Hypothalamic-pituitary dysfunction after irradiation of nonpituitary brain tumors in adults.
BACKGROUND
Hypothalamic-pituitary (HP) dysfunction is common in children treated with cranial radiotherapy (RT) for brain tumors, but there is little known about the risk of HP dysfunction in adults treated with RT for primary nonpituitary brain tumors.


OBJECTIVE
The objective was to study the frequency of HP dysfunction in adults after RT for nonpituitary brain tumors.


METHODS
We studied 56 adult patients who received external beam RT for primary nonpituitary brain tumors at time intervals of 12-150 months after RT. The control group consisted of 20 RT-naive patients with primary brain tumors. GH and adrenal axes were assessed using the insulin tolerance test or the glucagon stimulation test. Gonadotroph, thyrotroph, and lactotroph function were assessed using baseline blood measurements. The biological effective dose (BED) to the HP axis was calculated in the RT patients.


RESULTS
Hypopituitarism was present in 41% of patients. The frequency of GH, ACTH, gonadotropin, and TSH deficiencies, and hyperprolactinemia was 32, 21, 27, 9, and 32%, respectively. Any degree of hypopituitarism and GH deficiency was significantly associated with longer time interval from RT and greater BED. However, gonadotropin deficiency and hyperprolactinemia were only related to BED, whereas ACTH deficiency was only significantly associated with the time interval from RT. One RT-naive patient was GH deficient.


CONCLUSIONS
Adult patients treated with cranial irradiation for primary nonpituitary brain tumors are at high risk of hypopituitarism, which is time and dose dependent. Long-term surveillance and periodic evaluation are needed. We recommend that adult late effect clinics, similar to those for children, should be established.
Agha
Amar
A
Department of Endocrinology, Beaumont Hospital, Beaumont Road, Dublin 9, Ireland. amaragha@yahoo.com
Sherlock
Mark
M
Brennan
Sinead
S
O'Connor
Stephen A
SA
O'Sullivan
Eoin
E
Rogers
Bairbre
B
Faul
Clare
C
Rawluk
Daniel
D
Tormey
William
W
Thompson
Christopher J
CJ
D000324:Adrenocorticotropic Hormone / Q000172:deficiency; D000328:Adult; D001932:Brain Neoplasms / Q000532:radiotherapy*; D016022:Case-Control Studies; D016371:Cranial Irradiation / Q000009:adverse effects*; D004307:Dose-Response Relationship, Radiation; D005260:Female; D006062:Gonadotropins / Q000172:deficiency; D019382:Human Growth Hormone / Q000172:deficiency; D006801:Humans; D006966:Hyperprolactinemia / Q000209:etiology; D007018:Hypopituitarism / Q000209:etiology / Q000503:physiopathology; D007030:Hypothalamo-Hypophyseal System / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D010315:Particle Accelerators; D011832:Radiation Injuries / Q000150:complications / Q000503:physiopathology*; D012307:Risk Factors; D013972:Thyrotropin / Q000172:deficiency; D013997:Time Factors
D006062:Gonadotropins; D019382:Human Growth Hormone; D000324:Adrenocorticotropic Hormone; D013972:Thyrotropin