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

Background: Management of anterior skull base malignancies involves a multidisciplinary approach with multimodality treatment. In addition to evolving open and endoscopic surgical extirpation, radiation therapy remains a mainstay of definitive or adjuvant therapy. While often effective for tumor treatment, the regional toxicities of radiation include sialadenitis, xerostomia, mucositis and dysgeusia in the head and neck. The endocrinologic effects of radiation are also well established for neck radiation. Studies show 20–50% of patients develop post-treatment primary hypothyroidism, and standard of care dictates yearly thyroid serologies for delayed hypothyroidism. However, the endocrinologic effects of radiation to the anterior skull base on the pituitary gland remain poorly described for sinonasal malignancies. We aim to characterize the incidence of pituitary dysfunction after radiation for anterior cranial base malignancies and describe a comprehensive screening protocol utilized for surveillance.

Methods: A retrospective review of patients enrolled in an anterior skull base registry at an academic tertiary care center was performed. Patients seen in a multidisciplinary skull base clinic from June 2011 through June 2015 were reviewed. Inclusion criteria were a history of anterior skull base malignancy, history of external beam radiation to the primary site and consent obtained for the registry. Exclusion criteria were the absence of comprehensive post-treatment pituitary serologies and less than 1 year of post-radiation follow up. Starting in 2014, routine yearly pituitary laboratory screening was initiated for radiated cranial base patients at our institution. Standard serologies include 8 am cortisol, growth hormone, IGF-1, prolactin, free T4, TSH, FSH, LH, and bioavailable testosterone (male patients). Patients were either seen in pituitary endocrinology clinic or, after screening with the cranial base surgeons, serologies were reviewed with the senior endocrinologist (AB) to evaluate for pituitary dysfunction.

Results: 103 patients enrolled in the registry and received radiation for skull base malignancies, with 82 patients having comprehensive post-treatment pituitary laboratories. Fifty-eight patients (71%) with screening serologies demonstrated some laboratory abnormality. Twenty-six patients (31% of patients screened) demonstrated some evidence of hypopituitarism. Twenty-three patients (28%) showed evidence of central hypogonadism and 16 patients (19%) had central hypothyroidism. Seven patients (9%) had evidence of panhypopituitarism with 6 patients requiring hydrocortisone supplementation. Onset to laboratory abnormality was seen most frequently 12–36 months post-radiation (47%). Nine patients (11%) showed primary endocrinologic dysfunction (e.g., primary hypothyroidism or primary hypogonadism). Twenty-four patients total (29%) are taking endocrine supplementation.

Conclusion: Radiation for malignancies of the anterior skull base, regardless of the tumor subsite or dose to the pituitary gland, results in over 30% incidence of hypopituitarism in our series. We describe a comprehensive set of pituitary serologies that can be used for yearly surveillance of pituitary function. We recommend pituitary function be screened as part of routine surveillance in patients who have undergone skull base radiation.

No conflict of interest has been declared by the author(s).