• Credits
  • Section Writer: Dr. Om J Lakhani
  • Section Editor: Dr. Om J Lakhani

Q. What is the definition of delayed puberty?

• Absent or incomplete development of secondary sexual characteristics by the age when 95% of children of the same sex and culture have initiated sexual maturation

Q. What is the definition of delayed puberty in boys?

• Testicular volume <4 ml in boys >14 years of age

Q. What is the definition of delayed puberty in girls?

• Absent breast bud by 13 years
• No menarche five years after the development of breast bud
• No menarche by 15 years of age

Q. Classify and enlist the causes of delayed puberty in boys?

• 

• Hypergonadotropic hypogonadism

  • Congenital
    • Klinefelter's
    • Gonadal dysgenesis
    • Anorchia-
    • Vanishing testis syndrome
  • Acquired
    • Chemotherapy
    • Radiation
    • Surgery
    • Mumps orchitis
    • Trauma to testis

• Hypogonadotropic hypogonadism

• Congenital

  • Isolated GnRH deficiency – IHH
    • Without anosmia
    • With anosmia- Kallman
  • With obesity
    • Lawrence Bidel Moon
    • Prader Willi
  • Part of MPHD (Multiple pituitary hormone deficiencies)

• Acquired

  • Tumors
  • Head trauma
  • Pituitary apoplexy
  • Infiltrative
  • Hemochromatosis
  • Tuberculosis
  • Sarcoidosis
  • Granulomatous disease
  • Drugs – Marijuana

Q. What FSH value suggests hyper hypo vs. hypo hypo in boys?

• FSH < 2 – Hypo hypo
• FSH – 2-8 – intermediate
• FSH >8- Hyper hypo

Q. What is the most common cause of Hypo hypo in boys?

• CDGP is most common – in 60% of cases
• Functional hypo hypo- 20%
• Hypergonadotropic hypodonadism- 13%
• Idiopathic hypogonadotropic hypogonadism- 12 %

Q. What are pointers to Constitutional delay in growth and puberty (CDGP), and what are pointers to a pathological cause?

• Pointers to CDGP
  • No pubic hair
  • Delayed bone age
  • Short stature
• Pointers to a pathological cause
  • Presence of pubic hair
  • Normal stature
  • Normal bone age

Q. What is the typical pubertal development in Klinefelter syndrome?

• They have stalled puberty (Arrested puberty)
• Pubertal development takes place generally at first
• They have pubic hair development
• At around testicular volume of 8-10 ml- the puberty does not progress further – testis are small and sotty
• They also start having gynecomastia

Q. CDGP is more in boys or girls?

• More in boys

Q. How will you differentiate Constitutional delay of growth and puberty (CDGP) from Idiopathic hypogonadotropic hypogonadism in boys?

• Step 1: History and Examination
  • Points towards CDGP
    • 1. Family history of CDGP
      • o Age of menarche of Mother- >15 years is delayed (After 10th grade)
      • o Continued growth of father after completing school
      • o Growth spurt after 11th grade in father
      • o Started shaving after 11th grade
  • Points towards IHH
    • 1. Anosmia
    • 2. Testicular volume 1-2 ml with a bone age of >12 years
    • 3. Micropenis at birth
    • 4. Cryptorchidism at birth
    • 5. Midline defect
    • 6. Cleft lip / cleft palate
• Step 2: Basic Investigations
  • Tests to order
    • 1. Total Testosterone
    • 2. LH
    • 3. FSH
    • 4. Bone age
    • 5. DHEAS
    • 
• Step 3- Advanced Tests and Stimulation tests
  • 1. Inhibin B
  • 2. GnRH Agonist testing
  • 3. HCG stimulation test
    • Inhibin B
      • • Value < 35 pg/ml- IHH for sure
      • • 35-100 pg/ml- Either way-more in favor of CDGP
      • • >100 pg/ml- CDGP for Sure
• 2. GnRH agonist testing
  • LUPEROLIDE PROTOCOL (Lakhani protocol developed from Street et al.)
    • 1. Baseline LH
    • 2. Inj LUPRIDE 1 mg vial (0.5ml) in Insulin – 100 IU syringe order
      • a. 0.25 ml (0.5 mg) – 25 units in Insulin syringe
      • b. Inject Subcutaneously
    • 3. Repeat LH after 2 hr and 4 hr
      • Interpretation
        • 1. Peak LH > 6.1 - Suggestive of CDGP
        • 2. Peak LH <2.8 IHH
        • 3. 2.8-6.1- either way – Favour CDGP
  • TRIPTORELIN PROTOCOL
    • 1. Baseline LH
    • 2. Inj DECAPEPTYL (Triptorelin) 1 ml subcutaneous (100 ug)- 100 IU in insulin syringe
    • 3. Check LH and FSH after 2 hrs and 4 hrs
    • 4. If Peak LH >5 – suggestive of CDGP
      • a. Dergos et al. say 14 IU/l is more discriminatory
  • HCG stimulation test
    • 1. Baseline testosterone
    • 2. In HCG (FERTIGYN), 1500 IU IM on alternate days for 3 days
    • 3. Day 7 – Repeat testosterone
      • a. >230 ng/dl – CDGP
  • ALTERNATE SINGLE DOSE HCG PROTOCOL (DERGOS et al.)
  • 1. Baseline Testosterone
  • 2. Inj HCG (FERTIGYN) – 5000 IU im
  • 3. Repeat testosterone after 72 hrs
    • a. Tetosterone >260 ng/dl- CDGP
    • b. <86 ng/dl- IHH
  • Step 4- Follow Up
    • 1. Inj TESTOVIRON 50 mg monthly for 3 months
    • 2. Recheck Testosterone 1 month after the last injection
      • a. Testosterone > 300 ng/ml- Suggestive of CDGP
      • b. <300 ng/ml- IHH

#Clinicalpearl Gold standard is GnRH stimulation test

Q. Which is more important for assessment in a child with delayed puberty- FSH or LH?

• FSH- more important for a child with delayed puberty
• LH-more important for a child with precocious puberty

Q. Give an outline for Constitutional delay of growth and puberty (CDGP) management?

• inj Testosterone (Testoviron)-  100 mg – monthly injection – 3 times
• After the third injection- they generally have a push of puberty
• If no push- then wait for a few months and give a second course

Q. What is the importance of bilateral inguinal hernia in boys with delayed puberty?

• It could be testis which is inguinal. Suggests Undescended testis.

Q. What is cryptorchidism ?

• It is testis that is not present in the scrotum by 4 months of age. It could be either absent testis or undescended testis.

Q. What is anorchia ?

• 46 XY DSD with both testis absent at birth

Q. How will you interpret the past history of undescended testis in a  child presenting with delayed puberty at 15 years? What are the clinical conditions associated with bilateral cryptorchidism?

• Genetic disorders are more common in children with bilateral cryptorchidism than those without it

• Hypogonadism and Cryptorchidism
  • 46 XY DSD- Ovotesticular syndrome, mixed gonadal dysgenesis – esp if associated with hypospadias
  • Defects in testosterone secretion- Kallman, Klinefelter syndrome
  • Defects in testosterone action- Androgen insensitivity syndrome
  • Bilateral cryptorchidism is more associated with other conditions than unilateral

Q. What is the most common location for undescended testis?

• Just outside the external ring

Q. By what age do undescended testis generally descend?

• Generally, by 6 months of age
• If they don’t descend by that time- unlikely to descend further

Q. What pubertal development sign in boys is considered equivalent to menarche?

• Presence of nocturnal sperm emissions or sperm in urine

Q. What time before the development of pubic hair does testis tend to develop?

• About 6 months
• Testis development starts about 6 months before pubic hair development

Q. How will you ask for a history of Delayed puberty in parents?

• Mother- the onset of menses after 15 years of age
• Father
• Growth spurt after 16 years of age
• Continued to grow in height after graduating from school
• When did they start to shave

Q. What age do facial hair develop in children?

• About 2.5 years after growth of testis or about 2 years after growth of pubic hair
• Generally, boys develop facial hair at about 15 years of age
• However, facial hair is not a reliable sign because it depends on ethnicity

Q. Should DSD be considered in a case of bilateral cryptorchidism?

• Yes

Q. What will you suspect if the patient has tall stature and Hypogonadism?

• Klinefelter syndrome

Q. What about obesity and hypogonadism?

• Prader Willi syndrome
• Leptin deficiency

Q. What other physical examination findings would you look for?

• Upper segment: Lower segment ratio – would suggest eunuchoid proportion going in favor of Kleinfelter’s
• Whether testis appears atrophic or not

Q. What is Tanner Stage 3 pubic hair?

• Hair is dark, coarse, and curly
• Extends to the mid pubis

Q. What is DD of Clinodactyly with Hypogonadism?

• Klinefelter syndrome
• 46 XXYY

Q. What happens to bone age in Kleinfelter’s?

• Mild delay

Q. What are the facial dysmorphisms in 48, XXYY ?

• Asymmetry
• Upslating palpebrel fissures
• Hypertelorism