Ozlem Ozkaya AKAGUNDUZ, Banu Sarer YUREKLİ, Ilgin Yildirim SİMSİR, Mustafa ESASSOLAK

Assessment of pituitary function in patients with nasopharyngeal carcinoma: The effect of radiotherapy

Radiotherapy (RT) plays a very important role in nasopharyngeal carcinoma (NPC). The pituitary gland can be affected by radiation due to its proximity to the nasopha-ryngeal cavity. Our aim is to demonstrate the effect of radiotherapy given for NPC on anterior pituitary function with basal pituitary hormones and provocative tests. Patients with NPC that were treated with definitive chemoradioherapy were reviewed retrospectively. Serum ACTH, GH, PRL, FSH, LH, TSH and cortisol, DHEAS, IGF-1, E2, testosterone, fT3, fT4 levels were recorded to evaluate pituitary function. Insulin tolerance test was performed to investigate hypothalamic-pituitary-adrenal axis and GH -IGF-1 axis. Comparison between early tumor stage and advanced tumor stage for pituitary dysfunction was done. The median time interval between the RT and endocrinologic evaluation was 4.0 (1-13) years. ACTH deficiency was found to be most common hormonal problem with a frequency of 73.7%. Of these 71.4% were mild adrenal deficiencies. GH deficiency was seen in 60% of patients. fT3, TSH, GH and IGF-1 levels were significantly lower in patients with advanced tumor stage compared with early tumor stage (p = 0.033, p = 0.022, p = 0.043, p = 0.022, respectively). Growth hormone deficiency was found in all of advanced and in 43% of early tumor stage patients (p = 0.017). We found higher rates of ACTH and GH deficiencies followed by gonadotropin, corticotropin and thyrotropin deficiency. Basal pituitary hormones will not be sufficient to evaluate anterior pituitary failure. Annual and systematic dynamic tests together with basal anterior pituitary hormones would be needed

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1. Fernandez A, Brada M, Zabuliene L, et al. Radiation-induced hypopituitarism. Endocr Relat Cancer. 2009;16:733–72.

2. Al-Sarraf M, LeBlanc M, Giri PG, et al. Chemoradiotherapy versus radiotherapy in patients with advanced nasopharyngeal cancer: phase III randomized Intergroup study 0099. J Clin Oncol. 1998;16:1310–7.

3. Su SF, Han F, Zhao C, Chen CY, et al. Longterm outcomes of early-stage nasopharyngeal carcinoma patients treated with intensity-modulated radiotherapy alone. Int J Radiat Oncol Biol Phys. 2012;82:327–33.

4. Darzy KH. Radiation-induced hypopituitarism after cancer therapy: Who, how and when to test. Nat Clin Pract Endocrinol Metab. 2009;5:88–99.

5. Finucane FM, Liew A, Thornton E, et al. Clinical insights into the safety and utility of the insulin tolerance test (ITT) in the assessment of the hypothalamo- pituitary-adrenal axis. Clin Endocrinol (Oxf). 2008;9(4):603-7.

6. Mark E. Molitch, David R. et al. Evaluation and Treatment of Adult Growth Hormone Deficiency: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab.2011;96:1587–1609.

7. Persani L, Brabant G, Dattani M, et al. European Thyroid Association (ETA) Guidelines on the Diagnosis and Management of Central Hypothyroidism. Eur Thyroid J. 2018;7(5):225-237.

8. Lee AWM, Perez CA, Law CK, et al. Nasopharynx in Principles and practice of radiation oncology. 5th edition. Philadelphia: Lippincott Williams and Wilkin. 2008;820–57.

9. Littley MD, Shalet SM, Beardwell CG et al. Hypopituitarism following external radiotherapy for pituitary tumours in adults. Q J Med. 1989;70:145– 60.

10. Ipekci SH, Cakir M, Kiyici A, et al. Radiotherapy-induced hypopituitarism in nasopharyngeal carcinoma: the tip of an iceberg. Exp Clin Endocrinol Diabetes. 2015;123(7):411-8.

11. Lissett CA, Saleem S, Rahim A, et al. The impact of irradiation on growth hormone responsiveness to provocative agents is stimulus dependent: results in 161 individuals with radiation damage to the somatotropic axis. J Clin Endocrinol Metab.2001;86:663–8. 12. Dichtel LE, Yuen KC, Bredella MA, et al. Overweight/Obese adults with pituitary disorders require lower peak growth hormone cutoff values on glucagon stimulation testing to avoid overdiagnosis of growth hormone deficiency. J Clin Endocrinol Metab. 2014;99:4712.

13. Darzy KH, Aimaretti G, Wieringa Get al. The usefulness of the combined growth hormone (GH)-releasing hormone and arginine stimulation test in the diagnosis of radiation-induced GH deficiency is dependent on the post- irradiation time interval. J Clin Endocrinol Metab.2003;88: 95–102.

14. Constine LS, Woolf PD, Cann D et al. Hypothalamic–pituitary dysfunction after radiation for brain tumors. N Engl J Med.1993;328:87–94.

15. Livesey EA , Hindmarsh PC , Brook CG, et al. Endocrine disorders following treatment of childhood brain tumours. Br J Cancer.1990;61:622–25.

16. Toogood AA. Endocrine consequences of brain irradiation. Growth Horm IGF Res. 2004;14:118–24.

17. Littley MD, Shalet SM, Morgenstern GR, et al. Endocrine and reproductive dysfunction following fractionated total body irradiation in adults. Q J Med. 1991;78:265–74.

18. Ogilvy-Stuart AL, Clark DJ, WallaceWH, et al. Endocrine deficit after fractionated total body irradiation. Arch Dis Child. 1992;67:1107–10.

19. Oberfield SE et al. Thyroid and gonadal function and growth of long-term survivors of medulloblastoma/ PNET. In Late Effects of Treatment for Childhood Cancer. Eds Green DM and D’Angio GJ. 1992;55–62 New York: Wiley–Liss.

20. Lam KSL, Ho JHC, Lee AWM et al. Symptomatic hypothalamic-pituitary dysfunction in nasopharyngeal carcinoma patients following radiation- therapy – a retrospective study. Int J Radiat Oncol Biol Phys. 1987;13:1343– 50.

21. Bhandare N, Kennedy L, Malyapa RS et al. Hypopituitarism after radiotherapy for extracranial head and neck cancers. Head Neck. 2008;30:1182–92.

22. Snyers A, Janssens G, Twickler MB et al. Malignant tumors of the nasal cavity and paranasal sinuses: Long-term outcome and morbidity with emphasis on hypothalamic-pituitary deficiency. Int J Radiat Oncol Biol Phys. 2009;73:1343–51