Skip to main content
SpringerLink
Log in

Pre- and peri-operative characteristics, complications and outcomes of patients with biochemically silent pheochromocytomas; a case series

  • Original Article
  • Published:
Endocrine Aims and scope Submit manuscript

Abstract

Purpose:

Pheochromocytomas are rare tumors and biochemically silent ones with normal catecholamine levels are even rarer. Up to date, biochemically inactive pheochromocytomas are poorly investigated. We aimed to systematically assess the pre- and peri-operative characteristics and the outcomes of patients with these tumors who had been treated and followed-up in 2 tertiary centers.

Methods:

Clinical, laboratory and imaging data, treatment outcomes and follow-up of biochemically silent pheochromocytoma patients were recorded.

Results:

Ten patients (5 men) [median age at diagnosis 52.5 years (24–72)] were included. Adrenal masses were incidentally discovered in all patients except from one who presented with pheochromocytoma-related manifestations. Twenty-four-hour urine metanephrine and normetanephrine levels were in the low-normal, normal and high-normal range in 4, 4 and 2 patients and in 1, 6 and 3 patients, respectively. Tumors were unilateral [median size 46 mm (17–125)] and high density on pre-contrast CT imaging or high signal intensity on T2-weighted MRI scans were found in all cases. Pre-operatively, 5 patients were treated with phenoxybenzamine [median total daily dose 70 mg (20–100)]. Intra-operatively, 4 patients developed hypertension requiring vasodilator administration and 8 developed hypotension; vasoconstrictors were required in 5 cases. One patient, not pre-operatively treated with phenoxybenzamine, developed Takotsubo cardiomyopathy. During a median 24-month (12–88) follow-up period, one patient had disease progression.

Conclusions:

The majority (90%) of patients with biochemically silent pheochromocytomas developed hemodynamic instability during adrenal surgery. In patients with biochemically silent adrenal lesions and a high suspicion index for pheochromocytoma based on tumor imaging characteristics, pre-operative alpha-blockade treatment may be advisable.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. A.M.A. Berends, E. Buitenwerf, R.R. de Krijger, N. Veeger, A.N.A. van der Horst-Schrivers, T.P. Links, M.N. Kerstens, Incidence of pheochromocytoma and sympathetic paraganglioma in the Netherlands: A nationwide study and systematic review. Eur. J. Intern. Med. 51, 68–73 (2018). https://doi.org/10.1016/j.ejim.2018.01.015

    Article  PubMed  Google Scholar 

  2. A.A. Leung, J.L. Pasieka, M.D. Hyrcza, D. Pacaud, Y. Dong, J.M. Boyd, H. Sadrzadeh, G.A. Kline, Epidemiology of pheochromocytoma and paraganglioma: population-based cohort study. Eur. J. Endocrinol. 184(1), 19–28 (2021). https://doi.org/10.1530/eje-20-0628

    Article  CAS  PubMed  Google Scholar 

  3. L.M. Gruber, R.P. Hartman, G.B. Thompson, T.J. McKenzie, M.L. Lyden, B.M. Dy, W.F. Young, I. Bancos, Pheochromocytoma Characteristics and Behavior Differ Depending on Method of Discovery. J. Clin. Endocrinol. Metab. 104(5), 1386–1393 (2019). https://doi.org/10.1210/jc.2018-01707

    Article  PubMed  Google Scholar 

  4. R. Clifton-Bligh, Diagnosis of silent pheochromocytoma and paraganglioma. Expert Rev. Endocrinol. Metab. 8(1), 47–57 (2013). https://doi.org/10.1586/eem.12.76

    Article  CAS  PubMed  Google Scholar 

  5. M. Mannelli, J.W. Lenders, K. Pacak, G. Parenti, G. Eisenhofer, Subclinical phaeochromocytoma. Best practice & research. Clin. Endocrinol. Metab. 26(4), 507–515 (2012). https://doi.org/10.1016/j.beem.2011.10.008

    Article  Google Scholar 

  6. G.N. Zografos, A.K. Farfaras, E. Kassi, D.N. Vaidakis, A. Markou, G. Kaltsas, G. Piaditis, Laparoscopic resection of pheochromocytomas with delayed vein ligation. Surgical Laparosc., Endosc. percutaneous Tech. 21(2), 116–119 (2011). https://doi.org/10.1097/SLE.0b013e318213bb1f

    Article  Google Scholar 

  7. C. Aggeli, A.M. Nixon, C. Parianos, G. Vletsis, L. Papanastasiou, A. Markou, T. Kounadi, G. Piaditis, G.N. Zografos, Surgery for pheochromocytoma: A 20-year experience of a single institution. Hormones (Athens, Greece) 16(4), 388–395 (2017). https://doi.org/10.14310/horm.2002.1759

    Article  Google Scholar 

  8. J.H. Kim, H.C. Lee, S.J. Kim, S.B. Yoon, S.H. Kong, H.W. Yu, Y.J. Chai, J.Y. Choi, K.E. Lee, K.W. Lee, S.K. Min, C.S. Shin, K.J. Park, Perioperative hemodynamic instability in pheochromocytoma and sympathetic paraganglioma patients. Sci. Rep. 11(1), 18574 (2021). https://doi.org/10.1038/s41598-021-97964-3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. B.S. Aprill, A.J. Drake 3rd, D.H. Lasseter, K.M. Shakir, Silent adrenal nodules in von Hippel-Lindau disease suggest pheochromocytoma. Ann. Intern. Med. 120(6), 485–487 (1994). https://doi.org/10.7326/0003-4819-120-6-199403150-00006

    Article  CAS  PubMed  Google Scholar 

  10. N.B. Tütüncü, O. Gedik, Adrenal incidentaloma: report of 33 cases. J. surgical Oncol. 70(4), 247–250 (1999). 10.1002/(sici)1096-9098(199904)70:4<247::aid-jso9>3.0.co;2-o

    Article  Google Scholar 

  11. S.K. Kota, S.K. Kota, S. Panda, K.D. Modi, Pheochromocytoma: an uncommon presentation of an asymptomatic and biochemically silent adrenal incidentaloma. Malays. J. Med. Sci.: MJMS. 19(2), 86–91 (2012)

    PubMed  Google Scholar 

  12. M.G. Heavner, L.S. Krane, S.M. Winters, M. Mirzazadeh, Pheochromocytoma diagnosed pathologically with previous negative serum markers. J. surgical Oncol. 112(5), 492–495 (2015). https://doi.org/10.1002/jso.24031

    Article  CAS  Google Scholar 

  13. N. Sundahl, S. Van Slycke, N. Brusselaers, A rare case of clinically and biochemically silent giant right pheochromocytoma: case report and review of literature. Acta chirurgica Belgica. 116(4), 239–242 (2016). https://doi.org/10.1080/00015458.2016.1139838

    Article  PubMed  Google Scholar 

  14. H. Turkova, T. Prodanov, M. Maly, V. Martucci, K. Adams, J. Widimsky Jr., C.C. Chen, A. Ling, E. Kebebew, C.A. Stratakis, T. Fojo, K. Pacak, Characteristics and outcomes of metastatic SDHB and sporadic pheochromocytoma/paraganglioma: An national institutes of health study. Endocr. Pract.: Off. J. Am. Coll. Endocrinol. Am. Assoc. Clin. Endocrinologists. 22(3), 302–314 (2016). https://doi.org/10.4158/ep15725.or

    Article  Google Scholar 

  15. L. Petramala, A. Concistrè, F. Olmati, V. Saraceno, G. Iannucci, A. Ciardi, G. De Toma, C. Letizia, Silent Adrenal Pheochromocytoma Coexistent with Corticomedullary Hyperplasia: A Case Incidentally Discovered. Eur. J. case Rep. Intern. Med. 4(10), 000714 (2017). https://doi.org/10.12890/2017_000714

    Article  PubMed  PubMed Central  Google Scholar 

  16. S. Kumar, K.M. Parmar, D. Aggarwal, K. Jhangra: Simple adrenal cyst masquerading clinically silent giant cystic pheochromocytoma. BMJ case reports 12(9) (2019). https://doi.org/10.1136/bcr-2019-230730

  17. R.Z. El-Doueihi, I. Salti, M. Maroun-Aouad, A. El Hajj, Bilateral biochemically silent pheochromocytoma, not silent after all. Urol. Case Rep. 24, 100876 (2019). https://doi.org/10.1016/j.eucr.2019.100876

    Article  PubMed  PubMed Central  Google Scholar 

  18. K.M.A. Dreijerink, J.A. Rijken, C.J. Compaijen, H. Timmers, A.N.A. van der Horst-Schrivers, R.S. van Leeuwaarde, P.S. van Dam, C.R. Leemans, E. van Dam, C. Dickhoff, C.J. Dommering, P. de Graaf, G.J.C. Zwezerijnen, P. van der Valk, C.W. Menke-Van der Houven van Oordt, E.F. Hensen, E.P.M. Corssmit, E.M.W. Eekhoff, Biochemically Silent Sympathetic Paraganglioma, Pheochromocytoma, or Metastatic Disease in SDHD Mutation Carriers. J. Clin. Endocrinol. Metab. 104(11), 5421–5426 (2019). https://doi.org/10.1210/jc.2019-00202

    Article  PubMed  Google Scholar 

  19. A. Montebello, E. Ceci Bonello, M. Giordano Imbroll, M. Gruppetta, Biochemically silent phaeochromocytoma presenting with non-specific loin pain. BMJ case reports 14(8) (2021). https://doi.org/10.1136/bcr-2021-244258

  20. H.P.H. Neumann, W.F. Young Jr., C. Eng, Pheochromocytoma and Paraganglioma. N. Engl. J. Med. 381(6), 552–565 (2019). https://doi.org/10.1056/NEJMra1806651

    Article  CAS  PubMed  Google Scholar 

  21. J.W. Lenders, Q.Y. Duh, G. Eisenhofer, A.P. Gimenez-Roqueplo, S.K. Grebe, M.H. Murad, M. Naruse, K. Pacak, W.F. Young Jr,, Pheochromocytoma and paraganglioma: an endocrine society clinical practice guideline. J. Clin. Endocrinol. Metab. 99(6), 1915–1942 (2014). https://doi.org/10.1210/jc.2014-1498

    Article  CAS  PubMed  Google Scholar 

  22. M. Isaacs, P. Lee,, Preoperative alpha-blockade in phaeochromocytoma and paraganglioma: is it always necessary. Clin. Endocrinol. 86(3), 309–314 (2017). https://doi.org/10.1111/cen.13284

    Article  CAS  Google Scholar 

  23. H. Groeben, B.J. Nottebaum, P.F. Alesina, A. Traut, H.P. Neumann, M.K. Walz,, Perioperative α-receptor blockade in phaeochromocytoma surgery: an observational case series. Br. J. Anaesth. 118(2), 182–189 (2017). https://doi.org/10.1093/bja/aew392

    Article  CAS  PubMed  Google Scholar 

  24. P.F. Plouin, L. Amar, O.M. Dekkers, M. Fassnacht, A.P. Gimenez-Roqueplo, J.W. Lenders, C. Lussey-Lepoutre, O. Steichen, European Society of Endocrinology Clinical Practice Guideline for long-term follow-up of patients operated on for a phaeochromocytoma or a paraganglioma. Eur. J. Endocrinol. 174(5), G1–g10 (2016). https://doi.org/10.1530/eje-16-0033

    Article  CAS  PubMed  Google Scholar 

  25. H.J. Timmers, K. Pacak, T.T. Huynh, M. Abu-Asab, M. Tsokos, M.J. Merino, B.E. Baysal, K.T. Adams, G. Eisenhofer,, Biochemically silent abdominal paragangliomas in patients with mutations in the succinate dehydrogenase subunit B gene. J. Clin. Endocrinol. Metab. 93(12), 4826–4832 (2008). https://doi.org/10.1210/jc.2008-1093

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Author notes

  1. Georgia Ntali

    Present address: Department of Endocrinology, Diabetes and Metabolism, ‘Evangelismos’ General Hospital of Athens, Athens, Greece

Authors and Affiliations

  1. Unit of Endocrinology, and Diabetes Center, ‘G. Gennimatas’ General Hospital of Athens, Athens, Greece

    Athanasios Fountas, Georgia Kanti, Spyridoula Glycofridi, Athanasia Kalantzi, Irene Giagourta, Athina Markou, Theodora Kounadi & Labrini Papanastasiou

  2. Department of Endocrinology, University Hospital of Ioannina, Ioannina, Greece

    Maria A. Christou & Stelios Tigas

  3. Department of Endocrinology and Diabetes, ‘Alexandra’ Hospital, Athens, Greece

    Georgia Ntali

  4. Third Department of Surgery, ‘G. Gennimatas’ General Hospital of Athens, Athens, Greece

    Chrysanthi Aggeli & George N. Zografos

  5. Department of Anesthesiology, ‘G. Gennimatas’ General Hospital of Athens, Athens, Greece

    Eleftheria Saoulidou & Antonia Dimakopoulou

Authors
  1. Athanasios Fountas
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Georgia Kanti
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Spyridoula Glycofridi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Maria A. Christou
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Athanasia Kalantzi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Irene Giagourta
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Athina Markou
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Georgia Ntali
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Chrysanthi Aggeli
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Eleftheria Saoulidou
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Antonia Dimakopoulou
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. George N. Zografos
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Theodora Kounadi
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Stelios Tigas
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Labrini Papanastasiou
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Labrini Papanastasiou.

Ethics declarations

Conflict of interest

The authors declare no competing interests.

Ethics approval

The study was registered with and approved by the ‘G. Gennimatas’ General Hospital of Athens ethics committee and its reporting conforms to the Guidelines for Good Clinical Practice, Declaration of Helsinki.

Informed consent

Informed consent was obtained from all patients participating in the study.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Fountas, A., Kanti, G., Glycofridi, S. et al. Pre- and peri-operative characteristics, complications and outcomes of patients with biochemically silent pheochromocytomas; a case series. Endocrine 78, 570–579 (2022). https://doi.org/10.1007/s12020-022-03182-w

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12020-022-03182-w

Keywords

Search

Navigation