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

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.

1. Introduction

2. Background

Growth failure: defined as height velocity less than 2 SD

below the mean for age ( corresponds to approximately <

3rd percentile.

Definition

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

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

Stimulation testing

Definition of Biochemical GH deficiencyPeak 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 <20

Germany <30 2 (1 with low IGF-1 or IGFBP-3)

France <30 2

Netherlands <30 2

Spain <30 2

Sweden <24

Canada <24 2

Israel <24 2

Japan(<2005) <30 2

Japan(>2005)* <18 2

Taiwan <30 2

Indications for GH treatment in CH 1:

GHD

Turner syndrome

Somatropin (Growth hormon: 0,2-0,3 mg/kg/ week)

Follow up

Management

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

No Gender Age

1 M 10

2 M 9,5

3 F 4,5

4 M 5

5 M 11,5

6 M 12

7 F 12

Characteristics of the population

NoGender

Age Height (cm) Z-SCORE TARGET HEIGHT (cm)

1 M 10 114,5 -3,65 164

2 M 9,5 122 -2,28 161,5

3 F 4,5 78 -6,17 155

4 M 5 92,5 -3,43 165

5 M 11,5 134 -2 170,5

6 M 12 130 -2,57 170,5

7 F 12 120 -5,63 150

Characteristics of the population

Boys Height

Girls height

NoGender

Age Weight (Kg) BMI Z-SCORE

1 M 10 25 19,1 1,24

2 M 9,5 25,5 17,1 0,45

3 F 4,5 13 21,4 3,26

4 M 5 13 15,2 -0,02

5 M 11,5 30 16,7 -0,35

6 M 12 30 17,8 0,16

7 F 12 26 18,1 -0,55

Characteristics of the population

No Gender Age Bone age KARYOTYPE

1 M 10 7-8

2 M 9,5 8

3 F 4,5 1,5 46XX

4 M 5 2,5

5 M 11,5 6

6 M 12 9-10

7 F 12 7 46XX

Characteristics of the population

No Gender Age IGF1 (ng/ml) GH (ng/ml)

1 M 10 194 0,12

2 M 9,5 174 0,04

3 F 4,5 176 0,45

4 M 5 172 3,03

5 M 11,5 214 0,61

6 M 12 120 0,48

7 F 12 182 0,0

Characteristics of the population

NoTSH

(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

Characteristics of the population

NoGH

(ng/ml)Peak GH (exercise)

Peak GH (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

Stimulation test

Peak GH after 2 stimulation test < 10mU/l (<5 ng/ml)

No 2 6

MRI Small pituitary: 4x6x7 mm

Posterior pituitary lobe: absentAnterior pituitary lobe: normal

MRI

The others has normal brain MRI

Outcome of therapy

STTDose of GH(mg/Kg/day)

Time (month)

Height (before) (cm)

Height (after) (cm)

∆H(cm)∆H

/month

1 0.04 13 114,5 126 11,5 0,88

2 0,03 4 122 125 3 0.75

3 0,04 14 78 101 23 1.64

4 0,04 3.5 92,5 96 3.5 1.00

5 0,035 9.5 134 144 10 1.05

6 0,035 24 130 146,5 16.5 0.69

7 0,04 5 120 125 5 1.00

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)

NoIGF1

(ng/ml)IGF1 (ng/ml) (6 months)

Bone ageBA

(6 months) BA

(1 year)

1 194 186 7-8 9 9

2 174 - 8 - -

3 176 146 1,5 2 4

4 172 - 2,5 - -

5 214 172 6 6-7 -

6 120 - 9-10 - 11

7 182 214 7 7-8 -

Follow up

Side effects: We did not notice any side effect of GH in all cases

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.

Conclusion

Recommendations

Assessment of growth over time is an essential aspect of child health

care

More Scientific studies about GH treatment in Vietnam

Medical insurance

Thank you