short stature

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Short stature
Definition: Ht > 2 SD below expected mean for age Ht velocity < 3rd percentile or <4 cm at any age. By definition 2.5% of the population is short. However, the number of children with poor linear growth is higher given the frequency of chronic diseases of childhood short boys are more likely to come to medical attention than short girls.

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Causes
Normal variants -genetic(familial ) -constitutional Abnormalities intrinsic to growth plate - skeletal dysplasia - Chromosomal anomalies - IU growth retardation 2yr short stature - malnutrition - systemic illness - Endocrine causes

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Normal Variants
Familial Short Stature Ht < 2.5 SD Ht within MPH NL Ht velocity Bone age= chronological age 2subtypes NL puberty delayed puberty

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Normal Variants
Constitutional growth delay: No systemic illness,NL nutrition , NL physical examination. Growth deceleration 18-30 cm ,steady growth velocity Ht <2 SD Ht < MPH Bone age< chronological age Normal Adult Ht Delayed puberty



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Primary Growth plate Abnormality

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I.Osteochondroplasia
Heterogenous group with intrinsic abnormaliy in cartilage & bone Characterized by genetic transmission, abnormality in size & shape of bones, radiological abnormality of bone. AD+ new mutation >100 types Achondroplasia is commonest 1/26000 FGFR3 on Ch 4,AD,90% new mutation

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II.Chromosomal anomalies
Cause of growth failure is unknown,does not affect GH or IGF Examples include: Down Syndrome Turner syndrome( 95-100% short,SHOX , mild IUGR ,dec HT velocity 3-14 y, GH NL ,GH therapy) Others :Ch 5 p deletion ,Trisomy 13/18 Ch 18 q deletion

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III-Intrauterine Growth Retardation
IUGR=fetal BW & Lt <2 SD below mean GA Catch up growth 4y ( 15% fail) , Low IGF1 IGFBP 3 Etiology 1.Intrensic fetal abnormalities - chromosomal disorders - syndromes with primary growth failure,(russel silver ,seckel ,noonan, progeria, cockyane,bloom, rubestiein taybi..) IU infections 2.Placental abnormalities ( abnormal implantaion,vascular insufficiency..) 3.Maternal factors (malneutrition,smoking,drugs,uterine malformations,PET...)

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Secondary Growth Disorders

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I-Malnutrition
Commenest cause of growth failure worldwide Increase in GH & stimulated GH in kwashiorkor) Adaptive process spare protein due to lipolytic & anti insulin effect of GH NL GH in marasmus

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II-Chronic Illness
GI CV Renal Hematological Pulmonary Chronic infections Inborn error of metabolism Immunodeficiency DM

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Endocrine Causes
Account for 5 % of causes for short stature : Hypothyroidism Cushing syndrome Pseudo-hypoparathyroidism GH deficiency

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GH deficiency: hypothalamic dysfunction Pituitary GH deficiency GH insensitivity

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Hypothalmic Dysfunction
Congenital malformation of hypothalamus (holoproncephay, septo-optic dysplasia) Molecular defect of GHRH or GHRH receptor Trauma Inflammation Tumors Irradiation

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Pituitary GH deficiency
Genetic abnormality-combined def :HESX, Reigs,PROP..) Genetic abnormality in GH : - GHD IA,IB AR - GHD II AD - GHD III X linked Tumor ,trauma,infection,irradiation GH neurosecretary dysfunction Bio- inactive GH Psychosocial dwarfism

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GH insensitivity:
NL GH with failure to respond to exogenous GH GHI + dysmorphism =Laron syndrome 1ry: -GH receptor -post receptor abnormality -IGF1 biosynthesis 2ry: - Circulating Ab to GH - Circulating Ab to GH receptor - Illness

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Clinical Features Of GHI
NL BW & Lt & severe post natal growth failure Bone age delayed Miropenis Craniofacial :spares hair,frontal bossing small face, craniofacial disproportion, shallow orbit hypoplastic nasal bridge ,delayed dentition, blue sclera, high pitched voice Metabolic: hypoglycemia,delayed motor mile stones ,osteoporosis ,infantile fat distribution

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Diagnosis of GH Deficiency
GH secretion is pulsatile ,surge in slow wave sleep ( stage 3-4) Secretion varies with age, gender physiological state ,pubertal stage NL GH are low(< 1ng/ml) random GH level are useless in diagnosing GH deficiency Provocative test are indicated Neonate,random GH <2o ng/ml is diagnostic

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Biochemical Evaluation of Growth failure
Step I : defining the risk of GH deficiency:-Severe short stature SD < -3 Sd-Sever growth deceleration Ht velocity <2 SD in 12m-Ht <2 SD, HV <-1 SD over 12m-Ht<1.5SD, HV <1.5 SD over 2y-Risk factors : brain tumors,irradiation. if +ve step 2 If –ve re evaluate in 6 month


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Provocative test:
Types: Physiological: sleep,fasting,exercise Pharmacological test: *Screening:clonidine,L-dopa *Definitive: insulin,glucagon,arginine Sub optimal response <10ng/ml Neonate GH <20ng/m(random) 2 pharmacological tests needed for the diagnosis

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Step II: Scan for GH/IGF deficiency: A: lab tests: bone age,TFT,chromosomal analysis B: IGF1&IGFBP3 > -1 SD review in 6m <-2 SD GH testing Step III: Testing GH secretion -2 stimulation tests if both low step 4 *GH >15 - GHBP < -2SD IGF defect - GHBP NL follow in 6 month *GH 10-15 back to step 2 in 6m

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Step IV:Evaluate pituitary: -MRI -Test anterior pituitary hormones Step V:Growth promotion: -Initiate GH therapy

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Treatment of GH deficiency:
Objective: attain normal Ht in childhood & NL adult HT. Therapy: rhGH ( specie specific) Dose 25-50mcg/kg/day Accelerated effect in 1st 3-4 y,then progressive weaning of the effect Gain 10-12cm/y in 1st y then 7-9cm/y in 2-3rd y Patient should be monitored at 3-6month intervals

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Causes of Sub optimal response: Poor compliance In proper administration or preparation Chronic disease Glucocorticiod therapy Irradiation of spine Anti GH antibodies (10-20 %) Incorrect diagnosis

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Side effect of GH therapy: Leukemia Pseudotumor cerebri Slipped capital femoral epiphysis Gynecomastia Scoliosis,kyphosis Neurofibromatosis Sleep apnea &behavior changes Abnormal glucose tolerance Hyperlipidemia

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Evaluation Of Short Stature
History: length, weight, and head circumference at birth,relevant antenatal & post natal event Assessing the heights of both parents is absolutely essential.(MPH) Document pubertal timing in first-degree relatives. determine the age at onset of menarche for the child's mother and the age of adult height attainment for the father.

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History:
Review of symptoms by organ system Gastrointestinal Diarrhea, flatulence, ( suggest malabsorption). Vomiting can suggest an eating disorder or a (CNS) disorder. dietary intake and composition. In particular, ask about intake of carbonated beverages, juices, and other casual intake. Pain or abdominal discomfort suggests inflammatory bowel diseases.

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Cardiac disease: peripheral edema, murmurs, and cyanosis. Chronic infections: Poor wound healing and opportunistic infections are signs of potential immune deficiency. Pulmonary Sleep apnea can be a cause of short stature. Other diseases that may result in short stature include severe asthma associated with chronic steroid use and cystic fibrosis Neurological Visual field deficits often herald pituitary neoplasms. Vomiting, early morning nausea, polyuria, or polydipsia often is associated with masses of the CNS

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Renal Polyuria and polydipsia Chronic renal disease Social Participation in sports requiring weight control, may uncover anorexia nervosa or bulimia induced by the patient, peers, or coaches. Education ,bullying ,psychological impact

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Physical Exam
Measure standing height in triplicate using a calibrated wall-mounted stadiometer For children who cannot stand or recline completely arm span provides a reliable alternative for longitudinal assessment of long bone growth. Document growth velocity Weigh all patients.,BMI In infants, determine the HC sitting height,U/L Pubertal Assessment



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Thyroid enlargement Test visual fields for signs of pituitary and/or hypothalamic tumors Inspect fourth metacarpals, which are shortened in persons with pseudohypoparathyroidism-Turner syndrome, and Albright hereditary osteodystrophy. Inspect mucous membranes for ulcerative stomatitis, typical of Crohn disease and various trace mineral and vitamin deficiencies. Pretibial ulcerations observed in persons with IBD Rectal tags and clubbing are also typical in individuals with Crohn disease examine the midface. A single, central, maxillary incisor reflects a defect in midline facial development. bifid uvula ,submandibular cleft palate,.

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Investigations
Initial screen Full blood count, ESR, BUN and electrolytes, bone profile, liver function tests thyroid function Urinalysis Skeletal (bone) age Karyotype (girls) antiendomyseal antibody

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Specific investigations (when indicated)
Endocrine("provocation" tests) Gastrointestinal - for example, jejunal biopsy, antiendomyseal antibody Renal Respiratory Cardiac Radiological - for example, magnetic resonance imaging of the brain

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