Pituitary Dysfunction after Radiation for Anterior Skull Base Malignancies: Incidence and Screening

Abstract

Background Management of anterior cranial base malignancies requires multidisciplinary care. Radiation therapy remains a mainstay of definitive or adjuvant treatment. Apart from primary hypothyroidism, the effects of radiation on the hypothalamic–pituitary axis after high-dose treatment of head and neck malignancies remain poorly described. We describe a comprehensive screening protocol for surveillance and characterize the incidence of pituitary dysfunction after radiation for anterior cranial base malignancies. Methods A review of patients prospectively enrolled in a skull base registry at an academic center was performed. Included patients had a history of anterior skull base malignancy and external beam radiation to the primary site, with comprehensive post-treatment pituitary serologies and at least 1 year of post-radiation follow-up. Routine hormonal screening was initiated during the study period for all patients with anterior skull base irradiation. Results Eighty-one patients met inclusion. Fifty-eight patients (71%) demonstrated some laboratory abnormality. Thirty patients (37%) demonstrated evidence of hypopituitarism. Twenty-four (29%) demonstrated central hypogonadism, and 16% of patients showed central hypothyroidism. Ten patients (12%) displayed central adrenal insufficiency with six patients demonstrating panhypopituitarism. Primary tumor location and maximum dose of radiation to the gland appeared to correlate with incidence of hypopituitarism. Conclusion Radiation for malignancies of the anterior skull base resulted in a 37% incidence of hypopituitarism in our study. Given the potential morbidity of hypopituitarism, we recommend annual post-treatment screening in these patients. We describe a comprehensive set of serologies that can be utilized, and recommend updating clinical guidelines to reflect the necessity of this screening.

Assessing Quality of Life among Radiation-Induced Hypopituitary Patients

“…We found that the dose of skull base radiation (maximum dose to the primary tumor) did not significantly differ between the non-hypopituitarism and hypopituitarism groups (p 0.20). This seemingly contradicts the long standing existing literature 5,6,[28][29][30][31] that suggests a positive doseresponsive relationship between radiation dose and incidence of hypopituitarism, especially in the three axes we analyze in this study, although the data is mixed 29 . However, almost all of our patients received relatively high doses of radiation (average 71.4 gy) due to the aggressive nature of these tumors, which is well above the thresholds discussed for developing hypopituitarism.…”

“…All rights reserved. from 37% over three years among our own institutional cohort of sinonasal malignancies 5 , to 41% at 6 years among adult survivors of nonpituitary brain tumors with radiation exposure 7 , and 82 8 -93% 9 for long-term survivors (greater than 10 years) of nasopharyngeal carcinoma. There is a well characterized dose-dependent sequence of pituitary derangements, with the somatotrophs more likely to be affected first at even low radiation doses; gonadal, adrenal, and thyroid axes are more likely to become dysfunctional with higher radiation doses and with increased time out from radiation 4,10 .…”

“…These tumors include cranial tumors not involving the hypothalamic-pituitary axis (HPA) and even oropharyngeal tumors whose radiation field include the sella 2,3 . Higher radiation doses (greater than 50 Gy), as commonly seen for anterior skull base malignancies and nasopharyngeal carcinoma, are associated with higher incidence of HPA dysfunction 1,[4][5][6] . The estimated cumulative incidence of RIH after high-dose radiation is broad, with estimates ranging…”

Proton Beam Therapy in the Treatment of Periorbital Malignancies

“…Hypopituitarism after radiation of nearby structures where the sella does not receive prescription dose is less well described. However, several series have shown that there is a linear dose response without a practical threshold, where increasing mean doses of radiation to the pituitary gland are more likely to cause hormone deficiencies [18][19][20]. As a result, the reduction in dose with the use of proton therapy seen in this study could be hypothesized to reduce the risk of hypopituitarism.…”

Sinonasal Neuroendocrine Carcinoma: 15 Years of Experience at a Single Institution

“…This is important because these high-grade cancers are more aggressive than other types of SNECs, and smCC has consistently been found to have lower survival than other types of SNEC. 5,[14][15][16][17] For these tumors, surgical resection may not be the ideal treatment. Not only can margins be difficult to clear, as they often extend well beyond gross tumor margins.…”