The Adrenal Glands and Addison Disease

by Robert Tallitsch, PhD | May 26, 2022

Adrenal Glands and Addison Disease Brain Builder

Video on the Adrenal Glands including an explanation of Addison's Disease!

Written By: Robert Tallitsch, PhD

This Brain Builder will briefly review the endocrine system, discuss the anatomy of the adrenal (suprarenal) glands, their secretions, followed by a discussion of Addison disease, a disease that can be fatal if not recognized early and treated appropriately.

The adrenal glands are part of the endocrine system. As was stated in our Endocrine System and Pancreatic Cancer Brain Builder, the endocrine system is composed of ductless glands that release chemical-signaling substances, termed hormones, into either the interstitial fluid, lymphatic system, or cardiovascular system. These hormones then diffuse away from their sources and exert their chemical effects at a group of cells or an organ that is either in close proximity to the endocrine gland or distant from it.

Anatomy of the Adrenal (Suprarenal) Glands 

The adrenal glands sit on the superior pole of each kidney, are surrounded by perirenal fat (fat surrounding the kidneys), and are separated from the kidney by a thin sheet of connective tissue. The left adrenal gland is the larger of the two, and is semilunar in shape. The smaller right gland is pyramidal in shape. The diaphragm is posterior to both adrenal glands. The left gland lies posterior to the pancreas and part of the stomach, while the right adrenal gland lies posterior to the inferior vena cava and part of the right lobe of the liver.

The blood supply to the adrenal glands is extensive, and typically arises from three sources:

  1. Inferior adrenal arteries branch off of the renal arteries.
  2. Middle adrenal arteries typically arise directly off of the abdominal aorta.
  3. Superior adrenal arteries branch off of the inferior phrenic arteries (which supply the diaphragm with blood).

Histologically the adrenal glands are composed of an outer adrenal cortex and an inner adrenal medulla, each of which has a different embryonic origin and produces different hormones. The adrenal cortex is divided into three zones:

  • The outermost zone is relatively thin, and is termed the zona glomerulosa. The cells within this zone are arranged into ovoid (egg-shaped) groups.
  • The second zone, termed the zona fasciculata, is the largest of the three zones, and the cells are arranged into long, parallel cords that are one or two cells thick.
  • The innermost zona reticularis is considerably smaller than the other two cortical zones. 

The cells of the medulla are arranged into anastomosing cords and possess many histological characteristics that are similar to cells of the sympathetic nervous system.  

Hormones of the Adrenal Cortex

The adrenal cortex secretes five steroid hormones:

  • Aldosterone (a mineralocorticoid) exerts its effects upon the kidney’s handling of sodium, potassium, and hydrogen ions. 
  • Cortisol and corticosterone are classified as glucocorticoids due to their effects upon the metabolism of glucose and other nutrients. In humans, cortisol is the more important of these two hormones.
  • Dehydroepiandrosterone (DHEA) and androstenedione are classified as androgen hormones, as is testosterone, which is secreted by the testes of the male. In the adult male, the effects of DHEA and androstenedione of the adrenal cortex are significantly less important than those of testosterone.

Hormones of the Adrenal Medulla

The two hormones secreted by the adrenal medulla, epinephrine and norepinephrine, are classified as amine hormones. The adrenal medulla secretes significantly more epinephrine than norepinephrine. 

The medulla of the adrenal gland is functionally part of the sympathetic nervous system and, therefore, epinephrine and norepinephrine exert effects that are very similar to the effects of increased stimulation of the sympathetic nervous system.

Addison Disease

Addison disease (often referred to as Addison’s Disease) is a rare condition that can be fatal if not promptly diagnosed and appropriately treated. 

Addison disease often results either from a primary adrenal insufficiency, or an acquired secondary adrenal insufficiency.

Primary adrenal insufficiency results from an autoimmune disease attacking the adrenal cortex. This typically results in bilateral death of the adrenal cortex. An acquired secondary adrenal insufficiency can be the result of Type 1 diabetes, autoimmune thyroiditis (inflammation of the thyroid gland), sepsis, tuberculosis, HIV, autoimmune pernicious anemia, and even celiac disease. Secondary adrenal insufficiency also often results in bilateral death of the adrenal cortex.

Early Addison disease typically presents with one or more nondescript symptoms, such as fatigue, weight loss, nausea, generalized weakness, abdominal pain, and/or dizziness. This often delays an accurate diagnosis. 

All too often the proper diagnosis is not arrived upon until the patient presents with an acute adrenal crisis, resulting in hypotension, hyponatremia (low plasma Na+), hyperkalemia (high plasma K+), and/or hypoglycemia (low blood glucose). 

Addison disease typically occurs in the 20s or 30s. Because it often presents with nondescript symptoms, physicians need to have a high degree of suspicion for Addison disease when evaluating a young patient with a combination of non-specific symptoms. 

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Key Terms:

Adrenal gland - A term that is synonymous with suprarenal gland, which is the other anatomical term for the pair of glands that sit on the poles of the kidneys and secrete numerous hormones.

Adrenal cortex - The most superficial portion of the adrenal gland.

Glucocorticoid hormone - A classification of hormones that exert effects upon the utilization of glucose and other nutrients.

Mineralocorticoid - A classification of hormones that exerts the kidneys handling of sodium, potassium, and hydrogen.

Superior adrenal artery - One of the three sets of arteries that supply blood to the adrenal glands. This artery branches off of the inferior phrenic artery.

Zona fasciculata - The middle, and largest of the three zones of the adrenal cortex.

Epinephrine - One of the two amine hormones secreted by the adrenal medulla.

Perirenal fat - Fat surrounding the kidneys.

Hyponatremia - Low plasma levels of sodium (Na+).

Hyperkalemia - High plasma levels of potassium (K+).


  1. True or False? Norepinephrine is secreted in much greater amounts by the adrenal medulla than is epinephrine.
    A: False

  2. List the three zones of the adrenal cortex, proceeding from the deepest layer to the most superficial layer.
    A: Zona reticularis, zona fasciculata, zona glomerulosa

  3. True or False? The adrenal medulla functions as part of the sympathetic branch of the autonomic nervous system.
    A: True

  4. List the three blood vessels that supply the adrenal glands.
    A: Superior adrenal arteries, middle adrenal arteries, and inferior adrenal arteries

  5. What hormone of the adrenal glands is classified as a mineralocorticoid?
    A: Aldosterone

  6. What two hormones released by the adrenal glands are classified as amines?
    A: Epinephrine and norepinephrine

  7. What two hormones released by the adrenal glands are classified as glucocorticoids?
    A: Cortisol and corticosterone

  8. True or False? Cortisol exerts a greater effect upon glucose metabolism than corticosterone.
    A: True

  9. True or False? Addison disease typically manifests in older individuals.
    A: False, Addison disease typically manifests in the 20s or 30s.

  10. True or False? Addison disease typically presents with one or more nondescript symptoms, which often delays an accurate diagnosis.
    A: True

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