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An in-depth investigation into cushing's syndrome, a condition characterized by the overproduction of cortisol by the adrenal gland. Indications for testing, first and second line screening tests, and the principles behind various diagnostic tests such as the overnight dexamethasone suppression test, low dose dexamethasone suppression test, and yanovski test. It also discusses the role of acth levels in diagnosis and references several studies for further reading.
Typology: Study notes
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Title of Document: Investigation of Cushing’s Syndrome Q Pulse Reference No: BS/CB/DCB/EN/11 Version NO 6 Authoriser: Paul Thomas Page 1 of 3
Cushing’s syndrome is a collective name for a number of endocrine conditions associated with the overproduction of cortisol by the adrenal gland. Cortisol production is controlled by the secretion of adrenocorticotrophic hormone (ACTH) from the pituitary and is under negative feedback control from cortisol. Excess cortisol production can be secondary to an ACTH secreting pituitary tumour (Cushing’s disease, 70% of cases), ectopic secretion of ACTH (12% of cases) or an adrenal adenoma/carcinoma (18% of cases).
Testing for Cushing’s syndrome in adults, after excluding exogenous glucocorticoid use, is recommended with:
Random cortisol is not an effective screening tool Those that may be used are:
In general, these tests have equal accuracy in detecting Cushing’s syndrome but 24 hour urine free cortisol can be increased by high fluid intake, stress and medications, whilst midnight salivary cortisol may be affected in shift workers, depression and the critically unwell. There are also difficulties with collecting saliva and 24 hour urine so the local policy is to recommend an overnight dexamethasone suppression test which is more appropriate in morbid obesity, depression, alcohol excess and diabetes.
There are some special circumstances that apply;
Title of Document: Investigation of Cushing’s Syndrome Q Pulse Reference No: BS/CB/DCB/EN/11 Version NO 6 Authoriser: Paul Thomas Page 1 of 3
The endocrinologist has to choose second-line tests:
Low dose dexamethasone Suppression test (LDDST)
Failure to suppress cortisol to <50nmol/L suggests the diagnosis of Cushing's Syndrome. False positives can still occur, however there are fewer false positives compared to the overnight dexamethasone suppression test.
Yanovski test, using ovine CRH
Similar to low dose dexamethasone test; it is used to try and differentiate pseudo-Cushing’s syndrome from true Cushing’s syndrome.
There is controversy regarding its specificity. Note that usually ovine CRH is used in the USA, and human CRH is used in Europe. The cut-off currently applied to the test derives from work carried out with ovine CRH and cannot be automatically superimposed for those employing human CRH. European Endocrine guidelines suggest that it is not as specific as LDDST but is included here as it is occasionally used.
Cushing’s syndrome is excluded by suppression of cortisol < 50nmol/l after the LDDST and cortisol < 38nmol/l 15 minutes after CRH