Growth Hormone Deficiency Predicts Cardiovascular Risk in Young Adults Treated for Acute Lymphoblastic Leukemia in Childhood

Link, Katarina; Maaser, Christian; Garwicz, Stanislaw; Cavallin‐Ståhl, Eva; Björk, Jonas; Thilén, Ulf; Åhrén, Bo; Erfurth, Eva Marie

doi:10.1210/jc.2004-0126

Cited by 140 publications

(197 citation statements)

References 45 publications

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“…Large waist circumference is a strong independent risk factor for insulin resistance, 38,39 and untreated GH deficiency is associated with an array of unfavorable cardiovascular risk factors and outcomes 23,24,[40][41][42][43] and may also be a risk factor for insulin resistance. 13,23,44,45 The risk profile for diabetes that we observed in ALL survivors with GH deficiency is notable. Whether or not GH treatment is advisable for GH-deficient ALL survivors 19,46 is beyond the scope of our study, but assessment of hypothalamus and pituitary functioning and GH secretion among ALL survivors appears warranted, even in those who did not receive cranial irradiation, given that 20% of those subjects were found to be GH-deficient.…”

Section: Discussionmentioning

confidence: 78%

“…Of the 8 cases with indicators of metabolic syndrome, 4 received cranial radiation and 4 did not. Similarly, Link et al 13 evaluated GH deficiency and cardiovascular risk fac-tors in 44 adult survivors of childhood ALL, all of whom were treated with cranial irradiation. They found that all subjects, using the same cutoff points as in our study, were either GH-deficient (91%) or GH-insufficient (9%).…”

Section: Discussionmentioning

confidence: 99%

“…4 Understanding the long-term medical and psychosocial consequences of childhood ALL and its treatment is important because there are thousands of young adult survivors of childhood ALL who are confronting a variety of adverse health outcomes, including a higher than expected frequency of obesity [5][6][7][8][9] and early mortality from cardiovascular disease. 10,11 Some evidence indicates that cancer survivors in general, 12 and survivors of childhood ALL in particular, [13][14][15][16] are at increased risk for metabolic syndrome. Metabolic syndrome, a constellation of disorders related to insulin resistance, is characterized clinically by central (abdominal) obesity, elevated plasma glucose, dyslipidemia, hypertension, and a prothrombotic and proinflammatory state.…”

mentioning

confidence: 99%

“…25 Human studies specific to ALL indicate that GH deficiency is related to metabolic syndrome and cardiovascular disease risk factors. 13,15,16,26 Studies in humans have shown that GH replacement reduces abdominal visceral adiposity 27 and improves cardiovascular risk measures 28 and muscle strength. 28,29 Therefore, in this clinical research study of 75 young adult survivors of childhood ALL we sought to determine the prevalence of metabolic syndrome, GH deficiency, and other cardiovascular risk factors among those with and without past cranial radiation treatment.…”

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confidence: 99%

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Metabolic syndrome and growth hormone deficiency in adult survivors of childhood acute lymphoblastic leukemia

Gurney

Ness

Sibley

et al. 2006

Cancer

236

188

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BACKGROUND. The purpose of the study was to determine the prevalence of metabolic syndrome, growth hormone deficiency, and cardiovascular risk factors among adult survivors of childhood acute lymphoblastic leukemia (ALL) treated with or without cranial irradiation. METHODS. Follow‐up was undertaken of 75 randomly selected long‐term childhood ALL survivors. Testing included fasting insulin, glucose, lipids, and growth hormone (GH) releasing hormone plus arginine stimulation test. The prevalence of metabolic syndrome was compared with population norms from 1999–2002 National Health and Nutrition Examination Study (NHANES) data, and internally between those with and without past cranial irradiation and those with normal (>16.5 μg/L) versus insufficient (9–16.5 μg/L) versus deficient (<9 μg/L) peak GH secretion. RESULTS. The mean subject age was 30 years and the mean time since ALL diagnosis was 25 years. The prevalence of metabolic syndrome did not differ statistically (P = .87) between study subjects (16.6%) and same‐age, same‐sex population norms (17.5%). However, 60% of subjects treated with cranial irradiation, compared with 20% of those who were not, had 2 or more of the 5 components of metabolic syndrome. Untreated abnormally low GH was present in 64% of subjects overall and 85% of those who received past cranial irradiation. Cranial irradiation was strongly related to GH deficiency, and in turn lower insulin‐like growth factor 1 (IGF‐1), higher fasting insulin, abdominal obesity, and dyslipidemia, particularly in women. CONCLUSIONS. Hematologists who treat childhood ALL patients, and particularly those who provide primary care to adult survivors, should be aware of the potential for long‐term GH deficiency and adverse cardiovascular and diabetes risk profiles as a consequence of leukemia treatment. Cancer 2006. © 2006 American Cancer Society.

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Section: Discussionmentioning

confidence: 78%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Metabolic syndrome and growth hormone deficiency in adult survivors of childhood acute lymphoblastic leukemia

Gurney

Ness

Sibley

et al. 2006

Cancer

236

188

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“…Each patient was matched with a control subject, which was randomly selected from a computerized population register described elsewhere, similar in age, sex, residence (rural/non-rural), and smoking habits (16). Among female controls, seven used oral contraceptives, all with a combination of 35 mg ethinyl E 2 and 250 mg levonorgestrel or up to 0.75 mg norethisterone, and one control was postmenopausal and without sex steroid substitution.…”

Section: Controlsmentioning

confidence: 99%

Hypothalamic involvement and insufficient sex steroid supplementation are associated with low bone mineral density in women with childhood onset craniopharyngioma

Holmer

Popović²,

Ekman³

et al. 2011

European Journal of Endocrinology

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Context: Data on bone mineral density (BMD) are lacking in adults with childhood onset (CO)-craniopharyngioma (CP) with hypothalamic damage from the tumor. In patients with CO GH deficiency, BMD increases during GH treatment. Objective: The aims were to evaluate BMD in adults with CO-CPs on complete hormone replacement, including long-term GH and to evaluate the impact of hypothalamic damage on these measures. Design and participants: BMD (dual-energy X-ray absorptiometry), markers of bone turn over, physical activity and calcium intake were assessed in 39 CO-CP adults (20 women), with a median age of 28 (17-57) years, in comparison with matched population controls. Results: Late puberty induction was recorded in both genders, but reduced androgen levels in females only. Only CP women had lower BMD (PZ0.03) at L2-L4, and reduced Z-scores at femoral neck (PZ0.004) and L2-L4 (PZ0.004). Both genders had increased serum leptin levels (PZ0.001), which significantly correlated negatively with BMD at L2-L4 (PZ0.003; rZK0.5) and 45% of CP women had Z-score levels %K2.0 S.D. Furthermore, 75% of those with a Z-score %K2.0 S.D. had hypothalamic involvement by the tumor. Calcium intake (PZ0.008) and physical activity (PZ0.007) levels were reduced in CP men only. Levels of ostecalcin and crossLaps were increased in CP men only. Conclusions: Despite continuous GH therapy, low BMD was recorded in CO-CP females. Insufficient estrogen and androgen supplementation during adolescence was the main cause, but hypothalamic involvement with consequent leptin resistance was also strongly associated with low BMD in both genders.

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Diabetes Mellitus in Long-term Survivors of Childhood Cancer

Meacham¹,

Sklar²,

Li³

et al. 2009

Arch Intern Med

286

124

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Background Childhood cancer survivors are at increased risk of morbidity and mortality. To further characterize this risk, this study aimed to compare the prevalence of diabetes mellitus (DM) in childhood cancer survivors and their siblings. Methods Participants included 8599 survivors in the Childhood Cancer Survivor Study (CCSS), a retrospectively ascertained North American cohort of long-term survivors who were diagnosed 1970–1986, and 2936 randomly selected siblings of CCSS survivors. The main outcome was self-reported DM. Results Survivors and siblings had mean ages of 31.5 years (range, 17.0–54.1) and 33.4 years (range, 9.6–58.4), respectively. DM was reported in 2.5% of survivors and 1.7% of siblings. Adjusting for body mass index (BMI), age, sex, race/ethnicity, household income, and insurance, survivors were 1.8 times more likely to report DM (95% confidence interval [CI], 1.3–2.5; P<0.001) than siblings, with survivors who received total body irradiation (odds ratio [OR], 12.6; 95% CI, 6.2–25.3; P<0.001), abdominal irradiation (OR, 3.4; 95% CI, 2.3–5.0; P<0.001) and cranial irradiation (OR, 1.6; 95% CI 1.0–2.3; P=0.03) at increased risk. In adjusted models, increased risk of DM was associated with: total body irradiation (OR 7.2; 95% CI, 3.4–15.0; P<0.001); abdominal irradiation (OR 2.7; 95% CI, 1.9–3.8; P<0.001); alkylating agents (OR 1.7; 95% CI, 1.2–2.3; P<0.01); and younger age at diagnosis (0–4 years; OR 2.4; 95% CI 1.3–4.6; P<0.01). Conclusions Childhood cancer survivors treated with total body or abdominal irradiation have an increased risk of diabetes that appears unrelated to BMI or physical inactivity.

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Growth Hormone Deficiency Predicts Cardiovascular Risk in Young Adults Treated for Acute Lymphoblastic Leukemia in Childhood

Cited by 140 publications

References 45 publications

Metabolic syndrome and growth hormone deficiency in adult survivors of childhood acute lymphoblastic leukemia

Metabolic syndrome and growth hormone deficiency in adult survivors of childhood acute lymphoblastic leukemia

Hypothalamic involvement and insufficient sex steroid supplementation are associated with low bone mineral density in women with childhood onset craniopharyngioma

Diabetes Mellitus in Long-term Survivors of Childhood Cancer

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