From the Guidelines
Dexamethasone at high doses suppresses pituitary adenoma-induced Cushing's syndrome but not adrenal Cushing's due to the different feedback mechanisms involved. In pituitary Cushing's, the adenoma still retains some sensitivity to negative feedback from glucocorticoids, so high-dose dexamethasone can suppress ACTH production from the pituitary tumor, as discussed in the consensus guideline update on Cushing's disease management 1. When dexamethasone is administered, it mimics cortisol's negative feedback effect, telling the pituitary to reduce ACTH output. Some key points to consider include:
- The high-dose dexamethasone suppression test is used to differentiate between pituitary and adrenal causes of Cushing's syndrome
- Pituitary adenomas retain some sensitivity to negative feedback from glucocorticoids
- Adrenal Cushing's produces cortisol independently of ACTH control, making it unresponsive to dexamethasone In contrast, adrenal Cushing's (caused by adrenal tumors or hyperplasia) produces cortisol independently of ACTH control, as noted in the guideline update 1. These adrenal sources autonomously secrete cortisol regardless of feedback signals, so dexamethasone has no effect on their cortisol production. Understanding the underlying physiology of the hypothalamic-pituitary-adrenal axis and how feedback mechanisms work differently in these conditions makes the concept more intuitive and easier to remember, rather than simply memorizing the fact.
From the FDA Drug Label
CLINICAL PHARMACOLOGY Dexamethasone sodium phosphate injection has a rapid onset but short duration of action when compared with less soluble preparations. Because of this, it is suitable for the treatment of acute disorders responsive to adrenocortical steroid therapy Naturally occurring glucocorticoids (hydrocortisone and cortisone), which also have salt-retaining properties, are used as replacement therapy in adrenocortical deficiency states. Their synthetic analogs, including dexamethasone, are primarily used for their potent anti-inflammatory effects in disorders of many organ systems. Glucocorticoids cause profound and varied metabolic effects In addition, they modify the body's immune responses to diverse stimuli. At equipotent anti-inflammatory doses, dexamethasone almost completely lacks the sodium-retaining property of hydrocortisone and closely related derivatives of hydrocortisone.
The FDA drug label does not answer the question.
From the Research
Dexamethasone Suppression Test
- The dexamethasone suppression test is used to differentiate between pituitary and adrenal Cushing's syndrome 2, 3, 4.
- High-dose dexamethasone suppression testing can suppress cortisol production in patients with pituitary-dependent Cushing's syndrome, but not in those with adrenal Cushing's syndrome 2, 3.
- The test is based on the principle that pituitary adenomas are more sensitive to glucocorticoid feedback than adrenal tumors 5, 6.
Mechanism of Action
- Dexamethasone acts by binding to glucocorticoid receptors in the pituitary gland, which inhibits the production of adrenocorticotropic hormone (ACTH) 5, 6.
- In pituitary-dependent Cushing's syndrome, the high dose of dexamethasone can suppress ACTH production, leading to a decrease in cortisol levels 2, 3.
- In adrenal Cushing's syndrome, the adrenal tumor is not responsive to glucocorticoid feedback, and cortisol production is not suppressed by dexamethasone 2, 3.
Diagnostic Accuracy
- The high-dose dexamethasone suppression test has a sensitivity of 81.0% and specificity of 66.7% for diagnosing pituitary-dependent Cushing's syndrome 2.
- The test can be used in combination with other diagnostic tests, such as bilateral petrosal sinus sampling and pituitary magnetic resonance imaging, to improve diagnostic accuracy 5, 4.
- A new pathway that combines low-dose dexamethasone suppression test and bilateral petrosal sinus sampling can differentiate between pituitary and adrenal Cushing's syndrome with high sensitivity and specificity 4.