Pubertal Delay

Delayed Adolescence in Phenotypic Male or Female
Girls:
1. Delayed Breast development
  1. No Breast development by age 13 years
  2. No Breast development 5 years after Menarche
2. No Menses by age 15 years (Primary Amenorrhea)
Boys:
1. Testicular length under 2.5 cm by age 14 years
2. Genital growth not complete five years from start

Timing of secondary sexual characteristics
1. Body odor
2. Breast Development or Testicular Development
3. Pubic and axillary hair
4. Acne
Exposures
1. Chemotherapy or radiation exposure (Hypogonadism)
2. Head Trauma
Conditions
1. Cryptorchidism (Hypogonadism)
2. Turner Syndrome (Webbed Neck, Short Stature)
3. Family History of Delayed Puberty
Symptoms
1. Abdominal Pain (gastrointestinal disorders)
2. Anosmia (Kallmann Syndrome)
3. Galactorrhea (Hyperprolactinemia)
4. Headache or Vision changes (intracranial pathology)
5. Hyperthyroidism or Hypothyroidism symptoms
6. Vasomotor symptoms in girls, such as Hot Flushes (ovarian insufficiency)
7. Weight loss, decreased Caloric Intake, excessive Exercise (e.g. Eating Disorder)

Follicle Stimulating Hormone (FSH)
Luteinizing Hormone (LH)
Estradiol Level (in girls)
Testosterone Level (in boys)
Labs for abnormal Growth Velocity
1. Serum Thyroid Stimulating Hormone (TSH)
2. Serum Prolactin
3. Insulinlike Growth Factor I
Labs for suspected chromosomal abnormalities (Step 2b below)
1. Consider Chromosome Analysis
Labs for suspected Hypogonadotropic Causes of Delayed Puberty
1. Consider GnRH Stimulation Test (Step 2a below)

Evaluation
Step 2 - Follicle Stimulating Hormone (FSH) and Luteinizing Hormone (LH) interpretation

Above Prepubertal range LH or FSH
1. Hypergonadotropic Hypogonadism (5-10% of boys, 25% of girls)
2. Repeat FSH and LH
3. Obtain karyotype
4. Refer to pediatric endocrinology
Pubertal range LH or FSH
1. Constitutional delay of growth and Puberty (see above)
2. Repeat measurements in 1-3 months
Prepubertal range LH or FSH
1. Persistent Hypogonadotropic Hypogonadism (10% of boys, 20% of girls)
  1. Dysmorphic features (e.g. Turner Syndrome)
  2. Radiation exposure
  3. Head Trauma
  4. Brain Tumor
2. Constitutional delay of growth and Puberty (60% of boys, 30% of girls)
  1. Most common cause of Delayed Puberty (diagnosis of exclusion)
  2. Consistent findings
    1. Delayed Bone Age
    2. Family History of Delayed Puberty (75% have parental Pubertal Delay)
  3. Consider Jump Start Therapy
    1. Indications
      1. Girls over age 13 years and boys over 14 years
      2. No spontaneous Puberty after 6 months of observation
    2. Example protocol for boys
      1. Testosterone cypionate or enanthate 50 -100 mg IM per month
    3. Example protocol for girls
      1. Estradiol 6.2 mcg (25% of 25 mcg patch) applied to skin overnight for 3-6 months
  4. Consider referral to pediatric endocrinology
    1. No pubertal progression after 4-6 months after jump start therapy
3. Functional Hypogonadotropic Hypogonadism (20% of boys, 20% of girls)
  1. Malnutrition or chronic disease (e.g. Celiac Disease, Diabetes Mellitus, Thyroid disease)

Findings
1. Unremarkable exam except Delayed Puberty
2. Patient has not yet experienced growth spurt
3. Bone Age less than Chronological age
Differential Diagnosis
1. Constitutional delay
2. See Hypogonadotropic Causes of Delayed Puberty
3. Primary gonadal failure
4. Serious athletic training
Further evaluation
1. Observation
2. Laboratory testing as above
3. Imaging evaluation as above
Management
1. Counseling and reassurance
2. Consider sex Hormone Replacement for some patients

Findings
1. Abnormal exam suggests chromosomal abnormality
2. Bone Age may be less than Chronological age
Diagnosis
1. Girls: Turner's Syndrome
2. Boys: Klinefelter's Syndrome
3. Noonan's Syndrome
Further evaluation
1. Chromosome analysis
Management
1. Counseling
2. Sex Hormone Replacement
3. Oophorectomy in Turner's Syndrome (malignancy risk)

Findings suggestive of chronic disease
1. Overt chronic illness signs or symptoms
2. Short Stature
3. Slow growth rate
4. Bone Age less than Chronological age
Differential Diagnosis
1. Anorexia Nervosa
2. Malnutrition
3. Kallmann's Syndrome
4. Iatrogenic
5. Hypopituitarism
  1. Findings
    1. Growth failure
    2. Hypothyroidism
    3. Adrenal Insufficiency
    4. Diabetes Insipidus
    5. Delayed Puberty
  2. Causes
    1. Intracranial lesion (esp. involving pituitary)
    2. Infection of Pituitary Gland (e.g. Tuberculosis)
    3. Head Injury
6. Chronic Systemic Illness
  1. Malignancy
  2. Chronic infection
  3. Chronic metabolic disease
Further evaluation
1. Work-up suspected underlying chronic disease