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Department of Pediatrics and Adolescent Medicine, Aarhus University Hospital, Aarhus, Denmark
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Department of Pediatrics and Adolescent Medicine, Aarhus University Hospital, Aarhus, Denmark
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Department of Pediatrics and Adolescent Medicine, Aarhus University Hospital, Aarhus, Denmark
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Department of Pediatrics and Adolescent Medicine, Aarhus University Hospital, Aarhus, Denmark
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Department of Pediatrics and Adolescent Medicine, Aarhus University Hospital, Aarhus, Denmark
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Department of Pediatrics and Adolescent Medicine, Aarhus University Hospital, Aarhus, Denmark
Steno Diabetes Center Aarhus, Aarhus University Hospital, Aarhus, Denmark
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Objective
Growth hormone deficiency (GHD) is the most common endocrine late effect in irradiated survivors of childhood brain tumors. This study aimed to determine the prevalence of GHD in adults treated with proton or photon irradiation for a brain tumor in childhood and to detect undiagnosed GHD.
Design
This study is a cross-sectional study.
Methods
We investigated GHD in 5-year survivors from two health regions in Denmark treated for childhood brain tumors with cranial or craniospinal irradiation in the period 1997–2015. Medical charts were reviewed for endocrinological and other health data. Survivors without a growth hormone (GH) test at final height were invited to a GH stimulation test.
Results
Totally 41 (22 females) survivors with a median age of 21.7 years (range: 15.1–33.8 years) at follow-up and 14.8 years (range: 5.1–23.4 years) since diagnosis were included; 11 were treated with proton and 30 with photon irradiation; 18 of 21 survivors were previously found to have GHD; 16 of 20 survivors with no GH test at final height were tested, 8 (50 %) had GHD. In total, 26 of 41 patients (63%) had GHD. Insulin-like growth factor-1 (IGF-1) is associated poorly with the insulin tolerance test (ITT).
Conclusion
This study identified a high prevalence of undiagnosed GHD in survivors with no GH test at final height. The results stress the importance of screening for GHD at final height in survivors of childhood brain tumors with prior exposure to cranial irradiation, irrespective of radiation modality and IGF-1.
Significance statement
This cross-sectional study reports a prevalence of 63% of GHD in irradiated childhood brain tumor survivors. Furthermore, the study identified a considerable number of long-term survivors without a GH test at final height, of whom, 50% subsequently were shown to have undiagnosed GHD. Additionally, this study confirmed that a normal serum IGF-1 measurement cannot exclude the diagnosis of GHD in irradiated survivors. This illustrates the need for improvements in the diagnostic approach to GHD after reaching final height in childhood brain tumor survivors at risk of GHD. In summary, our study stresses the need for GHD testing in all adult survivors treated with cranial irradiation for a brain tumor in childhood irrespective of radiation modality.
Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden
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Department of Medicine, Karlstad Hospital, Karlstad, Sweden
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Growth hormone deficiency (GHD) syndrome is associated with adverse levels of several risk factors for cardiovascular diseases (CVD), including metabolic inflammation. However, the impact of GHD and GH treatment on low-grade inflammation is unknown. The aim of the study was to establish the level of the low-grade inflammation biomarker soluble urokinase plasminogen activator receptor (suPAR) in adults with GHD and the response to long-term GH treatment. Measurements of suPAR and CRP were performed in bio-bank serum samples from 72 adults, 34 males and 38 females, with GHD before and during at least 5 years of GH treatment. Mean age was 52.5 ± 15.5 years, BMI 27.3 ± 5 kg/m2. Clinical evaluations and blood sampling were performed at routine visits. Data on demography, anthropometry, lab results and clinical events were retrieved from post-marketing surveillance study databases and medical records. suPAR and high-sensitive (hs) CRP were analysed using ELISA and immunochemistry, respectively. At baseline blood pressure, lipid profile and fasting glucose were within the normal reference range. Baseline geometric mean and 95% CI of suPAR was 2.9 (2.7–3.3) ng/mL and of CRP 2.3 (0.6–4.0) mg/L. Mean follow-up was 8 ± 2 years. The suPAR levels remained stable during follow-up, although individual increases were seen on occurrence or presence of co-morbidities. In contrast, levels of CRP decreased. In conclusion, the decrease in CRP and indirectly the absence of an expected increase in suPAR over time indicates a favourable effect of GH on low-grade inflammation.
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growth hormone replacement . Frontiers in Endocrinology 2013 4 64. doi:10.3389/fendo.2013.00064. 12 Kargi AY Merriam GR Diagnosis and treatment of growth hormone deficiency in adults . Nature Reviews: Endocrinology 2013 9 335 – 345
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samples. Quality of life assessment Quality of life was assessed using the disease-specific Quality of Life Assessment of Growth Hormone Deficiency in Adults (QoL-AGHDA), a patient needs-based instrument developed specifically to detect deficits in
Centre for Endocrinology, Diabetes and Metabolism, Birmingham Health Partners, Birmingham, UK
Department of Endocrinology, Queen Elizabeth Hospital, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
School of Nursing and Midwifery, Institute of Clinical Sciences, University of Birmingham, UK
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Department of Endocrinology, Queen Elizabeth Hospital, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
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Centre for Endocrinology, Diabetes and Metabolism, Birmingham Health Partners, Birmingham, UK
Department of Endocrinology, Queen Elizabeth Hospital, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
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Centre for Endocrinology, Diabetes and Metabolism, Birmingham Health Partners, Birmingham, UK
Department of Endocrinology, Queen Elizabeth Hospital, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
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endocrine clinicians who participated in this survey. References 1 Melmed S . Pathogenesis and diagnosis of growth hormone deficiency in adults . New England Journal of Medicine 2019 380 2551 – 2562 . ( https://doi.org/10.1056/NEJMra1817346
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Department of Pediatrics, Aarhus University Hospital, Aarhus, Denmark
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Steno Diabetes Center Aarhus (SDCA), Aarhus University Hospital, Aarhus, Denmark
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BMK Radovick S Carmichael JD Jasim S Pantalone KM & Hoffman AR . American Association of Clinical Endocrinologists and American College of Endocrinology guidelines for management of growth hormone deficiency in adults and patients
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of growth hormone deficiency in adults and patients transitioning from pediatric to adult care . Endocrine Practice 2019 25 1191 – 1232 . ( https://doi.org/10.4158/GL-2019-0405 ) 6 Ratku B Sebestyen V Erdei A Nagy EV Szabo Z & Somodi
Department of Emergency Medicine, Landspitali – The National University Hospital of Iceland, Reykjavik, Iceland
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Department of Psychology, School of Social Sciences, Reykjavik University, Reykjavik, Iceland
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School of Engineering and Natural Sciences, University of Iceland, Reykjavik, Iceland
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Department of Medicine, Landspitali – The National University Hospital of Iceland, Reykjavik, Iceland
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. European Journal of Endocrinology 2011 165 881 – 889 . ( https://doi.org/10.1530/EJE-11-0599 ) 25 Rosén T Johannsson G Johansson JO & Bengtsson BA . Consequences of growth hormone deficiency in adults and the benefits and risks of recombinant
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life, HRQoL): GH deficiency (Assessment of Growth Hormone Deficiency in Adults, AGHDA) ( 18 ), acromegaly (Acromegaly Quality of Life questionnaire, AcroQoL) and Cushing’s syndrome (Cushing Quality of Life questionnaire, CushingQoL) ( 19 ). Along the
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clinical practice for growth hormone use in adults and children – UPDATE . Endocrine Practice 9 64 – 76 . doi:10.4158/EP.9.1.64 . 3 de Boer H Blok GJ Van der Veen EA 1995 Clinical aspects of growth hormone deficiency in adults . Endocrine Reviews
