Skip to main content
SpringerLink
Log in

Diabetes insipidus in pediatric germinomas of the suprasellar region: characteristic features and significance of the pituitary bright spot

  • Clinical Study
  • Published:
Journal of Neuro-Oncology Aims and scope Submit manuscript

Abstract

The pituitary bright spot is acknowledged to indicate functional integrity of the posterior pituitary gland, whilst its absence supports a diagnosis of central diabetes insipidus (DI). This feature was evaluated, together with the incidence and clinical characteristics of DI in children with suprasellar/neurohypophyseal germinomas. We performed a review of all suprasellar (SS) or bifocal (BF) germinoma pediatric patients treated in Toronto since 2000. Demographics, symptomatology, treatment outcome and imaging were evaluated. Nineteen patients fulfilled inclusion criteria (10 SS, 9 BF; median age 12.5 years (6.2–16.8 years)). All remained alive at 6.4 years median follow-up (1.2–13.7 years) after receiving chemotherapy and radiotherapy (13 focal/ventricular, four whole brain, two neuraxis), with only one progression. All had symptoms of DI at presentation with a symptom interval above one year in eight cases (42 %). Desmopressin was commenced and maintained in 16 patients (84 %). The pituitary bright spot was lost in most diagnostic interpretable cases, but was appreciated in three patients (18 %) who had normal serum sodium values compared to ‘absent’ cases (p = 0.013). For two such cases, spots remained visible until last follow-up (range 0.4–3.3 years), with one still receiving desmopressin. No case of bright spot recovery was observed following therapy. Protracted symptom intervals for germinoma-induced central DI may reflect poor clinical awareness. Explanations for persistence of the pituitary bright spot in symptomatic patients remain elusive. Desmopressin seldom reverses the clinical features of germinoma-induced DI to allow discontinuation, nor does treatment cause bright spot recovery.

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

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Echevarria ME, Fangusaro J, Goldman S (2008) Pediatric central nervous system germ cell tumors: a review. Oncologist 13:690–699

    Article  PubMed  Google Scholar 

  2. Hoffman HJ, Otsubo H, Hendrick EB, Humphreys RP, Drake JM, Becker LE, Greenberg M, Jenkin D (1991) Intracranial germ-cell tumors in children. J Neurosurg 74:545–551

    Article  CAS  PubMed  Google Scholar 

  3. Sawamura Y (1996) Current diagnosis and treatment of central nervous system germ cell tumours. Curr Opin Neurol 9:419–423

    Article  CAS  PubMed  Google Scholar 

  4. Sawamura Y, Ikeda J, Shirato H, Tada M, Abe H (1998) Germ cell tumours of the central nervous system: treatment consideration based on 111 cases and their long-term clinical outcomes. Eur J Cancer 34:104–110

    Article  CAS  PubMed  Google Scholar 

  5. Calaminus G, Kortmann R, Worch J, Nicholson JC, Alapetite C, Garre ML, Patte C, Ricardi U, Saran F, Frappaz D (2013) SIOP CNS GCT 96: final report of outcome of a prospective, multinational nonrandomized trial for children and adults with intracranial germinoma, comparing craniospinal irradiation alone with chemotherapy followed by focal primary site irradiation for patients with localized disease. Neuro Oncol 15:788–796

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  6. Jennings MT, Gelman R, Hochberg F (1985) Intracranial germ-cell tumors: natural history and pathogenesis. J Neurosurg 63:155–167

    Article  CAS  PubMed  Google Scholar 

  7. Matsutani M, Sano K, Takakura K, Fujimaki T, Nakamura O, Funata N, Seto T (1997) Primary intracranial germ cell tumors: a clinical analysis of 153 histologically verified cases. J Neurosurg 86:446–455

    Article  CAS  PubMed  Google Scholar 

  8. Kobayashi T, Kageyama N, Kida Y, Yoshida J, Shibuya N, Okamura K (1981) Unilateral germinomas involving the basal ganglia and thalamus. J Neurosurg 55:55–62

    Article  CAS  PubMed  Google Scholar 

  9. Lafay-Cousin L, Millar BA, Mabbott D, Spiegler B, Drake J, Bartels U, Huang A, Bouffet E (2006) Limited-field radiation for bifocal germinoma. Int J Radiat Oncol Biol Phys 65:486–492

    Article  PubMed  Google Scholar 

  10. Maghnie M, Cosi G, Genovese E, Manca-Bitti ML, Cohen A, Zecca S, Tinelli C, Gallucci M, Bernasconi S, Boscherini B, Severi F, Arico M (2000) Central diabetes insipidus in children and young adults. N Engl J Med 343:998–1007

    Article  CAS  PubMed  Google Scholar 

  11. Afzal S, Wherrett D, Bartels U, Tabori U, Huang A, Stephens D, Bouffet E (2010) Challenges in management of patients with intracranial germ cell tumor and diabetes insipidus treated with cisplatin and/or ifosfamide based chemotherapy. J Neurooncol 97:393–399

    Article  CAS  PubMed  Google Scholar 

  12. Wang Y, Zou L, Gao B (2010) Intracranial germinoma: clinical and MRI findings in 56 patients. Childs Nerv Syst 26:1773–1777

    Article  PubMed  Google Scholar 

  13. Ono N, Kakegawa T, Zama A, Nakamura M, Inoue HK, Misumi S, Tamura M (1992) Suprasellar germinomas; relationship between tumour size and diabetes insipidus. Acta Neurochir (Wien) 114:26–32

    Article  CAS  Google Scholar 

  14. Ramelli GP, von der Weid N, Stanga Z, Mullis PE, Buergi U (1998) Suprasellar germinomas in childhood and adolescence: diagnostic pitfalls. J Pediatr Endocrinol Metab 11:693–697

    Article  CAS  PubMed  Google Scholar 

  15. Tao Y, Lian D, Hui-juan Z, Hui P, Zi-meng J (2011) Value of brain magnetic resonance imaging and tumor markers in the diagnosis and treatment of intracranial germinoma in children. Zhongguo Yi Xue Ke Xue Yuan Xue Bao 33:111–115

    PubMed  Google Scholar 

  16. Douglas JG, Rockhill JK, Olson JM, Ellenbogen RG, Geyer JR (2006) Cisplatin-based chemotherapy followed by focal, reduced-dose irradiation for pediatric primary central nervous system germinomas. J Pediatr Hematol Oncol 28:36–39

    CAS  PubMed  Google Scholar 

  17. Phi JH, Kim SK, Lee J, Park CK, Kim IH, Ahn HS, Shin HY, Kim IO, Jung HW, Kim DG, Paek SH, Wang KC (2013) The enigma of bifocal germ cell tumors in the suprasellar and pineal regions: synchronous lesions or metastasis? J Neurosurg Pediatr 11:107–114

    Article  PubMed  Google Scholar 

  18. Sethi RV, Marino R, Niemierko A, Tarbell NJ, Yock TI, MacDonald SM (2013) Delayed diagnosis in children with intracranial germ cell tumors. J Pediatr 163:1448–1453

    Article  PubMed  Google Scholar 

  19. Merchant TE, Sherwood SH, Mulhern RK, Rose SR, Thompson SJ, Sanford RA, Kun LE (2000) CNS germinoma: disease control and long-term functional outcome for 12 children treated with craniospinal irradiation. Int J Radiat Oncol Biol Phys 46:1171–1176

    Article  CAS  PubMed  Google Scholar 

  20. Baranzelli MC, Patte C, Bouffet E, Couanet D, Habrand JL, Portas M, Lejars O, Lutz P, Le Gall E, Kalifa C (1997) Nonmetastatic intracranial germinoma: the experience of the French Society of Pediatric Oncology. Cancer 80:1792–1797

    Article  CAS  PubMed  Google Scholar 

  21. Kellie SJ, Boyce H, Dunkel IJ, Diez B, Rosenblum M, Brualdi L, Finlay JL (2004) Intensive cisplatin and cyclophosphamide-based chemotherapy without radiotherapy for intracranial germinomas: failure of a primary chemotherapy approach. Pediatr Blood Cancer 43:126–133

    Article  PubMed  Google Scholar 

  22. Crawford JR, Santi MR, Vezina G, Myseros JS, Keating RF, LaFond DA, Rood BR, MacDonald TJ, Packer RJ (2007) CNS germ cell tumor (CNSGCT) of childhood: presentation and delayed diagnosis. Neurology 68:1668–1673

    Article  CAS  PubMed  Google Scholar 

  23. Sawamura Y, Shirato H, Ikeda J, Tada M, Ishii N, Kato T, Abe H, Fujieda K (1998) Induction chemotherapy followed by reduced-volume radiation therapy for newly diagnosed central nervous system germinoma. J Neurosurg 88:66–72

    Article  CAS  PubMed  Google Scholar 

  24. Kitamura K, Shirato H, Sawamura Y, Suzuki K, Ikeda J, Miyasaka K (1999) Preirradiation evaluation and technical assessment of involved-field radiotherapy using computed tomographic (CT) simulation and neoadjuvant chemotherapy for intracranial germinoma. Int J Radiat Oncol Biol Phys 43:783–788

    Article  CAS  PubMed  Google Scholar 

  25. Czernichow P, Garel C, Leger J (2000) Thickened pituitary stalk on magnetic resonance imaging in children with central diabetes insipidus. Horm Res 53(Suppl 3):61–64

    Article  CAS  PubMed  Google Scholar 

  26. Fujisawa I (2004) Magnetic resonance imaging of the hypothalamic-neurohypophyseal system. J Neuroendocrinol 16:297–302

    Article  CAS  PubMed  Google Scholar 

  27. Colombo N, Berry I, Kucharczyk J, Kucharczyk W, de Groot J, Larson T, Norman D, Newton TH (1987) Posterior pituitary gland: appearance on MR images in normal and pathologic states. Radiology 165:481–485

    Article  CAS  PubMed  Google Scholar 

  28. Ozata M, Tayfun C, Kurtaran K, Yetkin I, Beyhan Z, Corakci A, Caglayan S, Alemdaroglu A, Gundogan MA (1997) Magnetic resonance imaging of posterior pituitary for evaluation of the neurohypophyseal function in idiopathic and autosomal dominant neurohypophyseal diabetes insipidus. Eur Radiol 7:1098–1102

    Article  CAS  PubMed  Google Scholar 

  29. Maghnie M, Genovese E, Bernasconi S, Binda S, Arico M (1997) Persistent high MR signal of the posterior pituitary gland in central diabetes insipidus. AJNR Am J Neuroradiol 18:1749–1752

    CAS  PubMed  Google Scholar 

  30. Kurokawa H, Fujisawa I, Nakano Y, Kimura H, Akagi K, Ikeda K, Uokawa K, Tanaka Y (1998) Posterior lobe of the pituitary gland: correlation between signal intensity on T1-weighted MR images and vasopressin concentration. Radiology 207:79–83

    Article  CAS  PubMed  Google Scholar 

  31. Holder CA, Elster AD (1997) Magnetization transfer imaging of the pituitary: further insights into the nature of the posterior “bright spot”. J Comput Assist Tomogr 21:171–174

    Article  CAS  PubMed  Google Scholar 

  32. Abla O, Palmert MR (2012) Reversal of LCH-related diabetes insipidus and reappearance of posterior pituitary bright spot with low-dose chemotherapy. Pediatr Blood Cancer 59:201–202

    Article  PubMed  Google Scholar 

  33. Keene D, Johnston D, Strother D, Fryer C, Carret AS, Crooks B, Eisenstat D, Moghrabi A, Wilson B, Brossard J, Mpofu C, Odame I, Zelcer S, Silva M, Samson Y, Hand J, Bouffet E (2007) Epidemiological survey of central nervous system germ cell tumors in Canadian children. J Neurooncol 82:289–295

    Article  CAS  PubMed  Google Scholar 

  34. Bouffet E, Jakacki R, Goldman S, Hargrave D, Hawkins C, Shroff M, Hukin J, Bartels U, Foreman N, Kellie S, Hilden J, Etzl M, Wilson B, Stephens D, Tabori U, Baruchel S (2012) Phase II study of weekly vinblastine in recurrent or refractory pediatric low-grade glioma. J Clin Oncol 30:1358–1363

    Article  CAS  PubMed  Google Scholar 

  35. Chong AL, Pole JD, Scheinemann K, Hukin J, Tabori U, Huang A, Bouffet E, Bartels U (2013) Optic pathway gliomas in adolescence–time to challenge treatment choices? Neuro Oncol 15:391–400

    Article  CAS  PubMed  Google Scholar 

  36. Nicolin G, Parkin P, Mabbott D, Hargrave D, Bartels U, Tabori U, Rutka J, Buncic JR, Bouffet E (2009) Natural history and outcome of optic pathway gliomas in children. Pediatr Blood Cancer 53:1231–1237

    Article  PubMed  Google Scholar 

  37. Schemper M, Smith TL (1996) A note on quantifying follow-up in studies of failure time. Control Clin Trials 17:343–346

    Article  CAS  PubMed  Google Scholar 

  38. Kretschmar C, Kleinberg L, Greenberg M, Burger P, Holmes E, Wharam M (2007) Pre-radiation chemotherapy with response-based radiation therapy in children with central nervous system germ cell tumors: a report from the Children’s Oncology Group. Pediatr Blood Cancer 48:285–291

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  39. Packer RJ, Cohen BH, Cooney K (2000) Intracranial germ cell tumors. Oncologist 5:312–320

    CAS  PubMed  Google Scholar 

  40. Phi JH, Kim SK, Lee YA, Shin CH, Cheon JE, Kim IO, Yang SW, Wang KC (2013) Latency of intracranial germ cell tumors and diagnosis delay. Childs Nerv Syst 29:1871–1881

    Article  PubMed  Google Scholar 

  41. Kato T, Sawamura Y, Tada M, Murata J, Abe H, Shirato H, Fujieda K (1998) Occult neurohypophyseal germinomas in patients presenting with central diabetes insipidus. Neurosurg Focus 5:e6

    Article  CAS  PubMed  Google Scholar 

  42. Wilne S, Collier J, Kennedy C, Jenkins A, Grout J, Mackie S, Koller K, Grundy R, Walker D (2012) Progression from first symptom to diagnosis in childhood brain tumours. Eur J Pediatr 171:87–93

    Article  PubMed  Google Scholar 

  43. Wilne S, Koller K, Collier J, Kennedy C, Grundy R, Walker D (2010) The diagnosis of brain tumours in children: a guideline to assist healthcare professionals in the assessment of children who may have a brain tumour. Arch Dis Child 95:534–539

    Article  PubMed  Google Scholar 

  44. Cote M, Salzman KL, Sorour M, Couldwell WT (2014) Normal dimensions of the posterior pituitary bright spot on magnetic resonance imaging. J Neurosurg 120:357–362

    Article  PubMed  Google Scholar 

  45. Robinson AG, Verbalis, JG (2011) Posterior pituitary; Williams textbook of endocrinology. In: Melmed S, Polonsky KS, Reed Larsen P, Kronenberg HM (eds) 12th edn. Elsevier, Philadelphia, 291–323

  46. Fujisawa I, Asato R, Kawata M, Sano Y, Nakao K, Yamada T, Imura H, Naito Y, Hoshino K, Noma S et al (1989) Hyperintense signal of the posterior pituitary on T1-weighted MR images: an experimental study. J Comput Assist Tomogr 13:371–377

    Article  CAS  PubMed  Google Scholar 

  47. Sato N, Tanaka S, Tateno M, Ohya N, Takata K, Endo K (1995) Origin of posterior pituitary high intensity on T1-weighted magnetic resonance imaging. Immunohistochemical, electron microscopic, and magnetic resonance studies of posterior pituitary lobe of dehydrated rabbits. Invest Radiol 30:567–571

    Article  CAS  PubMed  Google Scholar 

  48. Maghnie M, Villa A, Arico M, Larizza D, Pezzotta S, Beluffi G, Genovese E, Severi F (1992) Correlation between magnetic resonance imaging of posterior pituitary and neurohypophyseal function in children with diabetes insipidus. J Clin Endocrinol Metab 74:795–800

    Article  CAS  PubMed  Google Scholar 

  49. Miyamoto S, Sasaki N, Tanabe Y (1991) Magnetic resonance imaging in familial central diabetes insipidus. Neuroradiology 33:272–273

    Article  CAS  PubMed  Google Scholar 

  50. Grois N, Flucher-Wolfram B, Heitger A, Mostbeck GH, Hofmann J, Gadner H (1995) Diabetes insipidus in Langerhans cell histiocytosis: results from the DAL-HX 83 study. Med Pediatr Oncol 24:248–256

    Article  CAS  PubMed  Google Scholar 

  51. Cacciari E, Zucchini S, Carla G, Pirazzoli P, Cicognani A, Mandini M, Busacca M, Trevisan C (1990) Endocrine function and morphological findings in patients with disorders of the hypothalamo-pituitary area: a study with magnetic resonance. Arch Dis Child 65:1199–1202

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  52. Rivarola MA, Mendilaharzu H, Warman M, Belgorosky A, Iorcansky S, Castellano M, Caresana A, Chaler E, Maceiras M (1992) Endocrine disorders in 66 suprasellar and pineal tumors of patients with prepubertal and pubertal ages. Horm Res 37:1–6

    Article  CAS  PubMed  Google Scholar 

Download references

Conflict of interest

All authors declare no conflict of interest.

Funding

The work was supported by funding from B.R.A.I.N.child, Canada.

Author information

Authors and Affiliations

  1. Department of Haematology/Oncology (Children’s Brain Tumour Research Network), Royal Manchester Children’s Hospital, Oxford Road, Manchester, Greater Manchester, M13 9WL, UK

    John-Paul Kilday

  2. Division of Neuro-Radiology, Hospital for Sick Children, University of Toronto, Toronto, ON, M5G 1X8, Canada

    Suzanne Laughlin

  3. Department of Paediatric Endocrinology, Hospital for Sick Children, University of Toronto, Toronto, ON, M5G 1X8, Canada

    Stacey Urbach

  4. Department of Paediatric Neuro-Oncology, Division of Haematology/Oncology, Hospital for Sick Children, University of Toronto, Toronto, ON, M5G 1X8, Canada

    Eric Bouffet & Ute Bartels

Authors
  1. John-Paul Kilday
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Suzanne Laughlin
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Stacey Urbach
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Eric Bouffet
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ute Bartels
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to John-Paul Kilday.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kilday, JP., Laughlin, S., Urbach, S. et al. Diabetes insipidus in pediatric germinomas of the suprasellar region: characteristic features and significance of the pituitary bright spot. J Neurooncol 121, 167–175 (2015). https://doi.org/10.1007/s11060-014-1619-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11060-014-1619-7

Keywords

Search

Navigation