Hypopituitarism in adult patients with non-pituitary brain cancer following radiation therapy

Introduction:  The purpose and our novelty of the current study were to evaluate the HPA function in adult survivors of primary non-pituitary brain tumors and its association with treatment-related factors such as received dose to the organs at risk, age at irradiation, surgery, and adjuvant chemotherapy in patients treated with RT for brain tumors. Moreover, it aimed to achieve the threshold incidence of late effects because of irradiation to HPA, improve the management of these patients, and improve their quality of life after treatment. Methods and Materials: Thirty-one (31) patients treated with primary or postoperative radiotherapy (RT) for various cancers in the brain region without pre-existing hypothalamic pituitary (HP) disorder from other causes were prospectively evaluated. Serum samples were obtained from the patients to determine levels of growth hormone (GH), thyroid- stimulating hormone (TSH), and free thyroxine (FT4). Serum samples were measured before treatment, 3 and 6 months after completion of radiation therapy (RT). The hypothalamus- pituitary axis (HPA) and dose volume histograms (DVH) of the patients were derived from their computed tomography-based treatment plans. Results: Clinical hypopituitarism was not observed, but 83% of patients who tested for hypopituitarism demonstrated subclinical hypopituitarism after a median interval of 6 months. Subclinical GH and TSH deficiency were observed in 17 (54%) and 9 (29%) participants, respectively. Significant declines in TSH (p < 0.021), FT4 (p < 0.009), and T4 (p < 0.036) levels after the RT course that can be interpreted as subclinical central hypothyroidism were observed. Adjuvant chemotherapy and surgery did not significantly influence the hypopituitarism (p = 0.698, p = 0.287, respectively). The doses of radiation to the HPA region ranged from 241 to 5941 cGy (2.4-59.4 Gy). The mean received dose (Dmean) and biological effective dose (BED) to the pituitary were 36 and 59.6 Gy, respectively. Conclusions: Subclinical findings of late radiation effects were observed in the HPA. Radiation-induced hypopituitarism and central hypothyroidism are regarded as primary damage to the pituitary gland. The damage is dependent on follow-up. Neuronal cell death and degeneration because of the direct effects of radiation seem to play basic roles