Adrenal glands

The adrenal glands (Latin: glandula suprarenalis), also called suprarenal glands, are two small endocrine glands located on top of both kidneys. The adrenal glands regulate metabolism, immune system, blood pressure, and even response to stress by producing and secreting steroid hormones in the bloodstream. The adrenal glands have two parts, the cortex, and the medulla, with each secreting different substances.

Adrenal glands anatomy

The adrenal glands are located at the back part of the abdomen, with the peritoneum covering them from the anterior side, making the adrenal glands retroperitoneal organs. The glands lie on the top of both kidneys and are slightly medial to them. The adrenal glands are different in their shapes; the right adrenal gland is pyramid-shaped, while the left one is semilunar-shaped and a bit larger. The weight of both adrenal glands together is around 7-10 grams, the length is 5 cm, the width 3 cm, and they are 1 cm thick. 

The adrenal glands are slightly yellow. The fatty capsule is surrounding both of the glands, and they lie within the perinephric or renal fascia together with the kidneys. Perirenal fat separates the adrenal glands from the kidneys. The glands are located directly under the diaphragm. To the anterior side of the right adrenal gland are the inferior vena cava and right lobe of the liver, while to the posterior side is the right crus of the diaphragm. The stomach, pancreas, and spleen are located in front of the left adrenal gland, while the left crus of the diaphragm is behind the left gland.

Parts of the adrenal glands 

The adrenal glands consist of two parts: the adrenal cortex and the adrenal medulla. Both parts are different in their function, secreting hormones, structure, and embryonic development, so they can be considered as two separate endocrine glands.

The adrenal cortex 

The adrenal cortex is the outer part of the adrenal glands, also the largest part. The adrenal cortex totally encloses the adrenal medulla. During the embryonic period, the cortex is derived from the embryonic mesoderm. The cortex is yellowish. The cells of the adrenal cortex are divided into three types, which are arranged in zones. The adrenal cortex has three layers based on the cell zones responsible for producing and secreting specific hormones. The adrenal cortex is responsible for glucocorticoids (cortisol), mineralocorticoids (aldosterone), and androgens. These three zones are (from the outermost to innermost):

  • Zona glomerulosa
  • Zona fasciculata
  • Zona reticularis.

Zona glomerulosa

Zona glomerulosa is the outer part of the adrenal cortex. This zone is located immediately below the previously mentioned fatty capsule surrounding the adrenal glands. Zona glomerulosa has cells arranged in clusters and resembles balls of wool. Zona glomerulosa is only 5-7 cells thick, but it depends on the physiological state. For example, a person with chronic sodium deprivation will have larger zona glomerulosa than a person with a typical intake. Cell groups are separated from each other with connective tissue. 

Cells have steroid-secreting cell characteristics with lipid droplets and large numbers of mitochondria. Connective tissues have many capillaries in them, so the secreted hormones can get directly into the bloodstream. Zona glomerulosa is responsible for secreting aldosterone, mineralocorticoid. Aldosterone plays a part in the regulation of blood pressure. Aldosterone affects kidneys to conserve salt and water. 

Zona fasciculata 

The middle zone is called zona fasciculata. Zona fasciculata is much thicker than the other two layers, accounting for approximately 80% of the adrenal cortex. Zona fasciculata has pale staining vacuolated cells containing lipid droplets, abundant mitochondria, and a smooth endoplasmic reticulum. These cells also, the same as in zona glomerulosa, have steroid-secreting characteristics. 

The cells are arranged in parallel radial cords that look like long strings, stretching from the zona glomerulosa down to the adrenal medulla. The cells remind bundles of sticks. Zona fasciculata is responsible for secreting cortisol and corticosterone, glucocorticoids that affect metabolism, increase blood glucose levels, and take part in the immune system. 11-deoxycorticosterone is also secreted from here. Zona fasciculata also secretes adrenal androgens, but less than zona reticularis.

Zona reticularis 

Zona reticularis is the most inner part of the adrenal cortex. Zona reticularis consists of cells forming a loose network. Also in this zone, cells remind steroid-secreting cells with lipid droplets and mitochondria. Zona reticularis is mainly responsible for secreting dehydroepiandrosterone (DHEA), DHEA sulfate, and androstenedione, adrenal androgens or sex hormones. Zona reticularis also produces glucocorticoids but in smaller amounts than zona fasciculata. 

The adrenal medulla

The adrenal medulla can be considered as an interface between the endocrine and nervous systems, so it has characteristics of both systems. The adrenal medulla is the innermost part of the adrenal glands, thinner compared to the adrenal cortex. The adrenal medulla looks darker than the cortex. The adrenal medulla consists of chromaffin cells that are brownish. 

The adrenal medulla cells can be easily differentiated from the cells in the adrenal cortex; chromaffin cells do not have lipid droplets but have many secretory granules. These cells are connected to the sympathetic part of the autonomic nervous system. Chromaffin cells are modified postganglionic neurons with preganglionic autonomic fibers leading to them directly from the central nervous system. 

Even though catecholamines also work as neurotransmitters, they are released into the bloodstream instead of the synaptic cleft. The hormones from the adrenal medulla are more rapid and short-lived than other hormones. The adrenal medulla is considered to be neural tissue with direct neural input, thus functioning like a modified sympathetic ganglion. This shows that the adrenal medulla is an interface between two systems. 

The chromaffin cells produce catecholamines, epinephrine (adrenaline), norepinephrine (noradrenaline), and dopamine. The adrenal medulla is responsible for around 20% of norepinephrine and 80% of epinephrine production. As the medulla has many capillaries within, epinephrine is secreted directly into the capillaries. 

Vasculature and innervation of the adrenal glands 

Like any other organ, the adrenal glands are highly vascularized because they release hormones directly into the bloodstream. Innervation and neural input are interesting as the adrenal medulla is partly sympathetic ganglion itself.

Arterial supply 

The adrenal glands have one of the most significant blood supply rates per gram of tissue than any other organs. Around 60 small arteries enter each adrenal gland. Each adrenal gland is supplied by three main arteries: the superior suprarenal artery, the middle suprarenal artery, the inferior suprarenal artery. 

The superior suprarenal artery is a branch of the inferior phrenic artery. The inferior phrenic arteries are branches from the anterior surface of the abdominal aorta. At the upper medial part of the adrenal glands, the inferior phrenic arteries branch into the superior suprarenal arteries. 

The middle suprarenal artery is a branch directly from the abdominal aorta. The middle suprarenal arteries go horizontally from the aorta enter the adrenal glands at the lower medial part of them in the way of many smaller branches. 

The inferior suprarenal artery is a branch of the renal artery. The left inferior suprarenal artery goes vertically and cranially to the glans, but the right artery is more horizontal towards the gland. 

Venous drainage 

Venous drainage from the adrenal glands happens through suprarenal veins, one for each gland. The right suprarenal vein goes horizontally and drains into the inferior vena cavaThe left suprarenal vein goes vertically and drains into the left renal vein, but it can also drain into the left inferior phrenic vein. 

In the adrenal medulla is located an unusual type of vein, the central adrenomedullary vein. Its main difference is in its structure; the smooth muscle in tunica media is arranged differently in longitudinally oriented bundles. 

Innervation 

The adrenal glands are regulated by neuronal and hormonal stimulation. Innervation of the adrenal glands comes from the celiac, aorticorenal, and renal autonomic ganglia through their fibers. These fibers connect to the posterior vagus nerve, phrenic nerve, and greater and lesser splanchnic nerves. 

The adrenal cortex gets its impulse from the adrenocorticotropic hormone produced by the anterior pituitary gland. Adrenocorticotropic hormone stimulates the adrenal cortex to produce corticosteroids. Preganglionic nerve fibers innervate the adrenal medulla. These fibers leave the spinal cord from the T5-T8 segments and bypass the paravertebral sympathetic ganglion. 

Afterward, the fibers form the greater splanchnic nerve. Some of the nerve fibers will synapse at the celiac ganglion, and its post-synaptic fibers innervate the blood vessels that supply the adrenal glands, while other fibers will avoid celiac ganglion and go to the adrenal glands to innervate the chromaffin cells in the adrenal medulla. The chromaffin cells work as post-ganglion fibers that release neurotransmitters directly into the bloodstream. 

Lymphatic drainage 

The adrenal glands have two lymphatic plexuses, one in the medulla and one in the adrenal capsule. Most of the lymph drains into the lateral aortic lymph nodes and the para-aortic nodes. Smaller amounts of lymph drain into the thoracic duct or the posterior mediastinum. 

The adrenal glands functions 

The adrenal functions are based on the hormones it secretes. Each hormone has its function, but their functions may overlap. The adrenal cortex and adrenal medulla secrete entirely different hormones. 

The adrenal cortex hormones

The adrenal cortex produces glucocorticoids, mineralocorticoids, and androgens. 

Mineralocorticoids 

Aldosterone is the primary mineralocorticoid produced by the adrenal cortex in the zona glomerulosa. Its leading role is in water and salt balance. Aldosterone controls homeostasis of blood pressure, plasma sodium, and potassium levels. Aldosterone is a part of the renin-angiotensin-aldosterone system. 

When the body has reduced renal perfusion or a low sodium level in plasma, the kidneys' juxtaglomerular cells sense it and release renin into the bloodstream. Renin, through proteolysis, cleaves angiotensinogen, produced by the liver, to create angiotensin I. Angiotensin I is a small protein that circulates through the blood and is again cleaved by an angiotensin-converting enzyme to form angiotensin II. 

Angiotensin II stimulates zona glomerulosa via its receptors to produce and secrete aldosterone. Aldosterone promotes sodium and water retention and lowers potassium levels in plasma. By influencing the reabsorption of sodium and excretion of potassium, aldosterone indirectly affects water retention or loss, blood pressure, and blood volume. The sympathetic nerves also stimulate aldosterone production. Pain, emotions, anxiety increases aldosterone levels. 

If baroreceptors sense decreased blood pressure, aldosterone is released and causes sodium and water retention leading to increased blood volume and blood pressure. If aldosterone is produced too much, it is known as hyperaldosteronism, while too little aldosterone is known as hypoaldosteronism. Adrenocorticotropic hormone released from the anterior pituitary gland after its stimulation by a corticotropin-releasing hormone from the hypothalamus stimulates the formation of deoxycorticosterone that is a precursor of aldosterone. 

Glucocorticoids

Zona fasciculata is responsible for secreting glucocorticoids like cortisol, corticosterone, and 11-deoxycorticosterone. Cortisol release depends on stress and low blood glucose levels. Cortisol stimulates gluconeogenesis to generate glucose from glycogen in the liver. Cortisol indirectly affects glycogenolysis, breaking down of the glycogen. Increased amounts of cortisol can start the breakdown of proteins.

Cortisol also takes part in the immune response. It stops the release of the substances that cause inflammation. Cortisol blocks the production of interleukin-12, interferon-gamma, interferon-alpha, and tumor necrosis factor-alpha. Indirectly cortisol stimulates osteoclasts that can lead to reduced formation of bones. Interestingly, cortisol works with adrenaline to form short-term memories. Cortisol also takes part in electrolyte balance by increasing sodium absorption through the small intestine and increasing potassium excretion. 

The hypothalamus also regulates the release of cortisol. The hypothalamus secretes a corticotropin-releasing hormone that stimulates the anterior pituitary gland to secrete the adrenocorticotropic hormone that works on the adrenal cortex to release cortisol, other glucocorticoids, also mineralocorticoids, and dehydroepiandrosterone. 

Corticosterone does not have a significant role in our bodies. It has only a small potency of glucocorticoids and mineralocorticoids, so it can be considered as having characteristics of both types of corticosteroids. Corticosterone is an essential part of the rare kind of congenital adrenal hyperplasia due to 17 alpha-hydroxylase deficiency. Corticosterone may have effects on memory. It is associated with long-term memory associated with fear and stress. Its levels increase when people reactivate fear or stressed memories. 

11-deoxycorticosterone (DOC) is a mineralocorticoid, but it has glucocorticoid activity. DOC is a precursor for the production of aldosterone. DOC regulates electrolyte balance by reabsorbing sodium un excreting potassium. 

Androgens

Androgens secreted by zona reticularis are dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEA-S), and androstenedione, as well as testosterone, but less than 5% of the whole testosterone. DHEA is an intermediate in the biosynthesis of the androgen and estrogen sex steroids. DHEA is a precursor to testosterone and dihydrotestosterone. 

Together with other androgens, it is responsible for androgenic effects during adrenarche: axillary and pubic hair growth, adult-type odor, oiliness of skin and hairs, and acne. DHEA is more potent androgen than estrogen. DHEA can be converted into estradiol and give estrogenic effects in some tissues, like the vagina. DHEA also works on some neurotransmitter receptors, like NMDA or GABAa receptors. 

DHEA-S can be turned into DHEA, which then can be transformed into testosterone and dihydrotestosterone. DHEA-S works on the same neurotransmitter receptors. Androstenedione is a weak androgen and a part of the biosynthesis of estrone and testosterone from DHEA. Androstenedione increases during adrenarche. It also affects how children develop and understand sexual attraction. The adrenocorticotropic hormone also stimulates the production of androgens. 

The adrenal medulla hormones

The adrenal medulla produces catecholaminesepinephrinenorepinephrine, and dopamine. Epinephrine and norepinephrine are similar neurotransmitters and hormones. 

Epinephrine affects the heart, while norepinephrine works more on the blood vessels. Epinephrine and norepinephrine act on adrenergic receptors. Epinephrine increases heart rate and contractility, induces relaxation of breathing tubes resulting in faster breathing, raises blood glucose levels, increases blood pressure by vasoconstriction, and increases physical performance and strength. Norepinephrine mainly increases blood pressure by vasoconstriction. 

The adrenal medulla produces only small amounts of dopamine. Dopamine is a neurotransmitter that makes us feel pleasure. It is released when we are doing anything that makes us happy, boosting our mood, motivation, and attention. 

Adrenal gland disorders 

Adrenal disorders are characterized by hyper- or hypofunction of the gland leading to excess or too little production of hormones. Significant conditions are pheochromocytoma, Addison`s disease, adrenal crisis, adrenal insufficiency, congenital adrenal hyperplasia, Cushing´s syndrome, hyperaldosteronism, and hypoaldosteronism. 

Pheochromocytoma 

Pheochromocytoma is a rare, benign tumor of the chromaffin cells of the adrenal medulla. It causes the adrenal medulla to release tremendous amounts of catecholamines. It also explains the symptoms as they caused by catecholamines:

  • high blood pressure
  • tremors
  • rapid heartbeat
  • panic attack symptoms
  • shortness of breath
  • headache.

Pheochromocytoma can lead to complications due to excess catecholamines:

  • hypertensive crisis
  • myocardial ischemia
  • cardiomyopathy
  • arrhythmias
  • stroke
  • acute renal failure.

The primary way to treat pheochromocytoma is with surgeryMedicine will still need to be taken, like alpha-blockers to decrease blood pressure, beta-blockers to lower heart rate. In the rare cases when pheochromocytoma becomes malignant, also chemotherapy and radiotherapy are choices. 

Addison`s disease 

Addison`s disease is the most common cause of adrenal insufficiency. It is caused by too little production of cortisol and aldosterone. The reasons for inadequate production can be genetics and autoimmune adrenalitis, which is the most common reason in the world. Symptoms usually develop over time and are:

  • fatigue
  • weight loss
  • hyperpigmentation
  • low blood pressure
  • salt craving
  • abdominal pain
  • irritability
  • muscle or joint pain
  • low blood glucose levels
  • depression
  • women have body hair loss, irregular menstrual cycles.

Treatment usually is to give additional cortisol and aldosterone. If undiagnosed or untreated, it can lead to an adrenal crisis that is a life-threatening condition. The adrenal crisis needs immediate emergency treatment. Symptoms are:

  • sudden pain in legs or lower back
  • confusion
  • low blood pressure
  • severe weakness
  • convulsions
  • fever
  • syncope
  • blood tests - hyperkalemia, hypercalcemia, hypoglycemia, hyponatremia.

Treatment includes giving intravenous saline, hydrocortisone, and glucose. 

Adrenal insufficiency 

Adrenal insufficiency means that there is not enough production of cortisol and aldosterone. It is the same as Addison`s disease mentioned above, which is the leading cause of insufficiency. Less common primary causes are idiopathic insufficiency, adenoma of the adrenal gland, congenital adrenal hyperplasia. The symptoms and treatment are the same as in Addison`s disease. Secondary causes are problems with the pituitary gland or hypothalamus.

Congenital adrenal hyperplasia 

Congenital adrenal hyperplasia is an autosomal recessive disorder with affected cortisol synthesis. It has many subtypes based on which of the five enzymes needed for the synthesis of cortisol is affected. The most common type is so-called classic adrenal hyperplasia. Symptoms can be:

  • vomiting with the following dehydration - inadequate mineralocorticoids
  • too much androgens can cause:
    • excessive virilization
    • ambiguous genitalia in infants
    • early pubic hair in children
    • early or delayed puberty
    • irregular menstrual cycles
    • infertility
  • too little androgens and estrogens:
    • XY males can have female external genitalia
    • in women infertility, no development of sexual characteristics.

The treatment is based on lowering or increasing hormone amounts. Hyperplasia can be reduced by giving enough glucocorticoids. Enough glucocorticoids can also help with the overproduction of androgens and mineralocorticoids. If the deficiency is in mineralocorticoids, then additional mineralocorticoids are given. If puberty is too late or not efficient, replacement treatment of testosterone or estrogen is needed. 

Cushing`s syndrome 

Cushing`s syndrome is a collection of symptoms caused by too much cortisol production. The most common cause is pituitary adenoma causing excessive secretion of adrenocorticotropic hormone, with the second most common being Cushing`s disease. Cushing`s syndrome can also develop after long-term usage of cortisol. Cushing`s syndrome symptoms usually are:

  • weight gain
  • high blood pressure
  • irritability
  • excess hair growth in women
  • moon face
  • immunological function disorders
  • extra fat around the neck
  • irregular menstrual cycles
  • red face
  • poor concentration. 

If the cause is a pituitary adenoma, the first line of treatment is surgical resection. Also, medications to control the production of cortisol can be given. If it is caused by glucocorticoid medication, then the dosage may need to be decreased. 

Summary on the adrenal glands

Where are my adrenal glands?

The glands lie on the top of both kidneys and are slightly medial to them. The adrenal glands are different in their shapes; the right adrenal gland is pyramid-shaped, while the left one is semilunar-shaped and a bit larger. The weight of both adrenal glands together is around 7-10 grams, the length is 5 cm, the width 3 cm, and they are 1 cm thick.

What are the signs of adrenal gland problems?

There are no specific symptoms for the adrenal gland problems, but a combination of some of the followings may be a warning sign: weight loss, fatigue, headaches, nausea, vomiting, high or low blood pressure, irregular menstrual cycles in women, too early or too late puberty in children, rapid heartbeat, tremors, panic attack like symptoms, depression, salt craving, irritability. 

What is the function of the adrenal gland?

The adrenal glands are secreting hormones that regulate metabolism, the immune system, blood pressure, and stress response. Androgens act as a precursor for sex hormones and help to regulate puberty. 

What happens when the adrenal gland is not functioning correctly?

If the adrenal gland is not functioning correctly, it could lead to adrenal insufficiency resulting in inadequate production of cortisol or aldosterone. This can cause fatigue, weight loss, hyperpigmentation, low blood pressure, irritability, abdominal pain, depression, low glucose level.  

How many hormones do the adrenal glands produce?

The adrenal glands produce three types of hormones:

  • mineralocorticoids - primarly aldosterone
  • glucocorticoids - dominant cortisol, also corticosterone
  • adrenal androgens - mainly dehydroepiandrosterone, also dehydroepiandrosterone sulfate, and androstenedione, with very little testosterone.

Do you need both adrenal glands?

No, we can live with only one adrenal gland. If one is damaged or removed, the other adrenal gland quickly increases in size and takes over the work of the damaged or removed one. People can lose one adrenal gland without any adverse effects, but not having both adrenal glands can be fatal if cortisol is not administered. 

What diseases affect the adrenal glands?

The adrenal glands can be affected by malignant or benign tumors, Addison`s disease, Cushing`s disease, congenital adrenal hyperplasia. Also, tumors in the pituitary gland can lead to problems with adrenal gland function. 

What are the symptoms of adrenal crisis?

The adrenal crisis needs immediate emergency treatment. Symptoms are sudden pain in the legs or lower back, confusion, low blood pressure, severe weakness, convulsions, fever, syncope, blood tests - hyperkalemia, hypercalcemia, hypoglycemia, hyponatremia.

What is the most common cause of adrenal insufficiency?

Adrenal insufficiency means that there is not enough production of cortisol and aldosterone. The most common cause of adrenal insufficiency is Addison`s disease. Less common primary causes are idiopathic insufficiency, adenoma of the adrenal gland, congenital adrenal hyperplasia. Secondary causes are problems with the pituitary gland or hypothalamus.

What does low cortisol feel like?

People can experience fatigue, low blood pressure, syncope, salt craving, weight loss, hyperpigmentation, low blood glucose levels, nausea, vomiting, abdominal pain.

What helps the adrenal gland function?

Dietary wise a diet with high sugar, caffeine levels can be helpful. Also, avoiding or having little alcohol, flour products, fried and processed food can help. All of these products affect blood pressure and blood glucose levels that the adrenal glands help to regulate. You should include products that are high in vitamin C, vitamins B, and magnesium. The important thing is to regulate blood glucose, balancing protein, healthy fats, and high quality, nutrient-dense carbohydrates.