Growth Hormone Deficiency,GHD
生长激素缺乏症
Department of Endocrinology
Children’s Hospital
Fudan University
? GHD is a disorder involves the pituitary
gland
? Pituitary gland does not produce enough GH
? Growth velocity is slower than normal
? GHD can occur at any age
Introduction
? Growth hormone (GH) is a hormone that
stimulates normal growth of bones and
tissues
? GHD may result from disruption of the GH
axis
? GHD may be isolated (isolated GHD) or
associated with other pituitary deficiencies
Pathogenesis
? GH is stimulated by GH-releasing hormone
(GHRH) from the hypothalamus
? GH is stimulated by certain GH-releasing
peptides (GHRPs)
? Somatostatin is secreted by the hypothalamus
inhibits GH secretion
Pathogenesis
GH Axis
Bone epiphysis
Hypothalamus
Anterior pituitary
SS
(-)
GHRH
(+)
GH
Liver
IGF-1
(-)
Gonads
T E2
Thyroid gland
T3 T4
? insulinlike growth factor 1 (IGF-1) is secreted and acts
locally at the site of growing bone
? IGF-1 binds to one of several IGF-binding proteins
(IGFBPs) and circulates almost entirely (>99%) in the
bound state
? IGFBP-3 accounts for the majority of IGF-I binding
and this binding protein’s activity depends directly on
GH
Pathogenesis
? Most causes of GHD are idiopathic
? Secondary causes
? Brain tumors,most commonly
craniopharyngioma
? CNS surgery
? CNS radiation
? Anatomical abnormalities (eg,septooptic
dysplasia,empty sella syndrome)
? Genetic GHD
Etiology
? Short stature
? Low growth velocity for age and pubertal stage
? Increased amount of adipose tissue around the
waist
? The child may look younger
? Delayed tooth development
? Delayed onset of puberty
? Episodes of hypoglycemia
Clinical Presentation
1,GH stimulation test
? Provocative stimuli include insulin,arginine,levodopa
(l-dopa),clonidine and glucagon
? GH response to insulin is the most reliable test for
GHD.
? GH response ( GH level <10 ng/ml) after given 2
provocative stimuli diagnoses GH deficiency
Laboratory Studies
2,Bone age
3,Head MRI or CT
4,IGF-1 and IGFBP-3 levels
– Low values of IGF-1 and IGFBP-3
suggest GHD
5,Other pituitary hormones
6,Karyotype
Laboratory Studies
? A height below the 3rd percentile or less than 2
SD on a growth chart
? The growth velocity is slow ( ? 4 cm/y from age
2y to puberty )
? The peak growth hormone < 10 μg/Ｌ
? Delayed bone age
Diagnosis
14岁患者 （ 右 ） 患侏儒症, 与
同年龄发育正常男孩 （ 左 ） 比较
(left) Normal 14yo male
(right) 14yo GHD male
7岁生长激素缺乏症
患者腕部 X线摄片
－－腕部骨化中心
的发育符合 3岁年龄
7yo male with
3yo bone age
Patient Results
GH Level 0’ 20’ 30’ 60’ 90’ 120’
Insulin 0.72 0.29 1.53 1.49 1.44 1.76
(?g/L)
Arginine 0.13 --- 3.69 1.52 2.20 0.22
(?g/L)
Reference range
IGF－ 1 30ng/ml >70ng/ml
IGFBP－ 3 1.05 ng/ml >1.82ng/ml
Patient Results
? Constitutional growth delay
? Familial short stature
? Intrauterine growth retardation
? Chronic diseases and systemic disorders
? Achondroplasia
? Bone and cartilage disorders
? Genetic syndromes
? Psychosocial dwarfism
Differential Diagnosis
Constitutional growth delay
? Most common in males
? Seen in 1/3 of patients presenting with short
stature
? Family history of delayed growth and puberty
? Bone age mirrors height age instead of
chronologic age
Familial short stature
? Family history suggestive of short stature
? Clinical features,normal birthweight,
normal growth velocity
? Normal GH level
Turner Syndrome
? Incidence 1/2500 – 1/5000
? Chromosomes 45 XO,45XO/46XX,
46 XXq-,46 XXp-
? Clinical features,webbed neck,shield
chest,widely-spaced nipples,streak
ovaries,amenorrhea,absence of
secondary sex characteristics
13yo Turner
Syndrome
female
Achondroplasia
? Incidence of 1/5000 – 2/26000
? Clinical features,frontal bossing,midface
hypoplasia,normal trunk length,shortened limbs
with trident hands and brachydactyly
? Xrays with contracted skull base,square-shaped
long bones,chevron-shaped distal femoral epiphysis,
shortened growth plates
? GH replacement
? The drug is given subcutaneously once
daily at a dosage of 0.1U/kg
? Other pituitary deficiencies should be
treated
? Surgical resection of brain tumors
Treatment
使用 Pen（ 新型注射器）患儿可安全自行注射生长激素
? Most children with GHD reach normal adult stature
? Initiate GH therapy as early as possible and continue
therapy through adolescence to ensure the best chance
of achieving height potential
? Average adult height for untreated patients with
severe isolated GHD is 143 cm in men and 130 cm in
women
Prognosis
谢谢
谢谢
生长激素缺乏症
Department of Endocrinology
Children’s Hospital
Fudan University
? GHD is a disorder involves the pituitary
gland
? Pituitary gland does not produce enough GH
? Growth velocity is slower than normal
? GHD can occur at any age
Introduction
? Growth hormone (GH) is a hormone that
stimulates normal growth of bones and
tissues
? GHD may result from disruption of the GH
axis
? GHD may be isolated (isolated GHD) or
associated with other pituitary deficiencies
Pathogenesis
? GH is stimulated by GH-releasing hormone
(GHRH) from the hypothalamus
? GH is stimulated by certain GH-releasing
peptides (GHRPs)
? Somatostatin is secreted by the hypothalamus
inhibits GH secretion
Pathogenesis
GH Axis
Bone epiphysis
Hypothalamus
Anterior pituitary
SS
(-)
GHRH
(+)
GH
Liver
IGF-1
(-)
Gonads
T E2
Thyroid gland
T3 T4
? insulinlike growth factor 1 (IGF-1) is secreted and acts
locally at the site of growing bone
? IGF-1 binds to one of several IGF-binding proteins
(IGFBPs) and circulates almost entirely (>99%) in the
bound state
? IGFBP-3 accounts for the majority of IGF-I binding
and this binding protein’s activity depends directly on
GH
Pathogenesis
? Most causes of GHD are idiopathic
? Secondary causes
? Brain tumors,most commonly
craniopharyngioma
? CNS surgery
? CNS radiation
? Anatomical abnormalities (eg,septooptic
dysplasia,empty sella syndrome)
? Genetic GHD
Etiology
? Short stature
? Low growth velocity for age and pubertal stage
? Increased amount of adipose tissue around the
waist
? The child may look younger
? Delayed tooth development
? Delayed onset of puberty
? Episodes of hypoglycemia
Clinical Presentation
1,GH stimulation test
? Provocative stimuli include insulin,arginine,levodopa
(l-dopa),clonidine and glucagon
? GH response to insulin is the most reliable test for
GHD.
? GH response ( GH level <10 ng/ml) after given 2
provocative stimuli diagnoses GH deficiency
Laboratory Studies
2,Bone age
3,Head MRI or CT
4,IGF-1 and IGFBP-3 levels
– Low values of IGF-1 and IGFBP-3
suggest GHD
5,Other pituitary hormones
6,Karyotype
Laboratory Studies
? A height below the 3rd percentile or less than 2
SD on a growth chart
? The growth velocity is slow ( ? 4 cm/y from age
2y to puberty )
? The peak growth hormone < 10 μg/Ｌ
? Delayed bone age
Diagnosis
14岁患者 （ 右 ） 患侏儒症, 与
同年龄发育正常男孩 （ 左 ） 比较
(left) Normal 14yo male
(right) 14yo GHD male
7岁生长激素缺乏症
患者腕部 X线摄片
－－腕部骨化中心
的发育符合 3岁年龄
7yo male with
3yo bone age
Patient Results
GH Level 0’ 20’ 30’ 60’ 90’ 120’
Insulin 0.72 0.29 1.53 1.49 1.44 1.76
(?g/L)
Arginine 0.13 --- 3.69 1.52 2.20 0.22
(?g/L)
Reference range
IGF－ 1 30ng/ml >70ng/ml
IGFBP－ 3 1.05 ng/ml >1.82ng/ml
Patient Results
? Constitutional growth delay
? Familial short stature
? Intrauterine growth retardation
? Chronic diseases and systemic disorders
? Achondroplasia
? Bone and cartilage disorders
? Genetic syndromes
? Psychosocial dwarfism
Differential Diagnosis
Constitutional growth delay
? Most common in males
? Seen in 1/3 of patients presenting with short
stature
? Family history of delayed growth and puberty
? Bone age mirrors height age instead of
chronologic age
Familial short stature
? Family history suggestive of short stature
? Clinical features,normal birthweight,
normal growth velocity
? Normal GH level
Turner Syndrome
? Incidence 1/2500 – 1/5000
? Chromosomes 45 XO,45XO/46XX,
46 XXq-,46 XXp-
? Clinical features,webbed neck,shield
chest,widely-spaced nipples,streak
ovaries,amenorrhea,absence of
secondary sex characteristics
13yo Turner
Syndrome
female
Achondroplasia
? Incidence of 1/5000 – 2/26000
? Clinical features,frontal bossing,midface
hypoplasia,normal trunk length,shortened limbs
with trident hands and brachydactyly
? Xrays with contracted skull base,square-shaped
long bones,chevron-shaped distal femoral epiphysis,
shortened growth plates
? GH replacement
? The drug is given subcutaneously once
daily at a dosage of 0.1U/kg
? Other pituitary deficiencies should be
treated
? Surgical resection of brain tumors
Treatment
使用 Pen（ 新型注射器）患儿可安全自行注射生长激素
? Most children with GHD reach normal adult stature
? Initiate GH therapy as early as possible and continue
therapy through adolescence to ensure the best chance
of achieving height potential
? Average adult height for untreated patients with
severe isolated GHD is 143 cm in men and 130 cm in
women
Prognosis
谢谢
谢谢
