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Laurie E. Cohen, M.D.

•  Normal growth rates •  Growth patterns •  Growth hormone deficiency
short stature --- less than 2 stdev below the normal

Children’s Hospital Boston

What is Short Stature?
•  Definition:
Height < 2 SDS below the mean for age and sex •  Approximately 3% of all children

Human Variation
•  Hormones play a
major role in human growth, but not the only factor. •  Genetics, nutrition, psychological wellbeing, and other factors also determine ultimate adult height.

Postnatal Growth
•  Rapid growth velocity that declines •  Frequent crossing of percentiles as
prenatal influences diminish
in utero growth in v. rapid . first 6 mos v rapid growth

Ranges of Normal Growth Velocity (Tanner and Davies)
boys girls

progressively after birth



“slow”: <25th percentile

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Jan/Feb 2002 Monitoring Growth •  Accurate measurements at regular intervals •  Correct data recording – Record and plot data – Use correct growth charts – Plot data at correct age •  Proper equipment Page 2 .Adolescence •  Rapid and highly variable growth rate due to increased production of adrenal and gonadal hormones •  Pubertal development occurs earlier in girls (10 yrs) than boys (12 yrs) •  Pubertal growth spurt in girls is a relatively earlier event in pubertal progression Adolescence Late Adolescence / Early Adulthood •  Growth rate declines markedly after puberty – Bone growth ceases – Epiphyseal plates fuse – Height is stable (barring presence of degenerative disease/condition or trauma) Monitoring Growth Josef Gast. University of Pennsylvania Gazette.

who is now very tall Bone Age F MPH M http://emedicine.88 SD (1 SD = 5 cm**) * 13 cm ≅ 5 inches.Calculating Target Heights Midparental height Girls: (F + M) .13 cm* 2 Boys: (F + M) + 13 cm 2 F = father’s height (cm) M = mother’s height (cm) Target height = midparental height ± Constitutional Delay “Late Bloomer” •  Slowing of growth during first 2-3 years of life. ** 5 cm ≅ 2 inches Familial (Genetic) Short Stature •  Family history of short stature •  Normal birth length and weight •  Height < 3rd percentile for chronologic •  Normal annual growth rate •  Predicted adult height < 3rd percentile •  Normal onset of puberty •  No other cause of growth failure age late bloomer -.medscape. but normal annual growth rate thereafter •  Family history of similar pattern of growth and delayed puberty •  Delayed bone age closer to height age •  Normal predicted adult height in context of family pattern F MPH M height age -age at which child height is 50 percentile Page 3 . really short kid .late.

W.Normal Patterns of Growth •  Familial or genetic short stature •  Constitutional growth delay parents are really high so child may not get up there! so be concerend Turner Syndrome •  Multiple nevi •  Low posterior hairline •  Increased carrying angle •  Webbed neck •  Widely spaced nipples •  Cardiac abnormalities •  Renal abnormalities –  Horseshoe kidney –  Duplicated collecting system –  Aortic coarctation –  Left-sided defects postive correlation betwen parental height and height of turner syndrome patients. 16th ed. Saunders Company. B. 2000 Turner Syndrome •  Characteristic phenotypic features may not be present •  Should be considered in any girl who presents with unexplained short stature and no FH of short stature •  Positive correlation between parental height and height of Turner syndrome patient •  Definitive diagnosis is made with chromosomal testing Primary Growth Disturbances •  Intrauterine growth •  Genetic disorders –  Chromosomal defects / other syndromes »  Turner syndrome »  Down syndrome »  Noonan syndrome »  Prader-Willi syndrome »  Russell-Silver syndrome retardation •  Disproportionate short stature –  Skeletal dysplasias –  Spinal irradiation Page 4 .. From Behrman: Nelson Textbook of Pediatrics.

Childhood and Adolescence in Thyroid Disease Manager. http://www. coarse skin & nails –  Decreased heart rate –  Delayed DTR relaxation phase From Brown child --.under nutrition !!! Systemic Disorders •  Decreased weight-to-height ratio generally •  Absolute or relative nutritional deficiency –  IBD and celiac disease may otherwise be asymptomatic indicates a systemic illness typically results in decrease in rate of weight gain or weight loss prior to decreased linear growth •  Other chronic illnesses impair growth related to their disease activity Systemic Disorders •  Hypocaloric –  Malnutrition –  Gastrointestinal disease »  Malabsorption »  IBD »  Celiac disease –  Poorly controlled IDDM •  Metabolic –  Renal »  RTA »  Nephrogenic DI »  Renal failure –  Hepatic –  Cardiac (cyanotic) –  Hematologic (chronic anemias) –  Respiratory »  CF »  Severe asthma –  Chronic infections height affected more! but weight has fallen off. Endocrine Disorders •  Preserved weight gain or frank obesity associated with poor linear growth suggests an endocrine disorder Hypothyroidism •  Symptoms •  Signs –  Fatigue –  Cold intolerance –  Constipation –  Myxedema –  Dry. Disorders of the Thyroid Gland in Infancy.htm accessed 1/13/11 Hypothyroidism Page 5 .

Bercu BB. Contemporary Pediatrics 1998.Hypothyroidism •  Onset of signs and symptoms may be •  An overtly enlarged thyroid gland may •  Once treatment with L-T4 is initiated. 15:95-110 Growth Hormone •  Synthesized and secreted by cell types GH and its Receptor •  Receptors are present in a variety of •  Required for bone and soft tissue growth after the postnatal period somatotrophs in the anterior pituitary uses janus kinase to phosp Page 6 . not be present there is a rapid increase in growth velocity •  A permanent height deficit may remain related to duration of thyroid hormone deficiency before treatment subtle Growth Hormone (GH) Deficiency •  Immature endocrine disorder wt maintained height lost •  Large calvarium nasal bridge fat appearance •  Underdeveloped (frontal bossing) •  “Ripply” abdominal From Shulman DI.

neonatal hepatitis –  Small phallus in boys •  Mild GH deficiency usually presents after 6 months of age with subnormal growth rate Page 7 . 15:95-110 IGF from liver circulates IGF BP -3 carrier for IGF 1 -. Contemporary Pediatrics 1998. 1993 GH Deficiency •  1/4. many interleukins – Class II cytokine receptor » Many are receptors for interferon or interferon-like cytokines – TNF-receptor family – Chemokine-receptor family GH Receptor Signaling nucleus -IGF1 IGF-1 Levels IGF levels increase in adolescence short children low levels of IGF 1 From Shulman DI. GH.1/10. J Clin Endocrinol Metab 77:1294.GH Receptor •  Cytokine family of receptors – Class I cytokine receptor (hematopoietinreceptor family) » Includes erythropoietin.000 . Bercu BB. but varies only modestly with age •  Less nutritionally dependent than IGF-1 From Smith et al.000 live births •  Normal birth weights and lengths •  Severe GH deficiency may be associated with multiple anterior pituitary hormone deficits and characterized in the newborn period by: –  Hypoglycemia –  Conjugated hyperbilirubinemia.used to screening test for GH secretion IGFBP-3 Levels •  Technically simpler assay •  Circulates in plasma at high levels (µg/ ml) •  Age dependent.

Lhx3. Ptx2. Prop-1. mutations Signal transduction (lacks stat5b activation) IGF-1 IGFBP-3 intracellular domain ALS ALS mutations Page 8 . anencephaly –  Pituitary aplasia. Lhx4.Etiologies of GH Deficiency: Congenital •  Syndromes •  CNS abnormalities –  Septo-optic dysplasia –  Cleft lip ± palate –  Empty sella syndrome –  Holoprosencephaly. hypoplasia –  Thin or absent pituitary stalk –  Hydrocephalus Single Central Incisor •  Genetic •  Idiopathic Ectopic Posterior Pituitary Bright Spot with GH Deficiency GH Deficiency ectopic ADH highly suggestive of GH deficiney Hesx1. Pit-1 GH gene mutations IGF-1 Deficiency: Abnormalities GH Receptor Signaling extracellular domain transmembrane domain IGF-1 Deficiency Laron Dwarfism IGF-1 mutations GH binding dimerization trafficking to cell membrane anchoring (mutant GHR containing extracellular domain only) Signaling defects (stat5b mutation) GHR IGF-1 rec.

Impact of SNPs on Short Stature •  A single IGF-1 allele is a major determinant of size in small dogs Etiologies of GH Deficiency: Acquired •  Trauma •  Infections –  Perinatal events –  Head injury –  Meningitis –  Granulomatous disease –  Histiocytosis –  Sarcoidosis •  Neoplasms –  Craniopharyngioma –  Germinoma –  Hypothalamic astrocytoma/optic glioma •  Infiltrative Sutter NB et al. Science 2006. not a disease •  May represent a variant of normal •  May indicate pathology growth UNC Radiology Teaching File Page 9 . 316(5821):112 •  Cranial irradiation Craniopharyngioma Short Stature •  A common clinical problem •  A symptom.