• Ahmed Imran Siddiqi 1 North Manchester General Hospital. Manchester
  • Muhammad Usamah Bin Noor


Cushing’s syndrome remains an uncommon diagnosis with majority of non-specific and few specific clinical features suggestive of the condition. Results of biochemical investigations are often affected by confounding factors making diagnosis of Cushing’s syndrome difficult and localisation of the disease even more challenging. Careful assessment of the individual patient and use of the most suitable test in that patient may allow improved outcome in diagnosing and localising the condition to devise an appropriate management plan.

Key words: Cushing’s syndrome, hypercortisolism, dexamethasone suppression test, Pseudo-Cushing’s


Cushing’s Syndrome. Available from: https://www.niddk. nih.gov/health-information/endocrine-diseases/cushingssyndrome. [Last accessed on 2017 Dec 01].

World Health Organisation; 2006. Available from: http:// www.who.int/dietphysicalactivity/publications/fa cts/ obesity/end. [Last accessed on 2017 Dec 01].

Guignat L, Bertherat J. The diagnosis of Cushing’s syndrome: An endocrine society clinical practice guideline: Commentary from a European perspective. Eur J Endocrinol 2010;163:9-13.

Nieman LK, Biller BM, Findling JW, et al. The diagnosis of Cushing’s syndrome: An endocrine society clinical practice guideline. J Clin Endocrinol Metab 2008;93:1526-40.

Zhang Q, Dou J, Gu W, et al. Reassessing the reliability of the salivary cortisol assay for the diagnosis of Cushing syndrome. J Int Med Res 2013;41:1387-94.

Brien TG. Human corticosteroid binding globulin. Clin Endocrinol (Oxf) 1981;14:193-212.

Nieman LK. Cushing’s syndrome: Update on signs, symptoms and biochemical screening. Eur J Endocrinol 2015; 173:M33-8.

Holleman F, Endert E, Prummel MF, et al. Evaluation of endocrine tests. B: Screening for hypercortisolism. Neth J Med 2005;63:348-53.

Ceccato F, Barbot M, Zilio M, et al. Screening tests for Cushing’s syndrome: Urinary free cortisol role measured by LC-MS/MS. J Clin Endocrinol Metab 2015;100:3856-61.

Raff H, Auchus RJ, Findling JW, et al. Urine free cortisol in the diagnosis of Cushing’s syndrome: Is it worth doing and, if so, how? J Clin Endocrinol Metab 2015;100:395-7.

Loriaux DL. Diagnosis and differential diagnosis of Cushing’s syndrome. N Engl J Med 2017;377:e3.

Crapo L. Cushing’s syndrome: A review of diagnostic tests. Metabolism 1979;28:955-77.

Mengden T, Hubmann P, Müller J, et al. Urinary free cortisol versus 17-hydroxycorticosteroids: A comparative study of their diagnostic value in Cushing’s syndrome. Clin Investig 1992;70:545-8.

Laudat MH, Billaud L, Thomopoulos P, et al. Evening urinary free corticoids: A screening test in Cushing’s syndrome and incidentally discovered adrenal tumours. Acta Endocrinol (Copenh) 1988;119:459-64.

Contreras LN, Hane S, Tyrrell JB. Urinary cortisol in the assessment of pituitary-adrenal function: Utility of 24-hour and spot determinations. J Clin Endocrinol Metab 1986; 62:965-9.

Meikle AW. Dexamethasone suppression tests: Usefulness of simultaneous measurement of plasma cortisol and dexamethasone. Clin Endocrinol (Oxf) 1982;16:401-8.

Yanovski JA, Cutler GB Jr., Chrousos GP, et al. Corticotropin-releasing hormone stimulation following low-dose dexamethasone administration. A new test to distinguish Cushing’s syndrome from pseudo-Cushing’s states. JAMA 1993;269:2232-8.

Cronin C, Igoe D, Duffy MJ, et al. The overnight dexamethasone test is a worthwhile screening procedure. Clin Endocrinol (Oxf) 1990;33:27-33.

Newell-Price J, Trainer P, Perry L, et al. A single sleeping midnight cortisol has 100% sensitivity for the diagnosis of Cushing’s syndrome. Clin Endocrinol (Oxf) 1995;43:545‑50.

Kennedy L, Atkinson AB, Johnston H, et al. Serum cortisol concentrations during low dose dexamethasone suppression test to screen for Cushing’s syndrome. Br Med J (Clin Res Ed) 1984;289:1188-91.

Lytras N, Grossman A, Perry L, et al. Corticotrophin releasing factor: Responses in normal subjects and patients with disorders of the hypothalamus and pituitary. Clin Endocrinol (Oxf) 1984;20:71-84.

Newell-Price J, Trainer P, Besser M, et al. The diagnosis and differential diagnosis of Cushing’s syndrome and pseudo- Cushing’s states. Endocr Rev 1998;19:647-72.

Aytug S, Laws ER Jr., Vance ML. Assessment of the utility of the high-dose dexamethasone suppression test in confirming the diagnosis of Cushing disease. Endocr Pract 2012;18:152-7.

Tyrrell JB, Findling JW, Aron DC, et al. An overnight high-dose dexamethasone suppression test for rapid differential diagnosis of Cushing’s syndrome. Ann Intern Med 1986;104:180-6.

Trainer PJ, Grossman A. The diagnosis and differential diagnosis of Cushing’s syndrome. Clin Endocrinol (Oxf) 1991; 34:317-30.

Weber A, Trainer PJ, Grossman AB, et al. Investigation, management and therapeutic outcome in 12 cases of childhood and adolescent Cushing’s syndrome. Clin Endocrinol (Oxf) 1995;43:19-28.

Delgrange E, Goethals P, Laka A, et al. An unusual case of bilateral virilizing adrenal adenoma co-secreting androgens and cortisol. J Endocrinol Invest 1996;19:377-81.

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

Fuller PJ, Lim AT, Barlow JW, et al. A pituitary tumor producing high molecular weight adrenocorticotropinrelated peptides: Clinical and cell culture studies. J Clin Endocrinol Metab 1984;58:134-42.

Kirk LF Jr., Hash RB, Katner HP, et al. Cushing’s disease: Clinical manifestations and diagnostic evaluation. Am Fam Physician 2000;62:1119-27, 1133-4.

Meinardi JR, Wolffenbuttel BH, Dullaart RP. Cyclic Cushing’s syndrome: A clinical challenge. Eur J Endocrinol 2007;157:245-54.

Tirabassi G, Boscaro M, Arnaldi G. Harmful effects of functional hypercortisolism: A working hypothesis. Endocrine 2014;46:370-86.

Besemer F, Pereira AM, Smit JW. Alcohol-induced Cushing syndrome. Hypercortisolism caused by alcohol abuse. Neth J Med 2011;69:318-23.

Rees LH, Besser GM, Jeffcoate WJ, et al. Alcohol-induced pseudo-Cushing’s syndrome. Lancet 1977;1:726-8.

How to Cite
Siddiqi AI, Noor MUB. DIAGNOSIS OF CUSHING’S SYNDROME; BIOCHEMICAL INVESTIGATIONS. J Cancer Allied Spec [Internet]. 2018Jan.1 [cited 2023Oct.3];3(4). Available from: https://journals.sfu.ca/jcas/index.php/jcas/article/view/154