Tertiary Adrenal Insufficiency (Hypoadrenalism)

Tertiary adrenal insufficiency is due to problems with the HPA axis from the hypothalamus. This can be due to malignancy, infection, trauma, or autoimmune disease. The functionality of the hypothalamus may be altered and affect its ability to release hormones that stimulate the pituitary and adrenal glands.

Signs and symptoms of tertiary adrenal insufficiency may be characterized by fatigue, low blood pressure, syncope, craving salty foods, hypoglycemia, nausea, emesis, diarrhea, muscle pain, irritability, and hyperpigmentation of skin and tissue. The signs and symptoms are very similar to primary and secondary conditions because there is minimal cortisol being produced.

CRH is not being produced in high enough quantities to elicit a response from the pituitary gland to make ACTH, which would then release cortisol from the adrenal cortex. Detection of an issue can be found by performing assays to stimulate CRH production. If, after administration of synthetic or exogenous CRH, the ACTH and cortisol levels increase, this helps confirm a tertiary cause of adrenal insufficiency.