RSS-Feed abonnieren
DOI: 10.1055/s-0029-1246191
© Georg Thieme Verlag KG Stuttgart · New York
Screening for Subclinical Cushing's Syndrome in Type 2 Diabetes Mellitus: Low False-Positive Rates with Nocturnal Salivary Cortisol
Publikationsverlauf
received 13.11.2009
accepted 22.12.2009
Publikationsdatum:
29. Januar 2010 (online)

Abstract
The diagnosis of subclinical Cushing's syndrome (SCS) is important, but its relative rarity amongst patients with common metabolic disorders requires a simple test with a low false-positive rate. Using nocturnal salivary cortisol (NSC), which we first validated in patients with suspected and proven Cushing's syndrome, we screened 106 overweight patients with type 2 diabetes mellitus, a group at high risk of SCS and nontumoral hypothalamic-pituitary-adrenal axis perturbations. Our hypothesis was that a lower false-positive rate with NSC was likely, compared with that reported with the dexamethasone suppression test (DST) (10–20%), currently the foundation of diagnosis of SCS. No participant had clinically apparent Cushing's syndrome. Three participants had an elevated NSC but further testing excluded SCS. In this study, NSC had a lower false-positive rate (3%) than previously reported for the DST. Given the reported excellent performance of NSC in detection of hypercortisolism, the low false-positive rate in SCS suggests NSC may be superior to the DST for SCS screening. The NSC and DST should be compared directly in metabolic disorder patients; although our data suggest the patient group will need to be substantially larger to definitively determine the optimal screening test.
Key words
adrenal - hypercortisolism - metabolic syndrome
References
- 1
Mantero F, Masini AM, Opocher G, Giovagnetti M, Arnaldi G.
Adrenal incidentaloma: an overview of hormonal data from the National Italian Study
Group.
Horm Res.
1997;
47
284-289
Reference Ris Wihthout Link
- 2
Rossi R, Tauchmanova L, Luciano A, Di Martino M, Battista C, Del Viscovo L, Nuzzo V, Lombardi G.
Subclinical Cushing's syndrome in patients with adrenal incidentaloma: Clinical and
biochemical features.
J Clin Endocrinol Metab.
2000;
85
1440-1448
Reference Ris Wihthout Link
- 3
Mantero F, Terzolo M, Arnaldi G, Osella G, Masini AM, Alì A, Giovanetti M, Opocher G, Angeli A.
A survey on adrenal incidentaloma in Italy.
J Clin Endocrinol Metab.
2000;
85
637-644
Reference Ris Wihthout Link
- 4
Bernini G, Moretti A, Iacconi P, Miccoli P, Nami R, Lucani B, Salvetti A.
Anthropometric, haemodynamic, humoral and hormonal evaluation in patients with incidental
adrenocortical adenomas before and after surgery.
Eur J Endocrinol.
2003;
148
213-219
Reference Ris Wihthout Link
- 5
Fernández-Real JM, Ricart W, Simò R, Salinas I, Webb SM.
Study of glucose intolerance in consecutive patients harbouring incidental adrenal
tumours.
Clin Endocrinol (Oxf).
1998;
49
53-61
Reference Ris Wihthout Link
- 6
Tauchmanovà L, Rossi R, Biondi B, Pulcrano M, Nuzzo V, Palmieri EA, Fazio S, Lombardi G.
Patients with subclinical Cushing's syndrome due to adrenal adenoma have increased
cardiovascular risk.
J Clin Endocrinol Metab.
2002;
87
4872-4878
Reference Ris Wihthout Link
- 7
Toniato A, Merante-Boschin I, Opocher G, Pelizzo MR, Schiavi F, Ballotta E.
Surgical versus conservative management for subclinical Cushing syndrome in adrenal
incidentalomas: a prospective randomized study.
Ann Surg.
2009;
249
388-391
Reference Ris Wihthout Link
- 8
Chiodini I, Torlontano M, Scillitani A, Arosio M, Bacci S, Di Lembo S, Epaminonda P, Augello G, Enrini R, Ambrosi B, Adda G, Trischitta V.
Association of subclinical hypercortisolism with type 2 diabetes mellitus: a case-control
study in hospitalised patients.
Eur J Endocrinol.
2005;
153
837-844
Reference Ris Wihthout Link
- 9
Catargi B, Rigalleau V, Poussin A, Ronci-Chaix N, Bex V, Vergnot V, Gin H, Roger P, Tabarin A.
Occult Cushing's syndrome in Type-2 Diabetes.
J Clin Endocrinol Metab.
2003;
88
5808-5813
Reference Ris Wihthout Link
- 10
Newsome S, Chen K, Hoang J, Wilson JD, Potter JM, Hickman PE.
Cushing's syndrome in a clinic population with diabetes.
Intern Med J.
2008;
38
178-182
Reference Ris Wihthout Link
- 11
Reimondo G, Pia A, Allasino B, Tassone F, Bovio S, Borretta G, Angeli A, Terzolo M.
Screening of Cushing's syndrome in adult patients with newly diagnosed diabetes mellitus.
Clin Endocrinol.
2007;
67
225-229
Reference Ris Wihthout Link
- 12 Terzolo M, Allasino B, Castello R, Scorsone A, Mormile A, Rinaldi R, Strollo F, Arvat E, Ciccarelli E, Crivellaro C, Mainini E, Montini M, Disoteo O, Ambrosi B, Chiodini I, Lanzi, R, Senni S, Balestrieri A, Cignarelli M, Solaroli E, Madeo B, De Giovanni R, Battista R, Scillitani A, Garofalo P, Papini E, Borretta G. Results of large-scale screening of Cushing's syndrome in diabetic clinics in Italy. [P1-619] US Endo 2009 Washington: D.C..
Reference Ris Wihthout Link
- 13
Caetano MSS, Silva RDC, Kater CE.
Increased diagnostic probability of subclinical Cushing's syndrome in a population
sample of overweight adult patients with type 2 diabetes mellitus.
Arq Bras Endocrinol Metab.
2007;
51
1118-1127
Reference Ris Wihthout Link
- 14
Leibowitz G, Tsur A, Chayen SD, Salameh M, Raz I, Cerasi E, Gross DJ.
Pre-clinical Cushing's syndrome: an unexpected frequent cause of poor glycaemic control
in obese diabetic patients.
Clin Endocrinol.
1996;
44
717-722
Reference Ris Wihthout Link
- 15
Raff H, Raff JL, Findling JW.
Late-night salivary cortisol as a screening test for Cushing's syndrome.
J Clin Endocrinol Metab.
1998;
83
2681-2686
Reference Ris Wihthout Link
- 16
Papanicolaou DA, Mullen N, Kyrou I, Nieman LK.
Nighttime salivary cortisol: a useful test for the diagnosis of Cushing's syndrome.
J Clin Endocrinol Metab.
2002;
87
4515-4521
Reference Ris Wihthout Link
- 17
Putignano P, Toja P, Dubini A, Pecori Giraldi F, Corsello S, Cavagnini F.
Midnight Salivary Cortisol versus Urinary free and midnight serum cortisol as screening
tests for Cushing's syndrome.
J Clin Endocrinol Metab.
2003;
88
4153-4157
Reference Ris Wihthout Link
- 18
Yaneva M, Mosnier-Pudar H, Dugu MA, Grabar S, Fulla Y, Bertagna X.
Midnight salivary cortisol for the initial diagnosis of Cushing's syndrome of various
causes.
J Clin Endocrinol Metab.
2004;
89
3345-3351
Reference Ris Wihthout Link
- 19
Viardot A, Huber P, Puder JJ, Zulewski H, Keller U, Müller B.
Reproducibility of nighttime salivary cortisol and its use in the diagnosis of hypercortisolism
compared with urinary free cortisol and overnight dexamethasone suppression test.
J Clin Endocrinol Metab.
2005;
90
5730-5736
Reference Ris Wihthout Link
- 20
Krug AW, Ehrhart-Bornstein M.
Adrenocortical dysfunction in obesity and the metabolic syndrome.
Horm Metab Res.
2008;
40
515-517
Reference Ris Wihthout Link
- 21
Alberti KGMM, Zimmet P, Shaw J. for the IDF Epidemiology Task Force Consensus Group .
The metabolic syndrome – a new worldwide definition.
Lancet.
2005;
366
1059-1062
Reference Ris Wihthout Link
- 22
Yaneva M, Kirilov G, Zacharieva S.
Midnight salivary cortisol, measured by highly sensitive electrochemiluminescence
immunoassay, for the diagnosis of Cushing's syndrome.
Cent Eur J Med.
2009;
4
59-64
Reference Ris Wihthout Link
- 23
Salehi M, Ferenczi A, Zumoff B.
Obesity and cortisol status.
Horm Metab Res.
2005;
37
193-197
Reference Ris Wihthout Link
- 24
Lamounier-Zepter V, Ehrhart-Bornstein M, Bornstein SR.
Metabolic syndrome and the endocrine stress system.
Horm Metab Res.
2006;
38
437-441
Reference Ris Wihthout Link
- 25
Kyrou I, Tsigos C.
Stress mechanisms and metabolic complications.
Horm Metab Res.
2007;
39
430-438
Reference Ris Wihthout Link
- 26
Nunes ML, Vattaut S, Corcuff JB, Rault A, Loiseau H, Gatta B, Valli N, Letenneur L, Tabarin A.
Late-night salivary cortisol for diagnosis of overt and subclinical Cushing's syndrome
in hospitalised and ambulatory patients.
J Clin Endocrinol Metab.
2009;
94
56-62
Reference Ris Wihthout Link
- 27
Gagliardi L, Torpy DJ.
Subclinical Cushing's syndrome in adrenal incidentaloma: a common problem or an artefact
of current diagnostic testing?.
Clin Endocrinol.
2009;
DOI: Doi: 10.1111/j.1365-2265.2009.03616.x
Reference Ris Wihthout Link
- 28
Kidambi S, Raff H, Findling JW.
Limitations of nocturnal salivary cortisol and urine free cortisol in the diagnosis
of mild Cushing's syndrome.
Eur J Endocrinol.
2007;
157
725-731
Reference Ris Wihthout Link
- 29
Masserini B, Morelli V, Bergamaschi S, Ermetici F, Eller-Vainicher C, Barbieri AM, Maffini MA, Scillitani A, Ambrosi B, Beck-Peccoz P, Chiodini I.
The limited role of midnight salivary cortisol levels in the diagnosis of subclinical
hypercortisolism in patients with adrenal incidentaloma.
Eur J Endocrinol.
2009;
160
87-92
Reference Ris Wihthout Link
- 30
Liu H, Bravata DM, Cabaccan J, Raff H, Ryzen E.
Elevated late-night salivary cortisol levels in elderly male type 2 diabetic veterans.
Clin Endocrinol.
2005;
63
642-649
Reference Ris Wihthout Link
- 31
Garde AH, Persson R, Hansen ÅM, Österberg K, Ørbæk P, Eek F, Karlson B.
Effects of lifestyle factors on concentrations of salivary cortisol in healthy individuals.
Scand J Clin Lab Invest.
2009;
69
242-250
Reference Ris Wihthout Link
Correspondence
Dr. L. Gagliardi
Royal Adelaide Hospital
Endocrine and Metabolic Unit
Level 7 Emergency Block
North Terrace
Adelaide, SA
Australia 5000
Telefon: +61/8/8222 2853
Fax: +61/8/8222 5908
eMail: lucia.gagliardi@health.sa.gov.au