Adrenal insufficiency: Pathology review

While doing your rounds, you see two individuals. First is Mike, a 50-year-old immigrant from Canada who comes in with a 5-month history of progressive fatigue, weight loss, and muscle pain. Personal history is unremarkable but there’s a family history of autoimmune disease. Examination reveals hypotension, and diffuse skin hyperpigmentation most pronounced around the oral mucosa, palmar creases, and knuckles.

Then you see Teresa, a 25-year-old who presents acute vomiting, abdominal pain, and fever. She was accompanied by her mother, who mentions Teresa recently underwent transsphenoidal resection of a pituitary tumor. Examination reveals severe hypotension and altered mental status.

Morning cortisol serum measurements showed decreased levels of serum cortisol in both individuals. Both people have adrenal insufficiency although their symptoms are very different.

Now, adrenal insufficiency is a condition where the adrenal glands don’t produce enough adrenal hormones, particularly cortisol and, sometimes, aldosterone. There are actually three types of adrenal insufficiency. First, primary adrenal insufficiency is when there’s a problem with the adrenal glands themselves. As a result, both cortisol and aldosterone production is deficient. It can be acute, usually due to a massive adrenal hemorrhage, or chronic, in which case it is called Addison disease. Now, a high yield concept to remember is that the most common cause for Addison in high income countries is autoimmune mediated damage to the adrenal glands. In the rest of the world, the most common cause is infection, especially from tuberculosis, but it can also be due to HIV or disseminated fungal infections. Finally, bilateral adrenal metastases of cancer from somewhere else in the body,can also cause chronic adrenal insufficiency.

Then, there’s central adrenal insufficiency which can be secondary or tertiary. In secondary adrenal insufficiency, the problem is not with the adrenal glands but with the pituitary, which secretes insufficient ACTH. And since ACTH only regulates cortisol production, in this case there’s cortisol deficiency, but aldosterone levels are normal. This can happen with panhypopituitarism, when the entire pituitary gland is affected, and all the hormones secreted by it are deficient. Panhypopituitarism can be a result of any condition that affects the entire pituitary, like trauma, and pituitary tumors or large central nervous system tumors in its vicinity. And finally, there’s tertiary adrenal insufficiency, where the problem originates with the hypothalamus and there’s insufficient CRH secretion.