Abnormalities In Growth And Puberty In Duchenne Muscular Dystrophy: Effects Of Corticosteroid Therapy Jarod Wong Developmental Endocrinology Research Group Division of Developmental Medicine Royal Hospital For Children Glasgow, UK [email protected]1882 1914 1971 1451
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Abnormalities In Growth And Puberty In Duchenne Muscular Dystrophy: Effects Of Corticosteroid Therapy Jarod Wong Developmental Endocrinology Research Group.
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Abnormalities In Growth And Puberty In Duchenne Muscular Dystrophy:
Effects Of Corticosteroid Therapy
Jarod WongDevelopmental Endocrinology Research GroupDivision of Developmental MedicineRoyal Hospital For ChildrenGlasgow, [email protected]
1882 1914 19711451
Acknowledgements
Developmental Endocrinology Research GroupYorkhill-F Ahmed-S Joseph-A Mason-L Lucaccioni-M McMillan-J McNeilly
Importance of growth & puberty for bone development
40-50% total bone mass for life accumulated during puberty
Importance of puberty for muscle development
Growth And Short Stature In DMD
Poor growth in DMD predates the use of CS
0 years 5 years 10 years Eiholzer et al Eur J Pediatr 1988
Nagel BH et al Acta Paediatr 1999
Reasons for poor growth in DMD before CS
Unclear
Contiguous gene deletion
Intrinsic abnormality in DMD bone and growth plate
Subtle abnormality of GH secretion/GH resistance
Chronic inflammation- effects on growth factors and growth plate
Corticosteroid And Poor Growth In DMD
Bone Turnover In ALL
Growth rate lower leg
Bone formation
Bone resorption
High dose GC GCAhmed et al JPEM 1999, Crofton et al, JCEM,1998
Daily vs intermittent corticosteroid from Northstar Database360 DMD
Mean 4 years treatment
-1.8 SD -0.7 SD +1.5 SD +2.0 SD
Ricotti V et al J Neurol Neurosurg Psychiatry 2013
At age 10 years, boys with daily Deflazacort were 7 cm shorter than untreated At age 15 years, boys with daily Deflazacort were 21 cm shorter than untreated
Biggar WD et al Neuromuscul Disord 2006
Corticosteroid And Delayed Puberty/Hypogonadism In DMD
Delayed Puberty In DMD
6 out of 12 boys (50%) > 14 years with DMD treated with deflazacort no signs of puberty (Dooley JM et al Pediatr Neurol 2013)
4 out of 4 boys (100%) with DMD treated with alternate day Prednisolone had delayed puberty and 3 required testosterone treatment (Merlini L et al Muscle Nerve 2012)
43 out of 44 boys (98%) aged > 13 years (31 boys > 14 years) with DMD treated with daily steroid were pre-pubertal (Bianchi ML et al Neuromuscul Disord 2011)
Strategies To Promote Growth In DMD
Challenges In Clinical Practice
1- Accurate measurement in wheel chair bound boys
Arm span / segmental growth Sitting height Measurement during DXA
Challenges In Clinical Practice
2- Assessment of puberty in adolescents with DMD
Accurate measurement of testes Self assessment charts
Bloods/ dynamic stimulation test
Urinary LHBone age x ray
GH-IGF1 Axis
Growth hormone
IGF-1
Growth Hormone In DMD
Rutter M et al Neuromuscul Disord 2012
Unanswered questions about use of rhGH-Dose-Long term effects on linear growth-Other benefits – bone and muscle-Adverse events: glucose homeostasis and insulin resistance
Possible role of rhIGF1-Ongoing trial in USA-Efficacy-Adverse events: hypoglycaemia-GH+ IGF1
Pubertal Induction In Chronic Disease
Testosterone therapy in boys with IBDMason A et al Horm Res 2011
Testosterone Therapy In DMD
Duration of treatment, dose, route of administration
No published study on effects on growth
May lead to progression in puberty but little or no growth