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- Björk, Jonas, et al.
(författare)
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The utility of the GHRH-arginine test for diagnosing GH deficiency in adults with childhood acute lymphoblastic leukemia (ALL) treated with cranial irradiation.
- 2005
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 90:11, s. 6048-6054
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Tidskriftsartikel (refereegranskat)abstract
- Context: The insulin tolerance test ( ITT) is the current standard diagnostic test for the diagnosis of adult GH deficiency ( GHD), but alternative tests, such as the GHRH- arginine test, have been proposed. Objective: We investigated the sensitivity and specificity of the GHRH- arginine test using ITT as the gold standard in diagnosing GHD in a group of young adults treated with cranial irradiation ( CRT) for childhood acute lymphoblastic leukemia ( ALL). We estimated the positive and negative predictive values of the GHRH- arginine test among patients as well as a number of individual characteristics and therapy- related factors during both the GHRH- arginine test and ITT. Design: Forty- three young adults, treated for childhood ALL with 18 - 30 Gy CRT and chemotherapy, were studied, and comparison was made with matched controls. Results and Conclusions: We evaluated four different cutoff levels for GHD in the GHRH- arginine test: 5, 7.5, 9, and 16.5 mu g/ liter. Using 7.5 mu g/liter as the cutoff yielded high specificity ( 94%), but at the same time the sensitivity was only 66%, which leads to a low negative predictive value ( 27%). In contrast, a failed GH response to the GHRH- arginine test accurately reflects the presence of radiationinduced GHD, illustrated by a high positive predictive value ( 95% at 7.5 mu g/ liter). Only age at CRT and body mass index remained significant predictors of the peak GH during the GHRH- arginine test. Because a high proportion of GHD patients show a normal response to the GHRH- arginine test, it cannot be used reliably to exclude GHD in these patients. Complementary ITT is also warranted to confirm GHD in obese patients.
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- Follin, Cecilia, et al.
(författare)
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Bone loss after childhood acute lymphoblastic leukaemia: an observational study with and without GH therapy
- 2011
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Ingår i: European Journal of Endocrinology. - 1479-683X. ; 164:5, s. 695-703
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Bone mineral density (BMD) in survivors of acute lymphoblastic leukaemia (ALL) seems to vary with time, type of treatments and GH status. We aimed to evaluate BMD in ALL patients with growth hormone deficiency (GHD), with and without GH therapy. DESIGN: Case-control study. METHODS: 44 (21 women) GHD patients (median 25 years), treated with cranial radiotherapy (18-24 Gy) and chemotherapy and matched population controls were examined for BMD with DXA (Dual-energy X-ray absorptiometry). Two subgroups; with (0.5 mg/day) (n=16) and without GH therapy (n=13), and matched controls, were followed for 5 and 8 years, respectively. RESULTS: At baseline, no significant differences in BMD or Z-scores at femoral neck and L2-L4 were recorded (all P > 0.3). After another 8 years with GHD, Z-scores at femoral neck had decreased significantly compared to baseline (0.0 to -0.5; P<0.03), and became lower at femoral neck (P=0.05), and at L2-L4 (P<0.03), compared to controls. After 5 years of GH therapy only female ALL patients had a significantly lower femoral neck Z-scores (P=0.03). The female ALL patients reached an IGF-I level of -0.7 SD and in men the level was +0.05 SD. CONCLUSIONS: On average 25 years since diagnosis GH deficient ALL patients experienced a significant decrease in Z-scores at femoral neck and if Z-scores continuous to decrease there is a premature risk for osteoporosis. GH therapy was not shown to have a clear beneficial effect on BMD. Whether higher GH doses, particularly in women, will improve Z-scores needs further investigation.
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- Follin, Cecilia, et al.
(författare)
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Cardiovascular Risk, Cardiac Function, Physical Activity, and Quality of Life with and without Long-Term Growth Hormone Therapy in Adult Survivors of Childhood Acute Lymphoblastic Leukemia.
- 2010
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 95, s. 3726-3735
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Tidskriftsartikel (refereegranskat)abstract
- Context: Long-term data are missing in GH-treated acute lymphoblastic leukemia (ALL) patients. GH therapy may result in poorer outcome regarding cardiovascular (CV) and particularly cardiac effects than in patients with hypothalamic-pituitary disease. Objective: Our objective was to evaluate GH therapy on CV risk, cardiac function, physical activity, and quality of life in ALL patients treated with cranial radiotherapy (18-24 Gy) and chemotherapy (anthracycline dose 120 mg/m(2)). Design and Setting: We conducted a 5- and 8-yr open nonrandomized prospective study in a university hospital clinic. Study Participants: Two groups of GH-deficient ALL patients (aged 25 yr; range 19-32 yr) and matched population controls participated. Interventions: One ALL group (n = 16) received GH for 5 yr, and the other ALL group (n = 13) did not receive GH therapy. Main Outcome Measures: We evaluated the prevalence of CV risk factors and metabolic syndrome (International Diabetes Federation consensus), cardiac function (echocardiography), and quality of life and physical activity questionnaires. Results: In comparison with 8 yr without, 5 yr with GH therapy resulted in significant positive changes in plasma glucose (-0.5 vs. 0.6 mmol/liter, P = 0.002), apolipoprotein B/apolipoprotein A1 ratio (-0.1 vs. 0.0, P = 0.03), and high-density lipoprotein-cholesterol (0.20 vs.-0.01 mmol/liter, P = 0.008) and a significant reduction in the prevalence of metabolic syndrome (P = 0.008). No significant difference in the left-ventricular systolic function or in physical activity and quality of life was recorded before and after 5 or 8 yr, respectively (all P > 0.3). Conclusion: GH therapy reduced the CV risk in this young ALL population but resulted in no clear benefit or deterioration in cardiac function.
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| 6. |
- Follin, Cecilia, et al.
(författare)
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Prolactin insufficiency but normal thyroid hormone levels after cranial radiotherapy in long-term survivors of childhood leukaemia.
- 2013
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Ingår i: Clinical Endocrinology. - : Wiley. - 1365-2265 .- 0300-0664. ; 79:1, s. 71-78
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Acute lymphoblastic leukaemia (ALL) patients treated with cranial radiotherapy (CRT) have an increased risk of GH deficiency (GHD). Little is known about insufficiencies of prolactin (PRL) and TSH, but also lactation failure has been reported in this population. OBJECTIVE: To study the long-term outcome of CRT on PRL and thyroid hormone levels in GHD ALL patients, and the prevalence of lactation failure. DESIGN: CASE-CONTROL STUDY: PATIENTS: We examined 40 GHD and 4 GH insufficient ALL patients, in median 20 years (range 8-27) after ALL diagnosis and 44 matched population controls. MEASUREMENTS: PRL secretion (area under the curve; AUC) after GHRH-arginine test in all patients and matched controls, and PRL and TSH AUC after a TRH test in 13 patients and 13 controls. And basal PRL and thyroid hormone levels after 5 years with GH therapy and 8 years without GH therapy. RESULTS: Compared to controls ALL patients had significantly lower basal and AUC PRL after GHRH-Arginine (P = 0.03, P = 0.02), and AUC PRL after TRH (P = 0.001). After 5 and 8 years, PRL levels decreased further (P = 0.01, P = 0.03), but thyroid hormones remained normal at baseline and at follow up. PRL insufficiency was significantly associated with increased levels of BMI and insulin. Six out of seven pregnant ALL women reported lactation failure. CONCLUSIONS: Long-term ALL survivors treated with CRT have GHD and PRL insufficiency, and a high prevalence of lactation failure, but thyroid hormones remained normal. PRL insufficiency was associated with cardiovascular risk. © 2012 Blackwell Publishing Ltd.
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- Holmer, Helene, et al.
(författare)
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Hypothalamic involvement predicts cardiovascular risk in adults with childhood onset craniopharyngioma on long-term GH therapy.
- 2009
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Ingår i: European Journal of Endocrinology. - 0804-4643 .- 1479-683X. ; 16, s. 671-679
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Tidskriftsartikel (refereegranskat)abstract
- Context: Craniopharyngioma patients without GH therapy are at an increased cardiovascular disease (CVD) risk and particularly concerning women. No previous study on long-term GH therapy in adults with childhood onset (CO) craniopharyngioma was identified. Objective: To investigate CVD risk in adults with CO craniopharyngioma on complete hormone replacement, including long-term GH therapy, and to investigate the impact of disease-related factors on CVD risk. Design and participants: In a cross-sectional study of operated CO craniopharyngiomas (1958–2000) from a defined area of Sweden (2.5 million), we enrolled 42 patients (20 women) with a median age of 28 years (range 17–57) and assessed CVD risk of 20 (4–40) years after first operation. Comparisons were made with matched controls and between patients with tumor growth into the third ventricle (TGTV) versus non-TGTV. GH therapy was 10–12 years in women and men. Results: In comparison with controls, both male and female patients had increased body mass index, fat mass, insulin, and leptin levels. Overall, while not significantly increased in male patients, 55–60% of female patients had a medium–high CVD risk, compared with 10–20% in controls. An increased CVD risk (all P<0.05) and higher levels of fat mass and insulin were recorded in the TGTV group versus the non-TGTV group. Late puberty induction and lack of androgens were shown in female patients. Conclusions: Adult patients with CO craniopharyngioma, especially those with TGTV, have persistently increased CVD risk. Conventional hormone substitution, including GH, is insufficient to normalize CVD risk, suggesting an important role for irreversible hypothalamic dysfunction.
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| 8. |
- Holmer, Helene, et al.
(författare)
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Reduced Energy Expenditure and Impaired Feeding-Related Signals But Not High Energy Intake Reinforces Hypothalamic Obesity in Adults with Childhood Onset Craniopharyngioma
- 2010
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : Endocrine Society. - 0021-972X .- 1945-7197. ; 95:12, s. 5395-5402
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Tidskriftsartikel (refereegranskat)abstract
- Context: Obesity is a frequent manifestation of hypothalamic damage from a craniopharyngioma (CP). It is not yet clarified whether the obesity is due to alterations in energy expenditure, i.e. basal metabolic rate (BMR) and physical activity, or to increased energy intake (EI). Objective: The aim was to investigate whether energy expenditure and EI differed between childhood onset CP patients and matched population controls and whether these measures were related to hypothalamic damage, as tumor growth into the third ventricle (TGTV). Design and Methods: Forty-two CP patients (20 women) aged 28 yr (range, 17-57 yr) operated between 1958 and 2000 in the South Medical Region of Sweden (population, 2.5 million) were studied. Body composition, satiety hormones, BMR (indirect calorimetry), physical activity, EI, and attitudes toward eating were assessed. Comparisons were made with matched controls and between patients with (n = 25) and without (n = 17) TGTV. Results: After adjustment, patients had lower BMR compared to controls (-90 kcal/24 h; P = 0.02) and also had lower EI (1778 vs. 2094 kcal/24h; P = 0.008), and the EI/BMR ratio was significantly lower in TGTV patients. Similar dietary macronutrient composition was found, and only significantly higher scales in restricting food intake were recorded in patients. Ghrelin levels were significantly lower in patients, whereas serum insulin and leptin levels were higher (P less than 0.001), and both ghrelin and insulin correlated significantly to tumor growth. Lower levels of physical activity (P less than 0.01) were recorded in patients. Conclusions: The major mechanisms that reinforced obesity were hypothalamic damage causing disrupted or impaired sensitivity to feeding-related signals for leptin, insulin, and ghrelin, and reductions in both BMR and physical activity.
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