Journal of Clinical Endocrinology & Metabolism, Vol 75, 826-832, Copyright © 1992 by Endocrine Society

ARTICLES

Preclinical Cushing's syndrome in adrenal "incidentalomas": comparison with adrenal Cushing's syndrome

M Reincke, J Nieke, GP Krestin, W Saeger, B Allolio and W Winkelmann
Department of Medicine II, Krankenhaus Merheim, University of Cologne, Germany.

Adrenal tumors are usually diagnosed by clinical symptoms of hormone excess. The increasing use of ultrasound and computed tomography results in the detection of a substantial number of incidentally discovered adrenal tumors. Most of these tumors are nonfunctional adrenocortical adenomas, but a few cases of subclinical cortisol production in "incidentalomas" have been reported. We investigated prospectively the prevalence of autonomous cortisol production in 68 patients (44 females and 24 males, aged 25-90 yr) with adrenal incidentalomas at our institution. As a screening procedure all patients with incidentalomas underwent an overnight dexamethasone suppression test (1 mg). Patients who failed to suppress serum cortisol below 140 nmol/L (5 micrograms/dL) underwent more comprehensive studies (prolonged dexamethasone suppression test, determination of the diurnal rhythm of cortisol secretion in saliva, and CRH stimulation test). Eight patients (12% of all patients with incidentalomas; 5 females and 3 males, aged 25-71 yr) were finally identified as having cortisol- producing tumors, and the findings in these patients were compared with those of overt Cushing's syndrome in 8 patients (8 females, aged 26-50 yr) suffering from cortisol-producing adrenal adenomas. The tumor size of patients with cortisol-producing incidentalomas ranged from 2-5 cm. No specific signs and symptoms of hypercortisolism were present, but arterial hypertension (seven of eight subjects), diffuse obesity (four of eight subjects), and noninsulin-dependent diabetes mellitus (NIDDM; two of eight subjects) were frequently observed. Baseline cortisol levels were in the normal to upper normal range, whereas baseline ACTH levels were suppressed in five of the eight patients. In none of the patients was serum cortisol suppressible by low dose or high dose dexamethasone. The ACTH and cortisol responses to CRH were normal in two, blunted in one, and suppressed in four patients. Unilateral adrenalectomy was performed in seven patients and resulted in temporary adrenal insufficiency in four of them. After surgery, improvement of arterial hypertension, a permanent weight loss in obese subjects, and a better metabolic control of NIDDM were noted in the majority of patients. The following conclusions were reached. Incidentally diagnosed adrenal tumors with pathological cortisol secretion in otherwise clinically asymptomatic patients are more frequently observed than previously assumed. Adrenocortical insufficiency is a major risk in these patients after adrenalectomy. After surgery, hypertension, obesity, and NIDDM may improve. Patients with asymptomatic adrenal incidentalomas, therefore, should be screened for cortisol production by means of an overnight dexamethasone suppression test.

This article has been cited by other articles:

				M. Sereg, A. Szappanos, J. Toke, K. Karlinger, K. Feldman, E. Kaszper, I. Varga, E. Glaz, K. Racz, and M. Toth Atherosclerotic risk factors and complications in patients with non-functioning adrenal adenomas treated with or without adrenalectomy: a long-term follow-up study Eur. J. Endocrinol., April 1, 2009; 160(4): 647 - 655. [Abstract] [Full Text] [PDF]

				C. Fagour, S. Bardet, V. Rohmer, Y. Arimone, P. Lecomte, N. Valli, and A. Tabarin Usefulness of adrenal scintigraphy in the follow-up of adrenocortical incidentalomas: a prospective multicenter study Eur. J. Endocrinol., February 1, 2009; 160(2): 257 - 264. [Abstract] [Full Text] [PDF]

				M.-L. Nunes, S. Vattaut, J.-B. Corcuff, A. Rault, H. Loiseau, B. Gatta, N. Valli, L. Letenneur, and A. Tabarin Late-Night Salivary Cortisol for Diagnosis of Overt and Subclinical Cushing's Syndrome in Hospitalized and Ambulatory Patients J. Clin. Endocrinol. Metab., February 1, 2009; 94(2): 456 - 462. [Abstract] [Full Text] [PDF]

				B. Masserini, V. Morelli, S. Bergamaschi, F. Ermetici, C. Eller-Vainicher, A. M. Barbieri, M. A. Maffini, A. Scillitani, B. Ambrosi, P. Beck-Peccoz, et al. The limited role of midnight salivary cortisol levels in the diagnosis of subclinical hypercortisolism in patients with adrenal incidentaloma Eur. J. Endocrinol., January 1, 2009; 160(1): 87 - 92. [Abstract] [Full Text] [PDF]

				D Vezzosi, D Cartier, C Regnier, P Otal, A Bennet, F Parmentier, M Plantavid, A Lacroix, H Lefebvre, and P Caron Familial adrenocorticotropin-independent macronodular adrenal hyperplasia with aberrant serotonin and vasopressin adrenal receptors Eur. J. Endocrinol., January 1, 2007; 156(1): 21 - 31. [Abstract] [Full Text] [PDF]

				R Nawar and D Aron Adrenal incidentalomas -- a continuing management dilemma Endocr. Relat. Cancer, September 1, 2005; 12(3): 585 - 598. [Abstract] [Full Text] [PDF]

				M. Terzolo, S. Bovio, A. Pia, P. A. Conton, G. Reimondo, C. Dall'Asta, D. Bemporad, A. Angeli, G. Opocher, M. Mannelli, et al. Midnight serum cortisol as a marker of increased cardiovascular risk in patients with a clinically inapparent adrenal adenoma Eur. J. Endocrinol., August 1, 2005; 153(2): 307 - 315. [Abstract] [Full Text] [PDF]

				R. G. Dluhy, M. M. Maher, and C.-L. Wu Case 7-2005 - A 59-Year-Old Woman with an Incidentally Discovered Adrenal Nodule N. Engl. J. Med., March 10, 2005; 352(10): 1025 - 1032. [Full Text] [PDF]

				I. Chiodini, G. Guglielmi, C. Battista, V. Carnevale, M. Torlontano, M. Cammisa, V. Trischitta, and A. Scillitani Spinal Volumetric Bone Mineral Density and Vertebral Fractures in Female Patients with Adrenal Incidentalomas: The Effects of Subclinical Hypercortisolism and Gonadal Status J. Clin. Endocrinol. Metab., May 1, 2004; 89(5): 2237 - 2241. [Abstract] [Full Text] [PDF]

				G. Mansmann, J. Lau, E. Balk, M. Rothberg, Y. Miyachi, and S. R. Bornstein The Clinically Inapparent Adrenal Mass: Update in Diagnosis and Management Endocr. Rev., April 1, 2004; 25(2): 309 - 340. [Abstract] [Full Text] [PDF]

				B. Catargi, V. Rigalleau, A. Poussin, N. Ronci-Chaix, V. Bex, V. Vergnot, H. Gin, P. Roger, and A. Tabarin Occult Cushing's Syndrome in Type-2 Diabetes J. Clin. Endocrinol. Metab., December 1, 2003; 88(12): 5808 - 5813. [Abstract] [Full Text] [PDF]

				P De, L M Evans, M F Scanlon, and J S Davies "Osler's phenomenon": misdiagnosing Cushing's syndrome Postgrad. Med. J., October 1, 2003; 79(936): 594 - 596. [Abstract] [Full Text] [PDF]

				G. La Cava, A. Imperiale, C. Olianti, G. R. Gheri, C. Ladu, M. Mannelli, and A. Pupi SPECT Semiquantitative Analysis of Adrenocortical 131I-6{beta}-Iodomethyl-Norcholesterol Uptake to Discriminate Subclinical and Preclinical Functioning Adrenal Incidentaloma J. Nucl. Med., July 1, 2003; 44(7): 1057 - 1064. [Abstract] [Full Text] [PDF]

				H. Raff and J. W. Findling A Physiologic Approach to Diagnosis of the Cushing Syndrome Ann Intern Med, June 17, 2003; 138(12): 980 - 991. [Full Text] [PDF]

				I. Chiodini, L. Tauchmanova, M. Torlontano, C. Battista, G. Guglielmi, M. Cammisa, A. Colao, V. Carnevale, R. Rossi, S. Di Lembo, et al. Bone Involvement in Eugonadal Male Patients with Adrenal Incidentaloma and Subclinical Hypercortisolism J. Clin. Endocrinol. Metab., December 1, 2002; 87(12): 5491 - 5494. [Abstract] [Full Text] [PDF]

				L. Tauchmanova, R. Rossi, B. Biondi, M. Pulcrano, V. Nuzzo, E.-A. Palmieri, S. Fazio, and G. Lombardi Patients with Subclinical Cushing's Syndrome due to Adrenal Adenoma Have Increased Cardiovascular Risk J. Clin. Endocrinol. Metab., November 1, 2002; 87(11): 4872 - 4878. [Abstract] [Full Text] [PDF]

				M. Terzolo, A. Pia, A. Ali, G. Osella, G. Reimondo, S. Bovio, F. Daffara, M. Procopio, P. Paccotti, G. Borretta, et al. Adrenal Incidentaloma: A New Cause of the Metabolic Syndrome? J. Clin. Endocrinol. Metab., March 1, 2002; 87(3): 998 - 1003. [Abstract] [Full Text] [PDF]

				I. Chiodini, M. Torlontano, V. Carnevale, G. Guglielmi, M. Cammisa, V. Trischitta, and A. Scillitani Bone Loss Rate in Adrenal Incidentalomas: A Longitudinal Study J. Clin. Endocrinol. Metab., November 1, 2001; 86(11): 5337 - 5341. [Abstract] [Full Text] [PDF]

				D. E. Schteingart, T. J. Giordano, R. S. Benitez, M. D. Burdick, M. N. Starkman, D. A. Arenberg, and R. M. Strieter Overexpression of CXC Chemokines by an Adrenocortical Carcinoma: A Novel Clinical Syndrome J. Clin. Endocrinol. Metab., August 1, 2001; 86(8): 3968 - 3974. [Abstract] [Full Text] [PDF]

				T. Takao, T. Mimoto, M. Yamamoto, and K. Hashimoto Preclinical Cushing Disease Arch Intern Med, March 26, 2001; 161(6): 892 - 893. [Full Text] [PDF]

				G. Osella, G. Reimondo, P. Peretti, A. Alì, P. Paccotti, A. Angeli, and M. Terzolo The Patients with Incidentally Discovered Adrenal Adenoma (Incidentaloma) Are Not at Increased Risk of Osteoporosis J. Clin. Endocrinol. Metab., February 1, 2001; 86(2): 604 - 607. [Abstract] [Full Text]

				R. Rossi, L. Tauchmanova, A. Luciano, M. Di Martino, C. Battista, L. Del Viscovo, V. Nuzzo, and G. Lombardi Subclinical Cushing's Syndrome in Patients with Adrenal Incidentaloma: Clinical and Biochemical Features J. Clin. Endocrinol. Metab., April 1, 2000; 85(4): 1440 - 1448. [Abstract] [Full Text]

				M. Terzolo, S. Bossoni, A. Alí, M. Doga, G. Reimondo, G. Milani, P. Peretti, F. Manelli, A. Angeli, and A. Giustina Growth Hormone (GH) Responses to GH-Releasing Hormone Alone or Combined with Arginine in Patients with Adrenal Incidentaloma: Evidence for Enhanced Somatostatinergic Tone J. Clin. Endocrinol. Metab., March 1, 2000; 85(3): 1310 - 1315. [Abstract] [Full Text]

				F. Mantero, M. Terzolo, G. Arnaldi, G. Osella, A. M. Masini, A. Alì, M. Giovagnetti, G. Opocher, and A. Angeli A Survey on Adrenal Incidentaloma in Italy J. Clin. Endocrinol. Metab., February 1, 2000; 85(2): 637 - 644. [Abstract] [Full Text]

				M. Torlontano, I. Chiodini, M. Pileri, G. Guglielmi, M. Cammisa, S. Modoni, V. Carnevale, V. Trischitta, and A. Scillitani Altered Bone Mass and Turnover in Female Patients with Adrenal Incidentaloma: The Effect of Subclinical Hypercortisolism J. Clin. Endocrinol. Metab., July 1, 1999; 84(7): 2381 - 2385. [Abstract] [Full Text]

				H. Raff, J. L. Raff, and J. W. Findling Late-Night Salivary Cortisol as a Screening Test for Cushing's Syndrome J. Clin. Endocrinol. Metab., August 1, 1998; 83(8): 2681 - 2686. [Abstract] [Full Text]

				L. Barzon, C. Scaroni, N. Sonino, F. Fallo, M. Gregianin, C. Macri’, and M. Boscaro Incidentally Discovered Adrenal Tumors: Endocrine and Scintigraphic Correlates J. Clin. Endocrinol. Metab., January 1, 1998; 83(1): 55 - 62. [Abstract] [Full Text]

				G. Osella, M. Terzolo, G. Reimondo, A. Piovesan, A. Pia, A. Termine, P. Paccotti, and A. Angeli Serum Markers of Bone and Collagen Turnover in Patients with Cushing's Syndrome and in Subjects with Adrenal Incidentalomas J. Clin. Endocrinol. Metab., October 1, 1997; 82(10): 3303 - 3307. [Abstract] [Full Text] [PDF]

				N. B. Watts and L. S. Blevins Jr Endocrinology JAMA, June 1, 1994; 271(21): 1666 - 1668. [Abstract] [PDF]

				S. P. Campos and M. H. MacGillivray Preclinical Cushing Syndrome Due to an Adrenocortical Adenoma Mimicking Late-Onset Congenital Adrenal Hyperplasia Clinical Pediatrics, April 1, 1994; 33(4): 246 - 248. [PDF]

				R. H. Caplan, P. J. Strutt, and G. G. Wickus Subclinical Hormone Secretion by Incidentally Discovered Adrenal Masses Arch Surg, March 1, 1994; 129(3): 291 - 296. [Abstract] [PDF]