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Growth hormone deficiency and neurocognitive function in adult survivors of childhood acute lymphoblastic leukemia
Author(s) -
Krull Kevin R.,
Li Chenghong,
Phillips Nicholas S.,
Cheung Yin Ting,
Brinkman Tara M.,
Wilson Carmen L.,
Armstrong Gregory T.,
Khan Raja B.,
Merchant Thomas E.,
Sabin Noah D.,
Srivastava DeoKumar,
Pui ChingHon,
Robison Leslie L.,
Hudson Melissa M.,
Sklar Charles A.,
Chemaitilly Wassim
Publication year - 2019
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.31975
Subject(s) - neurocognitive , medicine , growth hormone deficiency , quality of life (healthcare) , pediatrics , hormone , growth hormone , cognition , psychiatry , nursing
Background The impact of growth hormone deficiency (GHD) on neurocognitive function is poorly understood in survivors of childhood acute lymphoblastic leukemia (ALL). This study examined the contribution of GHD to functional outcomes while adjusting for cranial radiation therapy (CRT). Methods Adult survivors of ALL (N = 571; 49% female; mean age, 37.4 years; age range, 19.4‐62.2 years) completed neurocognitive tests and self‐reported neurocognitive symptoms, emotional distress, and quality of life. GHD was defined as a previous diagnosis of GHD or a plasma insulin‐like growth factor1 level less than −2.0 standard deviations for sex and age at the time of neurocognitive testing. Hypothyroidism, hypogonadism, sex, age at diagnosis, CRT dose, and intrathecal and high‐dose intravenous methotrexate were included as covariates in multivariable linear regression models. Results Of the 571 survivors, 298 (52%) had GHD, and those with GHD received higher doses of CRT ( P = .002). Survivors who had GHD, irrespective of prior growth hormone treatment, demonstrated poorer vocabulary (z‐score, −0.84 vs −0.61; P = .02), processing speed (z‐score, −0.49 vs −0.30; P = .04), cognitive flexibility (z‐score, −1.37 vs −0.94; P = .01), and verbal fluency (z‐score, −0.74 vs −0.44; P = .001), and they self‐reported more neurocognitive problems and poorer quality of life compared with survivors who did not have GHD. Multivariable and mediation models revealed that GHD was associated with small effects on quality of life (general health, P = .01; vitality, P = .01; mental health, P = .01); and CRT dose accounted for the lower neurocognitive outcomes. Conclusions Adult survivors of childhood ALL who receive CRT are at risk for GHD, although poor neurocognitive outcomes are determined by CRT dose and not by the presence of GHD.