PDF icon Download PDF
Horm Metab Res 2010; 42(4): 280-284
DOI: 10.1055/s-0029-1246191
Humans, Clinical

© 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

L. Gagliardi1 , 2 , I. M. Chapman1 , 2 , P. O’Loughlin3 , D. J. Torpy1 , 2
  • 1School of Medicine, University of Adelaide, Adelaide, South Australia, Australia
  • 2Endocrine and Metabolic Unit, Royal Adelaide Hospital, North Terrace, Adelaide, South Australia, Australia
  • 3Endocrine Laboratory, SA Pathology, Adelaide, South Australia, Australia
Further Information

Publication History

received 13.11.2009

accepted 22.12.2009

Publication Date:
29 January 2010 (online)

Also available ateRef
   Permissions and Reprints
Preview

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
    Search in Google Scholar
  • 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
    Search in Google Scholar
  • 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
    Search in Google Scholar
  • 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
    Search in Google Scholar
  • 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
    Search in Google Scholar
  • 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
    Search in Google Scholar
  • 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
    Search in Google Scholar
  • 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
    Search in Google Scholar
  • 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
    Search in Google Scholar
  • 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
    Search in Google Scholar
  • 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
    Search in Google Scholar
  • 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..
    Search in Google Scholar
  • 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
    Search in Google Scholar
  • 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
    Search in Google Scholar
  • 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
    Search in Google Scholar
  • 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
    Search in Google Scholar
  • 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
    Search in Google Scholar
  • 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
    Search in Google Scholar
  • 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
    Search in Google Scholar
  • 20 Krug AW, Ehrhart-Bornstein M. Adrenocortical dysfunction in obesity and the metabolic syndrome.  Horm Metab Res. 2008;  40 515-517
    Search in Google Scholar
  • 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
    Search in Google Scholar
  • 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
    Search in Google Scholar
  • 23 Salehi M, Ferenczi A, Zumoff B. Obesity and cortisol status.  Horm Metab Res. 2005;  37 193-197
    Search in Google Scholar
  • 24 Lamounier-Zepter V, Ehrhart-Bornstein M, Bornstein SR. Metabolic syndrome and the endocrine stress system.  Horm Metab Res. 2006;  38 437-441
    Search in Google Scholar
  • 25 Kyrou I, Tsigos C. Stress mechanisms and metabolic complications.  Horm Metab Res. 2007;  39 430-438
    Search in Google Scholar
  • 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
    Search in Google Scholar
  • 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
    Search in Google Scholar
  • 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
    Search in Google Scholar
  • 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
    Search in Google Scholar
  • 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
    Search in Google Scholar
  • 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
    Search in Google Scholar

Correspondence

Dr. L. Gagliardi

Royal Adelaide Hospital

Endocrine and Metabolic Unit

Level 7 Emergency Block

North Terrace

Adelaide, SA

Australia 5000

Phone: +61/8/8222 2853

Fax: +61/8/8222 5908

Email: lucia.gagliardi@health.sa.gov.au