How is Cushing's Syndrome Diagnosed? Cushing's Syndrome is diagnosed with Low Dose Dexamethasone Suppression Test. Cushing's Syndrome is caused when there is excess cortisol, a glucocorticoid hormone secreted by adrenal cortex. Why Random cortisol levels cannot be used to diagnose Cushing's Syndrome? One cannot simply measure random plasma cortisol to make a diagnosis of excess cortisol hormone in the body because cortisol levels fluctuate throughout the day, and can also be altered by other factors like illness and stress. Thus, the diagnosis of Cushing's Syndrome is made with Overnight Dexamethasone Suppression Test. What is overnight low dose dexamethasone test? It is a good outpatient test in which low dose ( 1 milligrams) of Dexamethasone is given at midnight and serum cortisol levels are measured next morning ( at 8 AM) . In normal individuals the midnight dose of dexamethasone suppresses the cortisol levels to <50 nmol/L
In the first step the diagnosis of Cushing's Syndrome is established with either low dose dexamethasone suppression test or 24 hour urinary free cortisol test.
Then in second step, various localization tests are performed to pinpoint the exact cause of Cushing's Disease.
The diagnosis of Cushing's Syndrome is made if there is NO suppression of morning plasma cortisol levels after a midnight low dose of dexamethasone. Alternatively, raised levels of 24 hour urinary free levels of cortisol is used.
Then to localize the cause of Cushing's Syndrome, first step is to measure plasma ACTH levels.
- If plasma ACTH level is undetectable then the source of increased cortisol level is likely an adrenal tumor/ hyperplasia. The feedback inhibition due to increased cortisol levels make ACTH levels undetectable. Next step is to go for imaging studies - Adrenal CT/MRI. If no mass is found, go for adrenal vein sampling.
- If ACTH levels are detectable then it means the cause of high cortisol levels is High ACTH levels. This increased ACTH is due to either pituitary cause or Ectopic ACTH secretion. Next step is to look if the cortisol levels respond to High Dose Dexamethasone Test or Not.
- If there is suppression in cortisol levels after high dose dexamethasone then the cause is most likely ACTH secreting Pituitary Adenoma. Next step is to perform imaging study of pituitary, MRI and bilateral inferior petrosal sinus blood sampling
- If there is no suppression in cortisol levels even after high dose dexamethasone then the cause is ectopic ACTH secretion most likely by small cell carcinoma of lung and carcinoid tumor. Next step is to look extensively for ACTH secreting tumors with CT chest +/- abdomen +/- pelvis with IV contrast.
Corticotropin Releasing Hormone Test (CRH) Test is an alternative test to High Dose Dexamethasone Suppression Test. After a dose of 100 mcg CRH IV, cortisol is measured after 120 minutes. Cortisol levels rise in case of pituitary disease but not in ectopic ACTH production.
Important points
First diagnose then search the cause.
Use low dose dexamethasone test or 24 hour urinary free cortisol to diagnose. Random plasma cortisol levels cannot be used.
Start with plasma ACTH levels to search for the cause.
Ectopic sources of ACTH - carcinoid or small cell cancer of lung - no suppression even with high dose dexamethasone suppression - @ CANCERS DO NO NOT GIVE A F😤
What is the difference between Cushing's Syndrome and Cushing's Disease?
If the increase in cortisol is caused by increase in ACTH secretion by a pituitary adenoma then it is known as Cushing's disease.
Cushing disease is most common endogenous cause of Cushing's syndrome.
Tags: endocrinology, adrenal, Cushing, Internal medicine review notes.
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