Diagnosis is made first by diagnosing Cushing's syndrome, which can be difficult to do clinically since the most characteristic symptoms only occur in a minority of patients. Some of the biochemical diagnostic tests used include salivary and blood serum cortisol testing, 24-hour urinary free cortisol (UFC) testing, the dexamethasone suppression test (DST), and bilateral inferior petrosal sinus sampling (IPSS or BIPSS for bilateral IPSS). No single test is perfect and multiple tests should always be used to achieve a proper diagnosis. Diagnosing<unk>  is a multidisciplinary process involving doctors, endocrinologists, radiologists, surgeons, and chemical pathologists. ACTH blood test Once Cushing's syndrome has been diagnosed, the first step towards finding the cause is measuring plasma adrenocorticotropic hormone (ACTH) concentration. A concentration consistently below 1.1 pmol/L is classified as corticotropin-independent and does not lead to a diagnosis of<unk> . In such cases, the next step is adrenal imaging with CT. If plasma corticotropin concentrations are consistently above 3.3 pmol/L, then corticotropin-dependent Cushing's syndrome is most likely. Any intermediate values need to be cautiously interpreted and a corticotropin-releasing hormone (CRH) test is advised in order to confirm corticotropin dependency. If corticotropin-dependent Cushing's syndrome is determined then the next step is to distinguish between<unk>  and ectopic corticotropin syndrome. This is done via a combination of techniques including CRH, high-dose DST, BIPSS, and pituitary MRI. Dexamethasone suppression test Two dexamethasone suppression tests (DSTs) are generally used, the overnight test and the 48 hour test. For both tests, a plasma cortisol level above 50 nmol/L is indicative of<unk> . However, 3–8% of patients with<unk>  will test negative due to a retention of dexamethasone suppression abilities. For non-Cushing or healthy patients, the false-positive rate is 30%. The 48-h DST is advantageous since it is more specific and can be done by outpatients upon proper instruction. In the high-dose 48-h DST, 2 mg of dexamethasone is given every 6 hours for 48 hours or a single dose of 8 mg is given. This test is not needed if the 48-h low-dose DST has shown suppression of cortisol by over 30%. These tests are based on the glucocorticoid sensitivity of pituitary adenomas compared to non-pituitary tumors. ACTH stimulation test An ACTH stimulation test involving administration of corticotropin-releasing hormone (CRH) or another agent can differentiate this condition from ectopic ACTH secretion. In a patient with<unk> , the tumor cells will be stimulated to release corticotropin and elevated plasma corticotropin levels will be detected. This rarely occurs with ectopic corticotropin syndrome and thus is quite useful for distinguishing between the two conditions. If ectopic, the plasma ACTH and cortisol levels should remain unchanged; if this is pituitary related, levels of both would rise. The CRH test uses recombinant human or bovine-sequence CRH, which is administered via a 100μg intravenous bolus dose. The sensitivity of the CRH test for detecting<unk>  is 93% when plasma levels are measured after fifteen and thirty minutes. However, this test is used only as a last resort due to its high cost and complexity. Imaging A CT or MRI of the pituitary may also show the ACTH-secreting tumor if present. However, in 40% of<unk>  patients MRI is unable to detect a tumor. In one study of 261 patients with confirmed pituitary<unk> , only 48% of pituitary lesions were identified using MRI prior to surgery. The average size of tumor, both those that were identified on MRI and those that were only discovered during surgery, was 6 mm. Inferior petrosal sinus sampling IPSS (inferior petrosal sinus sampling) or BIPSS (bilateral IPSS) is a more accurate but invasive test used to differentiate pituitary from ectopic or adrenal Cushing's syndrome. A corticotropin gradient sample via BIPSS is required to confirm diagnosis when pituitary MRI imaging and biochemical diagnostic tests have been inconclusive. A basal central:peripheral ratio of over 2:1, or a ratio over 3:1 when CRH is administered, is indicative of<unk> . This test has been the gold standard for distinguishing between<unk>  and ectopic corticotropin syndrome. The BIPSS has a sensitivity and specificity of 94% for<unk>  but it is usually used as a last resort due to its invasiveness, rare but serious complications, and the expertise required to perform it. Urinary free cortisol test Another diagnostic test used is the urinary free cortisol (UFC) test, which measures the excess cortisol excreted by the kidneys into the urine. Results of 4x higher cortisol levels than normal are likely to be<unk> . This test should be repeated three times in order to exclude any normally occurring periods of hypercortisolism. The UFC test has a specificity of 81% and thus has a high rate of false-positives that are due to pseudo-Cushing states, sleep apnea, polycystic ovary syndrome, familial glucocorticoid resistance, and hyperthyroidism. Late night (midnight) salivary cortisol test The late-night or midnight salivary cortisol test has been gaining support due to its ease of collection and stability at room temperature, therefore it can be assigned to outpatients. The test measures free circulating cortisol and have both a sensitivity and specificity of 95–98%. This test is especially useful for diagnosing children.
Cushing's disease
Cushing's syndrome
Addison's disease
complications of Acromegaly
complications of Graves' disease
Pseudo-Cushing's syndrome
Graves' disease
Sheehan's syndrome