Early and late puberty
Tim Cheetham
January 2011
1. Normal physiology
Adrenal
Gonad
Steroid producing tissues
Adrenal glands
Ovaries
Androgen
Oestrogen
Peripheral tissue
Oestrogen
Androgen
• Do men make oestrogen?
• Do women make testosterone?
Do babies make sex steroid?
Gn production in boys
Gn
2
Age
9
Normal physiology
What next?
Adrenarche
• Body odour
Pre-puberty
• Greasy hair
• Acne
• Pubic hair
cholesterol
Adrenal
• Adrenarche
A
Weak
Androgen
C
cholesterol
Adrenal
• Adrenarche
A
Weak
Androgen
C
Weak androgens
7 year old
• Body odour
• Greasy hair
Adrenal
• 2 or 3 pubic hairs
• Adrenarche
Body odour
Pubic Hair
What
next?
pituitary
LH, FSH
adrenal
gonad
• Adrenarche
Body odour
Pubic Hair
Girls - Bust development
Boys - Testicular enlargement
Ovarian volume
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
2. ‘Early puberty’
• Bust development in the very young child
• Early pubic hair
• Precocious puberty
Isolated premature thelarche
Gn
Bust tissue
2
Age
9
Early pubic hair
• Adrenarche
Body odour
Pubic Hair
Acne
Adrenarche
More pronounced or early if:
1. Obese
2. SGA
3. History of PCOS
cholesterol
• Adrenarche
• CAH
• Adrenal tumour
Body odour
Pubic Hair
Acne
A
C
Weak androgens
cholesterol
• Adrenarche
• CAH
• Adrenal tumour
Body odour
Pubic Hair
Acne
A
C
Androgens
Investigations?
• Nothing
• Morning 17-OHP and testosterone
Obesity
• Promotes growth (height) in early life
• Associated with an earlier onset of
puberty
Hence the Paediatricians interest in the
short, heavy child
True precocious puberty
• Bust development < 8 years in girls
• Testicular enlargement < 9 years in boys
Early puberty:
Idiopathic – girls
CNS lesion – boys
LH, FSH
Bust development
Testicular enlargement
Gonadotrophin independent
Bust development
Testicular enlargement
‘Pseudoprecocious puberty’
TSH - hypothyroidism
Bust development
Testicular enlargement
Case 1: Jordan
Age 20 months
Pubic hair
‘Large testes’
Tall
Healthy non-consanguinous parents
Examination
Height and weight 75th centile
Penile length +2 SD
Testicular volume 3 mls
Pubic hair stage 1
Investigations
Time (min)
0
30
60
LH (U/L)
<1
2.1
1.4
Urine steroid profile – normal
17 OHP – 1.3 nmol/L
Testosterone < 1nmol/l
FSH(IU/L)
<1
<1
<1
Jordan 3.2 years
Increase in size of genitalia
Temper tantrums
Testes 4-5 mls
Penile length 7 cm
PH stage 2
Concerns about gait
MPH
Investigations
Time (min)
0
30
60
Testosterone
LH (U/L)
2.9
22.8
19.7
FSH(IU/L)
2.5
4.4
4.4
11.2 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.
Jordan
Diagnosis – ‘Idiopathic’ GDPP’
Started on Leuprorelin acetate injections
Jordan – 6 years
Ongoing concerns about gait
Plan
• Neurodevelopmental assessment
• Repeat MRI
JH – high signal in the white matter
In keeping with perinatal ischaemic injury
Precocious puberty
and CNS lesions
Abnormal (enhanced) gonadotrophin
production can commence at a very early age
3. Delayed puberty
~ 14 years in girls
~ 15 years in boys
Delayed puberty
Scenario 1
LH, FSH
Delayed puberty
Scenario 1
LH, FSH
Causes
1. Late
2. Chronic illness
3. Endocrinopathy eg prolactinoma
tumour
Gn deficiency
Delayed puberty
Scenario 2
LH, FSH
Delayed puberty
Scenario 2
LH, FSH
Causes
1. Ovarian pathology
2. Abnormal karyotype
Case 1
CW
CW
Key features
• Family history of late puberty
• Well child – no evidence of chronic
illness
• Not dysmorphic
• Bone age delay
CW
Testosterone
‘Hares and tortoises’
Constitutional delay of growth and puberty
Pubertal growth
Males
~ 20 to 30 cm
Females
~15 to 25 cm
Case 2
• Short stature
• Late puberty
• Both parents short
• No family history of late puberty
Examination
• Prepubertal
• Not dysmorphic
• Obese
‘Short and heavy’
•
•
•
•
•
•
Simple obesity
PHP
Syndromes
Cushings
Hypothyroid
GHD / CPHD
Plan?
Plan?
• Thyroid function
• IGF-I
• 24h UFC
• TSH 1.27
• Free T4 9 (11 – 23)
• IGF-I 10 (25 – 67)
• 24h UFC normal
Further
investigations
Further
investigations
• Pituitary function tests
Time Glucose TSH
mmol/l
mins
mU/l
0
3.7
1.3
FT4
pmol/l
9
Cortisol
nmol/l
PRL
166
GH
mU/l
0.4
410
30
6.7
231
0.2
60
5.1
175
0.3
90
3.6
160
1.1
120
3.2
387
0.8
150
3.6
595
0.7
180
3.7
477
1.0
210
3.8
509
1.1
240
3.9
518
1.4
314
Diagnosis
• Isolated GH deficiency +/- gonadotrophin
deficiency dating from early life?
Clues?
• Short and heavy
• Thyroid function
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
