FP21-3 Hypothalamic Pituitary Dysfunction Amongst Nasopharyngeal Cancer Survivors: An Increased Risk With The Use Of Concurrent Chemo-Irradiation

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: FP21-HPA Axis: New Clinical Developments
Clinical
Sunday, June 16, 2013: 10:45 AM-11:15 AM
Presentation Start Time: 10:55 AM
Room 134 (Moscone Center)

Poster Board SUN-53
Jeyakantha Ratnasingam, N Karim, Alexander Tong Boon Tan, Shireene Vethakkan, Karen Choong and Siew Pheng Chan*
University of Malaya Medical Centre, Kuala Lumpur, Malaysia
Introduction: Radiotherapy is the mainstay of treatment for nasopharyngeal cancer (NPC). Radiation fields include areas adjacent to the primary tumour, placing the hypothalamic pituitary (HP) axis at risk. Concurrent chemo-irradiation (CCRT) has become the standard therapeutic regime used in recent years. There is little known about risk of HP dysfunction in patients treated with the CCRT regimen.

Objective/aims: The objective was to establish the prevalence and severity of HP dysfunction among NPC patients after radiotherapy alone / CCRT and identify predictive factors for the development of HP dysfunction.

Methods: In this cross–sectional study, we studied 58 patients who had completed treatment for NPC more than 3 years prior, with no pre-existing HP disorder. All patients had a baseline cortisol, ACTH, GH, IGF1, fT4, TSH, FSH, LH, oestradiol/testosterone, prolactin and renal function measured at 8am after an overnight fast. In addition 49 patients underwent dynamic testing with the insulin tolerance test (ITT) to assess the GH and corticotroph axes.

Results: Median age was 56 (48.8 - 63.3) years and median time elapsed from treatment was 8 (6.0-11.25) years. 43 patients (75 %) had concurrent chemo-irradiation (CCRT) while 15 patients (25 %) had radiotherapy alone. Hypopituitarism was present in 84 %, 31 % with single axis, 29 % with two axes, 18 % with three axes and 6 % with four axes deficiencies. GH was the most vulnerable to radiation damage (80%) while corticotroph, gonadotroph and thyrotroph deficiencies were 41, 19 and 3 % respectively. Twenty patients (41%) were found to have corticotroph deficiency (peak serum cortisol of less than 550 nmol/L during the ITT) including 4 patients who had severe deficiency, defined as peak cortisol less than 170 nmol/L during the ITT. None exhibited symptoms. The development of HP dysfunction was significantly associated with the use of CCRT compared to those who had radiotherapy alone, OR: 14.5(2.42-87.7), p=0.01. Time elapsed from therapy was also significantly associated with HP axis dysfunction.

Conclusion: HP dysfunction post-irradiation is widespread amongst NPC survivors (84%), the most common being GH-deficiency. Of clinical relevance, severe corticotroph deficiency requiring hormonal replacement was identified in 7% and suboptimal cortisol response to ITT in 34%.  These patients would require cortisone therapy in times of stress. Radiation-induced damage appears to be profoundly increased with the newer mode of therapy using CCRT. As these endocrinopathies result in significant morbidity and mortality we recommend periodic assessment of pituitary function post irradiation.

1. KSL Lam, Tse VK, Wang CI et al. Q J Med 1991;78:165-7 2. Appelman-Djikstra N, Kokshoorn NE, Dekkers OM et al. JCEM 2011; 96(8):0000-0000

Nothing to Disclose: JR, NK, ATBT, SV, KC, SPC

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm