What Causes Low Cortisol?

Addison's disease, which could be a contributing factor for low cortisol levels, has been listed as a 'rare disease' by the Office of Rare Diseases (ORD) of the National Institutes of Health (NIH). Approximately 70% of the cases of Addison's disease are associated with an autoimmune response, wherein the body's immune system attacks the outer layer of the adrenal glands, mistakenly conceiving them to be a threat.

Adrenal glands, which are also referred to as the suprarenal glands, are a pair of small endocrine glands, each of which is located on the top of a kidney. The adrenal cortex and inner medulla are structures within the gland that are responsible for the production of vital hormones.

The medulla releases catecholamines (epinephrine and norepinephrine) directly into the bloodstream, whereas the adrenal cortex produces steroid hormones such as cortisol, cortisone, and aldosterone.

Cortisol is a glucocorticoid that is secreted by the adrenal cortex of the adrenal glands. Basically, the term 'glucocorticoid' signifies the effect of these potent steroid hormones on the metabolism of glucose. Often referred to as the master stress hormone, cortisol is vital for producing the much-needed coping mechanism for stress.

Cortisol production increases when we encounter stressful events. Health problems are likely to arise in case of individuals who have low levels of cortisol for extended periods.

Cortisol helps us respond to stress in the following ways:

■ It speeds up the breakdown of proteins into amino acids, which are released from the tissues into the bloodstream. The amino acids can be directly used by the skeletal muscles for energy.
■ The amino acids are sent to the liver, wherein these are converted into glucose, which is then used for energy.

■ It stimulates the release of fatty acids from the adipose tissue, as well as the breakdown of glycogen into glucose.

Since cortisol plays such a vital role, reduced production of this hormone is bound to cause an adverse effect on one's health.

To understand the reasons behind the reduced production of this hormone, one needs to understand the series of events or processes that are involved in its production.

The following events take place when we encounter a stressful event.

■ Secretion of Corticotropin-releasing hormone (CRH) from the hypothalamus in the brain
■ Stimulation of the pituitary gland by the CRH to secrete Adrenocorticotropic hormone (ACTH)
■ Stimulation of the adrenal glands by the ACTH to produce cortisol

Therefore, inadequate secretion of this hormone might be linked to problems associated with the hypothalamus, pituitary gland, or the adrenal gland itself.

Addison's disease, which is also referred to as the primary adrenal insufficiency or hypocortisolism, was first described by the British physician, Thomas Addison in 1855. This is an endocrine disorder that is characterized by the reduced secretion of adrenocortical hormones such as cortisol and aldosterone.

It occurs when 90% or more of the adrenal cortex is destroyed. The destruction or dysfunction of the adrenal cortex is mostly attributed to an autoimmune response, wherein the immune system mistakenly attacks the adrenal glands.

While an autoimmune response is often the contributing factor for this condition in developed nations, tuberculosis is the second leading cause of primary adrenal insufficiency in the world. Adrenalectomy or the surgical removal of the adrenal glands could also cause this condition.

The other contributing factors for a primary adrenal insufficiency or Addison's disease include:

■ Congenital adrenal hyperplasia
■ Adrenal tumors
■ Infections affecting the adrenal glands (Tuberculosis, histoplasmosis, syphilis, HIV/AIDS)

■ Bilateral adrenal hemorrhage
■ Prolonged use of drugs such as ketoconazole, rifampin, phenytoin, etomidate
■ Unresponsiveness to ACTH

Secondary adrenal insufficiency occurs due to the deficiency of ACTH. Adrenal glands secrete hormones only when they receive the required stimulus from the pituitary gland and the hypothalamus.

When the pituitary gland is stimulated by corticotropin-releasing hormone that is produced by the hypothalamus, it secretes adrenocorticotropic hormone (ACTH), which stimulates the adrenal glands to produce cortisol.

If the hypothalamus or the pituitary gland are affected by any disorder, the adrenal glands will not get the required stimulus. Under such circumstances, cortisol will not be secreted.

The term 'secondary adrenal insufficiency' is used for signifying low cortisol levels due to low production of ACTH. Since this hormone is produced by the pituitary gland, this condition is observed in individuals affected by pituitary gland problems.

ACTH deficiency could either be idiopathic or might be caused due to the following factors:

■ Pituitary tumors
■ Hypopituitarism
■ Sheehan's syndrome (pituitary infarction)
■ Surgical removal of benign ACTH-producing tumors of the pituitary gland

■ Radiation treatment for pituitary tumors
■ Sarcoidosis
■ Hemochromatosis
■ Sudden withdrawal of synthetic glucocorticoids

Impairment in the release of CRH by the hypothalamus could affect the production of ACTH, which in turn might lead to low levels of cortisol.

Since cortisol helps one deal with stress, low cortisol levels will affect one's ability to cope in the event of stressful situations or the stresses that are normally tolerated. Individuals affected by Addison's disease might even go into a state of shock when faced with a stressful event.

This could give rise to symptoms such as:

■ Unusual fatigue
■ Muscle weakness
■ Dark tanning of the skin
■ Low blood pressure
■ Postural hypotension
■ Dizziness
■ Abdominal pain
■ Loss of appetite

■ Weight loss
■ Nausea
■ Vomiting
■ Irritability
■ Depression
■ Salt cravings

In case of people affected by secondary adrenal insufficiency, darkening of the skin and high potassium levels in the blood are not observed.

In case of acute adrenal insufficiency or Addisonian crisis, the affected individual might experience the following symptoms:

■ Pain in the abdomen, lower back, or legs
■ Vomiting and diarrhea
■ Low blood pressure
■ Loss of consciousness

■ Physical examination to examine the visible signs (tanning of skin) and other symptoms
■ ACTH stimulation test
■ CRH stimulation test
■ Insulin-induced hypoglycemia test

■ An early morning random cortisol test
■ Blood tests to check for antibodies
■ Abdominal ultrasound or abdominal X-ray examination
■ CT scan for checking the pituitary gland

In case of the ACTH stimulation test, the cortisol levels in blood are measured before and after the administration of a synthetic form of adrenocorticotropic hormone (ACTH). In case of the insulin-induced hypoglycemia test, glucose and cortisol levels in blood are measured.

Thereafter, fast-acting insulin is injected, and glucose and cortisol levels are measured 30, 45, and 90 minutes after the administration of insulin. In case of healthy individuals, the level of blood glucose should decrease, whereas cortisol levels should increase.

In case of individuals affected by adrenal insufficiency, there would hardly be any increase in the cortisol levels. The CRH stimulation test can help determine the underlying cause.

When it comes to the treatment, hormone replacement therapy is suggested to compensate for the inadequate secretion of the stress hormone.

In case of primary adrenal insufficiency, synthetic glucocorticoid (prednisone, hydrocortisone, or dexamethasone) and mineralocorticoid such as fludrocortisone acetate are recommended to compensate for low cortisone and aldosterone.

Since a variety of conditions can affect the production of cortisol, it's important that the underlying cause is identified and treated at the earliest. Cortisol also affects sodium and potassium levels, which is why any imbalance concerning these elements must also be corrected.

Sudden withdrawal of synthetic steroids should be avoided to prevent an adrenal crisis.

Disclaimer: The information provided in this story is solely for educating the reader. It is not intended to be a substitute for the advice of a medical expert.