Early and late puberty Tim Cheetham January 2011

1. Normal physiology Adrenal Gonad

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

Do men make oestrogen? Do women make testosterone?

Do babies make sex steroid?

Gn production in boys Gn 2 9 Age

Normal physiology What next?

Adrenarche Body odour Greasy hair Acne Pubic hair Pre-puberty

cholesterol Adrenal Adrenarche A C Weak Androgen

cholesterol Adrenal Adrenarche A C Weak androgens Weak Androgen

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

What next? Body odour Pubic Hair Adrenarche 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 9 Age

Early pubic hair

Adrenarche Body odour Pubic Hair Acne

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

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

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

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) LH (U/L) FSH(IU/L) 0 <1 <1 0 <1 <1 30 2.1 <1 60 1.4 <1 Urine steroid profile – normal 17 OHP – 1.3 nmol/L Testosterone < 1nmol/l

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

MPH

Investigations MRI brain No intra-cranial abnormality shown. Time (min) LH (U/L) FSH(IU/L) 0 2.9 2.5 30 22.8 4.4 60 19.7 4.4 Testosterone 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 Ovarian pathology 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

Constitutional delay of growth and puberty CW Testosterone ‘Hares and tortoises’ Constitutional delay of growth and puberty

Pubertal growth Males Females ~ 20 to 30 cm ~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 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

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