Anatomy of the Adrenal Glands

An adrenal gland is made of two main parts:

• The adrenal cortex is the outer region and also the largest part of an adrenal gland. It is divided into three separate zones: zona glomerulosa, zona fasciculata and zona reticularis. Each zone is responsible for producing specific hormones.

• The adrenal medulla is located inside the adrenal cortex in the center of an adrenal gland. It produces “stress hormones,” including adrenaline.

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

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.

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

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.

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. 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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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. Functional tumors, malignant tumors or nodules greater than 4 centimeters are recommended to be referred for surgical evaluation.

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.

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.)

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.

Excess of Adrenaline or Noradrenaline: 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.

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.

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.

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.