Skip to main content
Log in

Hypothalamic–pituitary–thyroid dysfunction induced by intensity-modulated radiotherapy (IMRT) for adult patients with nasopharyngeal carcinoma

  • Original Paper
  • Published:
Medical Oncology Aims and scope Submit manuscript

Abstract

The aim of this study is to investigate the status and dose–volume relationship of hypothalamic–pituitary–thyroid dysfunction induced by intensity-modulated radiotherapy (IMRT) for adult patients with nasopharyngeal carcinoma (NPC). The hormone levels of 98 patients treated with IMRT were retrospectively reviewed. Hormone values including prolactin (PRL), follicle-stimulating hormone (FSH), luteinizing hormone, adrenocorticotropic hormone, thyroid-stimulating hormone (TSH) and free thyroxine (FT4) were tested. The pituitary and thyroid glands were re-contoured to obtain dose–volume histograms. The relationship between the dose distributions and hormone values was analyzed, as well as combined chemotherapy, age, gender, stages and interval time. The median follow-up period was 17 months. Median values of mean radiation dose to the pituitary and thyroid were 51.2 and 49.72 Gy. Evidences of hormone disorder were found in 54.1 % patients. About 33.7 % patients experienced dysfunction of TSH, 20.4 % of sexual axis and 11.2 % of PRL. Twenty-nine patients presented central hypothyroidism, while 4 patients developed primary hypothyroidism. Dosimetric analysis showed that thyroid axis was significantly associated with Vt30-50 and Dmean of thyroid, V40 (p = 0.000) was the most significant parameters. In addition, TSH and FT4 were correlated with volume of pituitary receiving above 55 Gy (Vp55; p = 0.014, 0.035). Vp55 was most significantly influencing factor of PRL axis (p = 0.044) and gonad axis (p = 0.047). TSH dysfunction was more common with interval time longer than 10 months and age older than 45 years in both univariate and multivariate analysis. FSH and PRL were affected by both gender (p = 0.009, 0.001) and age (p = 0.004, 0.012). Hormone changes were not affected by either clinical stages or combined chemotherapy. At the era of IMRT, a high rate of endocrine deficiency was still seen. Hypothalamic–pituitary–thyroid dysfunction is more common in NPC patients. Regular monitoring is needed.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Jereczek-Fossa BA, Alterio D, Jassem J, Gibelli B, Tradati N, Orecchia R. Radiotherapy-induced thyroid disorders. Cancer Treat Rev. 2004;30:369–84.

    Article  CAS  PubMed  Google Scholar 

  2. Appelman-Dijkstra NM, Kokshoorn NE, Dekkers OM, Neelis KJ, Biermasz NR, Romijn JA, Smit JW, Pereira AM. Pituitary dysfunction in adult patients after cranial radiotherapy: systematic review and meta-analysis. J Clin Endocrinol Metab. 2011;96:2330–40.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  3. Darzy KH, Shalet SM. Hypopituitarism following radiotherapy revisited. Endocr Dev. 2009;15:1–24.

    Article  PubMed  Google Scholar 

  4. Agha A, Sherlock M, Brennan S, O’Connor SA, O’Sullivan E, Rogers B, Faul C, Rawluk D, Tormey W, Thompson CJ. Hypothalamic-pituitary dysfunction after irradiation of nonpituitary brain tumors in adults. J Clin Endocrinol Metab. 2005;90:6355–60.

    Article  CAS  PubMed  Google Scholar 

  5. Lin Z, Wu VW, Lin J, Feng H, Chen L. A longitudinal study on the radiation-induced thyroid gland changes after external beam radiotherapy of nasopharyngeal carcinoma. Thyroid. 2011;21:19–23.

    Article  PubMed  Google Scholar 

  6. Siala W, Mnejja W, Abid M, Ghorbel A, Frikha M, Daoud J. Thyroid toxicity after radiotherapy of nasopharyngeal carcinoma. Ann Endocrinol (Paris). 2011;72:19–23.

    Article  CAS  Google Scholar 

  7. Wu YH, Wang HM, Chen HH, Lin CY, Chen EY, Fan KH, Huang SF, Chen IH, Liao CT, Cheng AJ, Chang JT. Hypothyroidism after radiotherapy for nasopharyngeal cancer patients. Int J Radiat Oncol Biol Phys. 2010;76:1133–9.

    Article  PubMed  Google Scholar 

  8. Ulger S, Ulger Z, Yildiz F, Ozyar E. Incidence of hypothyroidism after radiotherapy for nasopharyngeal carcinoma. Med Oncol. 2007;24:91–4.

    Article  PubMed  Google Scholar 

  9. Alterio D, Jereczek-Fossa BA, Franchi B, D’Onofrio A, Piazzi V, Rondi E, Ciocca M, Gibelli B, Grosso E, Tradati N, Mariani L, Boboc GI, Orecchia R. Thyroid disorders in patients treated with radiotherapy for head-and-neck cancer: a retrospective analysis of seventy-three patients. Int J Radiat Oncol Biol Phys. 2007;67:144–50.

    Article  PubMed  Google Scholar 

  10. Lin Z, Chen L, Fang Y, Cai A, Zhang T, Wu VW. Longitudinal study on the correlations of thyroid antibody and thyroid hormone levels after radiotherapy in patients with nasopharyngeal carcinoma with radiation-induced hypothyroidism. Head Neck 2013. doi:10.1002/hed.23285.

  11. Su SF, Han F, Zhao C, Chen CY, Xiao WW, Li JX, Lu TX. Long-term outcomes of early-stage nasopharyngeal carcinoma patients treated with intensity-modulated radiotherapy alone. Int J Radiat Oncol Biol Phys. 2012;82:327–33.

    Article  PubMed  Google Scholar 

  12. Wang R, Wu F, Lu H, Wei B, Feng G, Li G, Liu M, Yan H, Zhu J, Zhang Y, Hu K. Definitive intensity-modulated radiation therapy for nasopharyngeal carcinoma: long-term outcome of a multicenter prospective study. J Cancer Res Clin Oncol. 2013;139:139–45.

    Article  CAS  PubMed  Google Scholar 

  13. Tham IW, Hee SW, Yeo RM, Salleh PB, Lee J, Tan TW, Fong KW, Chua ET, Wee JT. Treatment of nasopharyngeal carcinoma using intensity-modulated radiotherapy-the national cancer centre Singapore experience. Int J Radiat Oncol Biol Phys. 2009;75:1481–6.

    Article  PubMed  Google Scholar 

  14. Lu H, Yao M. The current status of intensity-modulated radiation therapy in the treatment of nasopharyngeal carcinoma. Cancer Treat Rev. 2008;34:27–36.

    Article  PubMed  Google Scholar 

  15. Baujat B, Audry H, Bourhis J, Chan AT, Onat H, Chua DT, Kwong DL, Al-Sarraf M, Chi KH, Hareyama M, Leung SF, Thephamongkhol K, Pignon JP. Chemotherapy in locally advanced nasopharyngeal carcinoma: an individual patient data meta-analysis of eight randomized trials and 1753 patients. Int J Radiat Oncol Biol Phys. 2006;64:47–56.

    Article  CAS  PubMed  Google Scholar 

  16. Al-Sarraf M, LeBlanc M, Giri PG, Fu KK, Cooper J, Vuong T, Forastiere AA, Adams G, Sakr WA, Schuller DE, Ensley JF. Chemoradiotherapy versus radiotherapy in patients with advanced nasopharyngeal cancer: phase III randomized Intergroup study 0099. J Clin Oncol. 1998;16:1310–7.

    CAS  PubMed  Google Scholar 

  17. Su SF, Huang SM, Han F, Huang Y, Chen CY, Xiao WW, Sun XM, Lu TX. Analysis of dosimetric factors associated with temporal lobe necrosis (TLN) in patients with nasopharyngeal carcinoma (NPC) after intensity modulated radiotherapy. Radiat Oncol. 2013;8:17.

    Article  PubMed Central  PubMed  Google Scholar 

  18. Peng G, Wang T, Yang KY, Zhang S, Zhang T, Li Q, Han J, Wu G. A prospective, randomized study comparing outcomes and toxicities of intensity-modulated radiotherapy versus conventional two-dimensional radiotherapy for the treatment of nasopharyngeal carcinoma. Radiother Oncol. 2012;104:286–93.

    Article  PubMed  Google Scholar 

  19. Wang SZ, Li J, Miyamoto CT, Chen F, Zhou LF, Zhang HY, Yang G, Wang WF, Guo M, Ni XC, Wang L. A study of middle ear function in the treatment of nasopharyngeal carcinoma with IMRT technique. Radiother Oncol. 2009;93:530–3.

    Article  PubMed  Google Scholar 

  20. Nutting CM, Morden JP, Harrington KJ, Urbano TG, Bhide SA, Clark C, Miles EA, Miah AB, Newbold K, Tanay M, Adab F, Jefferies SJ, Scrase C, Yap BK, A’Hern RP, Sydenham MA, Emson M, Hall E. Parotid-sparing intensity modulated versus conventional radiotherapy in head and neck cancer (PARSPORT): a phase 3 multicentre randomised controlled trial. Lancet Oncol. 2011;12:127–36.

    Article  PubMed Central  PubMed  Google Scholar 

  21. Lam KS, Tse VK, Wang C, Yeung RT, Ho JH. Effects of cranial irradiation on hypothalamic-pituitary function-a 5-year longitudinal study in patients with nasopharyngeal carcinoma. Q J Med. 1991;286:165–76.

    Google Scholar 

  22. Darzy KH, Shalet SM. Hypopituitarism following radiotherapy. Pituitary. 2009;12:40–50.

    Article  PubMed  Google Scholar 

  23. Bakhshandeh M, Hashemi B, Mahdavi SR, Nikoofar A, Edraki HR, Kazemnejad A. Evaluation of thyroid disorders during head-and-neck radiotherapy by using functional analysis and ultrasonography. Int J Radiat Oncol Biol Phys. 2012;83:198–203.

    Article  PubMed  Google Scholar 

  24. Chen MS, Lin FJ, Huang MJ, Wang PW, Tang S, Leung WM, Leung W. Prospective hormone study of hypothalamic-pituitary function in patients with nasopharyngeal carcinoma after high dose irradiation. Jpn J Clin Oncol. 1989;19:265–70.

    CAS  PubMed  Google Scholar 

  25. Perez C, Brady L. Principles and practice of radiation oncology. Philadelphia: Lippincott Williams & Wilkins; 2004.

    Google Scholar 

  26. Yoden E, Soejima T, Maruta T, Demizu Y, Nishimura H, Ejima Y, Sasaki R, Yamada K, Sugimura K. Hypothyroidism after radiotherapy to the neck. Nihon Igaku Hoshasen Gakkai Zasshi. 2004;64:146–50.

    PubMed  Google Scholar 

  27. Hancock SL, McDougall IR, Constine LS. Thyroid abnormalities after therapeutic external radiation. Int J Radiat Oncol Biol Phys. 1995;31:1165–70.

    Article  CAS  PubMed  Google Scholar 

  28. Bhandare N, Kennedy L, Malyapa RS, Morris CG, Mendenhall WM. Primary and central hypothyroidism after radiotherapy for head-and-neck tumors. Int J Radiat Oncol Biol Phys. 2007;68:1131–9.

    Article  PubMed  Google Scholar 

  29. Colevas AD, Read R, Thornhill J, Adak S, Tishler R, Busse P, Li Y, Posner M. Hypothyroidism incidence after multimodality treatment for stage III and IV squamous cell carcinomas of the head and neck. Int J Radiat Oncol Biol Phys. 2001;51:599–604.

    Article  CAS  PubMed  Google Scholar 

  30. Lo GA, Kuik DJ, Lips P, von Blomberg BM, Bloemena E, Leemans CR, Debree R. A prospective longitudinal study on endocrine dysfunction following treatment of laryngeal or hypopharyngeal carcinoma. Oral Oncol. 2013. doi:10.1016/j.oraloncology.2013.03.450.

  31. Laway BA, Shafi KM, Majid S, Lone MM, Afroz F, Khan S, Roohi R. Incidence of primary hypothyroidism in patients exposed to therapeutic external beam radiation, where radiation portals include a part or whole of the thyroid gland. Indian J Endocrinol Metab. 2012;16:S329–31.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

Download references

Conflict of interest

None.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Hongmei Ying.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Huang, S., Wang, X., Hu, C. et al. Hypothalamic–pituitary–thyroid dysfunction induced by intensity-modulated radiotherapy (IMRT) for adult patients with nasopharyngeal carcinoma. Med Oncol 30, 710 (2013). https://doi.org/10.1007/s12032-013-0710-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s12032-013-0710-9

Keywords

Navigation