Corticotroph tumor progression after bilateral adrenalectomy: data from ERCUSYN

in Endocrine-Related Cancer
Authors:
Elena ValassiIIB-Sant Pau and Department of Endocrinology/Medicine, Hospital Sant Pau and Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBER-ER, Unidad 747), ISCIII, Barcelona, Spain
Universitat Internacional de Catalunya (UIC), Barcelona, Spain

Search for other papers by Elena Valassi in
Current site
Google Scholar
PubMed
Close
https://orcid.org/0000-0002-3864-0105
,
Frédéric CastinettiDepartment of Endocrinology, Aix Marseille University, AP-HM, INSERM, Marseille Medical Genetics, Marmara Institute, La Conception Hospital, Marseille, France

Search for other papers by Frédéric Castinetti in
Current site
Google Scholar
PubMed
Close
,
Amandine FerriereDepartment of Endocrinology, Diabetes and Nutrition, University of Bordeaux, Bordeaux, France

Search for other papers by Amandine Ferriere in
Current site
Google Scholar
PubMed
Close
,
Stylianos TsagarakisDepartment of Endocrinology, Diabetes and Metabolism, Evangelismos Hospital, Athens, Greece

Search for other papers by Stylianos Tsagarakis in
Current site
Google Scholar
PubMed
Close
,
Richard A FeeldersErasmus Medical Center, Division of Endocrinology, Department of Internal Medicine, Rotterdam, The Netherlands

Search for other papers by Richard A Feelders in
Current site
Google Scholar
PubMed
Close
,
Romana T Netea-MaierDivision of Endocrinology, Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands

Search for other papers by Romana T Netea-Maier in
Current site
Google Scholar
PubMed
Close
,
Michael DrostePraxis für Endokrinologie Dr. med. Michael Droste, Oldenburg, Germany

Search for other papers by Michael Droste in
Current site
Google Scholar
PubMed
Close
,
Christian J StrasburgerDivision of Clinical Endocrinology, Department of Medicine CCM, Charité-Universitätsmedizin, Berlin, Germany

Search for other papers by Christian J Strasburger in
Current site
Google Scholar
PubMed
Close
,
Dominique MaiterService d’Endocrinologie et Nutrition, Cliniques universitaires Saint Luc, Brussels, Belgium

Search for other papers by Dominique Maiter in
Current site
Google Scholar
PubMed
Close
,
Darko KastelanDepartment of Endocrinology, University Hospital Zagreb, Zagreb, Croatia

Search for other papers by Darko Kastelan in
Current site
Google Scholar
PubMed
Close
,
Philippe ChansonInstitut National de la Santé et de la Recherche Médicale, U1185, Le Kremlin, Bicêtre, Paris, France

Search for other papers by Philippe Chanson in
Current site
Google Scholar
PubMed
Close
,
Susan M WebbIIB-Sant Pau and Department of Endocrinology/Medicine, Hospital Sant Pau and Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBER-ER, Unidad 747), ISCIII, Barcelona, Spain
Universitat Autònoma de Barcelona (UAB), Barcelona, Spain

Search for other papers by Susan M Webb in
Current site
Google Scholar
PubMed
Close
,
Frank DemtröderZentrum für Endokrinologie, Diabetologie, Rheumatologie Dr. Demtröder & Kollegen, Dortmund, Germany

Search for other papers by Frank Demtröder in
Current site
Google Scholar
PubMed
Close
,
Valdis PiragsPaula Stradiņa klīniskā universitātes slimnīca, Riga, Latvia

Search for other papers by Valdis Pirags in
Current site
Google Scholar
PubMed
Close
,
Olivier ChabreHospitalier Universitaire, Grenoble, France

Search for other papers by Olivier Chabre in
Current site
Google Scholar
PubMed
Close
,
Holger FranzLohmann & Birkner Health Care Consultimg GmbH, Berlin, Germany

Search for other papers by Holger Franz in
Current site
Google Scholar
PubMed
Close
,
Alicia SantosIIB-Sant Pau and Department of Endocrinology/Medicine, Hospital Sant Pau and Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBER-ER, Unidad 747), ISCIII, Barcelona, Spain
Universitat Autònoma de Barcelona (UAB), Barcelona, Spain

Search for other papers by Alicia Santos in
Current site
Google Scholar
PubMed
Close
, and
Martin ReinckeMedizinische Klinik UND Poliklinik IV, Campus Innestadt, Klinikum der Universität München, Ludwig-Maximilians-Universität München, Munich, Germany

Search for other papers by Martin Reincke in
Current site
Google Scholar
PubMed
Close

Correspondence should be addressed to E Valassi: EValassi@santpau.cat
Restricted access

USD  $0.01
USD  $0.01

USD  $0.01
USD  $0.01

USD  $0.01
USD  $0.01

USD  $0.01
USD  $0.01

USD  $0.01
USD  $0.01

USD  $0.01
USD  $0.01

USD  $0.01
USD  $0.01

USD  $0.01
USD  $0.01

Corticotroph tumor progression after bilateral adrenalectomy/Nelson’s syndrome (CTP-BADX/NS) is a severe complication of bilateral adrenalectomy (BADX). The aim of our study was to investigate the prevalence, presentation and outcome of CTP-BADX/NS in patients with Cushing’s disease (CD) included in the European Registry on Cushing’s Syndrome (ERCUSYN). We examined data on 1045 CD patients and identified 85 (8%) who underwent BADX. Of these, 73 (86%) had follow-up data available. The median duration of follow-up since BADX to the last visit/death was 7 years (IQR 2–9 years). Thirty-three patients (45%) experienced CTP-BADX/NS after 3 years (1.5–6) since BADX. Cumulative progression-free survival was 73% at 3 years, 66% at 5 years and 46% at 10 years. CTP-BADX/NS patients more frequently had a visible tumor at diagnosis of CD than patients without CTP-BADX/NS (P < 0.05). Twenty-seven CTP-BADX/NS patients underwent surgery, 48% radiotherapy and 27% received medical therapy. The median time since diagnosis of CTP-BADX/NS to the last follow-up visit was 2 years (IQR, 1–5). Control of tumor progression was not achieved in 16 of 33 (48%) patients, of whom 8 (50%) died after a mean of 4 years. Maximum adenoma size at diagnosis of CD was associated with further tumor growth in CTP-BADX/NS despite treatment (P = 0.033). Diagnosis of CTP-BADX/NS, older age, greater UFC levels at diagnosis of CD and initial treatment predicted mortality. In conclusion, CTP-BADX/NS was reported in 45% of the ERCUSYN patients who underwent BADX, and control of tumor growth was reached in half of them. Future studies are needed to establish effective strategies for prevention and treatment.

 

  • Collapse
  • Expand

Society for Endocrinology logo

  • Abu Dabrh AM, Singh Ospina NM, Al Nofal A, Farah WH, Barrionuevo P, Sarigianni M, Mohabbat AB, Benkhadra K, Carranza Leon BG & Gionfriddo MR et al.2016 Predictors of biochemical remission and recurrence after surgical and radiation treatments of Cushing’s disease: a systematic review and meta-analysis. Endocrine Practice 22 466475. (https://doi.org/10.4158/EP15922.RA)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Alexandraki KI, Kaltsas GA, Isidori AM, Storr HL, Afshar F, Sabin I, Akker SA, Chew SL, Drake WM & Monson JP et al.2013 Long-term remission and recurrence rates in Cushing’s disease: predictive factors in a single-centre study. European Journal of Endocrinology 168 639648. (https://doi.org/10.1530/EJE-12-0921)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Assié G, Bahurel H, Coste J, Silvera S, Kujas M, Durgue MA, Karray F, Dousset B, Bertherat J & Legmann P et al.2007 Corticotroph tumor progression after adrenalectomy in Cushing’s disease: a reappraisal of Nelson’s syndrome. Journal of Clinical Endocrinology and Metabolism 92 172179. (https://doi.org/10.1210/jc.2006-1328)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Barnett AH, Liversey JH, Friday K, Donald RA & Espiner EA 1983 Comparison of preoperative and postoperative ACTH concentrations after bilateral adrenalectomy in Cushing’s disease. Clinical Endocrinology 18 301305. (https://doi.org/10.1111/j.1365-2265.1983.tb03215.x)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Braun LT, Rubinstein G, Zopp S, Vogel F, Schmid-Tanwald C, Escudero MP, Honegger J, Ladurner R & Reincke M 2020 Recurrence after pituitary surgery in adult Cushing’s disease: a systematic review on diagnosis and treatment. Endocrine 70 218231. (https://doi.org/10.1007/s12020-020-02432-z)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Clayton RN, Jones PW, Reulen RC, Stewart PM, Hassan-Smith ZK, Ntali G, Karavitaki N, Dekkers OM, Pereira AM & Bolland M et al.2016 Mortality in patients with Cushing’s disease more than 10 years after remission: a multicentre, multinational, retrospective cohort study. Lancet: Diabetes and Endocrinology 4 569576. (https://doi.org/10.1016/S2213-8587(1630005-5)

    • Search Google Scholar
    • Export Citation
  • Fleseriu M, Auchus R, Bancos I, Ben-Shlomo A, Bertherart J, Biermasz NR, Boguszewski CL, Bronstein MD, Buchfelder M & Carmichael JD et al.2021 Consensus on diagnosis and management of Cushing’s disease: a guideline update. Lancet: Diabetes and Endocrinology 9 847875. (https://doi.org/10.1016/S2213-8587(2100235-7)

    • Search Google Scholar
    • Export Citation
  • Fountas A & Karavitaki N 2020 Nelson’s syndrome: an update. Endocrinology and Metabolism Clinics of North America 49 413432. (https://doi.org/10.1016/j.ecl.2020.05.004)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Fountas A, Lim ES, Drake WM, Powlson AS, Gurnell M, Martin NM, Seejore K, Murray RD, MacFarlane J & Ahluwalia R et al.2020 Outcomes of patients with Nelson’s syndrome after primary treatment: a multicenter study from 13 UK Pituitary Centers. Journal of Clinical Endocrinology and Metabolism 105 15271537. (https://doi.org/10.1210/clinem/dgz200)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Gil-Cardenas A, Herrera MF, Díaz-Polanco A, Rios JM & Pantoja JP 2007 Nelson’s syndrome after bilateral adrenalectomy for Cushing’s disease. Surgery 141 14715 1; discussion 151. (https://doi.org/10.1016/j.surg.2006.12.003)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Graffeo CS, Perry A, Carlstrom LP, Meyer FB, Atkinson JLD, Erickson D, Nippolst TB, Young WF Jr, Pollock BE & van Gompel JJ 2017 Characterizing and oredicting the Nelson-Salassa syndrome. Journal of Neurosurgery 127 12771287. (https://doi.org/10.3171/2016.9.JNS161163)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Grossman AB 2017 The molecular pathology of Cushing’s disease: are we nearly there? Journal of the Endocrine Society 1 144148. (https://doi.org/10.1210/js.2017-00036)

    • Search Google Scholar
    • Export Citation
  • Hamblin R, Vardon A, Akpalu J, Tampourlou M, Spilotis I, Sbardella E, Lynch J, Shankaran V, Mavilakaandy A & Gagliardi I et al.2022 Risk of second brain tumour after radiotherapy for pituitary adenoma or craniopharyngioma: a retrospective, multicentre, cohort study of 3679 patients with long-term imaging surveillance. Lancet: Diabetes and Endocrinology 10 581588. (https://doi.org/10.1016/S2213-8587(2200160-7)

    • Search Google Scholar
    • Export Citation
  • Jenkins PJ, Trainer PJ, Plowman PN, Shand WS, Grossmann AB, Wass JA & Bresser GM 1995 The long-term outcome after adrenalectomy and prophylactic pituitary radiotherapy in adrenocorticitropin-dependent Cushing’s syndrome. Journal of Clinical Endocrinology and Metabolism 80 165171. (https://doi.org/10.1210/jcem.80.1.7829606)

    • Search Google Scholar
    • Export Citation
  • Kasperlik-Zaluska AA, Bonicki W, Jeske W, Janik J, Zgliczynski W & Czernicki Z 2006 Nelson’s syndrome-46 years later: clinical experience with 37 patients. Zentralblatt für Neurochirurgie 67 1420. (https://doi.org/10.1055/s-2006-921430)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Kasperlik-Zaluska AA, Nelubowicz J, Wislawski J, Hartwig W, Zaluska J, Jeske W & Migdalska B 1983 Nelson’s syndrome: incidence and prognosis. Clinical Endocrinology 19 693698. (https://doi.org/10.1111/j.1365-2265.1983.tb00046.x)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Kemink L, Pieters G, Hermus A, Smals A & Kloppenborg P 1994 Patient’s age is a simple predictive factor for the development of Nelson’s syndrome after total adrenalectomy for Cushing’s disease. Journal of Clinical Endocrinology and Metabolism 79 887889. (https://doi.org/10.1210/jcem.79.3.8077377)

    • Search Google Scholar
    • Export Citation
  • Lambert JK, Goldberg L, Fayngold S, Kostadinov J, Post KD & Geer EB 2013 Predictors of mortality and long-term outcomes in treated Cushing’s disease: a study of 346 patients. Journal of Clinical Endocrinology and Metabolism 98 10221030. (https://doi.org/10.1210/jc.2012-2893)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Littley MD, Shalet SM, Beardwell CG, Ahmed SR & Sutton ML 1990 Long-term follow-up of low-dose external pituitary irradiation for Cushing’s disease. Clinical Endocrinology 33 445455. (doi:10.1111/j.1365-2265.1990.tb03883.x.)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • McCance DR, Russell CF, Kennedy TL, Hadden DR, Kennedy L & Atkinson AB 1993 Bilateral adrenalectomy: low mortality and morbidity in Cushing’s disease. Clinical Endocrinology 39 315321. (https://doi.org/10.1111/j.1365-2265.1993.tb02371.x)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Misra D, Kapur MM & Gupta DK 1994 Incidence of Nelson’s syndrome and residual adrenocortical function in patients with Cushing’s disease after bilateral adrenalectomy. Journal of the Association of Physicians of India 42 304305.

    • Search Google Scholar
    • Export Citation
  • Nagesser SK, van Seters AP, Kievit J, Hermans J, Krans HM & van de Velde CJ 2000 Long-term results of total adrenalectomy for Cushing’s disease. World Journal of Surgery 24 108113. (doi:10.1007/s002689910020.)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Nieman LK, Biller BM, Findling JW, Murad MH, Newell-Price J, Savage MO, Tabarin A & Endocrine Society 2015 Treatment of Cushing’s syndrome: an Endocrine Society clinical practice guideline. Journal of Clinical Endocrinology and Metabolism 100 28072831. (https://doi.org/10.1210/jc.2015-1818)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Oßwald A, Plomer E, Dimopoulou C, Milian M, Blaser R, Ritzel K, Mickisch A, Knerr F, Stanojevic M & Hallfeldt K et al.2014 Favorable long-term outcomes of bilateral adrenalectomy in Cushing’s disease. European Journal of Endocrinology 171 209215. (https://doi.org/10.1530/EJE-14-0214)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Pereira MA, Halpern A, Salgado LR, Mendonca BB, Nery M, Liberman B, Streeten DH & Wajchenberg BL 1998 A study of patients with Nelson’s syndrome. Clinical Endocrinology 49 533539. (doi:10.1046/j.1365-2265.1998.00578.x.)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Petersenn S, Beckers A, Ferone D, van der Lely A, Bollerslev J, Boscaro M, Brue T, Bruzzi P, Casanueva FF & Chanson P et al.2015 Therapy of endocrine disease: outcomes in patients with Cushing’s disease undergoing transsphenoidal surgery: systematic review assessing criteria used to define remission and recirrence. European Journal of Endocrinology 172 R227R239. (https://doi.org/10.1530/EJE-14-0883)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Ragnarsson O, Olsson DS, Papakokkinou E, Chantzichristos D, Dahlqvist P, Segerstedt E, Olsson T, Petersson M, Berinder K & Bensing S et al.2019 Overall and disease-specific mortality in patients with Cushing’s disease: a Swedish Nationwide Study. Journal of Clinical Endocrinology and Metabolism 104 23752384. (https://doi.org/10.1007/s11102-021-01158-z)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Reincke M, Albani A, Assié G, Bancos I, Brue T, Buchfelder M, Chabre O, Ceccato F, Daniele A & Detomas M et al.2021 Corticotroph tumor progression after bilateral adrenalectomy (Nelson’s syndrome): systematic review and expert consensus recommendations. European Journal of Endocrinology 184 P1P16. (https://doi.org/10.1530/EJE-20-1088)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Ritzel K, Beuschlein F, Mickisch A, Oßwald A, Schneider HJ, Schopohl J & Reincke M 2013 Clinical review: Outcome of bilateral adrenalectomy in Cushing’s syndrome: a systematic review. Journal of Clinical Endocrinology and Metabolism 98 39393948. (https://doi.org/10.1210/jc.2013-1470)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Roelfsema F, Biermasz NR & Pereira AM 2018 Clinical factors involved in the recurrence of pituitary adenomas after surgical remission: a structured review and meta-analysis. Pituitary 21 524534. (https://doi.org/10.1007/s11102-011-0347-7)

    • Search Google Scholar
    • Export Citation
  • Salehi F, Scheithauer BW, Moyes VJ, Drake WM, Syro LV, Manoranjan B, Sharma S, Horvath E & Kovacs K 2010 Low immunohistochemical expression of MGMT in ACTH secreting pituitary tumors of patients with Nelson’s syndrome. Endocrine Pathology 21 227229. (https://doi.org/10.1007/s12022-010-9138-3)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Smith PW, Turza KC, Carter CO, Vance ML, Laws ER & Hanka JB 2009 Bilateral adrenalectomy for refractory Cushing’s disease: a safe and definitive therapy. Journal of the American College of Surgeons 208 10591064. (https://doi.org/10.1016/j.jamcollsurg.2009.02.054)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Sonino N, Zielezny M, Fava GA, Fallo F & Boscaro M 1996 Risk factors and long-term outcome in pituitary-dependent Cushing’s disease. Journal of Clinical Endocrinology and Metabolism 81 26472652. (doi:10.1210/jcem.81.7.8675592.)

    • Search Google Scholar
    • Export Citation
  • Valassi E, Biller BM, Swearingen B, Pecori Giraldi F, Losa M, Mortini P, Hayden D, Cavagnini F & Klibanski A 2010 Delayed remission after transsphenoidal surgery in patients with Cushing’s disease. Journal of Clinical Endocrinology and Metabolism 95 601610. (https://doi.org/10.1210/jc.2009-1672)

    • Crossref
    • Search Google Scholar
    • Export Citation
  • Valassi E, Santos A, Yaneva M, Toth M, Strasburger CJ, Chanson P, Wass JAH, Chabre O, Pfeifer M & Feelders RA et al.2011 The European Registry on Cushing’s syndrome: a 2-year experience. Baseline demographic and clinical characteristics. European Journal of Endocrinology 165 383392. (https://doi.org/10.1530/EJE-11-0272)

    • Crossref
    • Search Google Scholar
    • Export Citation