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Absence of immunostaining for growth hormone in a subset of patients with acromegaly

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Abstract

The presence of growth hormone (GH) immunostaining in patients who lack the biochemical and clinical features of acromegaly has been described. In contrast, there is little information on the absence of GH immunostaining in patients with acromegaly. We describe five patients with acromegaly with no intratumoral immunostaining for GH. We reviewed all patients undergoing surgery for acromegaly. Out of 136 patients treated surgically in a 10 year period, five (3.7 %) were found to have no GH immunostaining on repetitive testing at pathological examination. Their pathology slides were re-examined by an experienced neuropathologist, along with twenty nonfunctional pituitary tumors and ten GH-positive adenomas as negative and positive controls, respectively. All patients had clinical features consistent with acromegaly and elevated baseline insulin-like growth factor-1 (IGF-1) and GH. All patients had no immunostaining for GH on multiple inspections. Of twenty patients with nonfunctional tumors, two had ≤25 % staining for GH in a scattered and non-coherent pattern and the rest were negative. In all ten positive control patients >25 % of the tumor cells stained diffusely for GH. All five patients achieved biochemical remission at 1.4–8 years post-op using a combination of primary surgery alone (n = 1), repeat surgery (n = 1), radiotherapy (n = 3) and/or medical therapy (n = 2). GH immunostaining of an adenoma may not be sufficient to confirm the diagnosis of acromegaly. All patients in our small series achieved remission by multimodality therapies. Further studies are needed to evaluate the significance of our observation and whether this subset of patients follows a distinct long term clinical course.

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References

  1. Sherlock M, Ayuk J, Tomlinson JW, Toogood AA, Aragon-Alonso A, Sheppard MC, Bates AS, Stewart PM (2010) Mortality in patients with pituitary disease. Endocr Rev 31(3):301–342. doi:10.1210/er.2009-0033

    Article  PubMed  Google Scholar 

  2. Bengtsson BA, Eden S, Ernest I, Oden A, Sjogren B (1988) Epidemiology and long-term survival in acromegaly. A study of 166 cases diagnosed between 1955 and 1984. Acta Med Scand 223(4):327–335

    Article  CAS  PubMed  Google Scholar 

  3. Rajasoorya C, Holdaway IM, Wrightson P, Scott DJ, Ibbertson HK (1994) Determinants of clinical outcome and survival in acromegaly. Clin Endocrinol (Oxf) 41(1):95–102

    Article  CAS  Google Scholar 

  4. Orme SM, McNally RJ, Cartwright RA, Belchetz PE (1998) Mortality and cancer incidence in acromegaly: a retrospective cohort study. United Kingdom Acromegaly Study Group. J Clin Endocrinol Metab 83(8):2730–2734

    CAS  PubMed  Google Scholar 

  5. Dekkers OM, Biermasz NR, Pereira AM, Romijn JA, Vandenbroucke JP (2008) Mortality in acromegaly: a metaanalysis. J Clin Endocrinol Metab 93(1):61–67. doi:10.1210/jc.2007-1191

    Article  CAS  PubMed  Google Scholar 

  6. Kauppinen-Makelin R, Sane T, Reunanen A, Valimaki MJ, Niskanen L, Markkanen H, Loyttyniemi E, Ebeling T, Jaatinen P, Laine H, Nuutila P, Salmela P, Salmi J, Stenman UH, Viikari J, Voutilainen E (2005) A nationwide survey of mortality in acromegaly. J Clin Endocrinol Metab 90(7):4081–4086. doi:10.1210/jc.2004-1381

    Article  PubMed  Google Scholar 

  7. Sidhaye A, Burger P, Rigamonti D, Salvatori R (2005) Giant somatotrophinoma without acromegalic features: more “quiet” than “silent”: case report. Neurosurgery 56(5), E1154; discussion E1154

  8. Baldeweg SE, Pollock JR, Powell M, Ahlquist J (2005) A spectrum of behaviour in silent corticotroph pituitary adenomas. Br J Neurosurg 19(1):38–42. doi:10.1080/02688690500081230

    Article  CAS  PubMed  Google Scholar 

  9. Kovacs K, Lloyd R, Horvath E, Asa SL, Stefaneanu L, Killinger DW, Smyth HS (1989) Silent somatotroph adenomas of the human pituitary. A morphologic study of three cases including immunocytochemistry, electron microscopy, in vitro examination, and in situ hybridization. Am J Pathol 134(2):345–353

    CAS  PubMed Central  PubMed  Google Scholar 

  10. Klibanski A, Zervas NT, Kovacs K, Ridgway EC (1987) Clinically silent hypersecretion of growth hormone in patients with pituitary tumors. J Neurosurg 66(6):806–811. doi:10.3171/jns.1987.66.6.0806

    Article  CAS  PubMed  Google Scholar 

  11. Sakharova AA, Dimaraki EV, Chandler WF, Barkan AL (2005) Clinically silent somatotropinomas may be biochemically active. J Clin Endocrinol Metab 90(4):2117–2121. doi:10.1210/jc.2004-0875

    Article  CAS  PubMed  Google Scholar 

  12. Horvath E, Kovacs K, Killinger DW, Smyth HS, Platts ME, Singer W (1980) Silent corticotropic adenomas of the human pituitary gland: a histologic, immunocytologic, and ultrastructural study. Am J Pathol 98(3):617–638

    CAS  PubMed Central  PubMed  Google Scholar 

  13. Yamada S, Sano T, Stefaneanu L, Kovacs K, Aiba T, Sawano S, Shishiba Y (1993) Endocrine and morphological study of a clinically silent somatotroph adenoma of the human pituitary. J Clin Endocrinol Metab 76(2):352–356

    CAS  PubMed  Google Scholar 

  14. Trouillas J, Sassolas G, Loras B, Velkeniers B, Raccurt M, Chotard L, Berthezene F, Tourniaire J, Girod C (1991) Somatotropic adenomas without acromegaly. Pathol Res Pract 187(8):943–949

    Article  CAS  PubMed  Google Scholar 

  15. Lloyd RV, Cano M, Chandler WF, Barkan AL, Horvath E, Kovacs K (1989) Human growth hormone and prolactin secreting pituitary adenomas analyzed by in situ hybridization. Am J Pathol 134(3):605–613

    CAS  PubMed Central  PubMed  Google Scholar 

  16. Lonser RR, Ksendzovsky A, Wind JJ, Vortmeyer AO, Oldfield EH (2012) Prospective evaluation of the characteristics and incidence of adenoma-associated dural invasion in Cushing disease. J Neurosurg 116(2):272–279. doi:10.3171/2011.8.JNS11456

    Article  PubMed  Google Scholar 

  17. Wade AN, Baccon J, Grady MS, Judy KD, O’Rourke DM, Snyder PJ (2011) Clinically silent somatotroph adenomas are common. Eur J Endocrinol 165(1):39–44. doi:10.1530/EJE-11-0216

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  18. Kovacs K (1988) Pathology of growth hormone excess. Pathol Res Pract 183(5):565–568. doi:10.1016/S0344-0338(88)80011-6

    Article  CAS  PubMed  Google Scholar 

  19. Hofland LJ, van Koetsveld PM, Verleun TM, Lamberts SW (1989) Glycoprotein hormone alpha-subunit and prolactin release by cultured pituitary adenoma cells from acromegalic patients: correlation with GH release. Clin Endocrinol (Oxf) 30(6):601–611

    Article  CAS  Google Scholar 

  20. Trouillas J, Girod C, Lheritier M, Claustrat B, Dubois MP (1980) Morphological and biochemical relationships in 31 human pituitary adenomas with acromegaly. Virchows Arch A Pathol Anat Histol 389(2):127–142

    Article  CAS  PubMed  Google Scholar 

  21. Klijn JG, Lamberts SW, de Jong FH, van Dongen KJ, Birkenhager JC (1980) Interrelationships between tumour size, age, plasma growth hormone and incidence of extrasellar extension in acromegalic patients. Acta Endocrinol (Copenh) 95(3):289–297

    CAS  Google Scholar 

  22. Herzog T, Schlote W, Lorenz R, Jungmann E, Althoff PH (1993) Pituitary adenomas: serum hormone levels and immunohistochemical staining for ACTH GH and prolactin. Clin Neuropathol 12(2):117–120

    CAS  PubMed  Google Scholar 

  23. Ho DM, Hsu CY, Ting LT, Chiang H (2001) Plurihormonal pituitary adenomas: immunostaining of all pituitary hormones is mandatory for correct classification. Histopathology 39(3):310–319

    Article  CAS  PubMed  Google Scholar 

  24. Oka H, Kameya T, Sato Y, Naritaka H, Kawano N (1999) Significance of growth hormone-releasing hormone receptor mRNA in non-neoplastic pituitary and pituitary adenomas: a study by RT-PCR and in situ hybridization. J Neurooncol 41(3):197–204

    Article  CAS  PubMed  Google Scholar 

  25. Saeger W, Uhlig H, Baz E, Fehr S, Ludecke DK (1991) In situ hybridization for different mRNA in GH-secreting and in inactive pituitary adenomas. Pathol Res Pract 187(5):559–563

    Article  CAS  PubMed  Google Scholar 

  26. Figarella-Branger D, Trouillas J (2006) The new WHO classification of human pituitary tumors: comments. Acta Neuropathol 111(1):71–72. doi:10.1007/s00401-005-1099-0

    Article  PubMed  Google Scholar 

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Acknowledgments

We wish to thank the Melvin Burkhardt chair in neurosurgical oncology and the Karen Colina Wilson research endowment within the Brain Tumor and Neuro-oncology Center at the Cleveland Clinic Foundation (RJW). We are grateful, as well, to Christine Moore for her help in the preparation of this manuscript.

Conflict of interest

Each of the authors declares that he or she had no conflict of interest to report.

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Authors and Affiliations

  1. Department of Neurological Surgery, Cleveland Clinic, Cleveland, OH, 44195, USA

    Jason L. Schroeder, Alejandro M. Spiotta & Robert J. Weil

  2. Department of Endocrinology, Diabetes and Metabolism, Cleveland Clinic, Cleveland, OH, 44195, USA

    Maria Fleseriu & Amir H. Hamrahian

  3. Department of Anatomic Pathology, Cleveland Clinic, Cleveland, OH, 44195, USA

    Richard A. Prayson

  4. Rose Ella Burkhardt Brain Tumor and Neuro-Oncology Center, Desk S-70, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH, 44195, USA

    Jason L. Schroeder & Robert J. Weil

  5. ND4-40 LRI, Cleveland, OH, USA

    Robert J. Weil

Authors
  1. Jason L. Schroeder
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  2. Alejandro M. Spiotta
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  3. Maria Fleseriu
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  4. Richard A. Prayson
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  5. Amir H. Hamrahian
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  6. Robert J. Weil
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Corresponding author

Correspondence to Jason L. Schroeder.

Additional information

Jason L. Schroeder and Alejandro M. Spiotta: contributed equally to this study.

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Schroeder, J.L., Spiotta, A.M., Fleseriu, M. et al. Absence of immunostaining for growth hormone in a subset of patients with acromegaly. Pituitary 17, 103–108 (2014). https://doi.org/10.1007/s11102-013-0474-4

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  • DOI: https://doi.org/10.1007/s11102-013-0474-4

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