Adrenal Diseases

What are adrenal glands?

The adrenal glands are endocrine organs that secrete hormones directly into the bloodstream.  They are normally small golden-yellow triangle shaped glands located on top of each kidney. The gland consists of an outer part (cortex) and inner part (medulla). The adrenal glands make hormones that are essential for body functions. The outer layer (cortex) of the adrenal glands makes three types of steroid hormones: (i) aldosterone, which is required for salt and water balance, (ii) cortisol required as our body’s main stress hormone, and (iii) androgens (male hormones). The inner layer of the gland (medulla) makes adrenaline and noradrenaline , responsible for our ‘fight or flight’ response.

Cortisol is one of the body’s most important hormones; its principal role is to help the body respond to stress. Cortisol also contributes to other roles including:

  • Maintaining blood pressure and cardiovascular function
  • Contributing to maintenance of blood sugar levels, together with insulin
  • Suppressing the immune system's inflammatory response
  • Regulating the metabolism of proteins, carbohydrates, and fats

The hormone aldosterone, together with the kidneys, regulates the balance of sodium and potassium in the body and plays a major role in maintaining normal blood pressure.
The adrenal medulla normally produces adrenaline (epinephrine) and noradrenaline (norepinephrine) in stressful situations.
Disorders of adrenal function can be broadly broken down into three groups:

  • Diseases of underactivity – Adrenal insufficiency & Addison’s disease
  • Diseases of overactivity – Cushing’s syndrome, Conn’s syndrome, phaeochromocytoma
  • Tumours - both benign and malignant.



Addison's Disease, Adrenal Insufficiency & Adrenal Fatigue

What is adrenal insufficiency (AI)?

Adrenal insufficiency (AI) is a condition in which the cortex does not make enough steroid hormones. There are two kinds of AI:

  • Primary AI, also called Addison’s disease. In this rare condition, the adrenal glands don’t work properly and cannot make enough cortisol. Usually, production of aldosterone and androgens is also low.
  • Secondary AI. This far more common type of AI results when the pituitary gland, a small gland near the brain, doesn’t signal the adrenal glands to make cortisol.

Contrary to popular belief, the adrenal glands do not “fatigue” or lose function as a result of mental or physical stress. Also, there is no deficiency of the inner medulla and consequent impaired adrenaline or noradrenaline production.  True AI is a rare but potentially fatal condition that should only be diagnosed by an endocrinologist using standard testing procedures. Patients who believe they are suffering with adrenal fatigue require careful evaluation of their adrenal function to exclude true AI.


What causes primary AI?

The most common cause of primary AI is autoimmune disease, meaning the body’s defense system attacks and destroys the body’s own tissues. When adrenal glands are damaged, they can’t produce hormones. Other causes of primary AI include bleeding within the glands, infections, genetic diseases, and surgical removal of the adrenal glands.


What causes secondary AI?

Problems with the pituitary gland cause secondary AI. Normally, the pituitary gland makes a hormone called adrenocorticotrophic hormone (ACTH), which stimulates the adrenal glands to make cortisol. But in secondary AI, the pituitary gland doesn’t send ACTH to the adrenal glands. No cortisol is made. Some causes may be temporary, such as taking certain prescription medicines like prednisolone, hydrocortisone, or dexamethasone. Other causes may be permanent, such as hormone problems present at birth, tumours or infections in the pituitary, or surgical or radiation damage to the pituitary.


What are the symptoms of AI?

Symptoms begin little by little. They include:

  • Fatigue,
  • Muscle weakness,
  • Decreased appetite,
  • Weight loss.
  • Nausea, vomiting, and diarrhea
  • Pain in the muscles and joints
  • Low blood pressure leading to dizziness upon standing
  • Cravings for salt (in primary AI)
  • Symptoms of low blood glucose, such as sweating
  • Darkened skin on the face, neck, and back of the hands (in primary AI)
  • Irregular menstrual periods in women

Some people don’t know they have AI until they have a sudden worsening of symptoms called an adrenal crisis.


How is Adrenal Insufficiency diagnosed?

Doctors review a patient’s symptoms and medical history. They check blood levels of cortisol, other hormones, sodium, potassium, and glucose to diagnose AI and help determine the cause. The gold standard test is the Short Synacthen Test (SST). This involves an injection of synthetic ACTH (Synacthen) with the cortisol level being measured before and at 30 and 60 minutes after injection. Saliva cortisol measurement is not a validated and accepted means of assessing AI by most endocrinologists.
It may also be necessary to look at the adrenal glands or the pituitary gland with imaging tests, such as CT or MRI scans.


What is the treatment for AI?

The goal of treatment is to ensure proper hormone levels day-to-day. You may need daily replacement of hormones for life. You will take glucocorticoids to replace the cortisol your body no longer makes. You may also need mineralocorticoids if your body doesn’t make aldosterone. Extra glucocorticoids may be needed during times of stress, such as serious illness or surgery. Your doctor will provide personalized advice on adjusting medicines for stress. Understanding your disease and knowing when and how to adjust your medications can help you live a long and healthy life with AI
Cortisol (a glucocorticoid)—helps the body cope with stress, illness, and injury. It regulates blood glucose and blood pressure levels. Aldosterone (a mineralcorticoid)— helps keep a proper balance of salt and water in the body. It regulates blood volume and blood pressure.
Adrenal Androgens (weak male sex hormones present in both sexes)— Helps regulate pubic and armpit hair growth in women


Adrenal Crisis

Physical stress caused by illness, infection, surgery, or an accident can suddenly make symptoms of AI much worse, an emergency condition called an adrenal crisis. If untreated, adrenal crisis can cause death. Adrenal crisis occurs mainly in people with primary AI. Symptoms of an adrenal crisis include sudden pain in the back, abdomen, or legs; severe nausea and vomiting; and diarrhoea. People in adrenal crisis may be dehydrated and confused. They can have low blood pressure and might pass out or even die. People in adrenal crisis need an injection of glucocorticoids (medicines that replace cortisol) right away. Then they need to go to the hospital for more treatment. If you have AI, you should know the warning signs of adrenal crisis. You also should tell family and friends what to do if a crisis occurs. Always carry a medical alert bracelet and have a steroid card.



Hormone Excess And Tumours

Cushing's Disease & Syndrome

The overproduction of cortisol by the adrenal glands leads to Cushing's syndrome but this can also, and more commonly, be caused by the prolonged and excessive intake of glucocorticoid drugs such as prednisolone, methylprednisolone, or dexamethasone. Glucocorticoids are often present in skin creams used for eczema or psoriasis and will be absorbed through the skin resulting in Cushing’s syndrome. The overproduction of cortisol by the adrenal glands can be caused by a pituitary tumor producing too much ACTH (adrenocorticotropic hormone) or due to a benign or malignant tumor outside the pituitary such as in the lung, thymus gland, or pancreas. The pituitary form of the disease is called Cushing's disease. Cushing’s syndrome is caused by a primary overproduction of cortisol by the adrenal gland, often associated with a tumor.

Cushing's syndrome is characterized by:

  • obesity - characteristically sparing the arms and legs resulting in a round, reddish face, a so called buffalo hump and a large abdomen.
  • fatigue
  • weak muscles
  • ulcers
  • thin skin
  • high blood pressure
  • high blood sugar.
  • Irritability, anxiety, and depression.

Women with Cushing's syndrome will usually have excess inappropriate hair growth on their face, neck, chest, abdomen and thighs that can be disfiguring. In women the menstrual periods may be irregular. Men may have decreased fertility and a reduced desire for sex.

The diagnosis of Cushing’s syndrome requires special tests and scans. The only definitive cure of an adrenal tumour producing excess cortisol is surgery. This is usually key hole surgery: either laparoscopic or retroperitoneoscopic.


Conn’s Syndrome

Conn’s syndrome is a condition characterised by the excess production of aldosterone. This may be produced either by both adrenal glands that are dysfunctional or by a single adrenal benign tumour (adenoma). The hormone aldosterone plays a key role in the maintenance of normal salt balance in the blood. The excess production of aldosterone in Conn’s syndrome causes a high blood pressure typically but not necessarily with a low serum potassium. The disease can be treated medically but if caused by a single adenoma is cured by surgical removal of the affected adrenal gland (adrenalectomy), which today is generally performed via a key hole technique – a laparoscopic or retroperitoneoscopic adrenalectomy.



Pheochromocytomas are tumours of the adrenal medulla. Most phaeochromocytomas produce excess amounts of adrenaline or noradrenaline and as such may cause episodic severe elevations in blood pressure, which can be fatal. The typical symptoms of this disease include:

  • recurring unexplained sweating episodes
  • headaches
  • feelings of high anxiety or of impending doom
  • palpitations
  • tremors
  • chest pain or tightness
  • hypertension.

The diagnosis of a pheochromocytoma relies on having an index of suspicion that initiates the biochemical investigations. These include a 24 hour urine collections to measure levels of adrenaline and noradrenaline, and their breakdown products, metanephrines. Blood levels of metanephrines may also be measured. Once the biochemical diagnosis has been made localization studies are required to identify the site of the hormone overproduction. These include CT, ultrasound and MRI scans and  radionucleide imaging.

Once diagnosed the biochemical effects of excess catecholamine secretion must be treated immediately in order to make the patient safe from the potentially fatal blood pressure fluctuations. This should be followed by surgery that usually takes the form of a laparoscopic (key hole) adrenalectomy.



Adrenal Surgery

When Is Adrenal Surgery Needed?

An adrenalectomy (the surgical removal of the adrenal gland) may be required in cases of hormone overproduction or if there is a concern that a mass of the adrenal gland may be a cancer. The four scenarios where hormone excess requires adrenalectomy are Cushing's Syndrome, Conn's Syndrome, phaeochromocytomas and less commonly due to sexual hormone excess. 
Adrenal tumours that are non functioning can be encountered during other radiological tests on the abdomen. Adrenalectomy may be required in such cases because the risk of cancer increases as the size of the gland increases or because there are other concerning features on the scans of the mass.


How Is Adrenal Surgery Usually Performed?

Adrenalectomy may be performed as an open procedure or a minimally invasive (key hole) procedure. Open operations may be performed through the back (sometimes requiring partial removal of a rib), the flank, or the front of the abdomen. Minimally invasive procedures as their name suggests require much smaller incisions either from the front/side in the case of laparoscopic adrenalectomy or via the back in the newer technique of retroperitoneoscopic adrenalectomy.
The method of adrenalectomy adopted is highly patient specific and will depend on the disease being treated, tumour size, and general patient health but overall with the exception of definite cancer the retroperitoneoscopic or laparoscopic approaches are preferred. Approximately 95% of adrenal surgery is performed via a key hole technique.


Laparoscopic Adrenalectomy

The first pioneering laparoscopic adrenalectomy was performed in the 1992 and following refinement of the technique this replaced open surgery for removing benign adrenal tumours. Laparoscopic adrenal surgery has numerous advantages over the older open technique including smaller incisions and therefore less stress for the patient, less post-operative pain, and therefore earlier mobility after the operation and as a result fewer chest and clot related complications. The operation involves the use of 3 or 4 small cuts through which a telescope and special instruments are passed which allow the operation to be performed with the benefit of magnification on a TV screen. 


Retroperitoneoscopic Adrenalectomy

This is a minimally invasive technique that appears to have additional advantages in appropriately selected cases. The operation is performed by the insertion of a small camera and 2 small ports for special instruments as in the laparoscopic approach. The operation is associated with less pain and suggests a statistically significant shorter stay with nearly all patients discharged on the day following surgery.