A Prospective Study on Hypopituitarism after Radiotherapy in Non Pituitary Brain Tumors.

ABSTRACT

Objective: Pituitary function and hypopituitarism have not been well evaluated in adult patients with non-pituitary brain cancer. Methods: 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), thyroidstimulating 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. Subclinical findings of late radiation effects were observed in the HPA. Conclusion: Radiation-induced hypopituitarism and central hypothyroidism are regarded as primary damage to the pituitary gland. Time after therapy is critical and so with time the incidence of growth hormone deficiency and thyroid stimulating hormone deficiency is likely to significantly increase and to no longer be subclinical. Neuronal cell death and degeneration because of the direct effects of radiation seem to play basic roles.