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Cushing's syndrome: a practical approach to diagnosis and differential diagnoses
  1. Joseph M Pappachan1,
  2. Christian Hariman1,
  3. Mahamood Edavalath2,
  4. Julian Waldron3,
  5. Fahmy W Hanna4
  1. 1Department of Endocrinology & Diabetes, New Cross Hospital, The Royal Wolverhampton Hospitals NHS Trust, Wolverhampton, UK
  2. 2Department of Endocrinology & Diabetes, Imperial College London Diabetes Centre, Abu Dhabi, UAE
  3. 3Department of Clinical Biochemistry, University Hospitals of North Midlands NHS Trust, Stoke-on-Trent, UK
  4. 4Department of Endocrinology & Diabetes, University Hospitals of North Midlands NHS Trust & North Staffordshire University, Stoke-on-Trent, UK
  1. Correspondence to Dr Joseph M Pappachan, Department of Endocrinology & Diabetes, New Cross Hospital, The Royal Wolverhampton Hospitals NHS Trust, Wolverhampton WV10 0QP, UK; drpappachan{at}


Diagnosis of Cushing's syndrome (CS) and identification of the aetiology of hypercortisolism can be challenging. The Endocrine Society clinical practice guidelines recommends one of the four tests for initial screening of CS, namely, urinary-free cortisol, late night salivary cortisol, overnight dexamethasone suppression test or a longer low-dose dexamethasone suppression test, for 48 hours. Confirmation and localisation of CS requires additional biochemical and radiological tests. Radiological evaluation involves different imaging modalities including MRI with or without different radio-nuclear imaging techniques. Invasive testing such as bilateral inferior petrosal sinus sampling may be necessary in some patients for accurate localisation of the cause for hypercortisolism. This best practice review discusses a practical approach for the diagnostic evaluation of CS with a brief discussion on differential diagnoses, and cyclical CS, to enhance the skills of clinicians and laboratory personnel.

  • diagnostic screening

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  • Handling editor Tahir Pillay

  • Contributors JMP and CH contributed equally to the preparation of the manuscript. All authors contributed to literature search and final editing of the manuscript in the present form. A new author, a laboratory scientist, is added in the revision as suggested by the reviewer considering his substantial contribution to the paper revision.

  • Competing interests None declared.

  • Provenance and peer review Commissioned; externally peer reviewed.

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