Beruflich Dokumente
Kultur Dokumente
causes of premature
adrenarche in girls
Liz Okokon
The chicken and
the egg thesis
In girls,
which comes first,
Boobs or Pubs ?
Pubertal development
Puberty – process of sexual
development
9-14 years in girls 10-16 years in boys
Initiated by activation of hypothalamo-
pituitary-gonadal axis (HPG)
Breast development first sign in girls
Maturation of the ovaries or testes
Pubertal development 2
Adrenarche - onset of pubic hair (PH)
development (pubarche)
Axillary hair, adult body odour and acne
From 9 years in girls and 10 years in boys
Increased plasma adrenal androgen
dehydroepiandrosterone (DHEA)
Maturation of the zona reticularis of the
adrenal cortex
Changes in mean Plasma Testosterone
with stage of life (in males)
Does Puberty
initiate
Adrenarche,
or vice versa ?
Does Adrenarche cause
Puberty?
Under-treated CAH develop true
precocious puberty
Pathological adrenal androgen levels may
induce HPG
Normal Adrenarche at normal time in
Precocious puberty
N or N or N AM Ovarian androgen
tumours
N or N or N DM Adrenal androgen
tumours
1800
Androgen metabolite excretion (ug/24hrs)
1600
1400
1200
1000
800
600
400
200
0
0.0 2.0 4.0 6.0 8.0 10.0
Age (years)
Cortisol metabolite excretion in girls
with PA less than 10-years
12000
Cortisol metabolite excretion (ug/24hrs)
10000
8000
6000
4000
2000
0
0.0 2.0 4.0 6.0 8.0 10.0
Age (years)
Girls with PA in study
32 girls with Premature adrenarche recruited
3 with PCO on U/S (@ 6.3, 8 & 17-yrs)
Age at presentation < 6-yrs in 14
Bone age advanced in 17/19 reported
Low birth weight in 3/11 weight known
F/H metabolic syndrome reported in 4
Complete data on 22 (age 3.7 to 9.1-yrs,
mean age = 7.1 +/-1.6-yrs)
The relationship between bone age
& chronological age in girls with PA
Chronological age ■ Bone age■
12
11
10
9
AGE (years)
7 AGE
6 BA
2
IGF-1 SDS in girls with PA
6
3
IGF-1 SDS
0
4 6 8 10 12 14 16 18 20
-1
-2
Age (yrs)
Normal controls
2 Primary schools in South East
SFT, HT, WT, pubertal stage & ethnicity
24-Hr Urine steroid profiles
Compared
% Body fat(SFT), BSA, BMISDS to
Cortisol, androgen & DHEA excretion
Relationship between age and androgen
metabolite excretion in normal children
1200
1000
800
AM (ug/24hrs)
600
400
200
0
4 5 6 7 8 9 10 11 12
Age (years)
4
2
BMI SDS
-1
-2
4 5 6 7 8 9 10
Age (yrs)
1000
900
DHA Excretion (ug/24hrs.m-2)
800
700
600
500
400
300
200
100
0
4 5 6 7 8 9 10 11 12
Age (yrs)
1.40
1.20
1.00
FM/EM Ratio
0.80
0.60
0.40
0.20
0.00
4.0 5.0 6.0 7.0 8.0 9.0 10.0 11.0 12.0 13.0 14.0
Age (yrs)
Dexamethasone suppression of
lymphocyte stimulation in girls with PA
130
% stimulation by PHA in presence of
120
110
100
90
80
DEX
70
60
50
40
30
20
10
0
0 E-10 E-9 E-8 E-7 E-6
[DEX] (M)
IC 50 ([DEX] @ 50 %
LYMPHOCYTE SUPPRESSION)
0.001
0.01
0.1
1
10
100
PA
Wild type and allelic variant in Intron 3 of
the GCR gene
Variant:
C A/G A C
Variant:
C A/G A C
Wild type:
C CAA C
PCOS: a life-long history
Many thanks to
Andoline Okokon, John Graves, Kwame and Ama Graves-Okokon, Susan and Josephine
Okokon, Dr Carol Gayle and Alan Hardy. Dr Susan Hawes, Dr Kim Khodakah (nee Johnson)
and Professor William Collins (formerly of the Department of Obstetrics and Gynaecology,
KCH.) Dr Sandra Strautnieks (KCH), Dr Richard Thompson (KCH), James Turton (UCL),
Nurse Sara Schilg (Maidstone), and all the STPEG paediatricians:
Dr. Ruth Ayling KCH Dr. Neal Martin Kent & Cant
Dr. Mike Ryalls Guildford Dr. Dorothy Garvie Lewisham
Dr. Tony Hulse Maidstone Dr. Andrew Long Farnborough
Dr. Christine Burren St. Helier Dr. Andrew Evans Greenwich
Dr Norman Taylor, Dr Charles Buchanan, Dr Hagosa Abraha, Belinda Asonganyi, Yiltan
Kani, (Dr) Walid Jervis, Dr Liz Want, Dr Caje Moniz, Dr Roy Sherwood, Dr. J. Alaghband-
Zadeh and my colleagues in Department of Clinical Biochemistry, KCH
Dedicated to the memory of my father
Dr Charles Offiong Ita Okokon
MB, BCh, BAO, DCMT, MRCP, FRCP, FWACP
R.I.P.