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==Diagnosis== [[File:Diagnostic algorithm of suspected Cushing's syndrome.png|thumb|upright|Diagnostic algorithm of suspected Cushing's syndrome:<ref name=Fleseriu2021>{{cite journal |vauthors=Fleseriu M, Auchus R, Bancos I, Ben-Shlomo A, Bertherat J, Biermasz NR | display-authors=etal| title=Consensus on diagnosis and management of Cushing's disease: a guideline update. | journal=Lancet Diabetes Endocrinol | year= 2021 | volume= 9 | issue= 12 | pages= 847β875 | pmid=34687601 | doi=10.1016/S2213-8587(21)00235-7 | pmc=8743006 }}</ref><br>ACTH=adrenocorticotropic hormone.<br>CBG=corticosteroid-binding globulin.<br>CRH=corticotropin-releasing hormone.<br>DST=dexamethasone suppression test.<br>IPSS=inferior petrosal sinus sampling.<br>UFC=urinary free cortisol.<br>*There is consensus that all patients with lesions smaller than 6 mm in diameter should have IPSS and those with lesions of β₯10 mm do not need IPSS, but expert opinions differed for lesions 6β9 mm in diameter.<br>β This alternative option does not have clear consensus and needs further research, and this is indicated by darker boxes.<br>Green boxes indicate points to consider<br>Darker colors indicate less validated testing pathways.]] The 24-hour urine-free cortisol test, the low-dose dexamethasone suppression test, and the measurement of midnight plasma cortisol or late-night salivary cortisol are the three primary tests used to diagnose Cushing's syndrome.<ref name="Lancet 2006">{{cite journal | last1=Newell-Price | first1=John | last2=Bertagna | first2=Xavier | last3=Grossman | first3=Ashley B | last4=Nieman | first4=Lynnette K | title=Cushing's syndrome | journal=The Lancet | publisher=Elsevier BV | volume=367 | issue=9522 | year=2006 | issn=0140-6736 | doi=10.1016/s0140-6736(06)68699-6 | pages=1605β1617| pmid=16698415 }}</ref> Hypercortisolism is related with routine chemistry abnormalities such as neutrophilic leucocytosis, hyperglycemia, hypokalaemia, hypercholesterolemia, and hypercoagulability.<ref name="Lancet 2001">{{cite journal | last1=Boscaro | first1=Marco | last2=Barzon | first2=Luisa | last3=Fallo | first3=Francesco | last4=Sonino | first4=Nicoletta | title=Cushing's syndrome | journal=The Lancet | publisher=Elsevier BV | volume=357 | issue=9258 | year=2001 | issn=0140-6736 | doi=10.1016/s0140-6736(00)04172-6 | pages=783β791| pmid=11253984 }}</ref> Urinary cortisol levels directly reflect circulating free cortisol.<ref name="Lancet 2006"/> Excess cortisol saturates binding proteins and is eliminated in urine as free cortisol, making it a helpful diagnostic for hypercortisolemia.<ref name="Diagnostic Tests">{{cite journal | last=Kaye | first=Todd B. | title=The Cushing Syndrome: An Update on Diagnostic Tests | journal=Annals of Internal Medicine | publisher=American College of Physicians | volume=112 | issue=6 | date=1990-03-15 | pages=434β444 | issn=0003-4819 | doi=10.7326/0003-4819-76-3-112-6-434 | pmid=2178536 }}</ref> Values four times higher than the top range of normal are uncommon, especially in Cushing's disease.<ref name="Glucocorticoid Action">{{cite journal | last1=Yanovski | first1=Jack A. | last2=Cutler | first2=Gordon B. | title=Glucocorticoid Action and the Clinical Features of Cushing's Syndrome | journal=Endocrinology and Metabolism Clinics of North America | publisher=Elsevier BV | volume=23 | issue=3 | year=1994 | issn=0889-8529 | doi=10.1016/s0889-8529(18)30080-x | pages=487β509| pmid=7805650 }}</ref> A single measurement lacks sensitivity for people with intermittent hypercortisolemia.<ref name="Arnaldi Angeli Atkinson Bertagna 2003 pp. 5593β5602">{{cite journal | last1=Arnaldi | first1=G. | last2=Angeli | first2=A. | last3=Atkinson | first3=A. B. | last4=Bertagna | first4=X. | last5=Cavagnini | first5=F. | last6=Chrousos | first6=G. P. | last7=Fava | first7=G. A. | last8=Findling | first8=J. W. | last9=Gaillard | first9=R. C. | last10=Grossman | first10=A. B. | last11=Kola | first11=B. | last12=Lacroix | first12=A. | last13=Mancini | first13=T. | last14=Mantero | first14=F. | last15=Newell-Price | first15=J. | last16=Nieman | first16=L. K. | last17=Sonino | first17=N. | last18=Vance | first18=M. L. | last19=Giustina | first19=A. | last20=Boscaro | first20=M. | title=Diagnosis and Complications of Cushing's Syndrome: A Consensus Statement | journal=The Journal of Clinical Endocrinology & Metabolism | publisher=The Endocrine Society | volume=88 | issue=12 | year=2003 | issn=0021-972X | doi=10.1210/jc.2003-030871 | pages=5593β5602| pmid=14671138 }}</ref>
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