Short Stature and Growth Hormone Therapy – Flashcards

Length or Height more than 2 SD below the mean, Or less than the 3 rd percentile, for chronological age, sex & genetic background. A Symptom Not a disease !

Normal variant Or Pathologic disorder

growth rate below the app growth velocity for age

normal variant short statue 80%

short but N growth velocity ( ht is always proceeding along the same centile line) - genetic (familial) short st - constitutional short st

- non endocrinal . nutritional . non nutrional ( ch organ /system disorders, skeletal dysplasia, IUGR, chromosomal & dysmorphic S - endocrinal less than 10%

-born small -short parents -bone age is nearly equal to chronological age - puberty at N time - bcome a short adult (~ 10 cm below average)

- born N in size and crosses down percentiles to less than 3rd percentile over the 1st 2-3 years - hx of delayed puberty in one parent - bone age is delayed - delayed puberty & pubertal growth spurt - N adult ht & sexual development

Malnutrition

-Growth hormone deficiency. Growth hormone insensitivity. Hypothyroidism Cushing's syndrome Pseudohypoparathyroidism Poorly controlled diabetes. Precocious puberty "Tall as kid, Short as an adult"

• Intrauterine phase • Infancy phase • Pre-pubertal childhood phase • Pubertal phase

Little role for GH Insulin - IGF-I

Thyroxin - IGF-I - insulin- GH

GH - IGF-I - IGFBP-3

GH -- IGF-I sex steroids

Is the child really short ? Is the child growing slowly ? Is the child a normal variant short stature ? Does the child have a pathological short stature? Does the child need treatment & what is such tt?

• Family history. (shortness, puberty,syndromes) • Previous growth data (records &charts). • Size at birth. • Associated symptoms and medications used.

• Shortness of parents and relatives. • In childhood & in adulthood. • Short as kid, normal as an adult. • Timing of puberty in parents.

• Low birth wt & birth length points to IUGR due to : - Genetic syndrome. - Intrauterine infection. - Drug induced growth failure.

•Measurements plotted on appropriate charts. - Absolute height. - Height velocity. • Parental Heights (Mid-parental Height) • Indices of nutritional status ( wt for age, BMI/ MAC) • Body proportions. • Pubertal assessment. • Dysmorphology. • System review. • Skeletal Maturity.

• Stadiometer • Barefeet • Four points touching the wall • Frankfurt plane [line joining inferior orbital margin to ext auditory meatus] paralel to ground • Serial measurements better

For boys = Mother's height + Father's height + 13 over 2 For girls = Mother's height + Father's height - 13cm over 2 Predicted adult height = MPH ± 5 cm. Predicted adult height percentile usually match current Child's !

Normal U/L Ratio: Genetic. Constitutional delay, Hypopituitarism. High U/L Ratio: Cong hypothyroidism. Achondroplasia. Low U/L Ratio: Hurler syndrome. Morquio disease.

• Mid arm circumference. •Weight for age and • Weight for Ht. (BMI) • Subcutaneous Skin-fold Thickness.

•Often points to an organ system disease that may cause growth failure and short stature. • Associated poor nutritional indices is common in this group of disorders. • Poor growth may be the initial manifestation of A systemic disorder.

supporting a diagnosis of genetic disorders • Dysmorphic features • Disproportionate shortening • A history of IUGR • Mental retardation • Significant obesity

Short-limb dysplasia= Achondroplasia Short trunk dysplasia =Morquio disease

• It needs Expert Reader. • Very Useful Test. • Normal Bone Age Excludes Endocrine Causes. • Correlates Well with Onset of Puberty. • Delayed bone Age in Constitutional Delayed Growth Indicates Potential for Further Growth before puberty. also delay in malnutrition, hypothyroididm, hypopituitarism • advanced bone age in congenital adrenal hyperplasia for dx infantile rickets and metappyseal dysplasia for skeletal dysplasia (achondroplasia)

Familial short Stature. Severe IUGR. Genetic syndromes

Almost always due to endocrinal, metabolic or systemic disorder

Puberty is retarded. Continue growing longer Normal final Ht

Makes an endocrinal disease unlikely.

Laboratory determinations To detect or exclude -Blood :Hb, Ht, leukocytes, red cell indices, leukocyte differentiation, ESR To detect or exclude Anemia, infections & inflammatory disorders -Creatinine, sodium, potassium, calcium, phosphate, alkaline phosphatase, iron, ferritin, albumin To detect or exclude Renal disorders, calcium/ phosphate disorders, malabsorption -Acid-base balance (0-3 years)To detect or exclude Renal tubular acidosis IgA-anti-endomysium antibodies, IgA-anti-tissue transglutaminase antibodies , total IgA To detect or exclude Celiac disease -TSH, free T4 To detect or exclude Hypothyroidism - GH provocation testing, IGF-I, & IGFBP-3 To detect or exclude Growth hormone deficiency -Urine : Glucose, protein, blood, sediment To detect or exclude Kidney disorders -If the above tests are negative Chromosome analysis To detect or exclude Turner syndrome

Noonan syndrome GrowthHormoneDeficiency CRI Turner Syndrome Idiopathic short stature Prader Willi Syndrome SGA

• Short stature may be the only sign. • Cherubic face; fair complexion • Normal body proportions. • Normal IQ • Delayed bone age. • Broad forehead frontal bossing • Midfacial crowding • Micropenis • Truncal obesity, small hands and feet

• Random values are useless except in the newborn . • Exercise test is difficult to standardize and & positive predictive value 10 ug/l in two GH stimulation tests are required for diagnosis • Low IGF1 and IGF1-BP3 strongly suggest abnormal GH axis.

• Genetic syndrome • 1 in 2500 - 4000 live female births.. • Complete or partial loss of the second X chromosome. • Characteristic physical findings in its classic form

Early infancy • Severe central hypotonia. • Feeding difficulties. Late infancy & childhood • Abnormal regulation of food intake. • Progressive obesity. • Short stature • Characteristic facies. • Hypogonadism • Insulin resistance • Behaviour & cognitive abnormalities.

• Newborn infants. • Weight and/or crown-heel length is more than 2 SD below the mean for their gestational age and sex. • 10% of all live-born neonates are SGA

Majority catch-up growth spontaneously by 2 yr of age, • 10 % do not catch-up. • Those who do not catch-up - lower IGF-1, IGF1-BP3. - 25% have lower GH by prov. - 60% have low 24 hr GH profile. - No signs of classic GHD

Short children (More than 2.25 SD as accepted by the US FDA) below mean for age and sex who have : • Normal size for gestational age at birth. • Normal body proportions . • Normal nutritional indices. • Absence of an identifiable disease process including dysmorphic syndromes. • Absence of a psychiatric disorder. • No evidence of endocrine deficiency. • 60- 80% of all short children will fit this definition of ISS. • Includes constitutional delay short stature and familial short stature. • Molecular genetics might disclose the cause in some of ISS.

•Genetic dysmorphic syndrome • 1: 2500 - 1:4000 live births. •Mutations on chromosome 12 q • Short stature (80%). • Turner phenotype. • Normal Karyotype. • Unique facial features • Congenital heart dis (50%) • Pulm. stenos is. • Hypertrophic cardiomyopathy.