194. Growth and Development

Question 1

Fetal Growth

• how is it controlled?
• what are the main endocrine regulators?

Answer 1

intrauterine growth INDEPENDENT of fetal pit hormones

Influencers of growth: PLACENTA (main source of O2 and nutrition; supply compromised by infarction, vascular insufficiency), and MATERNAL influences (malnutrition, HTN, drugs, alcohol)

1. Insulin: MAJOR regulator (hyperinsulinism = macrosmia, leprechaunism - ins receptor mutation = born small)
2. IGFs: local production critical for normal intrauterine growth
3. Thyroid Hormone + GH - not important pre-natally

Question 2

Infancy and Childhood Growth

- what are the main endocrine regulators and how do they work on growth?

Answer 2

1. Thyroid hormone: direct effect on epiphyseal cartilage (increase chondrocyte proliferation - long bone growth and more epiphyseal fusion), permissive effect on GH secretion (hypothyroidism may cause GH deficiency)
2. GH: pulsatile secretion greatest amplitude overnight, affected by exercise (+), sleep (+), food intake (ghrelin +), age (peak in adolescence), body comp (fat -), other hormones (E, GCs, Androgens, IGF1)
   Action: bone (increase osteoclast differentiation and activity, increase osteoblast activity, increase bone mass by endochondral formation)
   Linear growth (increased epiphyseal growth, stim differentiation of prechondrocytes and local IGF1 expression)
   Adipose tissue (increase lipolysis and decrease lipogenesis)
   Muscle: build muscle (increase AA transport, N retention, EE, lean tissue)
   In childhood - promote LINEAR GROWTH (directly on bone and thru IGF1)
3. IGF1 - most important for post natal growth (rises significantly during puberty), secretion determined by GH, largely responsible for muscle + cartilage (high chondrocyte hypertrophy)
   IGFBP3 - binds IGF1 in circulation: production depends on GH level
   IGF1 and IGFBP3 DEPEND ON GH LEVELS

Question 3

Adolescent Phase
- what regulates linear growth

How do you measure growth as patients age?
How to determine Genetic Potential?

Imaging for growth

When is growth rate valuable? when are peak growth rates?

Red flags for growth?

Answer 3

Linear growth: T + E stim pit to increase GH pulse amplitude; E blocks IGF1 negative feedback, increases bone growth and fuses epiphyseal plate!!! WOW!

Age 0-2: measure supine (length)
Age 2+: measure standing (length 1 cm longer than height, may change %ile when 2 yo stands up)

Genetic potential: 0.5*[(Dad - 5) + (Mom + 5)] - depends if boy or girl for the 5 location

Bone Age: Xray to see growth plate maturation - calcify and fuse

Growth rate: poor correlation from 0-2 years, then improves after 2 years
Peak growth rates during 1st year of life (25cm/yr) and puberty (9-10cm/yr)

Red flags: Height <3rd %ile or below genetic potential; growth rate abnormally slow (crossing 2+ %iles after 2 yo)

Question 4

What is short stature?

Differentiate between primary and secondary growth disorders. (causes and differentiation techniques)

Answer 4

Short stature: height >-2 SDs for age-sex matched controls, 3% all children, NOT always pathological, could be primary/secondary growth abnormality, or idiopathic short stature

Primary Growth Disorders

• osteochondrodysplasias (skeletal dysplasias) - abnormality of size/shap of bones
• chromosomal abnromalities: Down’s or Turner
• NORMAL linear growth rate (but below growth curve)
• BA = CA

Secondary Growth Disorders

• Disorder of GH-IGF axis
• Endocrinopathy (Cushing’s, hypothyroidism)
• Malnutrition, IUGR
• Chronic disease, Inflammatory or Psychosocial Disorders
• SLOW linear growth rate (crossing %iles)
• DELAYED Skeletal age: BA < CA

Question 5

Give 4 endocrine causes of short stature

- what is Van Wyk Grumbach Syndrome?

Answer 5

1. Hypothyroidism: hypothyroid sx with profound growth deceleration/failures, delayed puberty
   Van Wyk Grumbach: severe hypothyroidism = very high TSH = crossover to FSH/LH receptor = high T/E
2. GC Excess: suppresses GH and IGF1 action at growth plate (Cushing’s Disease, Cortisol/CRH secreting tumor, Exogenous GCs), sx: central obesity, dorsocervical fat pad, purple striae, round moon facies, easy bruising, linear growth failure, red face, osteopenia, depression
3. GH Deficiency: caused by hypothalamic dysfx (impaired GHRH release) or pituitary dysfx (impaired GH release)
   sx: round face, truncal obesity, small hands/feet, prolonged neonatal hypoglycemia jaundice micropenis, hx of cranial irradiation/chemo-tx, midline defects (cleft lip/palate), high pitched voice, short stature
4. IGF Deficiency: LARON syndrome (GH resistance, abnormal GH receptor or post-receptor abnormalities of GH signal transduction) or primary defects of IGF1 resistance

Question 6

Non-pathologic causes of short stature (2)

Answer 6

1. Genetic or familial short stature (BA = CA)

2. Constitutional Delay of Growth or Puberty (BA < CA) - late bloomer, delayed yet normal