title: Associations between Metabolic Risk Factors and the Hypothalamic Volume in Childhood Leukemia Survivors Treated with Cranial Radiotherapy.
abstract: Metabolic complications are prevalent in individuals treated with cranial radiotherapy (CRT) for childhood acute lymphoblastic leukemia (ALL). The hypothalamus is a master regulator of endocrine and metabolic control. The aim of this study was to investigate whether the hypothalamic volume would be associated to metabolic parameters in ALL survivors. Thirty-eight (21 women) survivors participated in this study 34 years after diagnosis and with a median age of 38 (27-46) years. All were treated with a median CRT dose of 24 Gy and 11 years (3-13) of complete hormone supplementation. Comparisons were made to 31 matched controls. We performed analyses of fat mass, fat free mass, plasma (p)-glucose, p-insulin, Homa-Index (a measure of insulin resistance), serum (s)-leptin, s-ghrelin and of the hypothalamic volume in scans obtained by magnetic resonance imaging (MRI) at 3 Tesla. Serum leptin/kg fat mass (r = -0.4, P = 0.04) and fat mass (r = -0.4, P = 0.01) were negatively correlated with the HT volume among ALL survivors, but not among controls. We also detected significantly higher BMI, waist, fat mass, p-insulin, Homa-Index, leptin/kg fat mass and s-ghrelin and significantly lower fat free mass specifically among female ALL survivors (all P<0.01). Interestingly, s-ghrelin levels increased with time since diagnosis and with low age at diagnosis for childhood ALL. Our results showed that leptin/kg fat mass and fat mass were associated with a reduced HT volume 34 years after ALL diagnosis and that women treated with CRT after ALL are at high risk of metabolic abnormalities. Taken together our data suggest that the hypothalamus is involved in the metabolic consequences after CRT in ALL survivors.
authors.affiliation: Department of Endocrinology, Skåne University hospital and IKVL, Lund University, Lund, Sweden.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Follin
authors.affiliation: Translational Neuroendocrine Research Unit, Department of Experimental Medical Science, Lund University, Lund, Sweden.
authors.forename: Sanaz
authors.initials: S
authors.lastname: Gabery
authors.affiliation: Translational Neuroendocrine Research Unit, Department of Experimental Medical Science, Lund University, Lund, Sweden.
authors.forename: Åsa
authors.initials: Å
authors.lastname: Petersén
authors.affiliation: Department of Diagnostic Radiology, Skåne University Hospital and IKVL/Lund University, Lund, Sweden.
authors.forename: Pia C
authors.initials: PC
authors.lastname: Sundgren
authors.affiliation: Department of Diagnostic Radiology, Skåne University Hospital and IKVL/Lund University, Lund, Sweden.|Lund University Bioimaging Centre (LBIC), Lund University, Lund, Sweden.
authors.forename: Isabella
authors.initials: I
authors.lastname: Björkman-Burtcher
authors.affiliation: Department of Diagnostic Radiology, Skåne University Hospital and IKVL/Lund University, Lund, Sweden.
authors.forename: Jimmy
authors.initials: J
authors.lastname: Lätt
authors.affiliation: Department of Diagnostic Radiology, Skåne University Hospital and IKVL/Lund University, Lund, Sweden.
authors.forename: Peter
authors.initials: P
authors.lastname: Mannfolk
authors.affiliation: Department of Endocrinology, Skåne University hospital and IKVL, Lund University, Lund, Sweden.
authors.forename: Eva Marie
authors.initials: EM
authors.lastname: Erfurth
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D001823:Body Composition; D015992:Body Mass Index; D016022:Case-Control Studies; D016371:Cranial Irradiation; D005260:Female; D054439:Ghrelin / Q000097:blood; D013006:Growth Hormone / Q000627:therapeutic use; D020249:Hormone Replacement Therapy; D006801:Humans; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology / Q000528:radiation effects*; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D020738:Leptin / Q000097:blood; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000097:blood* / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy; D012306:Risk; D017741:Survivors
chemical_list: D001786:Blood Glucose; D054439:Ghrelin; D007328:Insulin; D020738:Leptin; D013006:Growth Hormone
references.citation: Med Pediatr Oncol. 2000 Aug;35(2):91-5
references.pmid: 10918229
references.citation: PLoS One. 2015;10(3):e0119882
references.pmid: 25785731
references.citation: Diabetes. 2001 Apr;50(4):707-9
references.pmid: 11289032
references.citation: Endocrinology. 2001 Oct;142(10):4163-9
references.pmid: 11564668
references.citation: Diabetes. 2002 Jan;51(1):124-9
references.pmid: 11756331
references.citation: Eur J Endocrinol. 2002 Feb;146(2):241-4
references.pmid: 11834435
references.citation: J Clin Endocrinol Metab. 2002 Aug;87(8):3997-4000
references.pmid: 12161550
references.citation: J Clin Endocrinol Metab. 2002 Dec;87(12):5461-4
references.pmid: 12466337
references.citation: Am J Physiol Endocrinol Metab. 2003 Feb;284(2):E313-6
references.pmid: 12531744
references.citation: J Clin Endocrinol Metab. 2003 Feb;88(2):611-6
references.pmid: 12574189
references.citation: J Clin Endocrinol Metab. 2003 Nov;88(11):5193-8
references.pmid: 14602749
references.citation: J Clin Endocrinol Metab. 2004 May;89(5):2192-9
references.pmid: 15126541
references.citation: Obes Rev. 2004 Nov;5(4):197-216
references.pmid: 15458395
references.citation: J Clin Endocrinol Metab. 2004 Oct;89(10):5003-12
references.pmid: 15472198
references.citation: Acta Paediatr Scand. 1981 Sep;70(5):609-14
references.pmid: 6948497
references.citation: IEEE Trans Med Imaging. 1998 Feb;17(1):87-97
references.pmid: 9617910
references.citation: Clin Endocrinol (Oxf). 1999 Feb;50(2):163-9
references.pmid: 10396357
references.citation: Brain. 2005 Jun;128(Pt 6):1301-13
references.pmid: 15705605
references.citation: J Clin Endocrinol Metab. 2006 May;91(5):1872-5
references.pmid: 16522695
references.citation: Harv Rev Psychiatry. 2006 May-Jun;14(3):141-51
references.pmid: 16787886
references.citation: J Clin Endocrinol Metab. 2007 Jan;92(1):297-303
references.pmid: 17032714
references.citation: Endocrinology. 2007 May;148(5):2251-63
references.pmid: 17303662
references.citation: Radiology. 2007 May;243(2):483-92
references.pmid: 17456872
references.citation: Eur J Endocrinol. 2007 Dec;157(6):695-700
references.pmid: 18057375
references.citation: Neurobiol Aging. 2010 Feb;31(2):244-56
references.pmid: 18455835
references.citation: Psychoneuroendocrinology. 2010 Jan;35(1):133-40
references.pmid: 19570613
references.citation: J Clin Endocrinol Metab. 2010 Aug;95(8):3726-35
references.pmid: 20484480
references.citation: J Clin Endocrinol Metab. 2010 Dec;95(12):5395-402
references.pmid: 20826582
references.citation: Diabetes Metab Res Rev. 2012 Jan;28(1):76-83
references.pmid: 21695767
references.citation: Dis Markers. 2013;35(4):249-59
references.pmid: 24344399
references.citation: Rev Endocr Metab Disord. 2013 Dec;14(4):365-75
references.pmid: 23959343
references.citation: J Endocrinol. 2014 Feb;220(2):T25-46
references.pmid: 24222039
references.citation: Endocrinology. 2014 Jul;155(7):2411-22
references.pmid: 24742194
references.citation: PLoS One. 2015;10(2):e0117593
references.pmid: 25659157
references.citation: Endocrinology. 2000 Dec;141(12):4797-800
references.pmid: 11108296