Causes Of Adrenal Insufficiency

October 9, 2023

Stress is part of life, but what happens when the organ in the body responsible for stress response, blood pressure, and metabolism no longer functions properly? For individuals facing adrenal insufficiency, the ability to regulate these vital bodily functions can be greatly impaired. Small, triangular-shaped organs located directly above each kidney, the adrenal glands secrete both cortisol and aldosterone, as well as adrenaline, glucocorticoids, and mineralocorticoids. However, many factors can impair kidney function and cause adrenal insufficiency.

Autoimmune Conditions

Considered to be the most common cause of primary adrenal insufficiency, autoimmune conditions cause the body’s immune system to attack healthy tissues, inadvertently causing damage. Addison's disease is the biggest culprit when it comes to autoimmune conditions causing adrenal insufficiency. Addison’s disease occurs when the immune system is incapable of differentiating healthy cells from invading foreign bodies and begins to attack and destroy cells in the adrenal glands. These glands may be incapable of producing the necessary amount of cortisol if the outer layer, known as the adrenal cortex, is significantly damaged.

While rare, a combination of concurrently occurring diseases may be the root cause of Addison’s disease. Specifically, autoimmune polyendocrine syndrome (APS) can lead to the development of Addison’s disease. APS is classified as type one or two, with type one beginning during childhood and type two developing in adulthood, typically between eighteen and thirty. Regardless of type, Addison’s disease can be a result of either type of these autoimmune diseases.


Tuberculosis, another significant cause of adrenal insufficiency globally, is a contagious infection that generally attacks the lungs, but may spread to other organs if left untreated. Spread in a similar fashion to the flu or a common cold, this disease is an airborne infection that relies on the tiny droplets released through coughing, sneezing, talking, laughing, or singing to travel from person to person.

Luckily, this disease is relatively difficult to catch, and is generally passed to family members, close friends, and colleagues. As this illness migrates to other parts of the body, the bacteria begin multiplying and attacking the healthy tissue, including the outer layer of the adrenal glands. As the glands sustain more and more damage, the resulting inflammation may make it difficult for the cells to function normally, leading to significant adrenal insufficiency.

Fungal Infection

In many ways, fungal infections of the adrenal glands are similar to other bacterial or viral infections. The most common form of adrenal fungal affliction, Paracoccidioides brasiliensis, may affect gland function at differing rates based on the health and immune response of the individual infected. Specifically, this dimorphic fungus may invade the adrenal tissue directly or may be introduced into the glands through biochemical modulators or other secondary mediators in the bloodstream. In either case, the fungus can cause the production of endotoxins, which may lead to damage and hemorrhaging within the tissue. This hemorrhaging, in turn, may lead to a condition known as Waterhouse-Friderichsen syndrome, a condition characterized by shock and acute adrenal insufficiency.


Similar to both tuberculosis or fungal infections, cytomegalovirus (CMV) is a common strain of the herpes virus that can, in certain circumstances, infect the adrenal glands. Many of the individuals infected with cytomegalovirus never know it, as the virus often has no symptoms and may lay dormant for years. However, this virus can cause serious, if not fatal, complications during pregnancy or for those with weakened immune systems.

Particularly prevalent in those who have HIV or AIDS, the CMV virus can attack the adrenal cortex, or outer layer, of the adrenal glands. Because immunocompromised individuals have few defenses against such viral attacks, cytomegalovirus can spread quickly and easily, causing inflammation and cellular damage that can impact essential adrenal functions.


As with tuberculosis, cytomegalovirus, and other infections, cancer can affect the adrenal glands and, with enough damage, may lead to adrenal insufficiency. This condition occurs when abnormal cells either travel to or from within the adrenal glands and then multiply. This condition may begin within the glands themselves, or may migrate from the kidneys, stomach, lymphoma, or even skin. Typically found in the outer layer, or adrenal cortex, of the glands, this condition usually manifests as a tumor.

Cancerous tumors found on this outer layer of the adrenal gland are considered to be adrenal cortical carcinomas, while non-cancerous tumors found in the same area are considered to be benign adenomas. The cancerous adrenal cortical carcinomas are generally bigger than their non-cancerous counterparts, and may grow so large that they press on other organs. Generally, tumors are found on only one of the two adrenal glands, although they can be found on both. Regardless of the tumor type, abnormal cell growth can disrupt or impede the growth of proper adrenal cells, damaging the adrenal cortex and dramatically reducing gland function.

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