生长激素缺乏症endocrine-1

nullGrowth Hormone Deficiency, GHD 生长激素缺乏症Growth Hormone Deficiency, GHD 生长激素缺乏症Department of Endocrinology Children’s Hospital Fudan University nullGHD 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 ageIntroductionnullGrowth 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 deficienciesPathogenesisnullGH 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 secretionPathogenesisGH AxisGH Axisnullinsulinlike 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 GHPathogenesisnullMost 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 GHDEtiologynullShort 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 hypoglycemiaClinical Presentationnull1. 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 deficiencyLaboratory Studiesnull2. 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. KaryotypeLaboratory StudiesnullA 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 Diagnosisnull14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 malenull7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 agePatient ResultsPatient 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)Patient ResultsPatient Results Reference range IGF－1 30ng/ml >70ng/ml IGFBP－3 1.05 ng/ml >1.82ng/mlnullConstitutional growth delay Familial short stature Intrauterine growth retardation Chronic diseases and systemic disorders Achondroplasia Bone and cartilage disorders Genetic syndromes Psychosocial dwarfism Differential DiagnosisConstitutional growth delayConstitutional growth delayMost 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 statureFamilial short statureFamily history suggestive of short stature Clinical features: normal birthweight, normal growth velocity Normal GH levelTurner SyndromeTurner SyndromeIncidence 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 null13yo Turner Syndrome femaleAchondroplasiaAchondroplasiaIncidence 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 platesnullGH 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 tumorsTreatmentnull使用Pen（新型注射器）患儿可安全自行注射生长激素nullnullnullMost 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 womenPrognosisnull