From the Guidelines
Secondary adrenal insufficiency is caused by deficient adrenocorticotropin hormone secretion by the pituitary gland, or deficient corticotropin-releasing hormone secretion by the hypothalamus.
Causes of Secondary Adrenal Insufficiency
- Deficient adrenocorticotropin hormone (ACTH) secretion by the pituitary gland
- Deficient corticotropin-releasing hormone (CRH) secretion by the hypothalamus
- Chronic administration of glucocorticoids, which can suppress the hypothalamo–pituitary–adrenal axis, sometimes referred to as tertiary adrenal insufficiency 1, 2 ### Key Points
- Daily doses of prednisolone of 5 mg or greater in adults and 10–15 mg.m2 hydrocortisone equivalent or greater in children may result in hypothalamo–pituitary–adrenal axis suppression if administered for 1 month or more 2
- Secondary adrenal insufficiency due to ACTH deficiency affects approximately 1 in 10,000 children and can be due to congenital causes such as developmental disorders of the hypothalamus and pituitary, or acquired causes such as brain tumours and their treatment 1
- Patients with secondary adrenal insufficiency are deficient in cortisol, but continue to secrete aldosterone in response to renin 1
From the Research
Causes of Secondary Adrenal Insufficiency
- The most frequent endogenous cause of secondary adrenal insufficiency (SAI) is a tumor of the hypothalamic-pituitary region, usually associated with panhypopituitarism secondary to tumor growth or to its treatment with surgery or irradiation 3.
- Less commonly, SAI is due to nontumoral disorders including infiltrative lesions, infective processes, vascular alterations, traumatic brain injury, empty sella or genetic disorders 3.
- Long-term administration of exogenous glucocorticoids can determine secondary and/or tertiary hypoadrenalism acting at the hypothalamic level and leading to prolonged suppression of the hypothalamic-pituitary-adrenal axis 3, 4.
- Pituitary destruction (pituitary masses, inflammation, or infiltration) and certain medications can also cause secondary adrenal insufficiency 5.
- Rarely, secondary adrenal insufficiency is associated with certain germline variants 5.
- Adrenocorticotropic hormone (ACTH) deficiency, which disrupts ACTH secretion by the pituitary gland, can lead to chronic hyponatremia and secondary adrenal insufficiency 6.
Underlying Mechanisms
- Secondary adrenal insufficiency results from hypothalamic or hypophyseal damage or from prolonged administration of supraphysiological doses of glucocorticoids 4.
- The lack of stimulation via pituitary adrenocorticotropic hormone or hypothalamic corticotropin-releasing hormone can lead to secondary adrenal insufficiency 7.