Overactive and Underactive Adrenal Gland (Cortex) Diseases

Adrenal Glands and Hormones

The adrenal glands, also known as the suprarenal glands, are two small structures that lie on the superior poles of each kidney. It has two distinct portions – the smaller inner adrenal medulla surrounded by the large outer adrenal cortex.

The medulla secretes the hormones epinephrine and norepinephrine when stimulated by the sympathetic system. Both these hormones are catecholamines that play significant roles in increasing the body’s ability to cope with sudden changes in the environment like emergency situations as part of the fight-or-flight response. The effects of these hormones include increasing the heart rate and breathing rate, constricting blood vessels and dilating the airways so that a person can react appropriately to the environmental stress. These effects are  usually short-lived.

The cortex secretes a different group of hormones known as the corticosteroids. These are natural corticosteroids and should not be confused with the drugs which have a similar effect. The mineralocorticoids, a type of corticosteroid, affect the fluid and electrolyte balance in the body. The main mineralocorticoid is aldosterone. The glucocorticoids are the other type of corticosteroids secreted by the adrenal cortex. It maintains the body’s metabolism – regulates blood pressure, glucose levels and metabolism of nutriente. The main glucocorticoid is cortisol. The corticosteroids have various other roles in the body and are stimulated by ACTH (adrenocorticotropic hormone) from the pituitary gland. A small amount of male sex hormones, androgens, are also secreted by the adrenal cortex.

Overactivity and Underactivity of the Adrenal Cortex

While the catecholamines from the medulla are important hormones, it is does not lead to any life threatening conditions. Even surgical removal of the adrenal medulla will not result in any serious clinical consequences. Therefore abnormal activity of the adrenal gland focuses primarily on the adrenal cortex. The adrenocortical hormones have a longer lasting effect on the body and disturbances in these hormone levels can therefore lead to serious diseases.

  • Overactive adrenal glands are known as hyperadrenalism or more specifically adrenocortical hyperfunction.
  • Underactive adrenal glands is known as hypoadrenalism or adrenocortical hypofunction / adrenocortical insufficiency.

Adrenocortical Hyperfunction

There are three main types of diseases associated with overactivity of the adrenal cortex.

  1. 1. Cushing syndrome – excess of cortisol
  2. 2. Hyperaldosteronism – excess of aldosterone
  3. 3. Virilization syndrome – excess of androgens

Cushing Syndrome

Also known as hypercortisolism, it is a condition that is characterized by an excess of glucorticoids particularly cortisol. This may arise due to external factors (exogenous causes) or internal factors (endogenous causes).  The most common exogenous (external) cause of Cushing syndrome is the administration of corticosteroid drugs (iatrogenic). Endogenous (internal) causes may or may not be related to ACTH, the hormone that stimulates glucorticoid secretion from the adrenal cortex. This is termed as ACTH-dependent and ACTH-independent causes.


This is a condition characterized by the excess of aldosterone, the predominant mineralocorticoid hormone secreted by the adrenal cortex. It may be of two types – primary or secondary. Primary hyperaldosteronism is a result of overproduction of aldosterone due to internal factors within the adrenal gland. Secondary hyperaldosteronism is due to factors outside of the adrenal gland which stimulate an excess of aldosterone secretion particularly through the activation of the renin-angiotensin system.

Androgenital Syndrome

Also known as virilization syndrome, this condition is characterized by an excess of androgens – male sex hormones. Adrenal androgen production and secretion are regulated by ACTH, the same hormone that regulates glucocorticoid secretion. The adrenal androgens are in two forms – ehydroepiandrosterone and androstenedione – which are converted into testosterone in the peripheral tissues. While an overproduction affects both males and females, it is often in females that its effects are more frequently highlighted – virilization. This excess may occur just before or after birth, in childhood or even adulthood.

Adrenocortical Insufficiency

Underactivity of the adrenal cortex may be primary or secondary. Primary adrenocortical insufficiency is due to disease within the adrenal gland that results in underactivity of the adrenal cortex. Secondary adrenocortical insufficiency is due to external factors that contribute to an underactive adrenal gland.

There are three main conditions associated with adrenocortical insufficiency.

  1. 1. Primary acute adrenocortical insufficiency – adrenal crisis
  2. 2. Primary chronic adrenocortical insufficiency – Addison disease
  3. 3. Secondary adrenocortical insufficiency

Adrenal Crisis

Primary acute adrenocortical insufficiency, also known adrenal crisis or Addisonian crisis, is an acute condition seen in patients with Addison disease. It is a sudden and severe exacerbation of symptoms which may be associated with suddenly stopping exogenous corticosteroids, during periods of stress when larger quantities of corticosteroids are needed but the body cannot respond or due to adrenal hemorrhage due to severe damage of the adrenal gland.

Addison Disease

Primary chronic adrenocortical insufficiency or Addison disease is a deficiency of glucocorticoids due to damage and destruction of the cortex. The adrenal cortex like any other part of the body is prone to a number of diseases that may cause tissue damage and cell death. This may be related to autoimmune, infectious, genetic and/or neoplastic conditions. There is usually a gradual decrease in the cortisol production and secretion with the risk of acute exacerbations known as an adrenal crisis.

Secondary Adrenocortical Insufficiency

With secondary insufficiency, the adrenal glands are not diseased but decreased stimulation by ACTH from the pituitary gland lowers the circulating glucocorticoid levels. Therefore the pathology often lies in the pituitary gland and adrenocortical functioning can return to normal by the administration of exogenous ACTH.

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