1. Growth disturbances Knut Dahl-Jørgensen Unit for Endocrinology and Diabetes Pediatric Dept. Ullevål University Hospital

2. Simple guidelines by short stature Examined by the doctor: –All children below 2.5 height percentile –All children decreasing more than two centile chanals Refer to Pediatric Dept. by increasing deviation Enclose by referal : –Family history (growth and puberty) –History of birth, development and diseases –Growth chart –Eventually Bone age and laboratory test results

3. Differential diagnoses by short stature Constitutional Growth Delay Family Short Stature Combination of the previous Nutritional Hypocaloric Chronic inflamatory bowel disease Malabsorption, Coeliac disease Endocrine Hypothyroidism Growth Hormone Deficiency Hypopituitarism Excessive cortisol Precosious puberty Chromosome defects Turner Syndrome Maternal deprivation Low birth weight Small for gestagional age Prematurity Fetal alcohol syndrome Bone development disorders Rickets Sceletal dysplasias Metabolic Kidney failure Hypoxic, Cardiac Liver diseases Inborn errors of metabolism Syndromes Noonans Aarskog

4. Routine examinations 1 Family history growth and puberty, growth treatment, syndromes Neonatal Getational age, birth weight, birth length, forceps, Hypoglycemia, hyperbilirubinemia, mikropenis Gatrointestinal symptoms Neurological symptoms Psycosocial problems

5. Routine examinations 2 Physical examination –Height –Weight –Growth velocity (cm per year) –Tanner stages –Teticular volume –Dysmorphology (evt. sitting height, arm span) –Blood pressure –General physical examination –Neurological examination

6. Routine examinations 3 Bone age and final height prediction Clinical chemistry –TSH and free thyroxin –GH, IGF-1, IGF-BP3 –At puberty: LH, FSH, estradiol or testosteron –Coeliac screening –Hemoglobin, ferritin, CRP Chromosomes (girls) Evt. Metabolic screen, liver, kidney, bone (PTH, Vit.D)

8. Prediction of final height Bone age estimation: Greulich & Pyle Atlas Prediction: Bailly and Pinneau Tables Causion ! Variability in bone age estimation by different radiologists Great SD in reference material Total variability: Young child + 5 cm, Late puberty + 3 cm If unpredicted early puberty: Height prediction will decrease. Other method: Tanner Whitehouse

10. Normal growth patterns Normal early puberty Normal late puberty Familial (genetic) short stature Constitutional delay of growth and puberty Obesity

16. Pathological growth patterns

24. Growth hormone deficiency Clinical appearance Puppy child Hypoplastic midface ? Evt. Hypoglycemia, hyperbilirubinemia, mikropenis Auxology Drop in height percentile Growth velocity (cm per year) < 10 perc. Delayed Bone Age

25. Causes of Growth hormone deficiency CNS malformations (midline defects) Hydrocephalus CNS injuries (birth, forceps) Meningitis, brain edema Congenital infections Hypothalamic or hypophyseal tumors Cranial radiation Congenital, genetic

26. Indications for Growth hormone treatment Main indication Growth Hormone Deficiency Other indications: Turner Syndrome Kidney failure Prader-Willi Syndrome Small for gestagional age without catch-up growth ?

27. Testing Growth hormone secretion Physiological tests One random sample Physical activity Continuous overnight sampling Continuous 24 hours sampling Stimulation tests (allways two tests) Insulin iv (hypoglycemia) Arginine iv Glucagone iv or im Clonidine (oral) GHRH IGF-1, IGF-BP3

33. Growth hormone treatment Daily subcutaneous injections Injection pens Disposable prefilled syringes Autoinjection systems Dosage: 0.033 mg/kg/day (0.1 U/kg/day)