What causes iatrogenic central pediatric adrenal insufficiency (Addison disease)?

Updated: Dec 03, 2020
  • Author: Kimberly Tafuri, DO; Chief Editor: Sasigarn A Bowden, MD  more...
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Most cases of adrenal insufficiency (Addison disease) are iatrogenic, caused by long-term administration of glucocorticoids. A mere 2 weeks' exposure to pharmacologic doses of glucocorticoids can suppress the corticotropin-releasing hormone (CRH)–adrenocorticotropic hormone (ACTH)–adrenal axis. The suppression can be so great that acute withdrawal or stress may prevent the axis from responding with sufficient cortisol production to prevent an acute adrenal crisis. Similar suppression can be seen in individuals on chronic high doses of inhalable glucocorticoids. [6]

Treatment with megestrol acetate, an orexigenic agent, has also resulted in iatrogenic adrenal suppression. The mechanism is presumably related to the glucocorticoid properties of megestrol acetate. [7]

A study by Gibb et al found that in four out of 48 patients on long-term opioid analgesia for chronic pain (8.3%), the basal morning plasma cortisol concentration was below 100 nmol/L (3.6 ng/dL), indicating that such treatment can suppress the hypothalamic-pituitary-adrenal axis in a clinically significant proportion of patients. [8]

Other causes of central adrenal insufficiency include congenital or acquired hypopituitarism and ACTH unresponsiveness.

Hypopituitarism with adrenal insufficiency can be a secondary manifestation of a sellar or suprasellar mass, an inflammatory or infiltrative process, surgery, or cranial irradiation. Congenital unresponsiveness to ACTH that can occur if the ACTH receptor is absent or altered can clinically mimic this condition. However serum ACTH concentrations can help to distinguish between the two. [9, 10]  ACTH unresponsiveness may be isolated (as in Familial Glucocorticoid Deficiency) (Online Mendelian Inheritance in Man database [OMIM] 202200), [9, 11] or it may be associated with achalasia and alacrima (as in achalasia-addisonism-alacrima syndrome, or triple A syndrome [AAAS]) (OMIM 231550). [12, 13] .

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