1. Early and late puberty
Tim Cheetham
January 2011

2. 1. Normal physiology
Adrenal
Gonad

3. Steroid producing tissues
Adrenal glands Ovaries
Androgen
Oestrogen Androgen
Peripheral tissue
Oestrogen

4. Do men make oestrogen?
Do women make testosterone?

5. Do babies make sex steroid?

6. Gn production in boys Gn
Age

7. Normal physiology
What next?

8. Adrenarche
Body odour
Greasy hair
Acne
Pubic hair
Pre-puberty

9. cholesterol
Adrenal
Adrenarche
A C
Weak
Androgen

10. cholesterol
Adrenal
Adrenarche
A C
Weak androgens
Weak
Androgen

11. 7 year old Body odour Greasy hair 2 or 3 pubic hairs Body odour
Adrenal
Adrenarche
Body odour
Pubic Hair

12. What next? Body odour Pubic Hair Adrenarche pituitary LH, FSH adrenal
gonad
Adrenarche
Body odour
Pubic Hair
Girls - Bust development
Boys - Testicular enlargement

14. Ovarian volume

15. Puberty
♀: Growth spurt 2 years before boys, at start of clinical puberty
Peak height velocity ~12 years
Followed by menarche
♂: Growth spurt when puberty already well established (testicular volume ~ 10 mls)
Peak height velocity ~14 years

16. 2. ‘Early puberty’ Bust development in the very young child
Early pubic hair
Precocious puberty

17. Isolated premature thelarcheGn
Bust tissue
Age

18. Early pubic hair

19. Adrenarche
Body odour
Pubic Hair
Acne

20. Adrenarche
More pronounced or early if:
Obese
SGA
History of PCOS

21. Adrenarche Body odour Pubic Hair Acne cholesterol A C Weak androgens
CAH
Adrenal tumour
A C
Weak androgens
Body odour
Pubic Hair
Acne

22. Adrenarche Body odour Pubic Hair Acne cholesterol A C Androgens CAH
Adrenal tumour
A C
Androgens
Body odour
Pubic Hair
Acne

23. Investigations?
Nothing
Morning 17-OHP and testosterone

24. Obesity Promotes growth (height) in early life
Associated with an earlier onset of puberty
Hence the Paediatricians interest in the
short, heavy child

27. True precocious puberty
Bust development < 8 years in girls
Testicular enlargement < 9 years in boys

28. Early puberty:
Idiopathic – girls
CNS lesion – boys
LH, FSH
Bust development
Testicular enlargement

29. Gonadotrophin independent
Bust development
Testicular enlargement

30. ‘Pseudoprecocious puberty’

32. TSH - hypothyroidism
Bust development
Testicular enlargement

33. Case 1: Jordan Age 20 months Pubic hair ‘Large testes’ Tall
Healthy non-consanguinous parents

34. Examination Height and weight 75th centile Penile length +2 SD
Testicular volume 3 mls
Pubic hair stage 1

35. Investigations Time (min) LH (U/L) FSH(IU/L) 0 <1 <1
0 <1 <1
<1
<1
Urine steroid profile – normal
17 OHP – 1.3 nmol/L
Testosterone < 1nmol/l

36. Jordan 3.2 years Concerns about gait Increase in size of genitalia
Temper tantrums
Testes 4-5 mls
Penile length 7 cm
PH stage 2
Concerns about gait

37. MPH

39. Investigations MRI brain No intra-cranial abnormality shown.
Time (min) LH (U/L) FSH(IU/L)
Testosterone nmol/L
MRI brain
No intra-cranial abnormality shown.
No mass lesion shown in the pituitary fossa nor in the hypo-thalamic region.
There is a little asymmetry in the lateral ventricles just above the foramen of Monro but there is no structural abnormality to account for this.

40. Jordan Diagnosis – ‘Idiopathic’ GDPP’
Started on Leuprorelin acetate injections

41. Jordan – 6 years Ongoing concerns about gait Plan
Neurodevelopmental assessment
Repeat MRI

42. JH – high signal in the white matter
In keeping with perinatal ischaemic injury

43. Precocious puberty and CNS lesions
Abnormal (enhanced) gonadotrophin
production can commence at a very early age

44. 3. Delayed puberty
~ 14 years in girls
~ 15 years in boys

45. Delayed puberty
Scenario 1
LH, FSH

46. Delayed puberty Scenario 1 LH, FSH Causes 1. Late 2. Chronic illness
3. Endocrinopathy eg prolactinoma
tumour
Gn deficiency

47. Delayed puberty
Scenario 2
LH, FSH

48. Delayed puberty Scenario 2 LH, FSH Causes Ovarian pathology
Abnormal karyotype

49. Case 1

50. CW

51. CW

52. Key features Family history of late puberty
Well child – no evidence of chronic illness
Not dysmorphic
Bone age delay

53. Constitutional delay of growth and pubertyCW
Testosterone
‘Hares and tortoises’
Constitutional delay of growth and puberty

54. Pubertal growth
Males Females
~ 20 to 30 cm ~15 to 25 cm

55. Case 2
Short stature
Late puberty

57. Both parents short
No family history of late puberty

58. Examination
Prepubertal
Not dysmorphic
Obese

60. ‘Short and heavy’ Simple obesity PHP Syndromes Cushings Hypothyroid
GHD / CPHD

61. Plan?

62. Plan?
Thyroid function
IGF-I
24h UFC

63. TSH 1.27
Free T4 9 (11 – 23)
IGF-I 10 (25 – 67)
24h UFC normal

64. Further investigations

65. Further investigations
Pituitary function tests

66. Time mins TSH mU/l FT4 GH PRL 3.7 1.3 9 166 0.4 314 30 6.7 231 0.2 410
Glucose
mmol/l
TSH
mU/l
FT4
pmol/l
Cortisol
nmol/l GH
PRL
3.7
1.3 9
166
0.4
314 30
6.7
231
0.2
410 60
5.1
175
0.3 90
3.6
160
1.1
120
3.2
387
0.8
150
595
0.7
180
477
1.0
210
3.8
509
240
3.9
518
1.4

67. Diagnosis
Isolated GH deficiency +/- gonadotrophin deficiency dating from early life?

71. Clues?
Short and heavy
Thyroid function

72. Summary
A knowledge of normal physiology valuable when faced with early/late puberty
Early pubic hair - ?Non-classical CAH
Early puberty – consider referral
Late puberty – well child?
- Family history?
Late puberty – beware short and heavy
- FSH/LH