neurons
secrete SST into the adenohypophyseal portal venous system, via the median eminence, to
exert effects on the anterior pituitary. SST has a short half-life of approximately 2 minutes as
it is rapidly inactivated by tissue peptidase in humans.

SST acts via a seven trans-membrane, G protein coupled receptor and, thus far, five subtypes
of the receptor have been identified in humans (SSTR1-5). Although all five receptor
subtypes are expressed in the human fetal pituitary, the adult pituitary only expresses 4
subtypes (SSTR1, SSTR2, SSTR3, SSTR5). Of these four subtypes, somatotrophs exhibit
more sensitivity to SSTR2 and SSTR5 ligands in inhibiting the secretion of GH in a
synergistic manner. Somatostatin inhibits GH release but not GH synthesis.

Physiology of IGF-I
The IGF-I receptor is expressed in many tissues in the body. GH acts both directly through its
own receptor and indirectly through the induced production of IGF-I. GH stimulates
synthesis of IGF-I in the liver and many other target tissues; about 75% of circulating IGF-I
is liver-derived. IGF-I is a 70 amino-acid peptide, found in the circulation, 99% bound to
transport proteins (IGFBP) in the circulation.

The IGF-I gene is a member of the insulin gene family and the IGF-I receptor is structurally
similar to the insulin receptor in its tetrameric structure, with 2 alpha and 2 beta subunits. The
alpha subunit binds IGF-I, IGF-II, and insulin; however, the subunit has a higher affinity
towards IGF-I compared to IGF-II and insulin. Although insulin and IGF-I share many
similarities, during evolution the functionality of the two molecules has become more
divergent, where insulin plays a more metabolic role and IGF-I is more involved in cell
growth.
 27

IGF-I is known as a global and tissue-specific growth factor as well as an endocrine factor. In
some tissues IGF-I acts as a potent inhibitor of cellular apoptosis.

Assignment
Write briefly on the relationship between Growth hormones and somatostadins with respect
to growth (Not more than 3pages, write with your handwriting, then scan/snap a clear copy
and submit – Don’t Copy Pls)

Function

Effects of growth hormone on the tissues of the body can generally be described
as anabolic (building up). Like most other protein hormones, GH acts by interacting with a
specific receptor on the surface of cells.

1 Growth

GH plays significant role in stimulating growth of nearly all body tissues and enhancing lean
body mass and weight of a variety of organs. Once the growth plates in the bones (epiphyses)
have fused growth hormone does not increase height. In adults, it does not cause growth but it
helps to maintain normal body structure and metabolism, including helping to keep
blood glucose levels within set levels.

2 Metabolic Effects

GH is an important modulator of total body metabolism and promotes tissue protein

deposition, utilization of body fat, and reduces utilization of body sugars. The effects of GH
on protein and lipid metabolism result in GH being a key factor maintaining lean body mass.
Most importantly, however, GH reduces utilization of sugars by promoting resistance of body
tissues to insulin, thus resulting in increased blood glucose concentration.

Other functions of growth hormone on the body are :

 Increases calcium retention, and strengthens and increases the mineralization of bones
 Increases muscle mass through sarcomere hypertrophy
 Promotes lipolysis
 Increases protein synthesis
 Stimulates the growth of all internal organs excluding the brain
 Plays a role in homeostasis
 Reduces liver uptake of glucose
 Promotes gluconeogenesis in the liver
 Contributes to the maintenance and function of pancreatic islets
 Stimulates the immune system
 Increases deiodination of T4 to T3

Pathology of GH

Growth Hormone Deficiency

 28

GH deficiency is one of the many causes of short stature and dwarfism. It results primarily
from damage to the hypothalamus or to the pituitary gland during fetal development
(congenital GH deficiency) or following birth (acquired GH deficiency). GH deficiency may
also be caused by mutations in genes that regulate its synthesis and secretion. Affected genes
include PIT-1 (pituitary-specific transcription factor-1) and POUF-1 (prophet of PIT-1).
Mutations in these genes may also cause decreased synthesis and secretion of other pituitary
hormones.

In some cases, GH deficiency is the result of GHRH deficiency, in which case GH secretion
may be stimulated by infusion of GHRH. In other cases, the somatotrophs themselves are
incapable of producing GH, or the hormone itself is structurally abnormal and has little
growth-promoting activity. In addition, short stature and GH deficiency are often found in
children diagnosed with psychosocial dwarfism, which results from severe emotional
deprivation. When children with this disorder are removed from the stressing,
nonnurturing environment, their endocrine function and growth rate normalize.

Children with isolated GH deficiency are normal in size at birth, but growth retardation
becomes evident within the first two years of life. Radiographs (X-ray films) of
the epiphyses (the growing ends) of bones show growth retardation in relation to the patient’s
chronological age. Although puberty is often delayed, fertility and delivery of normal
children is possible in affected women.

GH deficiency is most often treated with injections of GH. For decades, however, availability
of the hormone was limited, because it was obtained solely from human cadaver pituitaries.
In 1985, use of natural GH was halted in the United States and several other countries
because of the possibility that the hormone was contaminated with a type of pathogenic agent
known as a prion, which causes a fatal condition called Creutzfeldt-Jakob disease. That same
year, by means of recombinant DNA technology, scientists were able to produce a
biosynthetic human form, which they called somatrem, thus assuring a virtually unlimited
supply of this once-precious substance.

Children with GH deficiency respond well to injections of recombinant GH, often achieving
near-normal height. However, some children, primarily those with the hereditary inability to
synthesize GH, develop antibodies in response to injections of the hormone. Children with
short stature not associated with GH deficiency may also grow in response to hormone
injections, although large doses are often required.
 29

A rare form of short stature is caused by an inherited insensitivity to the action of GH. This
disorder is known as Laron dwarfism and is characterized by abnormal GH receptors,
resulting in decreased GH-stimulated production of IGF-1 and poor growth. Serum GH
concentrations are high because of the absence of the inhibitory action of IGF-1 on GH
secretion. Dwarfism may also be caused by insensitivity of bone tissue and other tissues to
IGF-1, resulting from decreased function of IGF-1 receptors.

GH deficiency often persists into adulthood, although some people affected in childhood
have normal GH secretion in adulthood. GH deficiency in adults is associated with fatigue,
decreased energy, depressed mood, decreased muscle strength, decreased muscle mass, thin
and dry skin, increased adipose tissue, and decreased bone density. Treatment with GH
reverses some of these abnormalities but can cause fluid retention, diabetes mellitus, and high
blood pressure (hypertension).

Growth Hormone Excess

Excess GH production is most often caused by a benign tumour (adenoma) of the
somatotroph cells of the pituitary gland. In some cases, a tumour of the lungs or of the
pancreatic islets of Langerhans produces GHRH, which stimulates the somatotrophs to
produce large amounts of GH. In rare cases, ectopic production of GH (production by tumour
cells in tissues that do not ordinarily synthesize GH) causes an excess of the hormone.
Somatotroph tumours in children are very rare and cause excessive growth that may lead to
extreme height (gigantism) and features of acromegaly.

Acromegaly refers to the enlargement of the distal (acral) parts of the body, including the
hands, feet, chin, and nose. The enlargement is due to the overgrowth of cartilage, muscle,
subcutaneous tissue, and skin. Thus, patients with acromegaly have a prominent jaw, a large
nose, and large hands and feet, as well as enlargement of most other tissues, including
the tongue, liver, heart, and kidneys.

In addition to the effects of excess GH, a pituitary tumour itself can cause severe headaches,
and pressure of the tumour on the optic chiasm can cause visual defects. Because the
metabolic actions of GH are antagonistic (opposite) to those of insulin, some patients with
acromegaly develop diabetes mellitus. Other problems associated with acromegaly include
high blood pressure (hypertension), cardiovascular disease, and arthritis. Patients with
acromegaly also have an increased risk of developing malignant tumours of the large
intestine. Some somatotroph tumours also produce prolactin, which may cause abnormal
lactation (galactorrhea).
 30

Patients with acromegaly are usually treated by surgical resection of the pituitary tumour.
They can also be treated with radiation therapy or with drugs which blocks the binding of
growth hormone to its receptors, and synthetic long-acting analogues of somatostatin, which
inhibit the secretion of GH.

PANCREAS
Introduction
The pancreas is an accessory organ and exocrine gland of the digestive system located
in the abdomen. It plays a hormone producing endocrine gland essential role in converting
the food we eat into fuel for the body's cells. The pancreas has two main functions: an
exocrine function that helps in digestion and an endocrine system function that regulates
blood sugar. About 95% of the pancreas consists of exocrine tissue that produces pancreatic
enzymes for digestion. The remaining tissue consists of endocrine cells called islets of
Langerhans. These clusters of cells look like grapes and produce hormones that regulate
blood sugar and regulate pancreatic secretions.

Diagram of the pancreas

The pancreas, gallbladder and duodenum

Anatomy
 31

 The pancreas is about 6 inches (approximately 15 cm) long and sits across the back of
the abdomen (lies obliquely across the posterior abdominal wall), behind the stomach
at the level of the L1 and L2 vertebral bodies.

 Anatomically, the pancreas is a retroperitoneal organ consisting of five parts; the head,
uncinate process, neck, body and tail, in addition to an internal system of ducts.

 The head of the pancreas is on the right side of the abdomen and is connected to the
duodenum through a small tube called the pancreatic duct.

 Projecting inferiorly from the head is the uncinate process, which extends posteriorly
towards the mesenteric artery.

 Continuing laterally from the head is the neck, a short structure of approximately 2 cm
that connects the head with the body.

 The posterior to the neck are the superior mesenteric artery and vein and the origin of
the hepatic portal vein formed by the union of the superior mesenteric and the splenic
vein

 After the neck, the pancreas continues with the body, which consists of two surfaces
(anterior and posterior) and two borders (superior and inferior). The narrow end of the
pancreas, called the tail, extends to the left side of the body.

 Traveling within the entire pancreatic parenchyma from the tail to the head is the main
pancreatic duct. It connects with the bile duct in the head of the pancreas to form the
hepatopancreatic duct, otherwise called the ampulla of Vater.

 Flow through the ampulla of Vater is controlled by a smooth muscle sphincter called
the (hepatopancreatic) sphincter of Oddi. It also prevents reflux of duodenal contents
into the hepatopancreatic duct.

 The terminal parts of the main pancreatic and bile ducts also have sphincters, which
play an important role in controlling the flow of pancreatic and bile fluids.

 In addition to the main duct, the pancreas also contains an accessory duct. It
communicates with the main pancreatic duct at the level of the pancreatic neck and
opens into the descending part of the duodenum at the minor duodenal papilla.
 32

 The pancreas comes in contact with several neighboring structures as it traverses

the epigastric, left hypochondriac, and a small portion of the umbilical regions of the
abdomen

Anatomy and relations of the pancreas (anterior view)

 33

Anatomy of the pancreatic ducts (anterior view)

Location of the Pancreas

 The pancreas is located behind the stomach in the upper left abdomen. It is
surrounded by other organs including the small intestine, liver, and spleen. It is
spongy and shaped like a flat pear or a fish extended horizontally across the abdomen.

 The wide part, called the head of the pancreas, is positioned toward the center of the
abdomen. The head of the pancreas is located at the juncture where the stomach meets
the first part of the small intestine. This is where the stomach empties partially
digested food into the intestine, and the pancreas releases digestive enzymes into
these contents.

 The central section of the pancreas is called the neck or body. The thin end is called
the tail and extends to the left side.

Blood Supply

 The pancreas receives its blood supply from several sources. The uncinate process and
head are supplied by the superior and inferior pancreaticoduodonal arteries which are
branches of the gastroduodenal and superior mesenteric arteries respectively.

 Each pancreaticoduodenal artery has anterior and posterior branches that project along
the respective faces of the pancreatic neck where they form pancreaticoduodenal
arcades and supply them with arterial blood.

 In turn, the body and tail of the pancreas are supplied by pancreatic arteries that stem
from the splenic, gastroduodenal, and superior mesenteric arteries. The major
contributor is the splenic artery.
 34

 Pancreatic veins are responsible for draining deoxygenated blood from the pancreas.
The anterior superior pancreaticoduodenal vein empties into the superior mesenteric
vein

 The posterior variant empties into the hepatic portal vein. Both the anterior and
posterior inferior pancreaticoduodenal veins drain into the superior mesenteric vein

 The pancreatic veins draining venous blood from the body and tail empty into the
splenic vein.

Arteries of the pancreas, duodenum and spleen (anterior view)

Innervations

 The pancreas receives involuntary innervation via the autonomic nervous system
(ANS).
 35

 Its parasympathetic innervation originates from the vagus nerve (CN X) and
its Sympathetic innervation from the greater and lesser splanchnic nerves (T5-T12).

 Inside the organ, they carry nerve impulses to the acinar cells and the pancreatic islets.
Parasympathetic fibers induce secretion from acinar cells, ultimately resulting in the
release of pancreatic juice, insulin and glucagon.

 In contrast, sympathetic fibers cause vasoconstriction and inhibition of exocrine

secretion, in other words, inhibition of pancreatic juice. In relation to hormonal release,
sympathetic innervation stimulates the release of glucagon but inhibits that of insulin.

Lymphatic supply

 Lymph is drained from the body and tail of the pancreas via lymphatic vessels that
empty into the pancreaticosplenic lymph nodes located along the splenic artery.
 The vessels draining the head empty into pyloric lymph nodes. Subsequently, lymph is
transported to the superior mesenteric or celiac lymph nodes.

Lymphatics of the pancreas, duodenum and spleen (anterior view)

Functions of the Pancreas

A healthy pancreas performs the following functions:

 36

1. Exocrine Function:

The pancreas contains exocrine glands that produce enzymes important to digestion. These
enzymes include trypsin and chymotrypsin to digest proteins; amylase for the digestion of
carbohydrates; and lipase to break down fats. When food enters the stomach, these pancreatic
juices are released into a system of ducts that culminate in the main pancreatic duct. The
pancreatic duct joins the common bile duct to form the ampulla of Vater which is located at
the first portion of the small intestine, called the duodenum. The common bile duct
originates in the liver and the gallbladder and produces another important digestive juice
called bile. The pancreatic juices and bile that are released into the duodenum helps the body
to digest fats, carbohydrates, and proteins.

2. Endocrine Function:
The endocrine component of the pancreas consists of islet cells (islets of Langerhans) that
create and release important hormones directly into the bloodstream. These hormones are
crucial in regulating glucose metabolism and gastrointestinal functions. Two of the main
pancreatic hormones are insulin, which acts to lower blood sugar, and glucagon, which acts
to raise blood sugar. These endocrine glands secrete hormones directly into the bloodstream
and consist of three main cell types (alpha, beta, and delta). The beta cells secrete insulin, alpha
cells release glucagon, and delta cells produce somatostatin. Maintaining proper blood sugar
levels is crucial to the functioning of key organs including the brain, liver, and kidneys.

Diseases of the Pancreas

Disorders affecting the pancreas are discussed as follows:

 Pancreatitis: The pancreas becomes inflamed and damaged by its own digestive
chemicals. Swelling and death of tissue of the pancreas can result. Although alcohol or
gallstones can contribute, sometimes a cause for pancreatitis is never found.
 Cystic fibrosis: A genetic disorder that affects multiple body systems, usually including
the lungs and the pancreas. Digestive problems and diabetes often result.
 Pancreatic pseudocyst: After a bout of pancreatitis, a fluid-filled cavity called a
pseudocyst can form. Pseudocysts may resolve spontaneously, or they may need surgical
drainage.
 Pancreatic cancer: The pancreas has many different types of cells, each of which can give
rise to a different type of tumor. The most common type arises from the cells that line the
 37

pancreatic duct. Because there are usually few or no early symptoms, pancreatic cancer is
often advanced by the time it’s discovered.
 Diabetes, type 1: The body’s immune system attacks and destroys the pancreas’ insulin-
producing cells. Lifelong insulin injections are required to control blood sugar.
 Diabetes, type 2: The pancreas loses the ability to appropriately produce and release
insulin. The body also becomes resistant to insulin, and blood sugar rises.
 Islet cell tumor: The hormone-producing cells of the pancreas multiply abnormally,
creating a benign or cancerous tumor. These tumors produce excess amounts of
hormones and then release them into the blood. Gastrinomas, glucagonomas, and
insulinomas are examples of islet cell tumors.
 Enlarged pancreas: An enlarged pancreas may mean nothing. You may simply have a
pancreas that is larger than normal. Or, it can be because of an anatomic abnormality. But
other causes of an enlarged pancreas may exist and require treatment

Pancreas Examinations

 Physical test: By pressing on the center of the belly, a doctor might check for a mass in
the pancreas. He or she can also look for other signs of pancreas conditions.
 Computer tomography (CT) scan: A CT scanner takes multiple X-rays, and a computer
creates detailed images of the pancreas and abdomen. Contrast dye may be injected into
your veins to improve the images.
 Ensoscopic Retrograde cholangiopancreatography (ERCP): Using a camera on a
flexible tube advanced from the mouth to the intestine, a doctor can access the area of the
pancreas head. Tiny surgical tools can be used to diagnose and treat some pancreas
conditions.
 Magnetic resonance imaging (MRI): Magnetic waves create highly detailed images of
the abdomen. Magnetic resonance cholangiopancreatography (MRCP) is an MRI that
focuses on the pancreas, liver, and bile system.
 Ultrasound scan: A probe is placed on the belly, and harmless sound waves create
images by reflecting off the pancreas and other organs.
 Sweat Chloride Tests: A painless electric current stimulates the skin to sweat, and the
chloride in perspiration is measured. People with cystic fibrosis often have high sweat
chloride levels.
 Amylase and Lipase Test: Blood tests showing elevated levels of these pancreatic
enzymes can suggest pancreatitis.
 Pancreas Biopsy: Either using a needle through the skin or a surgical procedure, a small
piece of pancreas tissue is removed to look for cancer or other conditions.
 38

 Genetic Testing: Many different mutations of a single gene can cause cystic fibrosis.
Genetic testing can help identify if an adult is an unaffected carrier or if a child will
develop cystic fibrosis.

Pancreas Treatments

 Insulin therapy: Injecting insulin under the skin causes body tissues to absorb glucose,
lowering blood sugar. Insulin can be created in a lab or purified from animal sources.
 Islet cell transplant: Insulin-producing cells are harvested from an organ donor’s
pancreas and transplanted into someone with type 1 diabetes. The still-experimental
procedure can potentially cure type 1 diabetes.
 Pseudocyst Drainage: A pseudocyst can be drained by inserting a tube or needle through
the skin into the pseudocyst. Alternately, a small tube or stent is placed between either the
pseudocyst and the stomach or the small intestine, draining the cyst.
 Pancreas transplant: An organ donor’s pancreas is transplanted into someone with
diabetes or cystic fibrosis. In some patients, a pancreas transplant cures diabetes.
 Pseudocyst Surgery: Sometimes, surgery is necessary to remove a pseudocyst. Either
laparoscopy (multiple small incisions) or laparotomy (one larger incision) may be needed.
 Pancreatic Cancer Resection (Whipple procedure): The standard surgery to remove
pancreatic cancer. In a Whipple procedure, a surgeon removes the head of the pancreas,
the gallbladder, and the first section of the small intestine (the duodenum). Occasionally,
a small part of the stomach is also removed.
 Pancreatic Enzymes: People with cystic fibrosis often must take oral pancreatic
enzymes to replace those that the malfunctioning pancreas doesn’t make.
 39

THYROID GLAND
The thyroid and parathyroid glands are cervical endocrine glands responsible for metabolism-
related functions. Thyroid is a butterfly shaped endocrine gland that is responsible for
producing thyroid hormones to provide energy to cells as well as regulate body's metabolism.
The thyroid as a ductless alveolar gland is superficial enough that you can locate your thyroid
with your fingers.

The function of thyroid gland is regulated by a feedback mechanism, which involves the
brain. When thyroid hormone levels are significantly low, the hypothalamus in brain
produces a hormone known as thyrotropin releasing hormone (TRH), causing the pituitary
gland (located at the base of brain) to release thyroid stimulating hormone (TSH). Thus,TSH
stimulates the thyroid gland to release more T4. Since the thyroid gland is controlled by
pituitary gland and hypothalamus, any disorder of these tissues can affect functioning of
thyroid.

Embryology of the thyroid gland

The thyroid gland is the first endocrine gland to develop in the human embryo. It develops at
the floor of the primitive pharynx at the same location of the base of the tongue. The
developing thyroid gland will migrate inferiorly along the anterior neck region to the lower
neck anteriorly to the trachea. The migration may leave behind embryonic remnants or
ectopic thyroid tissue that should atrophy, but may form developmental cysts.

Anatomy of the thyroid gland

The thyroid is an endocrine organ that is located in the anterior neck spanning between the C5 and
T1 vertebrae and caudal to the larynx and cephalic to the sternum just below the laryngeal
prominence (Adam’s apple). The gland has an “H” or “U” configuration and consists of right
and left lobes that consist of upper, middle, and lower poles that are connected across the
midline by a thin bridge of thyroid tissue called the isthmus, which is a thin band of
connective tissue. The isthmus straddles the trachea anteriorly, whereas the paired lobes
extend on either side of the trachea, bounded laterally by the common carotid arteries and
internal jugular veins. When present, the pyramidal lobe arises from the isthmus and tapers
superiorly just anterior to the thyroid cartilage. The pyramidal lobe is most commonly
 40

visualized in pediatric patients and usually atrophies with age. A fascia surrounds the thyroid,
trachea, esophagus, and parathyroid glands.

The thyroid gland contains an abundance of thyroid follicle, they are spheres that are lined by
simple cuboidal epithelium cells. The thyroid follicles contain a viscous colloid that has a
high concentration of dissolved proteins. They are important for the formation of
thyroglobulin, which are globular proteins that are synthesized by the follicle cells. The
amino acid base of this thyroglobulin proteins is tyrosine. Thyroglobulin are the building
blocks for the thyroid hormones.

Anterior view of the thyroid and parathyroid glands.

Cross section of the thyroid region showing the thyroid gland and the vascular and muscular
relationships to one another

The Thyroid gland has a network of capillaries the are important for delivering nutrients and
regulating hormones, as well as taking the thyroid hormones and waste material away from
the thyroid gland.

Blood supply
The thyroid gland is supplied by four arteries and considered highly vascular. Two superior
thyroid arteries branch from the external carotid arteries and descend to the upper poles of the
thyroid. Two inferior thyroid arteries arise from the thyrocervical trunk of the subclavian
arteries and ascend to the lower poles of the thyroid. Corresponding superior thyroid veins
drain into the internal jugular veins, and the inferior thyroid veins drain into the
brachiocephalic veins
 41

Lymphatic Drainage
The lymphatic drainage of the thyroid is multidirectional and extensive. It drains initially into peri-
thyroid nodes, and from there into prelaryngeal, pretracheal and paratracheal nodes. Laterally, the
gland drains into the superior and inferior deep cervical nodes.

Innervation
The thyroid gland is innervated by branches derived from the sympathetic trunk. However, these
nerves do not control endocrine secretion – release of hormones is regulated by pituitary gland.

Thyroid hormone secretion

When thyroid hormones are needed in the body, they are released into the bloodstream by the
action of thyrotropin, or thyroid-stimulating hormone (TSH), which is produced by the
pituitary gland. The secretion of TSH is regulated by thyrotropin-releasing hormone
(TRH), which is produced by the hypothalamus. The level of TRH is controlled by the basal
metabolic rate in a negative feedback system. Low concentration of thyroid hormones causes
a decrease in the basal metabolic rate, which results in an increase in TRH. This causes an
increased secretion of TSH and a subsequent increase in the release of thyroid hormones.
When the blood level of thyroid hormones is returned to normal, the basal metabolic rate
returns to normal and TSH secretion stops. In summary, the hypothalamus signals the
pituitary gland to tell the thyroid gland to produce more or less thyroid hormones.

Calcitonin decreases the concentration of calcium in the blood by first acting on bone to
inhibit its breakdown of calcium. When less calcium is being resorbed into the blood, less
calcium moves out of the bone into the blood with a decrease in blood calcium levels.
Calcitonin secretion will increase after any concentration of blood calcium increases.

Synthesis of thyroid hormones

The thyroid is responsible for the production of two hormones which are Thyroxine,
commonly known as T4, and Triiodothyronine, commonly known as T3. These hormones are
based on the amino acid tyrosine. In the thyroid follicle cells, tyrosine is formed into
thyroglobulin. From the thyroglobulin, thyroid hormones are produced by the following
seven steps.

Step 1 involves the transport of iodide ions that come from the diet through the bloodstream
from the digestive system to the thyroid gland. The basement membrane of the follicle cells
actively transports the iodide ions by the TSH-sensitive carrier proteins. These carrier
proteins carry the iodide ion into the cytoplasm of the follicle cells. The concentration of the
iodide ions within the follicle cells is normally much higher than the concentration in the
extracellular fluid.

Step 2 is where the iodine ion turns into Iodine atoms. This happens when the iodide ions
diffuse to the apical surface of the follicle cells and the ion loses its electron. The enzyme
thyroid peroxidase removes the electron that changes the charge of the ion to an atom. As
part of this reaction sequence at the apical surface one or two of the new iodine atoms are
attached to the tyrosine portion of a thyroglobulin molecule within the follicle cavity.

Step 3 is where the thyroid hormones are formed from the newly formed thyroglobulin with a
couple of iodine atom attached to it. The iodine atoms are connected to the tyrosine, as part of
the thyroglobulin, through a covalent bond to form the thyroid hormones. The same enzyme
from step 2, thyroid peroxidase, is thought to continue the pairing process that connects the
 42

iodine to the thyroid hormones. Thyroxine, or T4, has four iodine atoms attached to it
tyrosine amino acid backbone. Triiodothyronine, or T3, has three iodine atoms attached to the
tyrosine amino acid backbone. Within each thyroglobulin there can four to eight molecules of
T3 or T4 hormones. Within the thyroglobulin they are can T3, T4 or a mixture of both.

Step 4 is when the thyroglobulin is removed from the follicles by the follicle cells through
endocytosis.

Step 5 is when the thyroglobulin is then broken down by Lysosomal enzymes, which allows
the amino acids and newly produced thyroid hormones to enter the cytoplasm of the follicle
cell. Leftover amino acid are then recycled to reform new thyroglobulin.

Step 6 is when the newly formed thyroid hormones are released into the bloodstream. To get
to the bloodstreamT3 and T4 must diffuse across the basement membrane of the follicle cells.
Of the thyroid hormones secreted 90% is T4 and T3 is secreting significantly less.

Step 7 now that the thyroid hormones are released into the bloodstream 75% of T4 and 70%
of T3 attach to a transport protein. This transport protein is call thyroid-binding globulins
(TBGs). The rest attach to transthyretin also known as Thyroid-binding prealbumin (TBPA)
or to albumin one of the plasma protein present in the blood. A very small amount is left
unbound to a transport protein which allows them to freely diffuse into peripheral tissues.

Thyroid Hormone Regulation

The limiting factor that controls that rate of hormone production is the release of TSH. TSH
which stimulate the active transport of iodide ion into the cell and the formation
thyroglobulin is released from the pituitary gland. When the TSH has a low concentration in
the blood there is less stimulation of the thyroid gland. As a result, this limits how much
iodide ions are transported into the follicle cells and can stimulate the formation of the
thyroglobulin.
 43

This is achieved in a number of ways, such as increasing the size and number of mitochondria within
cells, increasing Na-K pump activity and increasing the presence of β-adrenergic receptors in tissues
such as cardiac muscle.

Function
The role of the thyroid is to maintain normal body metabolic processes (Thermogenesis,
Lipogenesis, Glycogenolysis, Gluconeogenesis, Protein synthesis and Basal Metabolic Rate), physical
and mental growth, and development by the synthesis, storage, and secretion of thyroid
hormones. Every cell in the body depends on thyroid hormones for regulation of their
metabolism. The mechanism for producing thyroid hormones is through iodine metabolism.
The thyroid follicular cells are the only cells in the body that can absorb iodine. Through a
series of chemical reactions, the thyroid produces triiodothyronine (T 3 ) and thyroxine (T 4 ).
Most endocrine glands do not store their hormones, but thyroid hormones are stored in the
colloid material of the gland to be secreted when needed into the blood.

The thyroid has a secondary function which is the regulation of calcium in the blood. This is
done by calcitonin (CT) hormone produced by the thyroid’s clear cells or parafollicular cell.
Commonly these cells are referred to as the C cells and are found just outside the
follicle. Calcitonin works with the Parathyroid hormones to regulate calcium in the blood
through the opposite actions of osteoclasts and stimulation of the calcium excretion from the
kidneys.

Disease of thyroid gland

Pathology of the thyroid gland
Pathology identified in the thyroid and adjacent neck structures should always be documented
in both longitudinal and transverse scan planes. The gland measurements and volume should
be obtained and parenchyma defined as homogeneous or heterogeneous. If a nodule is
visualized, the location should be noted in relationship to gland (e.g., right thyroid transverse
upper; left thyroid long lateral) and also measured in three dimensions. The sonographic
appearance should be demonstrated and echogenicity described (e.g., hypoechoic,
hyperechoic, and whether cystic, complex cystic, solid, and/or presence and type of
calcifications). In addition, the nodule borders should be described as ill defined or well
defined and whether a hypoechoic halo is surrounding the nodule. It is not uncommon for
sonography to demonstrate multiple nodules in a gland. Vascularity should also be
demonstrated with color or power Doppler and possibly pulsed wave Doppler.

Hypothyroidism.
Undersecretion of thyroid hormones is called hypothyroidism and is the most common
thyroid disorder. In the adult, it can be referred to as myxedema. Hypothyroidism can occur
spontaneously from inability of the thyroid to produce the proper amount of thyroid
hormones or a problem with the pituitary gland. Most commonly (75%), hypothyroidism is
caused by a chronic thyroid inflammatory process called Hashimoto’s thyroiditis. The
inflammatory process can also be the result of an autoimmune response that damages a large
percentage of thyroid cells where it is inadequate to produce sufficient hormones. Other
causes include medications or radiation exposure to the head or neck. Radiation treatments to
the neck and upper chest are associated with certain types of lymphoma

Hyperthyroidism.
The oversecretion of thyroid hormones is called hyperthyroidism. This occurs when the
entire gland is not functioning properly, usually from diffuse enlargement or localized nodule
 44

or adenoma causing overproduction of thyroid hormones called Graves’ disease . Box 22-
2 lists the common disorders associated with hyperthyroidism.

Nodular thyroid disease

Approximately 80% of nodular thyroid disease is due to hyperplasia or compensatory
hypertrophy forming micronodules and macronodules of the gland. This can lead to overall
enlargement (goiter) or multiple nodules (MNG) that may be unilateral or bilateral, seen more
commonly in women with increasing age. When evaluated microscopically, most benign
nodules are classified as hyperplastic, adenomatous, and colloid type nodules.

Congenital abnormalities of the thyroid gland

Congenital abnormalities of the thyroid gland include aplasia, hypoplasia, and ectopic
locations of the thyroid gland. Aplasia is congenital absence of gland and may affect one
lobe, the isthmus, or the entire gland. Complete absence of the thyroid gland has a severe
impact on physical and mental development. Hypoplasia refers to underdevelopment of any
part of the gland and may be associated with congenital hypothyroidism. Ectopic locations
may be present along the path of embryonic descent if the thyroid migrates too little or too
far. Most commonly, ectopic tissue may be present posterior to the tongue (sublingual or
lingual thyroid). Other ectopic locations include larynx (prelaryngeal thyroid) or mediastinum
(substernal thyroid). Scintigraphy is best for visualization of ectopic thyroid tissue.

The Parathyroid Gland

The parathyroid glands are small endocrine glands located in the anterior neck. They are
responsible for the production of parathyroid hormone (PTH).

The Parathyroid glands (small glands of endocrine system) are located in the neck behind the
thyroid.
The parathyroid glands release a hormone called parathyroid hormone. This hormone helps to
control the levels of three minerals in the body: Calcium, Phosphorus and
Magnesium. Parathyroid hormone has several effects in the body:
 It causes the release of calcium from bones.
 It causes calcium to be taken up (absorbed) into the blood from the intestine.
 It stops the kidneys from getting rid of (excreting) calcium in the urine.
 It causes the kidneys to excrete phosphate in the urine.
 It increases blood levels of magnesium

Anatomy

The parathyroid glands are located on the posterior, medial aspect of each lobe of the thyroid
gland. Anatomically, the glands can be divided into two pairs:

 Superior parathyroid glands – Derived embryologically from the fourth pharyngeal

pouch. They are usually located at the level of the inferior border of the cricoid
cartilage.
 Inferior parathyroid glands – Derived embryologically from the third pharyngeal
pouch. They are usually located near the inferior poles of the thyroid gland. However
in 1-5% of people they can be found deep in the superior mediastinum.
 45

Anatomical location of the parathyroid glands

Vascular Supply
The posterior aspect of the thyroid gland is supplied by the inferior thyroid
arteries. Thus its branches also supply the nearby parathyroid glands. Collateral
circulation is delivered by the superior thyroid arteries, laryngeal, tracheal and
oesophageal arteries. The parathyroid veins drain into the thyroid plexus of veins.

Lymphatics
The lymphatic vessels of the parathyroid glands drain (along with those of the thyroid gland) into
the deep cervical lymph nodes and paratracheal lymph nodes.

Nerves
The parathyroid glands have an extensive supply of nerves, derived from thyroid branches of the
cervical ganglia. It is important to note that these nerves are vasomotor, not secretomotor –
endocrine secretion of parathyroid hormone is controlled hormonally.

Parathyroid Hormone Synthesis

The synthesis of PTH begins within the rough endoplasmic reticulum, where pre-pro-PTH is
produced. Pre-pro-PTH is 115 amino acids long and consists of a biologically active
 46

The signal sequence is cleaved within the lumen of the endoplasmic reticulum, leaving pro-
PTH. After transfer to the Golgi apparatus the pro sequence is also cleaved, resulting in the
production of mature PTH, which can then be stored in secretory granules for release.

Parathyroid Hormone Actions

Parathyroid hormone (PTH) has three main actions, all of which act to increase
calcium levels in the body;

 Increased bone resorption– PTH acts directly on bone to increase bone resorption. It
induces cytokine secretion from osteoblasts that act on osteoclast cells to increase their
activity. Osteoclasts are responsible for the breakdown of bone and thus an increase in their
activity leads to increased bone break down. This leads to an increase in calcium in the
extracellular fluid.
 Increased reabsorption in the kidney- PTH increases the amount of calcium absorbed from
the Loop of Henle and distal tubules, however the mechanism is not fully understood. In
addition to this PTH increases the rate of phosphate excretion which is very important to
prevent to formation of calcium phosphate kidney stones.
 Vitamin D synthesis- Although PTH does not actively increase the absorption of calcium
from the gut it stimulates the formation of vitamin D, this subsequently increases absorption
from the gut.

Parathyroid Hormone Regulation

Like most endocrine organs the parathyroid gland is controlled by a negative feedback
loop. Chief cells have a unique G-protein calcium receptor (CaR) on their surface, which
regulates this.
When calcium levels in the blood are elevated PTH production must be stopped in
order to prevent further elevation of calcium which could lead to hypercalcaemia. Calcium
binds to the G protein CaR which subsequently leads to the production of a molecule
called phosphoinositide.
The activation of this molecule prevents PTH secretion thus calcium is deposited back
into the bones. Furthermore as mentioned above PTH stimulates vitamin D synthesis.
Vitamin D also acts directly on the parathyroid gland to decrease the transcription of the PTH
gene hence less PTH is synthesised.
When Calcium is reduced the reverse occurs. Lowered calcium means reduced
stimulation of CaR and decreased phosphoinositide. Subsequently PTH secretion is not
inhibited. Decreased Vitamin D results in upregulation of PTH gene transcription thus
more PTH is synthesised.

Disease of parathyroid gland

Hyperparathyroidism

Improper functioning of the parathyroid glands causes hyperparathyroidism,

which increases calcium levels in the blood. Primary hyperparathyroidism is caused by a
condition that affects one or more parathyroid glands, causing exaggerated release of its
hormone (parathyroid hormone or PTH). This condition could be a benign tumor of the
parathyroid gland called an adenoma, benign enlargement affecting multiple glands
(hyperplasia) or very rarely carcinoma (malignant tumor). The cause of those tumors are
unknown with certain theories being exposure to radiation of head and neck area in the past,
lithium use and, rarely, a syndrome that runs in the patient’s family.