Growth and Puberty disorders

Is she short?

Short stature Standing height > 2SD below the mean (< 2.5 percentile) for gender and chronological age. Investigation of children <-2SDS identifies pathology in 14% Investigation of children <-3SDS identifies pathology in 58% Compare the child’s height with that of a larger population of a similar background and mid-parental target height.

Genetic factor is also important

Key points Short stature is defined as standing height or recumbent length more than 2 standard deviations (SD) below the mean value for chronologic age. Height (growth) velocity (cm/year) is another key auxological parameter in the assessment of a child for short stature. Height of a child must always be defined in the context of genetic potential conferred by parental heights. Short stature must not be confused with failure to thrive.

Is she short?

Height velocity How to measure Ht? Ideally with calibrated stadiometer Wall mounted Tabletop recumbent (length)< 2 yrs old Children who can’t stand: Arm span should approximate the height (>8yrs old)

Growth velocity Most important aspect of growth evaluation Change in standing Ht over: Infants: 4 mo Children: 6mo Normal (cm/yr) 1y: 25 2y: 12 3y: 8 Then until puberty: 4-7 cm

Regulation of postnatal growth • Infancy: – Nutrition – GH/IGF-I • Childhood: – Thyroxine • Pubertal: – Sex steroids

Control of GH secretion and action

SS Causes 1 • Non-pathogenic – Constitutional Delay of Growth and Puberty – Familial short stature – Nutritional • Intra-Uterine Growth Restriction – Syndromic e.g Silver-Russell syndrome – Non-syndromic • Systemic disorders – Cardiovascular disease e.g. congenital heart disease – Renal e.g. chronic renal failure, RTA – Respiratory e.g. cystic fibrosis, asthma – Gastrointestinal disease e.g. IBD – Neurological e.g. brain tumour – Psychosocial e.g. anorexia nervosa, child abuse

ETIOLOGY OF SHORT STATURE Constitutional Delay of Growth and Development/Constitutional Delay of Growth and Adolescence

CDGP • Growth velocity may be transiently decreased in the first 2 to 3 years of life (“catch down”) but normal thereafter. In some cases, a decrease in growth velocity occurs just prior to the appearance of secondary sex characteristics. • Delayed skeletal maturation (bone age) and delayed onset of puberty •Height age same as bone age •Final adult height and progression of sexual development are normal. •Often with family history of delayed growth and onset of sexual development

Familial Short Stature Bone age generally not significantly delayed and often same as chronological age Normal length and weight at birth

CDGP Vs Familial SS

Appropiate target height CDGP Vs Familial SS Familiar (genetic) Constitutional BA=CA BA<CA N growth veloc Appropiate target height

Bone age (skeletal maturation) Greulich and Pyle (compare epyphiseal centers in hand and wrist)

Greulich & Pyle Atlas

Nutritional •Caloric insufficiency •Chronic inflammatory bowel disease •Malabsorption •Celiac disease

SS Causes 2: Endocrine causes GH-related causes • Growth hormone (GH) deficiency: isolated or combined with other pituitary hormone Deficiencies • GH insensitivity Hypothyroidism Glucocorticoid excess • Cushing syndrome • Poorly managed congenital adrenal hyperplasia • Exogenous corticosteroid administration Pseudohypoparathyroidism

SS Causes 3: Chromosomal and Genetic causes – Turner syndrome – Noonan syndrome – Down syndrome – Skeletal dysplasias –achondroplasia, hypochondroplasia, spondylo-epiphyseal dysplasia – Seckel syndrome – Prader-Willi syndrome – Miscellaneous other syndromes e.g. Rothmund- Thompson syndrome, Leri-Weill syndrome, Progeria, mucopolysaccharidoses

Chronic Disease Chronic renal disease Chronic liver disease Congenital heart disease Pulmonary (cystic fibrosis, asthma) Poorly controlled diabetes mellitus Anemias (sickle cell or thalassemia)

Chronic Use of Drugs/Medications Glucocorticoids High-dosage estrogens High-dosage androgens Methylphenidate Dextroamphetamines

EVALUATION OF SHORT STATURE Prenatal history, including maternal infection, consumption of alcohol or drugs, and smoking Pattern of growth (height and weight), including birth weight and length in relation to gestational age Family history, including parental heights and age of onset of puberty of parents and first-degree relatives Profile of patient’s pubertal development, including age of onset of breast development and menarche, testicular and penile enlargement, pubic hair, and body odor Nutrition

Evaluation of short stature Evidence of systemic disease (gastrointestinal, cardiac, pulmonary, renal) Drug administration (steroids, methylphenidate) Psychosocial milieu Neurologic symptoms, especially headache, visual disturbance

Physical Examination Accurate measurements of height, weight, head circumference, arm span, and upper and lower body segments Assessment of nutritional state and fat distribution Abnormal pigmentation of the skin Dysmorphic features Sexual maturity rating (Tanner staging) Neurological examination including fundoscopy and visual field tests Examination of the thyroid gland

Target height of the child BOYS: [Father’s ht (cm)+ (mother’s Ht (cm)+ 13)] 2 GIRLS: [(Father’s ht (cm) -13) + mother’s Ht(cm)] 2 Inches: change 13 for 5’’

Baseline investigations for short stature • Full blood count, ESR • Creatinine, urea, electrolytes • Calcium, phosphate, liver function tests • Ferritin, endomysial antibodies • Karyotype (in girls) • T4, TSH • Skeletal survey in dysmorphic children • Bone age X-ray (this is NOT a diagnostic investigation)

Further investigations Low levels of IGF-1 and IGFBP3 are suggestive of GH deficiency Provocative GH stimulation test (insulin, arginine, clonidine, glucagon, L-dopa) is the accepted method for confirming the diagnosis of GH deficiency.

FDA-Approved indications for growth hormone therapy GHD PWS SGA/IUGR Turner syndrome Noonan syndrome ISS Chronic renal insufficiency AIDS wasting Adult GHD SHOX deficiency

Side effects of GH therapy Hypothyroidism Edema and sodium retention Benign intracranial hypertension Insulin resistance Slipped capital femoral epiphysis Scoliosis Gynecomastia ???Development of cancers

Tall stature: Causes

In which of the following conditions is the BA consistent with chronological age (not delayed)? Acquired hypothyroidism Constitutional delay Familial short stature Glucocorticoid excess Psychological dwarfism

You are evaluating a 6yo girl for short stature You are evaluating a 6yo girl for short stature. Her growth chart reveals a birth length at 60th percentile, and a current height at 5th percentile. Her growth velocity in the last 3 yrs has been 3cm/yr. Her weight is at the 50th percentile. On PE: wnl, and her intelligence appears normal. There are no midline defects or dysmorphic features. Her BA is 4 yrs. What is the most llikely dx? Congenital hypothiroidism Crohn disease GH deficiency Spondilodysplasia Turner