Pituitary Dysfunction in Adult Patients after Cranial Radiotherapy: Systematic Review and Meta-Analysis

CONTEXT: Cranial radiotherapy is an important cause of hypopituitarism. The prevalence of hypopituitarism varies considerably between studies. OBJECTIVE: We conducted a systematic review and meta-analysis of reported prevalences of hypopituitarism in adults radiated for nonpituitary tumors. DATA SOURCES: We searched PubMed, EMBASE, Web of Science, and the Cochrane Library to identify potentially relevant studies. STUDY SELECTION: Studies were eligible for inclusion with the following criteria: 1) cranial radiotherapy for nonpituitary tumors and/or total body irradiation for hematological malignancies; 2) adult population (>18 yr old); and 3) report on endocrine evaluation. DATA EXTRACTION: Data review was done by two independent reviewers. Besides extraction of baseline and treatment characteristics, also endocrine tests, definitions, and cutoff values used to define pituitary insufficiency were extracted. RESULTS: Eighteen studies with a total of 813 patients were included. These included 608 patients treated for nasopharyngeal cancer (75%) and 205 for intracerebral tumors. The total radiation dose ranged from 14 to 83 and 40 to 97 Gy for nasopharyngeal and intracerebral tumors, respectively. The point prevalence of any degree of hypopituitarism was 0.66 95% confidence interval (CI), 0.55-0.76. The prevalence of GH deficiency was 0.45 (95% CI, 0.33-0.57); of LH and FSH, 0.3 (95% CI, 0.23-0.37); of TSH, 0.25 (95% CI, 0.16-0.37); and of ACTH, 0.22 (95% CI, 0.15-0.3), respectively. The prevalence of hyperprolactinemia was 0.34 (95% CI, 0.15-0.6). There were no differences between the effects of radiotherapy for nasopharyngeal vs. for intracerebral tumors. CONCLUSION: Hypopituitarism is prevalent in adult patients after cranial radiotherapy for nonpituitary tumors. Therefore, all patients treated by cranial radiotherapy should have structured periodical assessment of pituitary functions.