3. Boys With Delayed puberty
Professor of Pediatric Endocrinology
Isfahan University of Medical Sciences
M. Hashemipour

4. Delay in onset of secondary sexual development by age12-13
Delayed puberty
Girls
Delay in onset of secondary sexual development by age12-13
primary amenorhoe at y
Boys
Delay in onset of secondary sexual development by age 14y

5. .
mean duration from the onset of puberty to onset of menarche is ±1.1 years

6. .
Detained puberty
Puberty has started but has not concluded after 5 years

7. Detained puberty
A boy who has not completed his secondary sexual development, 4.5 years from the onset of puberty(T2)
A girl who does not experience menses within 5 years from the onset of puberty(B2)

8. Hypogonadotropin hypogonadism Hypergonadotropin hypogonadism
Delayed Puberty Types
Constitutional
Hypogonadotropin hypogonadism
Hypergonadotropin hypogonadism

9. Medical history
14yr old boy
Shortest in his class
No problem at school
Always looks small

10. What do you ask him?

11. No chronic disease
Normal sense of smell
Sexual function and patterns of body hair
Known testicular abnormalities

12. : Social and family history
Student
Non-smoker
No siblings
Mother has arthritis
Father did not grow till he entered college

13. What's important in Physical examination?

15. No dysmorphic features CVS, Resp, Abd Exam are normal BP = 110/76
Physical Examination
No dysmorphic features
CVS, Resp, Abd Exam are normal
BP = 110/76
Ht= 135cm Zcore = -3.9
Wt= 30kg

16. Arm span – height span= 2cm Growth Velocity =5cm/yr
Physical Examination
Arm span – height span= 2cm
Growth Velocity =5cm/yr

17. Normal Testicular consistency No Pubic & Axillary Hair No gynecomastia.
Testicular volume =2.5ml
Testicular length = 1.5cm
Penis length = 6cm
Normal Testicular consistency
No Pubic & Axillary Hair
No gynecomastia

18. What's your differential diagnoses?

19. What's your investigation?

20. Hormonal and Biochemical study
Normal BUN & ESR
Normal T4 &TSH
Low IGF1& IGFBP3 for age
Normal IGF1& IGFBP3 for BA
Normal GH stimulation test

21. Hormonal and Biochemical study
Testosterone= 0.15ng / ml
Celiac test= ok
Cortisol levels = ok
GnRH test shows no response
Low Gonadotropin
Normal prolactin

22. imaging
BA=11.5yr
MRI= Normal

23. What's your treatment ?

24. Vitamin A = 6000IU/week for 3 months
We prescribed
Oxandrolon for 6 months
Zinc 12.5 mg/day
Iron 12mg/day for 3 mo
Vitamin A = 6000IU/week for 3 months

25. But Testicular volume &Testicular length did not change

26. ,
Diagnosis?
Any comments?

27. Because of not response to treatment
We prescribe :
Testosteron 50mg every month for three months
Letrozol 2.5mg/day

28. Testosteron level was 0.8ng/ml Testicular volume =5ml
(Six month after stopping Testosteron)
Testosteron level was 0.8ng/ml
Testicular volume =5ml
Testicular length = 3cm

30. Diagnosis? .

31. Constitutional Delayed puberty

32. .
Discussion

33. CDGP is not a medical disorder, but a temporary condition
If treatment is necessary for a child, it must be emphasized that they are normal
Their “body clock” for puberty has just started later than their friends. .

34. CDGP is a common condition Boys > girls Boys look young
Normal physical examination
No evidence for systemic disease
No evidence for hormonal dysfunction
Usually normal nutrition.

35. CDGP
Short stature
HT at or below 3rd percentile

36. CDGP

37. HA < CA BA < CA GV= N . BA=HA p=BA p 8 8 8 8 8 8 8 8 8 8 8 8 8 8TH
HA < CA p
p=BA 8 8 8 8 8 8 8
BA < CA 8 8 8 8 8
BA=HA 8 8 8 8 8 8 8 8
GV= N 8

38. CDGP Delayed puberty and pubertal growth spurt
Family history of delayed puberty

40. CDGP Normal growth rate for bone age Delay bone age 1 -3 years
Normal height for bone age

41. HT reach within the lower part of mid parental target HT
Adult height
HT reach within the lower part of mid parental target HT

42. HA < CA BA < CA GV= N BA=HA p=BA p 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8TH
HA < CA p
p=BA 8 8 8 8 8 8 8
BA < CA 8 8 8 8 8
BA=HA 8 8 8 8 8 8 8 8
GV= N 8

43. HT deficit at onset of puberty.
HT deficit at onset of puberty

45. CDGP
IGF-I is normal for BA
Delayed Adrenarche

46. iron, and zinc deficiency
Nutrition CDGM
Decreased vitamins A and D
iron, and zinc deficiency

47. Diagnostic approach to delayed puberty

48. There is an overlap in physical and lab findings.
Differentiation between
HH and CDP is very difficult because:
There is an overlap in physical and lab findings

49. Growth Chart
Patients with HH have normal height in early or mid adolescence
Patients with CDP are short

50. initial Approach Bone Age
X-ray of the left hand and wrist to evaluate bone age

51. The onset of puberty correlates with BA BA=11-13y in girls .
The onset of puberty correlates with BA
BA=11-13y in girls
BA=12-14 in boys

52. patients with CDP usually continue pubertal development.
At Bone age :
11 to 13 years in girls
12 to 14 years in boys
patients with CDP usually continue pubertal development

53. If elevated In patients who are apparently healthy
Initial Approach
In patients who are apparently healthy
initial assessment of LH & FSH
If elevated
Hypergonadotropic Hypogonadism

54. Differential Diagnosis
If low
Hypogona Hypogo

55. If Gonadotropins low or lower limit of normal:
DDx:
Constitutional Delayed Puberty
Brain tumor
Hypopituitarism
Hypothyroidism
Hyperprolactinemia

56. If Gonadotropins low or lower limit of normal:
Malnutrition
Exercise intensity
Use of medications
Chronic disease

57. HA < CA BA < CA GV= N . BA=HA p=BA p 8 8 8 8 8 8 8 8 8 8 8 8 8 8TH
HA < CA p
p=BA 8 8 8 8 8 8 8
BA < CA 8 8 8 8 8
BA=HA 8 8 8 8 8 8 8 8
GV= N 8

58. Hypogonadotropin Hypogonadism
Differential Diagnosis:
Hypogonadotropin Hypogonadism
Adrenarche is at the normal age
Higher DHEAS than CDP

59. Isolated Gonadotropin Deficiency
After the age of 18:
Absence of first signs of puberty
Failure of a rise in gonadotropins
Failure of a rise in gonadal steroids

60. Isolated Gonadotropin Deficiency
serial Ht and testicular measurements made over 1-2 years will help clarify the diagnosis

61. Isolated Gonadotropin Deficiency
As no single test can distinguish between these two disorders, so we should rely on clinical clues and the natural evolution over time

62. Pituitary failure

63. Diagnostic Evaluation
Morning serum testosterone >0.2ng/ml
predicted increase in testicular size to >4 mL within
12mo in 77% in boys
15 mo in 100% of boys
In boys with < 0.2ng/ml
12.5% of boys will have puberty within 12mo

64. Treatment .

65. Treatment “watchful waiting” includes :
periodic evaluation of testes & testosterone every 6 mo
Reassurance
psychological counseling
Assurance to family

66. Treatment
Testosterone
Oxandrolone GH
Trace elements

67. Treatment Treatment In BA<10 y
Has the risk of accelerated BA& short adult height

68. ,
Testosterone therapy may be started as early as A bone age of 12–13 yr to decrease the psychological disturbance

69. Testosterone Therapy Testicular enlargement
At BA= CA=14–14.5 yr
50 mg once a month for three to six months
six months later.
It is Spontaneous pubertal development if
Testicular enlargement
increasing testosterone >50 ng/dl

70. Management
6-12 months after completing the first course of therapy If
Testosterone <50 ng/dl
Not Testicular enlargement
Give another course for 3-6 months

71. Management
Treatment should not continue
more than 2 courses
to differentiate CDP from permanent DP

72. Constitutional Delayed Puberty
After 2 courses
6-12 months after completing the second course of therapy
8am serum testosterone 50ng/dl:
PPV 100% PNV59%
LH peak> 14 IU 3 hours after triptorelin
PPV 100% PNV72%
Dx= CDGP

73. Aromatase inhibitors, alone or in combination with rh-GH

74. Growth Hormone Therapy:
The value is
controversial

75. Oxandrolone 1.25-2.5mg/day 0.05 mg/kg daily for 1 year
Pediatrics Dec;96(6):

76. Oxandrolone After oxandrolone withdrawal
Growth promoting effects is related to mild androgenic effects of it
After oxandrolone withdrawal
Increase in total serum testosterone
progress in puberty.

77. Any Question?

78. GnRHa
Decapeptyl
0·1 mg/m2 s.c..
(1–20 μg/ kg, 500 μg,
100 μg/m2

79. GnRHa After 4 h LH and FSH should be measured
LH>8 mIU/ml) in favor CDGP
LH assay by commercial chemiluminescent kit
All of these patients entered spontaneous puberty within 1 year

80. Constitutional Delay Puberty
First signs of secondary sexual development occur within 1 year after
LH rises to pubertal levels after administration of 100 μg GnRH
subcutaneous GnRH agonist
After GN and sex steroid begin to increase spontaneously above prepubertal values
An 8 am serum testosterone> 20 ng/dL puberty develop within 12 to 15 month

81. Use of GnRH agonist and human chorionic gonadotrophin tests for differentiating constitutional delayed puberty from gonadotrophin deficiency in boys
The GnRH-agonist test and the repeated-injection hCG test are reliable diagnostic tools for differentiating CDP from GD in boys.
Clinical Endocrinology (2002) 56, 603–607

82. synthetic LHRH
0·1 mg/m2 iv bolus Blood samples for of LH, FSH and testosterone levels were drawn prior to injection and 30 and 60
LH >7.5 IU/L usually precedes the first physical sign of sexual maturation by less than 1 year.

83. Buserelin test
LH, FSH at 0 and 4 hours were measured. low LH response to buserelin, HH could be diagnosed with a sensitivity of 100% and a specificity of 96%
Journal of Pediatrics 2006
Lh<5 HH LH>5 CDGP

84. ,
Kallmann

85. cdpuberty kallman
kallmann
Pituitary failure

86. LHRH test Time (min) -15 15 30 45 60 90 120 FSH mIU/ml 4.8 5.1 6.0 6.915 30 45 60 90
120
FSH
mIU/ml
4.8
5.1
6.0
6.9
8.5
10.1
12.5
14.1 LH
1.3
2.6
5.0
8.6
10.7
10.8
11.9
HGH:0.625 ng/ml , TSH:3.35 uIU/ml Cortisol:19 ug/dl
Prolactine:3.66

87. Laboratory assessment
HCG stimulation test units/m2 per injection
One to three injections daily or on alternate days
Testosterone should be obtained within 24 hours of the last injection
Testosterone levels greater than
170 ng/dl after a single injection
200 ng/dl on day 3
300 ng/dl on day 5
indicates normal testicular function

88. Pituitary failure

89. Prader-Willi syndrome

90. Diagnostic evaluation
BA=HA <CA  Constitutional delay puberty
Late onset growth failure specially with DI
 CNS tumor

91. Testicular volume >3-4 mL Longitudinal measurement> 2.5 cm
pubertal development
Testicular volume >3-4 mL
Longitudinal measurement> 2.5 cm
 Serum testosterone > o.5 ng/mL

92. Management If the LH level rises more than 2.5 SD above the mean value
Testosterone level decreases below the normal range for age
We think to HH

93. Birth : 1.7 3 years: 1.33 5 years : 1.17 10 years : 1.0
Upper to lower segment
The upper segment to lower segment ratio
Birth : 1.7
3 years: 1.33
5 years : 1.17
10 years : 1.0

94. Upper to lower segment pre-puberty ratio ≥ 1 During puberty ≤1
Adult men o.92
Adult woman