ADRENAL GLANDS

RIMSHA RIZWAN
ROLL NO: 206-BH-
CHEM-20
SEMESTER: VII (M)
SUBMITTED TO:
DR SAMINA

DEPARTMENT OF
CHEMISTRY
GOVERNMENT
UNIVERSITY,
LAHORE
Contents
Abstract............................................................................................................................................2
Adrenal glands.................................................................................................................................3
1.1 Anatomy of the Adrenal Glands................................................................................................3
1.1.1 Cortex.............................................................................................................................4
1.1.2 Medulla...........................................................................................................................5
1.2 Vasculature............................................................................................................................5
2. Embryology.................................................................................................................................8
3. Hormones of the Adrenal Glands................................................................................................9
3.1 Cortisol..............................................................................................................................9
3.1.1 How Adrenal Glands Work to Produce Cortisol..........................................................10
3.2 Aldosterone......................................................................................................................11
3.3 DHEA and Androgenic Steroids.....................................................................................11
3.4 Epinephrine (Adrenaline) and Norepinephrine (Noradrenaline).....................................12
4. Adrenal Gland Disorders...........................................................................................................13
4.1 Adrenal Insufficiency..........................................................................................................13
4.1.2 Congenital Adrenal Hyperplasia...................................................................................14
4.1.3 Addison's disease..........................................................................................................15
4.2 Overactive Adrenal Glands..................................................................................................15
4.2.1 Excess of Cortisol: Cushing Syndrome........................................................................16
4.2.2 Excess of Aldosterone: Hyperaldosteronism................................................................16
4.2.3 Pheochromocytoma......................................................................................................16
4.3 Adrenal Cancer................................................................................................................17
5. Conclusion.................................................................................................................................17
Abstract
The adrenal glands are essential endocrine organs located above the kidneys. This assignment
provides a brief overview of their structure, function, and significance. The adrenal glands
consist of two parts: the outer adrenal cortex and the inner adrenal medulla. The cortex produces
hormones like cortisol, which regulate metabolism and immune response, and aldosterone, which
controls electrolyte balance. Meanwhile, the medulla produces adrenaline and noradrenaline,
crucial for the body's "fight or flight" response. Understanding the adrenal glands is crucial for
comprehending stress, blood pressure regulation, and various medical conditions like Cushing's
syndrome and Addison's disease. This assignment aims to shed light on the pivotal role these
glands play in maintaining physiological balance.
 Adrenal glands

Adrenal glands may develop nodules

that can be benign or malignant,
which can potentially produce
excessive amounts of certain
hormones leading to various health.

The adrenal glands are located in the

posterior abdomen, between the
superomedial kidney and the
diaphragm. They are retroperitoneal,
with parietal peritoneum covering
their anterior surface only [2].

The right gland is pyramidal in shape, contrasting with the semi-lunar shape of the left gland.

Perinephric (or renal) fascia encloses the adrenal glands and the kidneys. This fascia attaches the
glands to the crura of the diaphragm. They are separated from the kidneys by the perirenal fat
[7].

The adrenal glands sit in close proximity to many other structures in the abdomen:

Right adrenal gland Left adrenal gland

Anterior Posterior Anterior Posterior

Stomach
Inferior vena cava Right crus of the
Pancreas Left crus of the diaphragm
Right lobe of the liver diaphragm
Spleen

1.1 Anatomy of the Adrenal Glands

An adrenal gland is made of two main parts:
The adrenal glands consist of an outer connective tissue capsule, a cortex and a medulla. Veins
and lymphatics leave each gland via the hilum, but arteries and nerves enter the glands at
numerous sites [1].

The outer cortex and inner medulla are the functional portions of the gland. They are two
separate endocrine glands, with different embryological origins:

 Cortex – derived from the embryonic mesoderm.

 Medulla – derived from the ectodermal neural crest cells.

The cortex and medulla synthesise different hormones.

1.1.1 Cortex

The cortex is yellowish in colour. It secretes two cholesterol derived hormones – corticosteroids
and androgens. Functionally, the cortex can be divided into three regions (superficial to deep):

 Zona glomerulosa – produces and secretes mineralocorticoids such as aldosterone.

 Zona fasciculata – produces and secretes corticosteroids such as cortisol. It also secretes
a small amount of androgens [4].
Zona reticularis – produces and secretes androgens such as dehydroepiandrosterone (DHES). It
also secretes a small amount of corticosteroids [1].

The function of these three zones can be remembered by the mnemonic "Salt, Sugar, Sex," as
they correlate to the function of the hormones produced in each layer of the adrenal cortex. The
names of these zones can also be recalled by remembering "GFR" for glomerulosa, fasciculata,
and reticularis.

The adrenal medulla synthesizes catecholamines. Catecholamines are made from the precursor of
dopamine and combined with tyrosine, thus resulting in norepinephrine. Once norepinephrine
has been created, it is then methylated via phenylethanolamine N-methyltransferase (PNMT),
which is only present in the adrenal medulla [9].

1.1.2 Medulla

The medulla lies in the centre of the gland, and is dark brown in colour. It contains chromaffin
cells, which secrete catecholamines (such as adrenaline) into the bloodstream in response to
stress. These hormones produce a ‘flight-or-fight‘ response. Chromaffin cells also secrete
enkephalins which function in pain control. The adrenal medulla is located inside the adrenal
cortex in the center of an adrenal gland. It produces “stress hormones,” including adrenaline [3].

The adrenal cortex and adrenal medulla are enveloped in an adipose capsule that forms a
protective layer around an adrenal gland.

1.2 Vasculature
The adrenal glands have a rich blood supply via three main arteries:

Superior adrenal artery – arises from the inferior phrenic artery

Middle adrenal artery – arises from the abdominal aorta.

Inferior adrenal artery – arises from the renal arteries.

Right and left adrenal veins drain the glands. The right adrenal vein drains into the inferior vena
cava, whereas the left adrenal vein drains into the left renal vein. As the adrenal glands produce
various systemically-important hormones, they require significant blood supply and are
extremely well vascularized [13]. The blood supply is tightly controlled by neuroendocrine and
paracrine mechanisms, which is one method of regulating the systemic levels of adrenal
hormones. Variations in adrenal artery origin are very common. The superior adrenal artery can
come off the abdominal aorta, celiac axis, or, more rarely, an intercostal artery. The superior
adrenal artery is also commonly found as multiple arteries [1].

1.3 Innervation

The adrenal glands are innervated by the coeliac plexus and greater splanchnic nerves.
Sympathetic innervation to the adrenal medulla is via myelinated pre-synaptic fibres, mainly
from the T10 to L1 spinal cord segments. The function of the adrenal gland is mediated by both
synaptic stimulation and hormonal stimulation. Adrenocorticotropic hormone (ACTH) secreted
from the anterior pituitary gland activates the adrenal cortex. Subsequently, ACTH activates the
respective cortical zones to generate corticosteroids. However, the adrenal medulla is innervated
by preganglionic nerve fibers (type B) arising from the intermediolateral cell column of the
spinal cord's lateral horn from the T5–T8 spinal cord segments [9].

These nerve fibers form the greater splanchnic nerve without entering the paravertebral
sympathetic ganglion chain. Some of the nerve fibers from the greater splanchnic nerve synapse
at the celiac ganglion. The blood vessels supplying the adrenal glands will then receive their
innervation from the celiac ganglion's postsynaptic fibers. On the other hand, some fibers of the
greater splanchnic nerve circumvent the celiac ganglion and directly enter the adrenal gland to
synapse at the chromaffin cells' membranes. This is the reason why the adrenal medulla acts as a
neuroendocrine junction between the two physiological segments. The chromaffin cells release
their neurohormones directly into the bloodstream to produce a widespread sympathetic response
and apparently act as a special type of postsynaptic neuron [5] .
1.4 Lymphatics

Lymph drainage is to the lumbar

lymph nodes by adrenal
lymphatic vessels. These vessels
originate from two lymphatic
plexuses – one deep to the
capsule, and the other in the
medulla.The venous drainage
from the adrenal glands is
dependent on the side of the
gland. The left adrenal gland is
anatomically further away from
the inferior vena cava, and
therefore the left adrenal vein drains into the left renal vein. The right adrenal vein is much closer
to the inferior vena cava and drains directly into this large vessel. Variations in adrenal venous
drainage are common, particularly on the left side. There are reports of venous connections
between the left adrenal vein and the left genital vein, and the inferior phrenic vein. Double left
adrenal veins are also common. [2]

2. Embryology
The adrenal gland is composed of two embryologically distinct tissues that contain two different
forms of signaling chemicals. One is the outer cortex of mesodermal origin, which produces
steroid hormones [4]. The other is a medulla that is derived from neuroectoderm and secretes
catecholamines. In the 5th week of development, an isolated cluster of cells emerges within the
urogenital ridge, identified as the adrenal-gonadal primordial germ cells. Mesothelial cells
penetrate the mesenchymal layer and form fetal adrenal cortex and Leydig cells [16].
Consequently, large acidophilic cells differentiate to form a primitive cortex. Smaller cells then
migrate and engulf these acidophilic cells; they will proceed to form the definitive cortex. During
the 7th week of development, neural crest cells formed at the apex of the neural folds migrate
into the adrenal primordium via a ventral pathway. These cells enter the gland from the medial
face and then differentiate into chromaffin cells centrally arranged in cords and masses. The
cortex engulfs and gradually encapsulates the whole medulla in the later stages of embryonic
development [7].

At a molecular level, many factors were described to be essential for the development of adrenal
glands. The most essential among them are steroidogenic factor-1, CITED-2, β-catenin, and
others [2].

3. Hormones of the Adrenal Glands

The role of the adrenal glands in your body is to release certain hormones directly into the
bloodstream. Many of these hormones have to do with how the body responds to stress, and
some are vital to existence. Both parts of the adrenal glands — the adrenal cortex and the adrenal
medulla — perform distinct and separate functions [3].

Each zone of the adrenal cortex secretes a specific hormone. The key hormones produced by
the adrenal cortex include:

3.1 Cortisol
Cortisol is a glucocorticoid hormone produced by the zona fasciculata that plays several
important roles in the body. It helps control the body’s use of fats, proteins and carbohydrates;
suppresses inflammation; regulates blood pressure; increases blood sugar; and can also decrease
bone formation. This hormone also controls the sleep/wake cycle. It is released during times of
stress to help your body get an energy boost and better handle an emergency situation.

3.1.1 How Adrenal Glands Work to Produce Cortisol

Adrenal glands produce hormones in response to signals from the pituitary gland in the brain,
which reacts to signaling from the hypothalamus, also located in the brain [4]. This is referred to
as the hypothalamic pituitary adrenal axis. As an example, for the adrenal gland to produce
cortisol, the following occurs:

 The hypothalamus produces corticotropin-releasing hormone (CRH) that stimulates the

pituitary gland to secrete adrenocorticotropin hormone (ACTH).
  ACTH then stimulates the adrenal glands to make and release cortisol hormones into the
blood.
 Normally, both the hypothalamus and the pituitary gland can sense whether the blood has
the appropriate amount of cortisol circulating. If there is too much or too little cortisol,
these glands respectively change the amount of CRH and ACTH that gets released. This
is referred to as a negative feedback loop.
 Excess cortisol production can occur from nodules in the adrenal gland or excess
production of ACTH from a tumor in the pituitary gland or other source [1].

3.2 Aldosterone

This mineralocorticoid hormone produced by the zona glomerulosa plays a central role in
regulating blood pressure and certain electrolytes (sodium and potassium). Aldosterone sends
signals to the kidneys, resulting in the kidneys absorbing more sodium into the bloodstream and
releasing potassium into the urine. This means that aldosterone also helps regulate the blood pH
by controlling the levels of electrolytes in the blood. [11]

3.3 DHEA and Androgenic Steroids

These hormones produced by the zona reticularis are weak male hormones. They are precursor
hormones that are converted in the ovaries into female hormones (estrogens) and in the testes
into male hormones (androgens). However, estrogens and androgens are produced in much larger
amounts by the ovaries and testes [7].

3.4 Epinephrine (Adrenaline) and Norepinephrine (Noradrenaline)

The adrenal medulla, the inner part of an adrenal gland, controls hormones that initiate the
flight or fight response. The main hormones secreted by the adrenal medulla include epinephrine
(adrenaline) and norepinephrine (noradrenaline), which have similar functions [8].

Among other things, these hormones are capable of increasing the heart rate and force of heart
contractions, increasing blood flow to the muscles and brain, relaxing airway smooth muscles,
and assisting in glucose (sugar) metabolism. They also control the squeezing of the blood vessels
(vasoconstriction), helping maintain blood pressure and increasing it in response to stress [2].
Like several other hormones produced by the adrenal glands, epinephrine and norepinephrine are
often activated in physically and emotionally stressful situations when your body needs
additional resources and energy to endure unusual strain [4].

4. Adrenal Gland Disorders

The two common ways in which adrenal glands cause health issues are by producing too little or
too much of certain hormones, which leads to hormonal imbalances. These abnormalities of the
adrenal function can be caused by various diseases of the adrenal glands or the pituitary gland.

4.1 Adrenal Insufficiency

Adrenal insufficiency is a rare disorder. It may be caused by disease of the adrenal glands
(primary adrenal insufficiency, Addison’s disease) or by diseases in the hypothalamus or the
pituitary (secondary adrenal insufficiency). It is the opposite of Cushing syndrome and is
characterized by low levels of adrenal hormones. The symptoms include weight loss, poor
appetite, nausea and vomiting, fatigue, darkening of skin (only in primary adrenal insufficiency),
abdominal pain, among other [7].

The causes of primary adrenal insufficiency may include autoimmune disorders, fungal and other
infections, cancer (rarely), and genetic factors.

Although adrenal
insufficiency usually
develops over time, it can
also appear suddenly as
an acute adrenal failure
(adrenal crisis). It has
similar symptoms, but the
consequences are more
serious, including life-
threatening shock,
seizures, and coma. These
may develop if the
condition is left untreated
[16] .

4.1.2 Congenital Adrenal Hyperplasia

Adrenal insufficiency can also result from a genetic disorder called congenital adrenal
hyperplasia. Children who are born with this disorder are missing an essential enzyme necessary
to produce cortisol, aldosterone or both. At the same time, they often experience excess of
androgen, which may lead to male characteristics in girls and precocious puberty in boys [18].

Congenital adrenal hyperplasia can remain undiagnosed for years depending on the severity of
the enzyme deficiency. In more severe cases, infants may suffer from ambiguous genitalia,
dehydration, vomiting and failure to thrive.
4.1.3 Addison's disease

Addison's disease refers to primary hypoadrenalism, which

is a deficiency in glucocorticoid and mineralocorticoid
production by the adrenal gland. In the Western world,
Addison's disease is most commonly an autoimmune
condition, in which the body produces antibodies against
cells of the adrenal cortex. Worldwide, the disease is more
frequently caused by infection, especially from tuberculosis.
A distinctive feature of Addison's disease is
hyperpigmentation of the skin, which presents with other
nonspecific symptoms such as fatigue [11].

Fig: Characteristic skin color in Addison’s Disease

4.2 Overactive Adrenal Glands

Sometimes, adrenal glands may develop nodules that produce too much of certain hormones.
Nodules 4 centimeters or larger and nodules that show certain features on imaging increase
suspicion for malignancy. Both benign and cancerous nodules may produce excessive amounts
of certain hormones, which is referred to as a functional nodule [1]. Functional tumors,
malignant tumors or nodules greater than 4
centimeters are recommended to be referred for
surgical evaluation [15].

4.2.1 Excess of Cortisol: Cushing Syndrome

Cushing syndrome results from excessive

production of cortisol from the adrenal glands.
The symptoms may include weight gain and
fatty deposits in certain areas of the body, such
as the face, below the back of the neck called a
buffalo hump and in the abdomen; thinning
arms and legs; purple stretch marks on the
abdomen; facial hair; fatigue; muscle weakness; easily bruised skin; high blood pressure;
diabetes; and other health issues [5].

Excess cortisol production can also be triggered by overproduction of ACTH by a benign tumor
in the pituitary gland or tumor elsewhere in the body. This is known as Cushing Disease.
Another common cause of Cushing syndrome is excessive and prolonged consumption of
external steroids, such as prednisone or dexamethasone, which are prescribed to treat many
autoimmune or inflammatory diseases (e.g., lupus, rheumatoid arthritis, asthma, inflammatory
bowel disease, multiple sclerosis, etc [6].

4.2.2 Excess of Aldosterone: Hyperaldosteronism

Hyperaldosteronism results from overproduction of aldosterone from one or both adrenal glands.
This is characterized by increase in blood pressure that often requires many medications to
control. Some people can develop low
potassium levels in the blood, which can cause
muscle aches, weakness and spasms. When
the cause is adrenal oversecretion, the disease
is called Conn syndrome [9].

Excess of Adrenaline or Noradrenaline:

4.2.3 Pheochromocytoma

Pheochromocytoma is a tumor that results in excess production of adrenaline or noradrenaline by

the adrenal medulla that often happens in bursts. Occasionally, neural crest tissue, which has
similar tissue to the adrenal medulla, may be the cause of overproduction of these hormones.
This known as a paraganglioma [13].

Pheochromocytomas may cause persistent or

sporadic high blood pressure that may be difficult
to control with regular medications. Other
symptoms include headaches, sweating, tremors,
anxiety and rapid heartbeat. Some people are
genetically predisposed to developing this type of
tumor [2].

4.3 Adrenal Cancer

Malignant adrenal tumors (adrenal cancer), such as

adrenocortical carcinoma, are rare and often have
spread to other organs and tissues by the time they
are diagnosed. These tumors tend to grow fairly
large and can reach several inches in diameter [3].

Cancerous adrenal tumors can be functional and release excess of one or more hormones
accompanied by corresponding symptoms, as listed above. Patients may also experience
abdominal pain, flank pain or a feeling of abdominal fullness, especially when the adrenal tumor
gets very large. Not all cancers found in adrenal glands originate from the gland itself. The
majority of adrenal tumors are metastasis, or cancer spread, from another primary tumor
elsewhere in the body[10].
5. Conclusion
The adrenal glands are like tiny factories in our bodies that make special chemicals called
hormones. These hormones help control many important things, like how we deal with stress,
how we use energy, and how our bodies keep the right balance of salt and water. The cortex
makes hormones like cortisol and aldosterone, which help us manage stress and keep our bodies
in balance [1]. The medulla makes adrenaline and noradrenaline, which make our hearts beat
faster and give us energy when we're in danger. Sometimes, the adrenal glands don't work as
they should, and that can cause health problems. We discussed conditions like Cushing's
syndrome and Addison's disease, which happen when these glands have trouble making the right
hormones [5].

Understanding the adrenal glands is essential for our health because they play a big part in
keeping our bodies working well. Doctors and scientists are always studying them to help people
stay healthy and deal with life's challenges effectively [12].
6. References
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