Growth Disorders in Adolescents

Normal Growth Phases

1. Infancy:
   • Driven by nutritional factors.
   • Lasts until approximately 24 months of age.
2. Childhood:
   • Growth hormone (GH) and insulin-like growth factor 1 (IGF-1) axis regulate growth.
3. Adolescence:
   • Sex steroids and puberty drive growth and bone mass accrual.
   • Occurs between 10 and 19 years of age.

Measuring Height

• Technique: Use a wall-mounted stadiometer, ensure the patient is barefoot, ankles together, and gaze forward.
• Accuracy: Apply gentle upward pressure on the mastoid processes to achieve true height.
• Context: Consider height in the context of mid-parental height, charted on a growth chart.
• Formulas for Mid-Parental Height:
  • Tanner Method:
    • Girls: [(father’s height + mother’s height) / 2] – 6.5 cm
    • Boys: [(father’s height + mother’s height) / 2] + 6.5 cm
  • Alternative Method:
    • Girls: Father’s height – 13 cm
    • Boys: Mother’s height + 13 cm

Effect of Normal Puberty on Growth

• Puberty Onset:
  • Girls:
    • Breast Development (Thelarche)
      • First sign of puberty.
      • Usually begins between ages 8-13.
      • Progresses from breast buds to full breast development over several years.
    • Pubic Hair Development (Pubarche)
      • Usually follows thelarche.
      • Initially fine and sparse, becoming coarser and more widespread over time.
    • Axillary (Underarm) Hair
      • Develops shortly after pubic hair.
    • Growth Spurt
      • Typically occurs between ages 10-14.
      • Peak height velocity usually around age 12.
    • Menarche (First Menstrual Period)
      • Usually occurs about 2-3 years after thelarche.
      • Typically between ages 10-16.
      • Irregular menstrual cycles are common in the first few years.
    • Hip Widening
      • Increase in body fat around the hips and thighs.
      • Part of the broader changes in body composition during puberty.
    • Skin Changes
      • Increased activity of sebaceous (oil) glands, leading to acne.
      • Sweating increases and body odor becomes more noticeable.
    • Vaginal Discharge
      • Increase in clear or white discharge is normal as estrogen levels rise.
      • Helps maintain vaginal health.
  • Boys:
    • Testicular Enlargement
      • First sign of puberty.
      • Increase in testicular volume (≥4 mL) at around age 11 (range 9-14 years)
      • measured with a Prader orchidometer
    • Penis Growth
      • Follows testicular enlargement.
      • Growth in length occurs first, followed by an increase in girth.
    • Pubic Hair Development
      • Appears after testicular enlargement.
      • Initially fine and sparse, becoming coarser and more widespread over time.
    • Axillary (Underarm) and Facial Hair
      • Develops after pubic hair.
      • Facial hair typically starts with the upper lip and then spreads to the cheeks and chin.
    • Growth Spurt
      • Typically occurs between ages 12-16.
      • Peak height velocity usually around age 13-14.
    • Voice Changes
      • Voice deepens due to growth of the larynx and vocal cords.
      • Usually occurs during the mid-to-late stages of puberty.
    • Increased Muscle Mass
      • Increase in muscle mass and strength.
      • Greater changes compared to females due to higher levels of testosterone.
    • Skin Changes
      • Increased activity of sebaceous (oil) glands, leading to acne.
      • Sweating increases and body odor becomes more noticeable.

• Growth Velocity:
  • Childhood: 5-7 cm/year.
  • Puberty: 6-10 cm/year for girls, 7-12 cm/year for boys.
  • Peak Growth: Girls around Tanner stage 3 and boys around age 13-14, contributing to the average height difference between sexes.

When to Suspect a Growth Disorder

• Assess Mid-Parental Height: Plot on growth chart and compare with child’s height.
• Growth Velocity: Multiple anthropometric measurements for accuracy.
• Detailed History and Examination: Essential for identifying underlying causes.

History and Examination

• History:
  • Birth: In utero growth, birth weight, gestation, maternal factors.
  • Neonatal: Floppiness, hypoglycemia, feeding issues.
  • Medical History: Illnesses, hospitalizations, chronic/systemic diseases, medications, developmental progress.
  • Systems Review: Exclude systemic diseases.
  • Dietary History: Malnutrition, eating disorders.
  • Family History: Consanguinity, parental/sibling heights, pubertal timing.
• Examination:
  • General Examination: Include specific systems based on history, dysmorphism.
  • Body Proportions: Arm span, upper and lower limb segments.
  • Height and Weight: Use calibrated scales.
  • Pubertal Assessment: Tanner staging.
  • Visual Field and Smell Assessment: Detect possible intracranial pathology.

Syndromes associated with:

Early Puberty	Delayed Puberty
Before age 8 in girls and before age 9 in boys.	No signs of puberty by age 13 in girls and age 14 in boys.
McCune-Albright Syndrome: Precocious puberty, café-au-lait spots, fibrous dysplasia of bones. Congenital Adrenal Hyperplasia (CAH): Enzyme deficiencies affecting cortisol synthesis, leading to excess androgen production. Ovarian or Adrenal Tumors: Produce excess sex hormones leading to early puberty.	Turner Syndrome (45,X): Short stature, webbed neck, lack of secondary sexual development. Klinefelter Syndrome (47,XXY): Tall stature, small testes, gynecomastia, learning difficulties. Kallmann Syndrome: Hypogonadotropic hypogonadism with anosmia. Androgen Insensitivity Syndrome: Genetically male but phenotypically female due to resistance to androgens. Hypopituitarism: Deficiency in pituitary hormones affecting growth and pubertal development. Chronic Illnesses: Conditions like cystic fibrosis, inflammatory bowel disease, chronic renal failure. Nutritional Deficiencies and Eating Disorders: Malnutrition or conditions like anorexia nervosa can delay puberty.

Short Stature in Adolescents

• Definition: Height less than two standard deviations below the 50th percentile (below the 3rd percentile).
• Common Causes:
  • Constitutional Delay of Growth and Puberty (CDGP): Most common, often familial.
  • Familial Short Stature (FSS): Height appropriate for genetic potential.
• Diagnosis of CDGP:
  • Girls: Lack of breast development by age 13.
  • Boys: Testicular volume <4 mL by age 14.
  • Emotional distress due to height and pubertal discrepancies often prompts referral.
  • Inheritance is often dominant, more common in boys (3:1 ratio).
  • Most undergo spontaneous puberty without intervention.
  • Low-dose testosterone may be used in males aged 14+ to induce puberty.
  • GH therapy is precluded if final height prediction is above the 1st percentile for age and gender.

Common Forms of Short and Tall Stature

Cause	Height	Bone Age	Growth Rate	Height Prognosis
Chronic Disease	Short	Possibly delayed	Slow	Depends on control of the condition
Constitutional Delay of Growth and Puberty	Short	Delayed	Slow	Generally good
Familial Short Stature	Short	Not delayed	Normal	In keeping with genetic potential
Familial Tall Stature	Tall	Not advanced	Normal	Good

Turner Syndrome

• Characteristics: 45 XO karyotype or mosaic variants, incidence 1 in 2000.
• Cause of Short Stature: SHOX gene haploinsufficiency.
• Consideration: Should be considered in any girl with short stature, stature shorter than mid-parental height, or delayed/arrested puberty.
• Treatment: GH therapy, though outcomes vary.

Acquired Growth Hormone Deficiency (GHD)

• Causes: Intracranial tumors, cranial radiation, brain trauma.
• Symptoms: Proportional short stature, declining growth velocity, symptoms of underlying causes.
• Diagnosis: Serum IGF-1 level screening, confirmed by provocation testing (glucagon, arginine, clonidine).
• Treatment: Recombinant human GH therapy showing significant catch-up growth.

Non-Endocrine Causes

• Antenatal Conditions: Pre-term gestation, intrauterine growth restriction, low birth weight.
• Nutritional Issues: Malnutrition, anorexia nervosa.
• Physical Activity: Extreme physical activity (e.g., gymnastics, ballet).
• Chronic Diseases: Inflammatory bowel disease, chronic kidney disease, celiac disease.
• Treatment Side Effects: Oncology treatments, glucocorticoids, stimulant medications for ADHD.

Growth Hormone (GH)

• Regulation: PBS-subsidized GH use is tightly regulated in Australia.
• Indications: “Short-slow growing” defined as height <1st percentile and growth velocity >25th percentile for bone age.
• Conditions for GH Therapy (Box 2):
  • Short stature and slow growth
  • Biochemical GHD
  • Turner syndrome or SHOX disorders
  • Prader-Willi syndrome
  • Growth retardation secondary to intracranial lesion or cranial irradiation
  • Chronic renal insufficiency

Tall Stature in Adolescents

• Definition: Height >97th percentile.
• Common Causes: Familial tall stature.
• Endocrine Causes: Precocious puberty, congenital adrenal hyperplasia, hyperthyroidism, GH excess.
• Chromosomal/Syndromic Causes: Klinefelter syndrome, homocystinuria, Marfan syndrome, Sotos syndrome.
• Obesity: Can lead to early adrenarche and increased linear growth, but early puberty results in earlier epiphyseal closure, aligning final height with genetic potential.

Referring to Specialist Services

• Indications for Referral:
  • Height <1st percentile or significantly below mid-parental height.
  • Growth velocity <25th percentile for bone age or level of maturation.
  • Height crossing two centile lines on growth chart.
  • Delayed puberty.
• Referral Types:
  • General paediatric medicine for non-endocrine causes.
  • Paediatric endocrinology for endocrine-related issues.

Investigations Before Referral

• Blood Tests for Non-Endocrine Causes:
  • Full blood count, urea and electrolytes, liver function, calcium/magnesium/phosphate, ESR, coeliac serology.
• Endocrine Tests:
  • Thyroid function (TSH, FT4), IGF-1.
  • Karyotype testing for girls with short stature or pubertal delay.
• Bone Age X-ray:
  • Assess skeletal maturity compared with Greulich-Pyle bone age atlas.
  • Best performed by experienced radiologists, with image review by specialists for concurrence.