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Down syndrome: Growth and endocrine impact
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
2009 (English)Doctoral thesis, comprehensive summary (Other academic)Alternative title
Tillväxt och hormonbalans vid Downs syndrom (Swedish)
Abstract [en]

Down syndrome (DS) is associated with psychomotor retardation, short stature and endocrine dysfunction.

Statural growth is a well-known indicator of health. The growth in DS differs markedly from that of other children and there is a 20 cm reduction of final height as compared to target height. We developed growth charts specific for Swedish children with DS, in order to facilitate early diagnosis of concomitant diseases that influence growth. The growth charts are available for paediatricians and child health care professionals in Sweden.

The mechanism underlying the impaired growth in DS is unknown. Height is influenced by parental factors, energy intake, hormone balance and general health. In DS, genetic factors deriving from the extra chromosome 21 further affect growth. Children with DS seem to have reasonable levels of growth hormone (GH), even though GH treatment for limited periods of time improves growth velocity. Within the present project, the subjects of a previous study on early GH therapy in DS were followed up regarding late effects. We found a larger adult head circumference and better psychomotor abilities in the previously treated subjects despite a lack of effect on final height.

In adult life, GH has effects on psychological well-being and metabolism. The clinical features in adults with DS might indicate impaired GH secretion. Ten young adults with DS were studied and compared with ten healthy controls. The GH secretion in the DS subjects did not differ from that in the controls. The fat body mass percentage was increased in DS, in line with the high prevalence of overweight/obesity. The finding of an increased HOMA index as well as a high relative rate of hepatic glucose production in DS indicates reduced insulin sensitivity both peripherally and in the liver.

Thyroid dysfunction is common in DS. There is a 30-fold increase in congenital hypothyroidism, and acquired hypothyroidism has been reported to be present in up to 50% of adults with DS. We collected neonatal screening results and hospital records for the first ten years of life of 68 children with DS. The mean TSH concentration was increased neonatally, indicating marginal hypothyroidism early in life in DS. However, the neonatal TSH level did not predict development of manifest hypothyroidism later in life.

Abstract [sv]

Downs syndrom (DS) är en vanlig kromosomavvikelse. Kortvuxenhet och psykomotorisk utvecklingsstörning är kardinaltecken vid DS. Endokrina avvikelser är också frekvent förekommande.

Tillväxt är en bra indikator på barns hälsa. Nyfödda barn med DS är kortare än andra nyfödda, och skillnaden i längd ökar under barndomen. Sjukdomar som påverkar tillväxten upptäcks ofta via ett förändrat tillväxtmönster. Detta kan lätt förbises vid DS eftersom tillväxten redan är avvikande. Användning av syndromspecifika tillväxtkurvor ökar möjligheterna till diagnostik av sjukdomar som stör längdtillväxten. Vi har framställt tillväxtkurvor för barn med DS, vilka finns tillgängliga inom svensk barnsjukvård och barnhälsovård.

Längdtillväxt styrs av nedärvda faktorer från föräldrarna liksom av nutrition, hälsa och hormoner. Genetiska faktorer, kopplade till kromosom 21, kan påverka tillväxten vid DS, men tillväxtstörningens exakta bakgrund är inte känd. I vuxen ålder är personer med DS ungefär 20 cm kortare än förväntat med hänsyn till föräldralängder. Trots att barn med DS har relativt normala nivåer av tillväxthormon (STH eller GH) förbättras deras tillväxt vid STH-behandling. Inom avhandlingsarbetet följde vi upp ungdomar med DS, vilka behandlats med STH i tidig barndom. Vi kunde påvisa större huvudomfång samt förbättrad kognitiv och motorisk förmåga, trots avsaknad av effekt på slutlängden.

Tillväxthormon har i vuxen ålder effekt både på ämnesomsättning och psykologiskt välbefinnande. Vuxna individer med DS uppvisar flera tecken förenliga med STH-brist. Vi jämförde tio unga vuxna med DS med tio friska kontrollindivider avseende förmågan att insöndra STH. STH-insöndringen hos individerna med DS skiljde sig inte från den hos kontrollerna. Vid samtidig undersökning av kroppssammansättning påvisades en ökad andel kroppsfett hos individerna med DS, resultat i linje med den frekventa förekomsten av övervikt/fetma. Individerna med DS hade en förhöjd glukosproduktion, som tillsammans med ett ökat HOMA-index talar för förekomst av minskad insulinkänslighet både på levernivå och perifert.

Brist på sköldkörtelhormon är mycket vanligt vid DS och upp till hälften av vuxna med DS kan ha hypotyreos. Vi studerade 68 barn med DS avseende nivåer av tyroideastimulerande hormon (TSH) vid PKU-provtagning. Vi följde också barnens journalhandlingar från de tio första levnadsåren i syfte att undersöka om den neonatala TSH-nivån kan prediktera framtida underfunktion av sköldkörteln. Resultaten visade att barn med DS har en förhöjd nivå av TSH neonatalt, vilket indikerar en brist på sköldkörtelhormon redan i nyföddhetsperioden, men nivån förutsäger inte utveckling av manifest hypotyreos senare under barndomen.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis , 2009. , p. 67
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 465
Keywords [en]
Down syndrome, growth, growth charts, body proportions, growth hormone, thyroid function, metabolism, body composition, cognition, motor development
Keywords [sv]
Downs syndrom, tillväxt, tillväxtkurvor, kroppsproportioner, tillväxthormon, sköldkörtelfunktion, metabolism, kroppssammansättning, kognitiv förmåga, motorisk utveckling
National Category
Pediatrics
Research subject
Pediatrics
Identifiers
URN: urn:nbn:se:uu:diva-106756ISBN: 978-91-554-7565-9 (print)OAI: oai:DiVA.org:uu-106756DiVA, id: diva2:226521
Public defence
2009-09-05, Auditorium Minus, Gustavianum, Uppsala, 09:15 (Swedish)
Opponent
Supervisors
Available from: 2009-08-17 Created: 2009-06-30 Last updated: 2009-08-17Bibliographically approved
List of papers
1. Late effects of early growth hormone treatment in Down syndrome
Open this publication in new window or tab >>Late effects of early growth hormone treatment in Down syndrome
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2010 (English)In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 99, no 5, p. 763-769Article in journal (Refereed) Published
Abstract [en]

Objective: Down syndrome (DS) is associated with short stature and psychomotor delay. We have previously shown that growth hormone (GH) treatment during infancy and childhood normalizes growth velocity and improves fine motor skill performance in DS. The aim of this study was to investigate late effects of early GH treatment on growth and psychomotor development in the DS subjects from the previous trial. Design: Twelve of 15 adolescents with DS (3 F) from the GH group and 10 of 15 controls (5 F) participated in this follow-up study. Fifteen other subjects with DS (6 F) were included as controls in anthropometric analyses. Cognitive function was assessed with the Leiter International Performance Scale-Revised (Leiter-R) and selected subtests of the Wechsler Intelligence Scale for Children, Third edition (WISC-III). The Bruininks-Oseretsky Test of Motor Proficiency, Second edition (BOT-2), was used to assess general motor ability. Results: Although early GH treatment had no effect on final height, the treated subjects had a greater head circumference standard deviation score (SDS) than the controls (-1.6 SDS vs. -2.2 SDS). The adolescents previously treated with GH had scores above those of the controls in all subtests of Leiter-R and WISC-III, but no difference in Brief IQ-score was seen between the groups. The age-adjusted motor performance of all subjects was below -2 SD, but the GH-treated subjects performed better than the controls in all but one subtest. Conclusion: The combined finding of a greater head circumference SDS and better psychomotor performance indicates that DS subjects may benefit from early GH treatment.

Keywords
Down syndrome, growth hormone, statural growth, motor function, cognitive function
National Category
Medical and Health Sciences
Research subject
Pediatrics
Identifiers
urn:nbn:se:uu:diva-106752 (URN)10.1111/j.1651-2227.2009.01679.x (DOI)000276034800028 ()20105143 (PubMedID)
Available from: 2009-06-30 Created: 2009-06-30 Last updated: 2017-12-13Bibliographically approved
2. Normal growth hormone secretion in young adults with Down syndrome
Open this publication in new window or tab >>Normal growth hormone secretion in young adults with Down syndrome
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(English)Manuscript (preprint) (Other academic)
Keywords
Down syndrome, growth hormone, insulin-like growth factor I, glucose production, lipolysis, metabolism, body composition, fat mass
National Category
Pediatrics
Research subject
Pediatrics
Identifiers
urn:nbn:se:uu:diva-106754 (URN)
Available from: 2009-06-30 Created: 2009-06-30 Last updated: 2017-01-25Bibliographically approved
3. Growth charts for Down's syndrome from birth to 18 years of age
Open this publication in new window or tab >>Growth charts for Down's syndrome from birth to 18 years of age
2002 (English)In: Archives of Disease in Childhood, Vol. 87, p. 97-Article in journal (Refereed) Published
Identifiers
urn:nbn:se:uu:diva-62930 (URN)
Available from: 2008-10-17 Created: 2008-10-17 Last updated: 2011-01-13
4. Increased neonatal thyrotropin in Down syndrome
Open this publication in new window or tab >>Increased neonatal thyrotropin in Down syndrome
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2009 (English)In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 98, no 6, p. 1010-1013Article in journal (Refereed) Published
Abstract [en]

AIM: Down syndrome (DS) is frequently associated with thyroid dysfunction. The aim of this study was to investigate the blood concentration of thyrotropin (TSH) observed at neonatal screening of infants with DS and its possible association with development of hypothyroidism during childhood. METHODS: TSH levels from neonatal screening of 73 children (34 F) with DS born in 1986-1996 were studied retrospectively and compared with those of controls. The DS children were followed up regarding thyroid function to the age of 10 years in this descriptive study. RESULTS: The DS infants had a higher mean TSH level and a higher TSH standard deviation score (SDS) than controls (7.0 +/- 7.45 mU/L vs. 3.9 +/- 2.43 mU/L and 1.1 +/- 2.67 vs. 0, respectively). The differences were mainly attributable to higher values in the male DS children. The TSH level at screening did not predict thyroid dysfunction during childhood. CONCLUSION: Infants with DS, especially boys, showed elevated levels of TSH at neonatal screening, indicating the occurrence of mild hypothyroidism already in early life. The TSH levels could not predict development of manifest thyroid disease later in childhood.

Keywords
children, Down syndrome, hypothyroidism, neonatal screening, TSH
National Category
Medical and Health Sciences
Research subject
Pediatrics
Identifiers
urn:nbn:se:uu:diva-106750 (URN)10.1111/j.1651-2227.2009.01245.x (DOI)000266636300018 ()19239410 (PubMedID)
Available from: 2009-06-30 Created: 2009-06-30 Last updated: 2017-12-13Bibliographically approved

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