MD.Trần Thị Bích Huyền Children hospital 1 Endocrine department Efficacy of exogenous Growth hormon (GH) treatment in children with growth hormon deficiency (GHD) in Children Hospital 1 MD.Trần Thị Bích Huyền Children hospital 1 Endocrine department
1. Introduction Growth hormon (GH): secreted by anterior pituitary lobe, stimulates cartilage growth. GH deficiency (GHD) causes growth failure in children. The etiology of GHD may be congenital or acquired. Incidence of short stature associated GHD : 1/3500-4000
1. Introduction In the world: GH has been available for management of short stature associated GHD from 1985 .. In1921: initial therapy with bovine GHnot efficiency. 1985: Recombinant DNA-derived human GH (hGH) has been available.
1. Introduction Vietnam: limitation in diagnosis and treatment GHD (laboratory, drugs) 2010 : diagnostic approach to short stature and started to use exogenous GH for GHD in Children hospital. We report the efficacy of GH therapy in 7 patients with GHD in my hospital.
2. Background
Definition Growth failure: defined as height velocity less than 2 SD below the mean for age ( corresponds to approximately < 3rd percentile.
Aetiology of GHD Congenital forms Acquired forms Tumours or defects of hypothalamus Pituitary: tumours, trauma, central nervous system disease, infections, late effects of cancer therapy ...
Diagnostic approach to Short stature Clinical and auxological assessment Baseline Investigations: Bone age Karyotype Systemic screen FBC, EUC, TSH, T4, Ca, Phos, urinalysis IGF-1, GH, LH, FSH, Testosterone/Estrogen Subsequent Investigations: GH stimulation tests Imaging studies as indicated (MRI)
Stimulation testing Clonidine, Arginine, Insulin, Glucagon, Levodopa, GHRH, exercise test. Diagnosis of GHD: 2 stimulation tests Children hospital 1: Insulin and exercise test
Stimulation testing Peak GH > 20mU/l (10ng/ml): normal Peak GH: 10-20mU/l (5-10ng/ml): partial GH deficiency Peak GH< 10mU/l (5ng/ml): GH deficiency
Definition of Biochemical GH deficiency Peak GH cut off for diagnosis of GHD mU/L No of provocative tests Australia 10 2 UK (Kirk 2006) <20 1 or 2 USA <30 New Zealand Germany 2 (1 with low IGF-1 or IGFBP-3) France Netherlands Spain Sweden <24 Canada Israel Japan(<2005) Japan(>2005)* <18 Taiwan
Management Indications for GH treatment in CH 1: GHD Turner syndrome Somatropin (Growth hormon: 0,2-0,3 mg/kg/ week) Follow up Side effects Plotting on growth charts and monitoring growth rate over a 3 to 6 month period Reassessment : IGF-1, bone age every 6-12 month period
GH side effects Uncommon overall Benign intracranial hypertension (1 in 1000) Slipped capital femoral epiphyses Odema Risk of diabetes Progression of scoliosis Cancer
3. Outcome
Characteristics of the population No Gender Age 1 M 10 2 9,5 3 F 4,5 4 5 11,5 6 12 7
Characteristics of the population No Gender Age Height (cm) Z-SCORE TARGET HEIGHT (cm) 1 M 10 114,5 -3,65 164 2 9,5 122 -2,28 161,5 3 F 4,5 78 -6,17 155 4 5 92,5 -3,43 165 11,5 134 -2 170,5 6 12 130 -2,57 7 120 -5,63 150
Boys Height
Girls height
Characteristics of the population No Gender Age Weight (Kg) BMI Z-SCORE 1 M 10 25 19,1 1,24 2 9,5 25,5 17,1 0,45 3 F 4,5 13 21,4 3,26 4 5 15,2 -0,02 11,5 30 16,7 -0,35 6 12 17,8 0,16 7 26 18,1 -0,55
Characteristics of the population No Gender Age Bone age KARYOTYPE 1 M 10 7-8 2 9,5 8 3 F 4,5 1,5 46XX 4 5 2,5 11,5 6 12 9-10 7
Characteristics of the population No Gender Age IGF1 (ng/ml) GH (ng/ml) 1 M 10 194 0,12 2 9,5 174 0,04 3 F 4,5 176 0,45 4 5 172 3,03 11,5 214 0,61 6 12 120 0,48 7 182 0,0
Characteristics of the population No TSH (uIU/ml) FT4 (ng/dl) Cortisol (g/dl) 1 1,3 1,68 8,25 2 1,39 1,57 14,7 3 4,65 0,86 15,15 4 3,13 1,72 8,97 5 3,67 1,19 8,87 6 3,52 0,96 8,9 7 4,53 0,83 6,8 Screening tests: FBC, EUC, Ca, Phos, urinalysis: normal
Stimulation test No GH (ng/ml) Peak GH (exercise) (test Insulin) 1 0,12 1,41 2,39 2 0,04 1,52 3,49 3 0,45 0,16 0,37 4 3,03 4,05 4,29 5 0,61 1,89 2,89 6 0,48 0,88 0,94 7 0,0 0,06 0,05 Peak GH after 2 stimulation test < 10mU/l (<5 ng/ml)
MRI No 2 6 MRI Small pituitary: 4x6x7 mm Posterior pituitary lobe: absent Anterior pituitary lobe: normal The others has normal brain MRI
Outcome of therapy STT Dose of GH (mg/Kg/day) Time (month) Height (before) (cm) Height (after) ∆H(cm) ∆H /month 1 0.04 13 114,5 126 11,5 0,88 2 0,03 4 122 125 3 0.75 0,04 14 78 101 23 1.64 3.5 92,5 96 1.00 5 0,035 9.5 134 144 10 1.05 6 24 130 146,5 16.5 0.69 7 120
Patient 1 TARGET HEIGHT (164cm)
Patient 2 TARGET HEIGHT (161,5cm)
Patient 3 TARGET HEIGHT (155cm)
Patient 4 TARGET HEIGHT (165cm)
Patient 5 TARGET HEIGHT (170,5cm)
Patient 6 TARGET HEIGHT (170,5cm)
Patient 7 TARGET HEIGHT (150cm)
Follow up No IGF1 (ng/ml) IGF1 (ng/ml) (6 months) Bone age BA (1 year) 194 186 7-8 9 2 174 - 8 3 176 146 1,5 4 172 2,5 5 214 6 6-7 120 9-10 11 7 182 Side effects: We did not notice any side effect of GH in all cases
Conclusion All patients were diagnosed and started to treat with GH at mean age 9,5 years. Height of cases less than 3 SD below the mean for age before treatment . There was a clear improvement of height in all patients and the mean of height velocity was 1cm/month in the first year . We did not notice any side effect of GH in all cases.
Recommendations Assessment of growth over time is an essential aspect of child health care More Scientific studies about GH treatment in Vietnam Medical insurance
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