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Cushing's Syndrome


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Diagnosis of Cushing’s Syndrome can be difficult with non-specific and varying symptoms seen among patients. This section will support you by providing information on diagnosis and how to differentiate between causal factors. A wide range of tests are discussed, used to gradually hone in on the specific cause of that particular case of Cushing's syndrome, such as the 24-hour urinary free cortisol test, the late-night salivary cortisol test, MRI/CT scans and the desmopressin test.


Diagnosis of CS is usually prompted by clinical suspicion in patients with multiple and progressive signs and symptoms.

Screening is also often considered in patients with other features of CS, for example poorly controlled diabetes, hypertension, or unexplained osteoporosis. Patients with an incidentally discovered adrenal mass should be evaluated (Newell-Price et al., 2006; Sharma et al., 2015).

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Differential diagnosis

Once the diagnosis of CS has been confirmed, a combination of blood tests and MRI/CT scans can be employed to determine the cause of the CS (Newell-Price et al., 2006; Sharma et al., 2015).

Figure 5. Identifying the cause of Cushing’s Syndrome.

Figure 5. Identifying the cause of Cushing’s Syndrome (Newell-Price, 2006).
AIMAH: Adrenocorticotropic hormone-independent macronodular adrenal hyperplasia; BIPSS: Bilateral inferior petrosal sinus sampling; CRH: Corticotropin-releasing hormone; CT: Computed tomography; HDDST: High-dose dexamethasone suppression test; MRI: Magnetic resonance imaging; PPNAD: Primary pigmented nodular adrenocortical disease.

Plasma (adrenocorticorticotropic hormone) ACTH levels

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Diagnosis references

Arnaldi G, Angeli A, Atkinson AB, Bertagna X, Cavagnini F, Chrousos GP, et al. Diagnosis and complications of Cushing’s Syndrome: A consensus statement. J Clin Endocrinol Metabol 2003;88:5593–602.

Alexandraki KI, Grossman AB. Is urinary free cortisol of value in the diagnosis of Cushing’s syndrome? Curr Opin Endocrinol Diabetes Obes 2011;18:259–63.

Avgerinos PC, Yanovski JA. Oldfield EH, Nieman LK, Cutler GB. The Metyrapone and Dexamethasone Suppression Tests for the Differential Diagnosis of the Adrenocorticotropin-dependent Cushing Syndrome: A Comparison. Ann Intern Med. 1994;121:318–327.

Berruti A, Baudin E, Gelderblom H, Haak HR, Porpiglia F, Fassnacht M, et al, on behalf of the ESMO Guidelines Working Group. Adrenal cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2012;31–138.

Ioachimescu AG, Remer EM, Hamrahian AH. Adrenal incidentalomas: a disease of modern technology offering opportunities for improved patient care. Endocrinol Metab Clin North Am 2015;44:335–54.

Martin NM, Dhillo WS, Banerjee A, Abdulali A, Jayasena CN, Donaldson M et al. Comparison of the dexamethasone-suppressed corticotropin-releasing hormone test and low-dose dexamethasone suppression test in the diagnosis of Cushing’s syndrome. J Clin Endocrinol Metab 2006;91:2582–6.

Moro M, Putignano P, Losa M, Invitti C, Maraschini C, Cavagnini F. The Desmopressin test in the differential diagnosis between Cushing’s Disease and pseudo-Cushing states. J Clin Endocrinol Metab 2000;85:3569–74.

Newell-Price J, Bertagna X, Grossman AB, Nieman LK. Cushing’s Syndrome. Lancet 2006;367:1605–17.

Nieman LK, Biller BMK, Findling JW, Newell-Price J, Savage MO, Stewart PM et al. The diagnosis of Cushing’s Syndrome: An Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2008;93:1526–40.

Peters CJ, Storr HL, Grossman AB, Savage MO. The role of corticotropin-releasing hormone in the diagnosis of Cushing’s Syndrome. Eur J Endocrinol 2006;155:S93–S98.

Sharma ST, Nieman LK, Feelders RA. Cushing’s Syndrome: epidemiology and developments in disease management. Clin Epidemiol 2015;7:281–93.