Skip to content

Primary adrenal insufficiency




Endocrine system

Adrenal gland disorders
Thyroid gland disorders
Parathyroid gland disorders
Pancreatic disorders
Pituitary gland disorders
Gonadal dysfunction
Polyglandular syndromes
Endocrine tumors
Endocrine system pathology review

Primary adrenal insufficiency


0 / 10 complete


1 / 6 complete
High Yield Notes
4 pages

Primary adrenal insufficiency

10 flashcards

USMLE® Step 1 style questions USMLE

6 questions

USMLE® Step 2 style questions USMLE

2 questions

A 54-year-old woman comes to the clinic because of long-term fatigue, nausea, and continuous craving of salty foods. She has had several occasions of fainting after standing quickly. Her temperature is 37°C (98.6°F), pulse is 110/min, respirations are 20/minute, and blood pressure is 80/50 mm Hg. Physical examination shows increased pigmentation of the skin on her elbows and oral mucosa. She has a family history significant for myasthenia gravis. Laboratory studies show:
Which of the following is the most likely diagnosis? 

External References

Content Reviewers:

Rishi Desai, MD, MPH


Tanner Marshall, MS

Primary adrenal insufficiency, is a rare endocrine disorder that happens when the adrenal gland isn’t able to produce enough of the hormones that the body needs, particularly aldosterone and cortisol.

The reason it’s called “primary” is that the underlying problem is localized to the adrenal gland itself, rather than a problem of a hormone that acts on the adrenal gland or elsewhere in the body.

Primary adrenal insufficiency can develop acutely or chronically, and a really famous example of someone having this condition is John F. Kennedy, who was diagnosed at age 30.

Now, there are two adrenal glands, one above each kidney, and each one has an inner layer called the medulla and an outer layer called the cortex which is subdivided into three more layers, the zona glomerulosa, zona fasciculata, and the zona reticularis.

The outermost layer is the zona glomerulosa, and it’s full of cells that make the hormone aldosterone.

Aldosterone is part of a hormone family or axis which work together and are called the renin-angiotensin-aldosterone system.

Together these hormones decrease potassium levels, increase sodium levels, and increase blood volume and blood pressure.

Aldosterone is secreted in response to elevated levels of renin, and it’s role is to bind to receptors on two types of cells along the distal convoluted tubule of the nephron.

First it stimulates the sodium/potassium ion pumps of the principal cells to work even harder.

These pumps drive potassium from the blood into the cells and from there it flows down its concentration gradient into the tubule to be excreted as urine.

At the same time, the pumps drive sodium in the opposite direction from the cell into the blood, which allows more sodium to flow from the tubule into the cell down its concentration gradient.

Since water often flows with sodium through a process of osmosis, water also moves into the blood, which increases blood volume and therefore blood pressure.

The other function of aldosterone is to stimulate the proton ATPase pumps in alpha-intercalated cells which causes more protons to get excreted into the urine.

Meanwhile, ion exchangers on the basal surface of the cell move the negatively charged bicarbonate into the extracellular space, causing an increase in pH.

The middle layer is the zona fasciculata, and the cells there make the hormone cortisol as well as other glucocorticoids.

Cortisol is also needed in times of emotional and physical stress like arguing with a friend or fleeing from a pack of raccoons.

In those situations, the hypothalamus—which is an almond-size structure which sits at the base of the brain, releases corticotropin-releasing hormone is released from, and received by the pituitary gland, the pea-sized structure sitting just underneath the hypothalamus.

In response, the pituitary gland sends out adrenocorticotropic hormone, or ACTH, which travels through the blood to the zona fasciculata of the adrenal glands and signals cells there to release cortisol.

Cortisol is a lipid-soluble molecule, meaning it can mingle with fats, which allows it to easily pass through the plasma membrane of cells and bind to the receptors inside.

In fact, almost every body cell has cortisol receptors, so it affects a huge variety of functions in the body!

One of cortisol’s main jobs though is to increase blood glucose levels by promoting gluconeogenesis in the liver, gluconeogenesis is the formation of glucose from noncarbohydrate sources, like amino acids or free fatty acids.

Cortisol also gets the muscles to break down proteins into amino acids and gets adipose tissues to break down fats into free fatty acids, both of which provide the liver with more raw materials to work with.

So basically, cortisol keeps blood glucose levels high, and this is in contrast top the hormone insulin, which causes glucose to be taken up by various body tissues, and so essentially cortisol acts to counteract this effect this in an effort to make sure that the body can respond appropriately to those raccoons, or other stressors.

Finally, the innermost layer is the zona reticularis, and cells there make a group of sex hormones called androgens, including one called dehydroepiandrosterone, which is the precursor of testosterone.

So the adrenal glands are involved in testosterone production in both men and women, but the amount that the adrenals contribute is pretty small, relative to the testes in men, which accounts for the very different levels of androgens in men versus women.

In men, high levels of androgens are responsible for the development of male reproductive tissues and secondary sex characteristics like facial hair and a large larynx or Adam’s apple.

In women, low levels of testosterone are responsible for a growth spurt in development, underarm and pubic hair during puberty, and an increased sex drive in adulthood.

The exact mechanism for adrenal androgen production is not well understood, but like cortisol, it seems to be stimulated by adrenocorticotropic hormone released from the pituitary gland.

So, that all brings us back to primary adrenal insufficiency, where the adrenal cortex gets damaged.

This can occur acutely or chronically.

Acute primary adrenal insufficiency can arise from Waterhouse-Friderichsen syndrome, which is when a sudden increase in blood pressure causes blood vessels in the adrenal cortex to rupture, filling up the adrenal glands with blood and causing tissue ischemia and adrenal gland failure.

Chronic primary adrenal insufficiency is also called Addison disease and in high-income countries, the most common cause is autoimmune destruction.

  1. "Robbins Basic Pathology" Elsevier (2017)
  2. "Harrison's Principles of Internal Medicine, Twentieth Edition (Vol.1 & Vol.2)" McGraw-Hill Education / Medical (2018)
  3. "Pathophysiology of Disease: An Introduction to Clinical Medicine 8E" McGraw-Hill Education / Medical (2018)
  4. "CURRENT Medical Diagnosis and Treatment 2020" McGraw-Hill Education / Medical (2019)
  5. "Addison's Disease 2001" Journal of Clinical Endocrinology & Metabolism (2001)
  6. "Diagnostic Complexities of Eosinophilia" Archives of Pathology & Laboratory Medicine (2013)