[en] Objective Limited data regarding adrenal involvement in multiple endocrine neoplasia type 1 (MEN1) is available. We describe the characteristics of MEN1-associated adrenal lesions in a large cohort to provide a rationale for their management. Methods Analysis of records from 715 MEN1 patients from a multicentre database between 1956 and 2008. Adrenal lesions were compared with those from a multicentre cohort of 144 patients with adrenal sporadic incidentalomas. Results Adrenal enlargement was reported in 20.4% (146/715) of patients. Adrenal tumours (>10 mm in size) accounted for 58.1% of these cases (10.1% of the whole patient cohort). Tumours were bilateral and >40 mm in size in 12.5 and 19.4% of cases respectively. Hormonal hypersecretion was restricted to patients with tumours and occurred in 15.3% of them. Compared with incidentalomas, MEN1-related tumours exhibited more cases of primary hyperaldosteronism, fewer pheochromocytomas and more adrenocortical carcinomas (ACCs; 13.8 vs 1.3%). Ten ACCs occurred in eight patients. Interestingly, ACCs occurred after several years of follow-up of small adrenal tumours in two of the eight affected patients. Nine of the ten ACCs were classified as stage I or II according to the European Network for the Study of Adrenal Tumors. No evident genotype/phenotype correlation was found for the occurrence of adrenal lesions, endocrine hypersecretion or ACC. Conclusions Adrenal pathology in MEN1 differs from that observed in sporadic incidentalomas. In the absence of relevant symptoms, endocrine biology can be restricted to patients with adrenal tumours and should focus on steroid secretion including the aldosterone-renin system. MEN1 is a high-risk condition for the occurrence of ACCs. It should be considered regardless of the size of the tumour.
Disciplines :
Endocrinology, metabolism & nutrition
Author, co-author :
Gatta-Cherifi, B.
Chabre, O.
Murat, A.
Niccoli, P.
Cardot-Bauters, C.
Rohmer, V.
Young, J.
Delemer, B.
Du Boullay, H.
Verger, M. F.
Kuhn, J. M.
Sadoul, Jean-Louis
Ruszniewski, P.
Beckers, Albert ; Université de Liège - ULiège > Département des sciences cliniques > Endocrinologie
Chandrasekharappa SC, Guru SC, Manickam P, Olufemi SE, Collins FS, Emmert-Buck MR, Debelenko LV, Zhuang Z, Lubensky IA, Liotta LA, Crabtree JS, Wang Y, Roe BA, Weisemann J, Boguski MS, Agarwal SK, Kester MB, Kim YS, Heppner C, Dong Q, Spiegel AM, Burns AL & Marx SJ. Positional cloning of the gene for multiple endocrine neoplasia-type 1. Science 1997 276 404-407. (doi:10.1126/science.276.5311.404)
Marx S, Spiegel AM, Skarulis MC, Doppman JL, Collins FS &Liotta LA. Multiple endocrine neoplasia type 1: clinical and genetic topics. Annals of Internal Medicine 1998 129 484-494. (Pubitemid 28428085)
Wermer P. Genetic aspects of adenomatosis of endocrine glands. American Journal of Medicine 1954 16 363-371. (doi:10.1016/0002-9343(54)90353-8)
Thakker RV. Multiple endocrine neoplasia type 1 (MEN1). Best Practice & Research. Clinical Endocrinology & Metabolism 2010 24 355-370. (doi:10.1016/j.beem.2010.07.003)
Burgess JR, Harle RA, Tucker P, Parameswaran V, Davies P, Greenaway TM & Shepherd JJ. Adrenal lesions in a large kindred with multiple endocrine neoplasia type 1. Archives of Surgery 1996 131 699-702. (Pubitemid 26243629)
Schaefer S, Shipotko M, Meyer S, Ivan D, Klose KJ, Waldmann J, Langer P & Kann PH. Natural course of small adrenal lesions in multiple endocrine neoplasia type 1: an endoscopic ultrasound imaging study. European Journal of Endocrinology 2008 158 699-704. (doi:10.1530/EJE-07-0635)
Whitley SA, Moyes VJ, Park KM, Brooke AM, Grossman AB, Chew SL, Rockall AG, Monson JP & Reznek RH. The appearance of the adrenal glands on computed tomography in multiple endocrine neoplasia type 1. European Journal of Endocrinology 2008 159 819-824. (doi:10.1530/EJE-08-0516)
Langer P, Cupisti K, Bartsch DK, Nies C, Goretzki PE, Rothmund M & Roher HD. Adrenal involvement in multiple endocrine neoplasia type 1.World Journal of Surgery 2002 26 891-896. (doi:10.1007/s00268-002-6492-4)
Skogseid B, Larsson C, Lindgren PG, Kvanta E, Rastad J, Theodorsson E, Wide L, Wilander E & Oberg K. Clinical and genetic features of adrenocortical lesions in multiple endocrine neoplasia type 1. Journal of Clinical Endocrinology and Metabolism 1992 75 76-81. (doi:10.1210/jc.75.1.76)
Skogseid B, Rastad J, Gobl A, Larsson C, Backlin K, Juhlin C, Akerstrom G & Oberg K. Adrenal lesion in multiple endocrine neoplasia type 1. Surgery 1995 118 1077-1082. (doi:10.1016/S0039-6060(05)80117-5)
Waldmann J, Bartsch DK, Kann PH, Fendrich V, Rothmund M &Langer P. Adrenal involvement in multiple endocrine neoplasia type 1: results of 7 years prospective screening. Langenbeck's Archives of Surgery 2007 392 437-443. (doi:10.1007/s00423-006-0124-7)
Barzon L, Pasquali C, Grigoletto C, Pedrazzoli S, Boscaro M &Fallo F. Multiple endocrine neoplasia type 1 and adrenal lesions. Journal of Urology 2001 166 24-27. (doi:10.1016/S0022-5347(05)66068-5)
Brandi ML, Gagel RF, Angeli A, Bilezikian JP, Beck-Peccoz P, Bordi C, Conte-Devolx B, Falchetti A, Gheri RG, Libroia A, Lips CJ, Lombardi G, Mannelli M, Pacini F, Ponder BA, Raue F, Skogseid B, Tamburrano G, Thakker RV, Thompson NW, Tomassetti P, Tonelli F, Wells SA Jr & Marx SJ. Guidelines for diagnosis and therapy of MEN type 1 and type 2. Journal of Clinical Endocrinology and Metabolism 2001 86 5658-5671. (doi:10.1210/jc.86.12.5658)
Gibril F & Jensen RT. Zollinger-Ellison syndrome revisited: diagnosis, biologic markers, associated inherited disorders, and acid hypersecretion. Current Gastroenterology Reports 2004 6 454-463. (doi:10.1007/s11894-004-0067-5)
Pieterman CR, Schreinemakers JM, Koppeschaar HP, Vriens MR, Rinkes IH, Zonnenberg BA, van der Luijt RB & Valk GD. Multiple endocrine neoplasia type 1 (MEN1): its manifestations and effect of genetic screening on clinical outcome. Clinical Endocrinology 2009 70 575-581. (doi:10.1111/j.1365-2265.2008. 03324.x)
Marini F, Falchetti A, Del Monte F, Carbonell Sala S, Gozzini A, Luzi E & Brandi ML. Multiple endocrine neoplasia type 1. Orphanet Journal of Rare Diseases 2006 1 38. (doi:10.1186/1750-1172-1-38)
Goudet P, Bonithon-Kopp C, Murat A, Ruszniewski P, Niccoli P, Menegaux F, Chabrier G, Borson-Chazot F, Tabarin A, Bouchard P, Cadiot G, Beckers A, Guilhem I, Chabre O, Caron P, Du Boullay H, Verges B & Bauters C. Gender-related differences in MEN1 lesion occurrence and diagnosis. A 734-case cohort study from the GTE (Groupe d'etude des Tumeurs Endocrines). European Journal of Endocrinology 2011 165 97-105. (doi:10.1530/EJE-10-0950)
Tabarin A, Bardet S, Bertherat J, Dupas B, Chabre O, Hamoir E, Laurent F, Tenenbaum F, Cazalda M, Lefebvre H, Valli N &Rohmer V. Exploration and management of adrenal incidentalomas. French Society of Endocrinology Consensus. Annales d'Endocrinologie 2008 69 487-500. (doi:10.1016/j.ando.2008.09.003)
Wautot V, Vercherat C, Lespinasse J, Chambe B, Lenoir GM, Zhang CX, Porchet N, Cordier M, Beroud C & Calender A. Germline mutation profile of MEN1 in multiple endocrine neoplasia type 1: search for correlation between phenotype and the functional domains of the MEN1 protein. Human Mutation 2002 20 35-47. (doi:10.1002/humu.10092)
Fromaget M, Vercherat C, Zhang CX, Zablewska B, Gaudray P, Chayvialle JA, Calender A & Cordier-Bussat M. Functional characterization of a promoter region in the human MEN1 tumor suppressor gene. Journal of Molecular Biology 2003 333 87-102. (doi:10.1016/j.jmb.2003.08.001)
Weiss LM, Medeiros LJ & Vickery AL Jr. Pathologic features of prognostic significance in adrenocortical carcinoma. American Journal of Surgical Pathology 1989 13 202-206. (doi:10.1097/00000478-198903000-00004)
Gicquel C, Bertagna X, Gaston V, Coste J, Louvel A, Baudin E, Bertherat J, Chapuis Y, Duclos JM, Schlumberger M, Plouin PF, Luton JP & Le Bouc Y. Molecular markers and long-term recurrences in a large cohort of patients with sporadic adrenocortical tumors. Cancer Research 2001 61 6762-6767. (Pubitemid 32896498)
de Reynies A, Assie G, Rickman DS, Tissier F, Groussin L, Rene-Corail F, Dousset B, Bertagna X, Clauser E & Bertherat J. Gene expression profiling reveals a new classification of adrenocortical tumors and identifies molecular predictors of malignancy and survival. Journal of Clinical Oncology 2009 27 1108-1115. (doi:10.1200/JCO.2008.18.5678)
Fassnacht M, Wittekind C & Allolio B. Current TNM classification systems for adrenocortical carcinoma. Der Pathologe 2010 31 374-378. (doi:10.1007/s00292-010-1306-1)
Beckers A, Abs R, Willems PJ, van der Auwera B, Kovacs K, Reznik M & Stevenaert A. Aldosterone-secreting adrenal adenoma as part of multiple endocrine neoplasia type 1 (MEN1): loss of heterozygosity for polymorphic chromosome 11 deoxyribonucleic acid markers, including the MEN1 locus. Journal of Clinical Endocrinology and Metabolism 1992 75 564-570. (doi:10.1210/jc.75.2. 564)
Papillon E, Rolachon A, Calender A, Chabre O, Barnoud R &Fournet J. A malignant gastrointestinal stromal tumour in a patient with multiple endocrine neoplasia type 1. European Journal of Gastroenterology & Hepatology 2001 13 207-211. (doi:10.1097/00042737-200102000-00021)
Thompson GB & Young WF Jr. Adrenal incidentaloma. Current Opinion in Oncology 2003 15 84-90. (doi:10.1097/00001622-200301000-00013)
Stowasser M. Update in primary aldosteronism. Journal of Clinical Endocrinology and Metabolism 2009 94 3623-3630. (doi:10.1210/jc.2009-1399)
Cawood TJ, Hunt PJ, O'Shea D, Cole D & Soule S. Recommended evaluation of adrenal incidentalomas is costly, has high false-positive rates and confers a risk of fatal cancer that is similar to the risk of the adrenal lesion becoming malignant; time for a rethink? European Journal of Endocrinology 2009 161 513-527. (doi:10.1530/EJE-09-0234)
Barzon L, Sonino N, Fallo F, Palu G & Boscaro M. Prevalence and natural history of adrenal incidentalomas. European Journal of Endocrinology 2003 149 273-285. (doi:10.1530/eje.0.1490273)
Abiven G, Coste J, Groussin L, Anract P, Tissier F, Legmann P, Dousset B, Bertagna X & Bertherat J. Clinical and biological features in the prognosis of adrenocortical cancer: poor outcome of cortisol-secreting tumors in a series of 202 consecutive patients. Journal of Clinical Endocrinology and Metabolism 2006 91 2650-2655. (doi:10.1210/jc.2005-2730)
Chiodini I, Morelli V, Masserini B, Salcuni AS, Eller-Vainicher C, Viti R, Coletti F, Guglielmi G, Battista C, Carnevale V, Iorio L, Beck-Peccoz P, Arosio M, Ambrosi B & Scillitani A. Bone mineral density, prevalence of vertebral fractures, and bone quality in patients with adrenal incidentalomas with and without subclinical hypercortisolism: an Italian multicenter study. Journal of Clinical Endocrinology and Metabolism 2009 94 3207-3214. (doi:10.1210/jc.2009-0468)
Terzolo M, Reimondo G, Gasperi M, Cozzi R, Pivonello R, Vitale G, Scillitani A, Attanasio R, Cecconi E, Daffara F, Gaia E, Martino E, Lombardi G, Angeli A & Colao A. Colonoscopic screening and follow-up in patients with acromegaly: a multicenter study in Italy. Journal of Clinical Endocrinology and Metabolism 2005 90 84-90. (doi:10.1210/jc.2004-0240)
Mantero F, Terzolo M, Arnaldi G, Osella G, Masini AM, Ali A, Giovagnetti M, Opocher G & Angeli A. A survey on adrenal incidentaloma in Italy. Study Group on Adrenal Tumors of the Italian Society of Endocrinology. Journal of Clinical Endocrinology and Metabolism 2000 85 637-644. (doi:10.1210/jc.85.2.637)
Terzolo M, Stigliano A, Chiodini I, Loli P, Furlani L, Arnaldi G, Reimondo G, Pia A, Toscano V, Zini M, Borretta G, Papini E, Garofalo P, Allolio B, Dupas B, Mantero F & Tabarin A. AME position statement on adrenal incidentaloma. European Journal of Endocrinology 2011 164 851-870. (doi:10.1530/EJE-10-1147)
Carty SE, Helm AK, Amico JA, Clarke MR, Foley TP, Watson CG &Mulvihill JJ. The variable penetrance and spectrum of manifestations of multiple endocrine neoplasia type 1. Surgery 1998 124 1106-1113 discussion 1113-1114. (doi:10.1067/msy.1998.93107)
Trump D, Farren B, Wooding C, Pang JT, Besser GM, Buchanan KD, Edwards CR, Heath DA, Jackson CE, Jansen S, Lips K, Monson JP, O'Halloran D, Sampson J, Shalet SM, Wheeler MH, Zink A & Thakker RV. Clinical studies of multiple endocrine neoplasia type 1 (MEN1). QJM 1996 89 653-669. (Pubitemid 26319017)
Schussheim DH, Skarulis MC, Agarwal SK, Simonds WF, Burns AL, Spiegel AM & Marx SJ. Multiple endocrine neoplasia type 1: new clinical and basic findings. Trends in Endocrinology and Metabolism 2001 12 173-178. (doi:10.1016/S1043-2760(00)00372-6)
Crabtree JS, Scacheri PC, Ward JM, Garrett-Beal L, Emmert-Buck MR, Edgemon KA, Lorang D, Libutti SK, Chandrasekharappa SC, Marx SJ, Spiegel AM & Collins FS. A mouse model of multiple endocrine neoplasia, type 1, develops multiple endocrine tumors. PNAS 2001 98 1118-1123. (doi:10.1073/pnas. 98.3.1118)
Bertherat J & Bertagna X. Pathogenesis of adrenocortical cancer. Best Practice & Research. Clinical Endocrinology & Metabolism 2009 23 261-271. (doi:10.1016/j.beem.2008.10.006)
Hamrahian AH, Ioachimescu AG, Remer EM, Motta-Ramirez G, Bogabathina H, Levin HS, Reddy S, Gill IS, Siperstein A & Bravo EL. Clinical utility of noncontrast computed tomography attenuation value (hounsfield units) to differentiate adrenal adenomas/hyperplasias from nonadenomas: Cleveland clinic experience. Journal of Clinical Endocrinology and Metabolism 2005 90 871-877. (doi:10.1210/jc.2004-1627)
Fassnacht M, Libe R, Kroiss M & Allolio B. Adrenocortical carcinoma: a clinician's update. Nature Reviews. Endocrinology 2011 7 323-335. (doi:10.1038/nrendo.2010.235)
Simonds WF, Varghese S, Marx SJ & Nieman LK. Cushing's syndrome in multiple endocrine neoplasia type 1. Clinical Endocrinology 2012 In press. (doi:10.1111/j.1365-2265.2011.04220.x)
