Skip to main content

Advertisement

SpringerLink
Log in

Aggressive pituitary tumors in the young and elderly

  • Published:
Reviews in Endocrine and Metabolic Disorders Aims and scope Submit manuscript

Abstract

Aggressive pituitary tumors (APTs) represent rare pituitary adenomas (PAs) with local invasion of surrounding tissues, increased risk for multiple recurrence, rapid tumor growth, or resistance to standard therapies. The most common APTs in children and adolescents are giant prolactinomas and somatotropinomas. Few cases of Crooke’s cell adenomas, silent corticotroph adenomas and pituitary carcinomas have also been reported in the literature. Pediatric patients with APTs have higher risk of harboring germline genetic defects, most commonly in the MEN1 and AIP genes. Since certain genetic defects confer a more aggressive behavior to PAs, genetic testing should be considered in tumors with young onset and positive family history. The management of pediatric APTs involves usually a combination of standard therapies (surgical, medical, radiation). Newer agents, such as temozolomide, have been used in few cases of pediatric pituitary tumors with promising results. In the elderly, PAs are more commonly non-functioning. Their management often poses dilemmas given the coexistence of age-related comorbidities. However, standard surgical treatment and temozolomide seem to be safe and well tolerated in elderly patients.

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.

Similar content being viewed by others

References

  1. Raappana A, Koivukangas J, Ebeling T, Pirila T. Incidence of pituitary adenomas in northern Finland in 1992-2007. J Clin Endocrinol Metab. 2010;95:4268–75. https://doi.org/10.1210/jc.2010-0537.

    Article  CAS  PubMed  Google Scholar 

  2. Ezzat S, Asa SL, Couldwell WT, Barr CE, Dodge WE, Vance ML, et al. The prevalence of pituitary adenomas: a systematic review. Cancer. 2004;101:613–9. https://doi.org/10.1002/cncr.20412.

    Article  PubMed  Google Scholar 

  3. Agustsson TT, Baldvinsdottir T, Jonasson JG, Olafsdottir E, Steinthorsdottir V, Sigurdsson G, et al. The epidemiology of pituitary adenomas in Iceland, 1955-2012: a nationwide population-based study. Eur J Endocrinol. 2015;173:655–64. https://doi.org/10.1530/EJE-15-0189.

    Article  CAS  PubMed  Google Scholar 

  4. Daly AF, Rixhon M, Adam C, Dempegioti A, Tichomirowa MA, Beckers A. High prevalence of pituitary adenomas: a cross-sectional study in the province of Liege, Belgium. J Clin Endocrinol Metab. 2006;91:4769–75. https://doi.org/10.1210/jc.2006-1668.

    Article  CAS  PubMed  Google Scholar 

  5. Keil MF, Stratakis CA. Pituitary tumors in childhood: update of diagnosis, treatment and molecular genetics. Expert Rev Neurother. 2008;8:563–74. https://doi.org/10.1586/14737175.8.4.563.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Yoo F, Kuan EC, Heaney AP, Bergsneider M, Wang MB. Corticotrophic pituitary carcinoma with cervical metastases: case series and literature review. Pituitary. 2018;21:290–301. https://doi.org/10.1007/s11102-018-0872-8.

    Article  CAS  PubMed  Google Scholar 

  7. WHO. Classifcation of tumours of endocrine organs. (IARC Publications, Lyon, 2017).

  8. Chatzellis E, Alexandraki KI, Androulakis II, Kaltsas G. Aggressive pituitary tumors. Neuroendocrinology. 2015;101:87–104. https://doi.org/10.1159/000371806.

  9. Raverot G, Burman P, McCormack A, Heaney A, Petersenn S, Popovic V, et al. European Society of Endocrinology Clinical Practice Guidelines for the management of aggressive pituitary tumours and carcinomas. Eur J Endocrinol. 2018;178:G1–G24. https://doi.org/10.1530/EJE-17-0796.

    Article  CAS  Google Scholar 

  10. Trouillas J, Roy P, Sturm N, Dantony E, Cortet-Rudelli C, Viennet G, et al. A new prognostic clinicopathological classification of pituitary adenomas: a multicentric case-control study of 410 patients with 8 years post-operative follow-up. Acta Neuropathol. 2013;126:123–35. https://doi.org/10.1007/s00401-013-1084-y.

    Article  Google Scholar 

  11. McCormack A, Dekkers OM, Petersenn S, Popovic V, Trouillas J, Raverot G, et al. Treatment of aggressive pituitary tumours and carcinomas: results of a European Society of Endocrinology (ESE) survey 2016. Eur J Endocrinol. 2018;178:265–76. https://doi.org/10.1530/EJE-17-0933.

    Article  CAS  Google Scholar 

  12. Trouillas J, et al. Aggressive pituitary tumours and carcinomas: two sides of the same coin? Eur J Endocrinol. 2018;178:C7–9. https://doi.org/10.1530/EJE-18-0250.

    Article  CAS  Google Scholar 

  13. Maiter D, Delgrange E. Therapy of endocrine disease: the challenges in managing giant prolactinomas. Eur J Endocrinol. 2014;170:R213–27. https://doi.org/10.1530/EJE-14-0013.

    Article  CAS  PubMed  Google Scholar 

  14. Shrivastava RK, Arginteanu MS, King WA, Post KD. Giant prolactinomas: clinical management and long-term follow up. J Neurosurg. 2002;97:299–306. https://doi.org/10.3171/jns.2002.97.2.0299.

    Article  PubMed  Google Scholar 

  15. Delgrange E, et al. Giant prolactinomas in women. Eur J Endocrinol. 2014;170:31–8. https://doi.org/10.1530/EJE-13-0503.

    Article  CAS  PubMed  Google Scholar 

  16. Jennings JE, Georgitsi M, Holdaway I, Daly AF, Tichomirowa M, Beckers A, et al. Aggressive pituitary adenomas occurring in young patients in a large Polynesian kindred with a germline R271W mutation in the AIP gene. Eur J Endocrinol. 2009;161:799–804. https://doi.org/10.1530/EJE-09-0406.

    Article  CAS  PubMed  Google Scholar 

  17. de Castro LF, Magalhães Gonzaga MF, Naves LA, Luiz Mendonça J, Oton de Lima B, Casulari LA. Beneficial effects of high doses of Cabergoline in the treatment of Giant Prolactinoma resistant to dopamine agonists: a case report with a 21-year follow-up. Horm Res Paediatr. 2018;89:63–70. https://doi.org/10.1159/000479511.

    Article  CAS  PubMed  Google Scholar 

  18. Wu ZB, et al. Bromocriptine treatment of invasive giant prolactinomas involving the cavernous sinus: results of a long-term follow up. J Neurosurg. 2006;104:54–61. https://doi.org/10.3171/jns.2006.104.1.54.

    Article  CAS  PubMed  Google Scholar 

  19. Huang HY, Zhai W, Tang H, Hui GZ, Wu ZB. Cabergoline for the treatment of bromocriptine-resistant invasive giant prolactinomas. Endocrine. 2018;62:464–9. https://doi.org/10.1007/s12020-018-1702-5.

    Article  CAS  PubMed  Google Scholar 

  20. Semple P, Fieggen G, Parkes J, Levitt N. Giant prolactinomas in adolescence: an uncommon cause of blindness. Childs Nerv Syst. 2007;23:213–7. https://doi.org/10.1007/s00381-006-0177-5.

    Article  PubMed  Google Scholar 

  21. Salenave S, Ancelle D, Bahougne T, Raverot G, Kamenický P, Bouligand J, et al. Macroprolactinomas in children and adolescents: factors associated with the response to treatment in 77 patients. J Clin Endocrinol Metab. 2015;100:1177–86. https://doi.org/10.1210/jc.2014-3670.

    Article  CAS  PubMed  Google Scholar 

  22. Cook RJ, Uttley D, Wilkins PR, Archer DJ, Bell BA. Prolactinomas in men masquerading as invasive skull base tumours. Br J Neurosurg. 1994;8:51–5.

    Article  Google Scholar 

  23. Rix M, et al. Cushing's disease in childhood as the first manifestation of multiple endocrine neoplasia syndrome type 1. Eur J Endocrinol. 2004;151:709–15.

    Article  CAS  Google Scholar 

  24. Makri A, et al. Children with MEN1 gene mutations may present first (and at a young age) with Cushing disease. Clin Endocrinol. 2018;89:437–43. https://doi.org/10.1111/cen.13796.

    Article  CAS  Google Scholar 

  25. Stratakis CA, Schussheim DH, Freedman SM, Keil MF, Pack SD, Agarwal SK, et al. Pituitary macroadenoma in a 5-year-old: an early expression of multiple endocrine neoplasia type 1. J Clin Endocrinol Metab. 2000;85:4776–80. https://doi.org/10.1210/jcem.85.12.7064.

    Article  CAS  PubMed  Google Scholar 

  26. Melmed S, Casanueva FF, Hoffman AR, Kleinberg DL, Montori VM, Schlechte JA, et al. Diagnosis and treatment of hyperprolactinemia: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011;96:273–88. https://doi.org/10.1210/jc.2010-1692.

    Article  CAS  PubMed  Google Scholar 

  27. Yu C, Wu Z, Gong J. Combined treatment of invasive giant prolactinomas. Pituitary. 2005;8:61–5. https://doi.org/10.1007/s11102-005-5087-0.

    Article  CAS  PubMed  Google Scholar 

  28. Acharya SV, Gopal RA, Menon PS, Bandgar TR, Shah NS. Giant prolactinoma and effectiveness of medical management. Endocr Pract. 2010;16:42–6. https://doi.org/10.4158/EP09221.OR.

    Article  PubMed  Google Scholar 

  29. Felker J, Patterson B, Wrubel D, Janss A. Successful treatment of a child with a prolactin secreting macroadenoma with temozolomide. J Pediatr Endocrinol Metab. 2016;29:1413–5. https://doi.org/10.1515/jpem-2016-0159.

    Article  CAS  PubMed  Google Scholar 

  30. Lasolle H, Cortet C, Castinetti F, Cloix L, Caron P, Delemer B, et al. Temozolomide treatment can improve overall survival in aggressive pituitary tumors and pituitary carcinomas. Eur J Endocrinol. 2017;176:769–77. https://doi.org/10.1530/EJE-16-0979.

    Article  CAS  PubMed  Google Scholar 

  31. Whitelaw BC, Dworakowska D, Thomas NW, Barazi S, Riordan-Eva P, King AP, et al. Temozolomide in the management of dopamine agonist-resistant prolactinomas. Clin Endocrinol. 2012;76:877–86. https://doi.org/10.1111/j.1365-2265.2012.04373.x.

    Article  CAS  Google Scholar 

  32. Rostomyan L, Daly AF, Petrossians P, Nachev E, Lila AR, Lecoq AL, et al. Clinical and genetic characterization of pituitary gigantism: an international collaborative study in 208 patients. Endocr Relat Cancer. 2015;22:745–57. https://doi.org/10.1530/ERC-15-0320.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Personnier C, et al. Clinical features and treatment of pediatric somatotropinoma: case study of an aggressive tumor due to a new AIP mutation and extensive literature review. Horm Res Paediatr. 2011;75:392–402. https://doi.org/10.1159/000327831.

    Article  CAS  PubMed  Google Scholar 

  34. Stratakis CA, Tichomirowa MA, Boikos S, Azevedo MF, Lodish M, Martari M, et al. The role of germline AIP, MEN1, PRKAR1A, CDKN1B and CDKN2C mutations in causing pituitary adenomas in a large cohort of children, adolescents, and patients with genetic syndromes. Clin Genet. 2010;78:457–63. https://doi.org/10.1111/j.1399-0004.2010.01406.x.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Katznelson L, Laws ER Jr, Melmed S, Molitch ME, Murad MH, Utz A, et al. Acromegaly: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2014;99:3933–51. https://doi.org/10.1210/jc.2014-2700.

    Article  CAS  PubMed  Google Scholar 

  36. Chiloiro S, et al. Pasireotide and Pegvisomant combination treatment in acromegaly resistant to second-line therapies: a longitudinal study. J Clin Endocrinol Metab. 2019;104:5478–82. https://doi.org/10.1210/jc.2019-00825.

    Article  PubMed  Google Scholar 

  37. Colao A, et al. Pasireotide versus octreotide in acromegaly: a head-to-head superiority study. J Clin Endocrinol Metab. 2014;99:791–9. https://doi.org/10.1210/jc.2013-2480.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Gadelha MR, Bronstein MD, Brue T, Coculescu M, Fleseriu M, Guitelman M, et al. Pasireotide versus continued treatment with octreotide or lanreotide in patients with inadequately controlled acromegaly (PAOLA): a randomised, phase 3 trial. Lancet Diabetes Endocrinol. 2014;2:875–84. https://doi.org/10.1016/S2213-8587(14)70169-X.

    Article  CAS  PubMed  Google Scholar 

  39. Daly, A. et al. AIP-mutated acromegaly resistant to first-generation somatostatin analogs: long-term control with pasireotide LAR in two patients. Endocr Connect, doi:https://doi.org/10.1530/EC-19-0004 (2019).

  40. Gupta P, Rai A, Mukherjee KK, Sachdeva N, Radotra BD, Punia RPS, et al. Imatinib inhibits GH secretion from Somatotropinomas. Front Endocrinol (Lausanne). 2018;9:453. https://doi.org/10.3389/fendo.2018.00453.

    Article  Google Scholar 

  41. Dutta P, Reddy KS, Rai A, Madugundu AK, Solanki HS, Bhansali A, et al. Surgery, Octreotide, Temozolomide, Bevacizumab, radiotherapy, and Pegvisomant treatment of an AIP MutationPositive child. J Clin Endocrinol Metab. 2019;104:3539–44. https://doi.org/10.1210/jc.2019-00432.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Nozieres C, et al. Sporadic and genetic forms of paediatric somatotropinoma: a retrospective analysis of seven cases and a review of the literature. Orphanet J Rare Dis. 2011;6:67. https://doi.org/10.1186/1750-1172-6-67.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Crooke AC, Purves HD, Russell DS, Thornton KR. Hyalinization and basophil adenomata in the pituitary gland. Proc R Soc Med. 1956;49:1014–20.

    CAS  PubMed  Google Scholar 

  44. George DH, Scheithauer BW, Kovacs K, Horvath E, Young WF Jr, Lloyd RV, et al. Crooke's cell adenoma of the pituitary: an aggressive variant of corticotroph adenoma. Am J Surg Pathol. 2003;27:1330–6.

    Article  Google Scholar 

  45. Oldfield EH, Vance ML, Louis RG, Pledger CL, Jane JA Jr, Lopes MB. Crooke's changes in Cushing's syndrome depends on degree of Hypercortisolism and individual susceptibility. J Clin Endocrinol Metab. 2015;100:3165–71. https://doi.org/10.1210/JC.2015-2493.

    Article  CAS  PubMed  Google Scholar 

  46. Di Ieva A, et al. Crooke's cell tumors of the pituitary. Neurosurgery. 2015;76:616–22. https://doi.org/10.1227/NEU.0000000000000657.

    Article  PubMed  Google Scholar 

  47. Daly AF, Yuan B, Fina F, Caberg JH, Trivellin G, Rostomyan L, et al. Somatic mosaicism underlies X-linked acrogigantism syndrome in sporadic male subjects. Endocr Relat Cancer. 2016;23:221–33. https://doi.org/10.1530/ERC-16-0082.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Giri D, Roncaroli F, Sinha A, Didi M, Senniappan S. Silent Crooke's cell corticotroph adenoma of the pituitary gland presenting as delayed puberty. Endocrinol Diabetes Metab Case Rep. 2017. https://doi.org/10.1530/EDM-16-0153(2017).

  49. Felix IA, Horvath E, Kovacs K. Massive Crooke's hyalinization in corticotroph cell adenomas of the human pituitary. A histological, immunocytological, and electron microscopic study of three cases. Acta Neurochir. 1981;58:235–43. https://doi.org/10.1007/bf01407130.

    Article  CAS  PubMed  Google Scholar 

  50. Holthouse DJ, Robbins PD, Kahler R, Knuckey N, Pullan P. Corticotroph pituitary carcinoma: case report and literature review. Endocr Pathol. 2001;12:329–41.

    Article  CAS  Google Scholar 

  51. Kovacs GL, et al. ACTH-secreting Crooke cell carcinoma of the pituitary. Eur J Clin Investig. 2013;43:20–6. https://doi.org/10.1111/eci.12010.

    Article  Google Scholar 

  52. Jahangiri A, et al. A comprehensive long-term retrospective analysis of silent corticotrophic adenomas vs hormone-negative adenomas. Neurosurgery. 2013;73:8–17; discussion 17–18. https://doi.org/10.1227/01.neu.0000429858.96652.1e.

    Article  PubMed  Google Scholar 

  53. Nishioka H, Inoshita N, Sano T, Fukuhara N, Yamada S. Correlation between histological subtypes and MRI findings in clinically nonfunctioning pituitary adenomas. Endocr Pathol. 2012;23:151–6. https://doi.org/10.1007/s12022-012-9208-9.

    Article  PubMed  Google Scholar 

  54. Cohen-Inbar O, Xu Z, Lee CC, Wu CC, Chytka T, Silva D, et al. Prognostic significance of corticotroph staining in radiosurgery for non-functioning pituitary adenomas: a multicenter study. J Neuro-Oncol. 2017;135:67–74. https://doi.org/10.1007/s11060-017-2520-y.

    Article  Google Scholar 

  55. Zoli M, Faustini-Fustini M, Mazzatenta D, Marucci G, de Carlo E, Bacci A, et al. ACTH adenomas transforming their clinical expression: report of 5 cases. Neurosurg Focus. 2015;38:E15. https://doi.org/10.3171/2014.11.FOCUS14679.

    Article  PubMed  Google Scholar 

  56. Scheithauer, B. W. et al. Clinically silent corticotroph tumors of the pituitary gland. Neurosurgery 47, 723–729; discussion 729–730, doi:https://doi.org/10.1097/00006123-200009000-00039 (2000).

  57. Cho HY, Cho SW, Kim SW, Shin CS, Park KS, Kim SY. Silent corticotroph adenomas have unique recurrence characteristics compared with other nonfunctioning pituitary adenomas. Clin Endocrinol. 2010;72:648–53. https://doi.org/10.1111/j.1365-2265.2009.03673.x.

    Article  Google Scholar 

  58. Oka H, Kameya T, Sasano H, Aiba M, Kovacs K, Horvath E, et al. Pituitary choristoma composed of corticotrophs and adrenocortical cells in the Sella turcica. Virchows Arch. 1996;427:613–7.

    Article  CAS  Google Scholar 

  59. Coire CI, et al. A composite silent corticotroph pituitary adenoma with interspersed adrenocortical cells: case report. Neurosurgery. 1998;42:650–4. https://doi.org/10.1097/00006123-199803000-00039.

    Article  CAS  PubMed  Google Scholar 

  60. Guzel A, Tatli M, Senturk S, Guzel E, Cayli SR, Sav A. Pituitary carcinoma presenting with multiple metastases: case report. J Child Neurol. 2008;23:1467–71. https://doi.org/10.1177/0883073808319078.

    Article  PubMed  Google Scholar 

  61. Tysome J, Gnanalingham KK, Chopra I, Mendoza N. Intradural metastatic spinal cord compression from ACTH-secreting pituitary carcinoma. Acta Neurochir. 2004;146:1251–4. https://doi.org/10.1007/s00701-004-0350-0.

    Article  CAS  PubMed  Google Scholar 

  62. Graf CJ, Blinderman EE, Terplan KL. Pituitary carcinoma in a child with distant metastases. J Neurosurg. 1962;19:254–9. https://doi.org/10.3171/jns.1962.19.3.0254.

    Article  CAS  PubMed  Google Scholar 

  63. Balili I, Sullivan S, McKeever P, Barkan A. Pituitary carcinoma with endolymphatic sac metastasis. Pituitary. 2014;17:210–3. https://doi.org/10.1007/s11102-013-0489-x.

    Article  CAS  PubMed  Google Scholar 

  64. Vroonen L, Jaffrain-Rea ML, Petrossians P, Tamagno G, Chanson P, Vilar L, et al. Prolactinomas resistant to standard doses of cabergoline: a multicenter study of 92 patients. Eur J Endocrinol. 2012;167:651–62. https://doi.org/10.1530/EJE-12-0236.

    Article  CAS  PubMed  Google Scholar 

  65. AbdelBaki MS, Waguespack SG, Salceda V, Jones J, Stapleton SL, Baskin DS, et al. Significant response of pituitary carcinoma to carboplatin, leucovorin and fluorouracil chemotherapy: a pediatric case report and review of the literature. J Neuro-Oncol. 2017;135:213–5. https://doi.org/10.1007/s11060-017-2554-1.

    Article  Google Scholar 

  66. Kaiser FE, Orth DN, Mukai K, Oppenheimer JH. A pituitary parasellar tumor with extracranial metastases and high, partially suppressible levels of adrenocorticotropin and related peptides. J Clin Endocrinol Metab. 1983;57:649–53. https://doi.org/10.1210/jcem-57-3-649.

    Article  CAS  PubMed  Google Scholar 

  67. Lormeau B, Miossec P, Sibony M, Valensi P, Attali JR. Adrenocorticotropin-producing pituitary carcinoma with liver metastasis. J Endocrinol Investig. 1997;20:230–6. https://doi.org/10.1007/BF03346909.

    Article  CAS  Google Scholar 

  68. Iacovazzo D, Hernandez-Ramirez LC, Korbonits M. Sporadic pituitary adenomas: the role of germline mutations and recommendations for genetic screening. Expert Rev Endocrinol Metab. 2017;12:143–53. https://doi.org/10.1080/17446651.2017.1306439.

    Article  CAS  PubMed  Google Scholar 

  69. Cuny T, et al. Genetic analysis in young patients with sporadic pituitary macroadenomas: besides AIP don't forget MEN1 genetic analysis. Eur J Endocrinol. 2013;168:533–41. https://doi.org/10.1530/EJE-12-0763.

    Article  CAS  PubMed  Google Scholar 

  70. Chandrasekharappa SC, Guru SC, Manickam P, Olufemi SE, Collins FS, Emmert-Buck MR, et al. Positional cloning of the gene for multiple endocrine neoplasia-type 1. Science. 1997;276:404–7. https://doi.org/10.1126/science.276.5311.404.

    Article  CAS  PubMed  Google Scholar 

  71. Occhi G, Regazzo D, Trivellin G, Boaretto F, Ciato D, Bobisse S, et al. A novel mutation in the upstream open reading frame of the CDKN1B gene causes a MEN4 phenotype. PLoS Genet. 2013;9:e1003350. https://doi.org/10.1371/journal.pgen.1003350.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Verges B, et al. Pituitary disease in MEN type 1 (MEN1): data from the France-Belgium MEN1 multicenter study. J Clin Endocrinol Metab. 2002;87:457–65. https://doi.org/10.1210/jcem.87.2.8145.

    Article  CAS  PubMed  Google Scholar 

  73. Trouillas J, Labat-Moleur F, Sturm N, Kujas M, Heymann MF, Figarella-Branger D, et al. Pituitary tumors and hyperplasia in multiple endocrine neoplasia type 1 syndrome (MEN1): a case-control study in a series of 77 patients versus 2509 non-MEN1 patients. Am J Surg Pathol. 2008;32:534–43. https://doi.org/10.1097/PAS.0b013e31815ade45.

    Article  PubMed  Google Scholar 

  74. Giusti F, Cianferotti L, Boaretto F, Cetani F, Cioppi F, Colao A, et al. Multiple endocrine neoplasia syndrome type 1: institution, management, and data analysis of a nationwide multicenter patient database. Endocrine. 2017;58:349–59. https://doi.org/10.1007/s12020-017-1234-4.

    Article  CAS  PubMed  Google Scholar 

  75. Delemer B. MEN1 and pituitary adenomas. Ann Endocrinol (Paris). 2012;73:59–61. https://doi.org/10.1016/j.ando.2012.03.038.

    Article  CAS  Google Scholar 

  76. Hernández-Ramírez L, C F, Faucz FR, Lodish M, Pankratz N, Chittiboina P, et al. Non-syndromic Cushing's disease due to CDKN1B mutations: novel mutations and phenotypic features in a large pediatric cohort. Journal of the Endocrine Society. 2019;3:OR24–6.

    Article  Google Scholar 

  77. de Laat JM, et al. Long-term natural course of pituitary tumors in patients with MEN1: results from the DutchMEN1 study group (DMSG). J Clin Endocrinol Metab. 2015;100:3288–96. https://doi.org/10.1210/JC.2015-2015.

    Article  CAS  PubMed  Google Scholar 

  78. Subasinghe CJ, Somasundaram N, Sivatharshya P, Ranasinghe LD, Korbonits M. Giant Prolactinoma of young onset: a clue to diagnosis of MEN-1 syndrome. Case Rep Endocrinol. 2018;2018:2875074. https://doi.org/10.1155/2018/2875074.

    Article  PubMed  PubMed Central  Google Scholar 

  79. Gan HW, Bulwer C, Jeelani O, Levine MA, Korbonits M, Spoudeas HA. Treatment-resistant pediatric giant prolactinoma and multiple endocrine neoplasia type 1. Int J Pediatr Endocrinol. 2015;15:6. https://doi.org/10.1186/s13633-015-0011-5.

    Article  Google Scholar 

  80. Kontogeorgos G, Kapranos N, Tzavara I, Thalassinos N, Rologis D. Monosomy of chromosome 11 in pituitary adenoma in a patient with familial multiple endocrine neoplasia type 1. Clin Endocrinol. 2001;54:117–20. https://doi.org/10.1046/j.1365-2265.2001.01031.x.

    Article  CAS  Google Scholar 

  81. Vannucci L, Marini F, Giusti F, Ciuffi S, Tonelli F, Brandi ML. MEN1 in children and adolescents: data from patients of a regional referral center for hereditary endocrine tumors. Endocrine. 2018;59:438–48. https://doi.org/10.1007/s12020-017-1322-5.

    Article  CAS  PubMed  Google Scholar 

  82. Vierimaa O, Georgitsi M, Lehtonen R, Vahteristo P, Kokko A, Raitila A, et al. Pituitary adenoma predisposition caused by germline mutations in the AIP gene. Science. 2006;312:1228–30. https://doi.org/10.1126/science.1126100.

    Article  CAS  PubMed  Google Scholar 

  83. Daly AF, Vanbellinghen JF, Khoo SK, Jaffrain-Rea ML, Naves LA, Guitelman MA, et al. Aryl hydrocarbon receptor-interacting protein gene mutations in familial isolated pituitary adenomas: analysis in 73 families. J Clin Endocrinol Metab. 2007;92:1891–6. https://doi.org/10.1210/jc.2006-2513.

    Article  CAS  PubMed  Google Scholar 

  84. Schofl C, et al. Frequency of AIP gene mutations in young patients with acromegaly: a registry-based study. J Clin Endocrinol Metab. 2014;99:E2789–93. https://doi.org/10.1210/jc.2014-2094.

    Article  CAS  PubMed  Google Scholar 

  85. Georgitsi M, et al. Aryl hydrocarbon receptor interacting protein (AIP) gene mutation analysis in children and adolescents with sporadic pituitary adenomas. Clin Endocrinol. 2008;69:621–7. https://doi.org/10.1111/j.1365-2265.2008.03266.x.

    Article  CAS  Google Scholar 

  86. Daly AF, Tichomirowa MA, Petrossians P, Heliövaara E, Jaffrain-Rea ML, Barlier A, et al. Clinical characteristics and therapeutic responses in patients with germ-line AIP mutations and pituitary adenomas: an international collaborative study. J Clin Endocrinol Metab. 2010;95:E373–83. https://doi.org/10.1210/jc.2009-2556.

    Article  PubMed  Google Scholar 

  87. Caimari F, et al. Risk category system to identify pituitary adenoma patients with AIP mutations. J Med Genet. 2018;55:254–60. https://doi.org/10.1136/jmedgenet-2017-104957.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Naves LA, Jaffrain-Rea ML, Vêncio SA, Jacomini CZ, Casulari LA, Daly AF, et al. Aggressive prolactinoma in a child related to germline mutation in the ARYL hydrocarbon receptor interacting protein (AIP) gene. Arq Bras Endocrinol Metabol. 2010;54:761–7.

    Article  Google Scholar 

  89. Joshi K, Daly AF, Beckers A, Zacharin M. Resistant Paediatric Somatotropinomas due to AIP mutations: role of Pegvisomant. Horm Res Paediatr. 2018;90:196–202. https://doi.org/10.1159/000488856.

    Article  CAS  PubMed  Google Scholar 

  90. Trivellin G, Daly AF, Faucz FR, Yuan B, Rostomyan L, Larco DO, et al. Gigantism and acromegaly due to Xq26 microduplications and GPR101 mutation. N Engl J Med. 2014;371:2363–74. https://doi.org/10.1056/NEJMoa1408028.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Beckers A, Lodish MB, Trivellin G, Rostomyan L, Lee M, Faucz FR, et al. X-linked acrogigantism syndrome: clinical profile and therapeutic responses. Endocr Relat Cancer. 2015;22:353–67. https://doi.org/10.1530/ERC-15-0038.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Naves LA, Daly AF, Dias LA, Yuan B, Zakir JC, Barra GB, et al. Aggressive tumor growth and clinical evolution in a patient with X-linked acro-gigantism syndrome. Endocrine. 2016;51:236–44. https://doi.org/10.1007/s12020-015-0804-6.

    Article  CAS  PubMed  Google Scholar 

  93. Reincke M, Sbiera S, Hayakawa A, Theodoropoulou M, Osswald A, Beuschlein F, et al. Mutations in the deubiquitinase gene USP8 cause Cushing's disease. Nat Genet. 2015;47:31–8. https://doi.org/10.1038/ng.3166.

    Article  CAS  PubMed  Google Scholar 

  94. Ma ZY, Song ZJ, Chen JH, Wang YF, Li SQ, Zhou LF, et al. Recurrent gain-of-function USP8 mutations in Cushing's disease. Cell Res. 2015;25:306–17. https://doi.org/10.1038/cr.2015.20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Faucz FR, Tirosh A, Tatsi C, Berthon A, Hernández-Ramírez LC, Settas N, et al. Somatic USP8 gene mutations are a common cause of pediatric Cushing disease. J Clin Endocrinol Metab. 2017;102:2836–43. https://doi.org/10.1210/jc.2017-00161.

    Article  PubMed  PubMed Central  Google Scholar 

  96. Albani A, et al. The USP8 mutational status may predict long-term remission in patients with Cushing's disease. Clin Endocrinol. 2018. https://doi.org/10.1111/cen.13802.

  97. Cohen M, et al. Germline USP8 mutation associated with pediatric Cushing disease and other clinical features: a new syndrome. J Clin Endocrinol Metab. 2019. https://doi.org/10.1210/jc.2019-00697.

  98. de Kock L, Sabbaghian N, Plourde F, Srivastava A, Weber E, Bouron-Dal Soglio D, et al. Pituitary blastoma: a pathognomonic feature of germ-line DICER1 mutations. Acta Neuropathol. 2014;128:111–22. https://doi.org/10.1007/s00401-014-1285-z.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Tatsi C, Stratakis CA. Neonatal Cushing syndrome: a rare but potentially devastating disease. Clin Perinatol. 2018;45:103–18. https://doi.org/10.1016/j.clp.2017.10.002.

    Article  PubMed  Google Scholar 

  100. Foulkes WD, Priest JR, Duchaine TF. DICER1: mutations, microRNAs and mechanisms. Nat Rev Cancer. 2014;14:662–72. https://doi.org/10.1038/nrc3802.

    Article  CAS  PubMed  Google Scholar 

  101. Tatsi C, et al. Large genomic aberrations in Corticotropinomas are associated with greater aggressiveness. J Clin Endocrinol Metab. 2019;104:1792–801. https://doi.org/10.1210/jc.2018-02164.

    Article  PubMed  Google Scholar 

  102. Bi WL, Horowitz P, Greenwald NF, Abedalthagafi M, Agarwalla PK, Gibson WJ, et al. Landscape of genomic alterations in pituitary adenomas. Clin Cancer Res. 2017;23:1841–51. https://doi.org/10.1158/1078-0432.CCR-16-0790.

    Article  CAS  PubMed  Google Scholar 

  103. Gilbert MR, et al. A phase II study of temozolomide in patients with newly diagnosed supratentorial malignant glioma before radiation therapy. Neuro-Oncology. 2002;4:261–7. https://doi.org/10.1093/neuonc/4.4.261.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Cefalo G, Massimino M, Ruggiero A, Barone G, Ridola V, Spreafico F, et al. Temozolomide is an active agent in children with recurrent medulloblastoma/primitive neuroectodermal tumor: an Italian multi-institutional phase II trial. Neuro-Oncology. 2014;16:748–53. https://doi.org/10.1093/neuonc/not320.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Grill J, Geoerger B, Gesner L, Perek D, Leblond P, Cañete A, et al. Phase II study of irinotecan in combination with temozolomide (TEMIRI) in children with recurrent or refractory medulloblastoma: a joint ITCC and SIOPE brain tumor study. Neuro-Oncology. 2013;15:1236–43. https://doi.org/10.1093/neuonc/not097.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Wattson DA, et al. Outcomes of proton therapy for patients with functional pituitary adenomas. Int J Radiat Oncol Biol Phys. 2014;90:532–9. https://doi.org/10.1016/j.ijrobp.2014.06.068.

    Article  PubMed  Google Scholar 

  107. Minniti G, Clarke E, Scaringi C, Enrici RM. Stereotactic radiotherapy and radiosurgery for non-functioning and secreting pituitary adenomas. Rep Pract Oncol Radiother. 2016;21:370–8. https://doi.org/10.1016/j.rpor.2014.09.004.

    Article  PubMed  Google Scholar 

  108. Estrada J, Boronat M, Mielgo M, Magallón R, Millan I, Díez S, et al. The long-term outcome of pituitary irradiation after unsuccessful transsphenoidal surgery in Cushing's disease. N Engl J Med. 1997;336:172–7. https://doi.org/10.1056/NEJM199701163360303.

    Article  CAS  PubMed  Google Scholar 

  109. Storr HL, Plowman PN, Carroll PV, François I, Krassas GE, Afshar F, et al. Clinical and endocrine responses to pituitary radiotherapy in pediatric Cushing's disease: an effective second-line treatment. J Clin Endocrinol Metab. 2003;88:34–7. https://doi.org/10.1210/jc.2002-021032.

    Article  CAS  PubMed  Google Scholar 

  110. Xu Z, Lee Vance M, Schlesinger D, Sheehan JP. Hypopituitarism after stereotactic radiosurgery for pituitary adenomas. Neurosurgery. 2013;72(630–637):636–7. https://doi.org/10.1227/NEU.0b013e3182846e44.

    Article  Google Scholar 

  111. Ghostine S, Ghostine MS, Johnson WD. Radiation therapy in the treatment of pituitary tumors. Neurosurg Focus. 2008;24:E8. https://doi.org/10.3171/FOC/2008/24/5/E8.

    Article  PubMed  Google Scholar 

  112. Hladik D, Tapio S. Effects of ionizing radiation on the mammalian brain. Mutat Res. 2016;770:219–30. https://doi.org/10.1016/j.mrrev.2016.08.003.

    Article  CAS  PubMed  Google Scholar 

  113. Kovacs K, Ryan N, Horvath E, Singer W, Ezrin C. Pituitary adenomas in old age. J Gerontol. 1980;35:16–22.

    Article  CAS  Google Scholar 

  114. Locatelli M, Bertani G, Carrabba G, Rampini P, Zavanone M, Caroli M, et al. The trans-sphenoidal resection of pituitary adenomas in elderly patients and surgical risk. Pituitary. 2013;16:146–51. https://doi.org/10.1007/s11102-012-0390-z.

    Article  CAS  PubMed  Google Scholar 

  115. Liu J, Li C, Xiao Q, Gan C, Chen X, Sun W, et al. Comparison of pituitary adenomas in elderly and younger adults: clinical characteristics, surgical outcomes, and prognosis. J Am Geriatr Soc. 2015;63:1924–30. https://doi.org/10.1111/jgs.13590.

    Article  PubMed  Google Scholar 

  116. Jaffrain-Rea ML, et al. A critical reappraisal of MIB-1 labelling index significance in a large series of pituitary tumours: secreting versus non-secreting adenomas. Endocr Relat Cancer. 2002;9:103–13.

    Article  CAS  Google Scholar 

  117. Ferrante L, Trillò G, Ramundo E, Celli P, Jaffrain-Rea ML, Salvati M, et al. Surgical treatment of pituitary tumors in the elderly: clinical outcome and long-term follow-up. J Neuro-Oncol. 2002;60:185–91.

    Article  Google Scholar 

  118. Turner HE, Adams CB, Wass JA. Pituitary tumours in the elderly: a 20 year experience. Eur J Endocrinol. 1999;140:383–9.

    Article  CAS  Google Scholar 

  119. Losa M, Bogazzi F, Cannavo S, Ceccato F, Curtò L, de Marinis L, et al. Temozolomide therapy in patients with aggressive pituitary adenomas or carcinomas. J Neuro-Oncol. 2016;126:519–25. https://doi.org/10.1007/s11060-015-1991-y.

    Article  CAS  Google Scholar 

Download references

Funding

This work was supported by the Intramural Research Program (Principal Investigator: CAS) of the Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD), National Institutes of Health (NIH), Bethesda, MD, USA.

Author information

Authors and Affiliations

  1. Section on Genetics and Endocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health, 10 Center Drive, Building 10, NIH-Clinical Research Center, Room 1-3330, MSC1103, Bethesda, MD, 20892, USA

    Christina Tatsi & Constantine A. Stratakis

Authors
  1. Christina Tatsi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Constantine A. Stratakis
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Constantine A. Stratakis.

Ethics declarations

Informed consent

The current study does not involve any new human or animal research that requires informed consent.

Conflict of interests

Dr. Stratakis holds patents on technologies involving PRKAR1A and related genes; his laboratory has received research funding support by Pfizer Inc.

Additional information

Publisher’s note

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

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Tatsi, C., Stratakis, C.A. Aggressive pituitary tumors in the young and elderly. Rev Endocr Metab Disord 21, 213–223 (2020). https://doi.org/10.1007/s11154-019-09534-8

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11154-019-09534-8

Keywords

Search

Navigation