Growth

Question 1

List 3 growth factors important in fetal life

Answer 1

1. Insulin
2. Epidermal growth factor
3. Fibroblast growth factor

Question 2

List 4 endocrine factors important for postnatal growth

Answer 2

1. Growth hormone and IGF1
2. Thyroid hormone
3. Sex steroids (pubertal growth spurt)
4. Glucocorticoids

Question 3

How does the upper:lower segment ratio change over time?

Answer 3

Question 4

Obesity ______ growth hormone and _______ IGF1

Answer 4

Obesity decreases GH and increases IGF1

Mechanism: increased GH receptors

Question 5

Growth charts are available for the following conditions:

Answer 5

• Achondroplasia
• Down syndrome
• Noonan syndrome
• Williams syndrome
• Turner syndrome
• Russell-Silver syndrome

Question 6

The majority of SGA infants show good catch-up growth. About ______% have lifelong short stature

Answer 6

20%

Question 7

List 3 endocrine sequelae of SGA after birth

Answer 7

• Premature adrenarche
• Precocious puberty/menarche
• Dyslipidemia
• Insulin resistance
• Obesity
• PCOS

Question 8

List 5 clinical features of congenital growth hormone deficiency

Answer 8

• Short stature
• Cherubic/pudgy appearance
• Immature high-pitched voice
• Delay in skeletal maturation
• Hyperlipidemia (elevated total chol and LDL)
• Microphallus
• Hypoglycemia and seizures
• Breech presentation
• Normal intelligence
• Midline defects (ex. SOD)

Question 9

______% of children do not have an adequate rise in GH when tested with one agent

Answer 9

10%

Therefore two methods are necessary to diagnose GHD

Question 10

List 4 agents that may be used to test for GHD

Answer 10

• Arginine (0.5 g/kg IV)
• Clonidine (0.1 mg/m2 PO)
• Glucagon (applies to GH and ACHT, 30 mcg/kg)
• Oral levodopa
• Insulin (no longer used, applies to GH, ACTH and cortisol)
• GHRH
• Synthetic GHRP’s (GH releasing peptides)

Question 11

What factors must one consider when interpreting IGF1? List 3

Answer 11

• Starvation lowers IGF1
• Patients with constitutional delay have low IGF1 for chronologic age but normal for skeletal age and will not benefit from GH therapy
• Patients with normal IGF1 may still benefit from GH therapy

Question 12

List 5 complications og GH therapy

Answer 12

• Slipped capital femoral epiphyses (most common in hypothyroid)
• Pseudotumor cerebri
• Tendency toward diabetes in predisposed patients
• Gynecomastia
• Theoretical risk of promoting growth of pre-existing cancerous cells (usually wait 1 year after cancer treatment to start GH)
• Elevated LDL, low HDL
• Development of GH antibodies/cessation of growth

Question 13

What conditions are approved by FDA for treatment with growth hormone?

Answer 13

• Turner syndrome
• Growth hormone deficiency
• Small for gestational age without catch-up growth
• Renal disease in childhood
• Noonan syndrome
• ?Prader Willi syndrome
• Idiopathic short stature (height below 2.25 SD for age, predicted to fall short of reaching normal adult height)

Question 14

List 1 condition which can be treated with recombinant IGF-1

Answer 14

• Laron dwarfism (GH resistance)

Question 15

List a differential diagnosis for genetic syndromes of tall stature

Answer 15

• Sotos syndrome (Cerebral gigantism, NSD1 gene)
• Marfan syndrome (FBN1 gene)
• Homocytinuria (CBS gene)
• Beckwith Wiedemann Syndrome (loss of maternal 11p15.5)
• XYY Syndrome
• Klinefelter

Question 16

What is the average adult height of untreated children with GHD?

Answer 16

Males: 143 cm

Females: 129 cm

Question 17

List 4 actions of IGF1

Answer 17

• Negative feedback to GHRH
• Decreases apoptosis
• Increases muscle mass
• Increases linear growth (via chondrocyte replication)
• “Insulin-like effect” - may induce hypoglycemia
• Lymphadenopathy, tonsillary hypertrophy
• Salt and water retention

Question 18

List 4 actions of GH

Answer 18

• Lipolysis
• Gluconeogenesis
• Increases IGF1 and IGFBP3
• Increases muscle mass
• Stimulates bone chondrocyte differentiation
• Increases insulin resistance