Puberty is controlled by the hypothalamic-pituitary-gonadal axis. Normal puberty occurs between ages 8-14 in girls and 9-14 in boys. It involves physical changes like growth spurts and development of secondary sex characteristics. Abnormal puberty can be delayed or precocious. Delayed puberty is usually due to constitutional factors but may have underlying causes. Genetic factors influence the timing of puberty.

1. Puberty – Normal and
Abnormal
For UG-2014

2. Puberty
• Disorders of puberty constitute one of
most common referrals to paediatric
endocrine clinics
• Careful history and examination
paramount
• Ensure sensitivity at all times
• Chaperone during pubertal examination

3. Puberty
• Physiological transition from childhood to
reproductive maturity
• Associated with:
– Growth spurt
– Appearance of both primary and secondary
sexual characteristics in children
– Occurs between 8 and 14yrs in girls
– Occurs between 9 and 14yrs in boys

4. Puberty
• Important to understand
– Range of normal
– Population differences

5. Normal Puberty: Endocrine control
• Onset of puberty signalled by the secretion of pulses of
Gonadotrophin Releasing Hormone (GnRH)
• Prior to puberty: hormonal feedback / central neural
suppression of GnRH release suppress onset of puberty
• Hypothalamo-pituitary-gonadal axis starts working in
foetus. After birth, sex hormones and gonadotrophins
(FSH, LH) found in adult levels
• Levels reduce in months after birth; pulsatile GnRH
reduces in childhood and increases in frequency and
amplitude before puberty
• For 2 yrs before puberty, rise in adrenal androgens
early pubic hair and spots

7. Physiology of Puberty
• Activation of the hypothalamic – pituitary –
gonadal axis
– Induces and enhances progressive ovarian
and testicular sex hormone secretion
– Responsible for the profound biological,
morphological and psychological changes
which adolescents experience

8. Influencing Factors
• Genetics: 50-80% of variation in pubertal timing
• Environmental factors e.g. nutritional status
• Leptin → regulates appetite and metabolism
through hypothalmus. Permissive role in
regulation of timing of puberty
• Adrenarche: development of pubic and axillary
hair, body odour and acne

9. Adrenal Steroids
• DHEA, DHEA-S, Androstenedione
– Begins before rise in gonadotrophin secretion
– Responsible for appearance of axillary hair ad
in part for appearance of pubic hair
(adrenarche)

11. Physical Changes
• 5 stages from childhood to full maturity
• Marshall and Tanner (P1 – P5)
• Reflect progression in changes of the
external genitalia and of sexual hair
• Secondary sexual characteristics
– Mean age 10.5yrs in girls
– Mean age 11.5 – 12yrs in boys

12. Puberty: Girls
• Breast enlargement usually first sign.
• Thelarche
• Often unilateral
• Menarche usually 2-3 yrs after breast
development
• Growth spurt peaks before menarche
• Pubic and axillary hair growth: sign of adrenal
androgen secretion
• Starts at similar stage of apocrine gland sweat
production and associated with adult body odour

13. Examination: Girls
• Examine in supine position. Helps differentiate
between true breast enlargement vs adiposity
• Genital exam: pubic hair, changes in vaginal
mucosa.
• Cliteromegaly suggests androgen excess and
virilisation
• Mild acne normal in early puberty but rapid
onset and progression may suggest androgen
excess
• Vaginal exam only if sexually active
• NEVER rectal exam

14. Pubertal Stages (Tanner)
Female
• P1 Prepubertal
• P2 Early development of subareolar
breast bud +/- small amounts of pubic and axillary
hair
• P3 Increase in size of palpable breast tissue and
areolae, increased dark curled pubic/axillary hair
• P4 Breast tissue and areolae protrude above breast
level. Adult pubic hair but no spread to medial
thighs.
• P5 Mature adult breast. Pubic hair extends to upper
thigh

16. Menarche
• During puberty oestradiol levels fluctuate widely
(reflecting successive waves of follicular
development that fail to reach ovulatory stage)
• Endometrium affected by oestradiol. Undergoes
cycles of proliferation and regression until point
where withdrawal of oestrogen results in the first
menstrual bleed (menarche)
• Increase of only 4% of final height after
menarche

17. Ovarian development
• Rising levels of plasma gonadotrophins
• Stimulate ovary to produce increasing
amounts of oestradiol
• Oestradiol ► secondary sex characteristics
– Breast growth and development
– Reproductive organ growth and development
– Fat redistribution (hips,breasts)
– Bone Maturation

18. Ovarian development
• Prepuberty volume –
0.3 – 0.9cm3
• > 1.0cm3 indicates
puberty has begun
• During puberty –
rapid increase in size
• Mean post pubertal
volume 4cm3

19. Ovulation
• First ovulation occurs 6 – 9 mths after
menarche
• Plasma progesterone remains at low
levels even if secondary sexual
characteristics have appeared
• Rising progesterone after usually ►
ovulation
• Plasma testosterone rise during puberty
(not as much as in male)

20. Development of Uterus
• Prepubertal uterus is tear-drop shaped
• Neck and isthmus account for up to 66%
of uterine volume
• Following production of oestrogens –
uterus becomes pear shaped
• Uterine body increases in length (max 5 –
8cm) and thickness (proportionately more
than cervix)

22. Puberty: Boys
• First signs often go unnoticed
• Testicular enlargement (12-13 yrs)
• Prepubertal testis – 2mls diameter
• Puberty begins when volume reaches
4mls
• Penile and scrotal enlargement occur
approx 1 yr after testicular enlargement.
Pubic hair appears at same time

23. Pubertal Growth Spurt: Boys
• Occurs later than in females
• Testosterone less of a stimulus to GH
responsiveness than oestradiol
• Testosterone required in larger
concentrations to produce same anabolic
effect
• Greater and later growth spurt in boys

24. Examination: Boys
• Testicular growth: associated with enlargement of
seminiferous tubules, epididymis, seminal vesicles and
prostate
• Testicular enlargement: FSH dependant
• Prader orchidometer: assessment of testicular volume
• Signs of androgen excess without commensurate
increase in testicular volume: worrisome e.g CAH,
testicular tumour
• Penile growth, scrotal changes, pubic hair occur 1-2 yrs
after testicular enlargement
• 50% of males varying degrees of breast hypertrophy
• Later signs: growth spurt, acne, voice deepening, facial
hair

25. Pubertal Stages (Tanner)
Male
• P1 Prepubertal, testicular volume < 2mls
• P2 Enlargement of scrotum and penis. Scrotum
slightly pigmented. Few long dark pubic hairs
• P3 Lenghtening of penis. Further growth of testes and
scrotum. Pubic hair darker, coarser and more
curled
• P4 Penis increases in length and thickness.
Increased pigmentation of scrotum. Adult pubic
but no spread to medial thighs
• P5 Genitalia adult in size and shape. Pubic hair spread
to thighs

27. Secondary sexual development
• First signs of puberty
– Testicular volume of
4mls
– Slight progressive
increase in scrotal
folds
– Slight increase in
scrotal pigmentation

28. Testicular Volume

30. Final height
• Puberty usually
completed within 3 - 4
yrs of onset
• Left wrist x-ray to
assess bone age
• Final adult height
results from complete
fusion of epiphyses
– Occurs approx 2yrs
after menarche

31. Assessment of abnormal puberty
• Many causes
• Aim of assessment: determine whether
underlying pathological abnormality vs
constitutional and benign pubertal
changes
• NB: recognise abnormal timing and
progression of puberty

32. What is abnormal?
• Delayed Puberty
• Early or Precocious Puberty
– More common in females
– Uncommon in males (usually pathological)
– < 8yrs in females
– < 9yrs in males
– May be associated with a growth spurt

33. Jameson, J.L. Rites of passage through puberty: A complex genetic ensemble. PNAS.
October 30, 2007. Vol 104, No. 44.

34. • NR0B1 gene is involved in development &
function of the adrenal gland & HPG axis for
gonadotropin secretion
• GPR54 gene mutations affect GnRH release
(these patients do respond to exogenous GnRH)
• PROP1 mutations lead to problems in
differentiation of gonadotropicc, somatotropic,
lactotropic & thyrotropic cells.

35. Pubertal Delay
• Based on statistical norms (>2 SD from
the population mean)
• Pubertal delay is most often seen in males
– Present far more often than females as delay
causes more significant psychosocial
implications
• Most commonly no pathology present

36. Timing of Puberty
• Consider pubertal delay if:
– No breast development by age 13 in a female
– No menses by age 15 in a female
– Testicular size < 2.5cm or 4mL or pubic hair is not
present by age 14 in a male
• Consider precocious puberty if:
– Breast development before age 8 or menarche before
age 10 in females
– Testes volume > 3ml before 9 years.
– Pubic hair development before 8 years in females,
and 9 years in males

37. Pubertal Delay
Pubertal Delay
Hypogonadotropic
Hypogonadism
Hypergonadotropic
Hypogonadism
Eugonadotropic
Hypogonadism
Low FSH, LH
Low sex steroids
High FSH, LH
Low sex steroids
Normal FSH, LH

38. Pubertal Delay
• Sedlmeyer et al. identified in their study
that delayed puberty in men could be
classified as
– Constitutional delay of growth & puberty in
63%
– Delay associated with underlying medical
condition 20%
– Hypogonadotropic hypogonadism 9%
– Hypergonadotropic hypogonadism 7%

39. Hypogonadotropic Hypogonadism
• Constitutional Delay of Puberty
• Malnutrition
• Excessive Exercise
• Growth Hormone Deficiency
• Isolated Gonadotropin Deficiency
• Endocrine Causes
• Miscellaneous syndrome complexes
• Brain tumors
– Craniopharyngioma, astrocytomas, gliomas, histiocytosis X,
germinomas, prolactinomas
• Iron overload (pituitary damage)
• GnRH receptor abnormalities

40. Constitutional Delay of Puberty
• Most common cause of pubertal delay
• Delayed puberty often found in siblings or
parents
• Diagnosis of exclusion
• Bone age is delayed & consistent with degree of
pubertal maturation (usually delayed by 2yrs or
more
• Often associated with constitutional short stature

41. Constitutional Delay of Puberty
cont’d…
• Progressive height gain, but along lower
limits of normal (contrast to isolated
gonadotropin deficiency which has normal
growth, but no pubertal growth spurt)
• Early morning testosterone levels >
0.7nmol/L predict puberty within 15
months (Wu et al)

42. Constitutional Delay of Puberty
cont’d…
• Differentiated by pathological gonadotropin
deficiency by observation over time (no definitive
test available)
– GnRH stimulation test occasionally used, but not
conclusive
• HPG axis responds to GnRH more strongly if it has already
been exposed to this (reflects previous stimulation)
– hCG stimulation test can also be undertaken (Degros
et al)
• Stimulated testosterone < 3 nmol/L suggestive of
hypogonadotropic hypogonadism
• Stimulated testosterone >9 nmol/L suggestive of CDGP

44. Kallman Syndrome
• A syndrome of isolated gonadotropin deficiency
• 1/10,000 males, 1/50,000 females
• Present with ANOSMIA or HYPOSMIA
• Can be difficult to differentiate from constitutional
delay
• KAL-1 gene encodes protein (anosmin) required
for GnRH neurons to migrate from olfactory
placode to cribiform plate
• Can also be associated with harelip, cleft palate,
and congenital deafness

45. Idiopathic Hypogonadotropic
hypogonadism
• Males often have eunochoid body proportions
(upper-to-lower segment ratio of < 1)
• Can be sporadic or familial
• Can be related to problems in the receptor for
GnRH
• Can present as infant with micropenis &
cryptorchidism. These infants will not show
normal gonadotropin increase in the first few
weeks of life

46. Excessive exercise
• Questions as to whether lack of puberty
related to low body weight or more as a
direct effect of exercise
– Interruption of training in ballet dancers,
runners

47. Syndromes Associated with Pubertal
Delay
• Prader-Willi syndrome
• Laurence Moon syndrome
• Septo-optic dysplasia
• Bardet-Biedl syndrome

48. Panhypopituitarism
• Pubertal delay is usually not presentation
(present with short stature earlier)

49. What controls the timing
of puberty? An update
on progress from genetic
investigations? Current
Opinion in Endocrinology. 2009

50. Hypergonadotropic hypogonadism
• Gonadal damage secondary to
chemotherapy/radiation
• Enzyme defects in the gonads
• Androgen insensitivity
• Ovarian/testicular dysgenesis (causes of
gonadal failure)

51. Gonadal Failure (bilateral)
• In these cases, circulating levels of LH & FSH are high
(hypergonadotropic hypogonadism)
• Congenital
– Turner Syndrome
– Klinefelter’s Syndrome
– Complete androgen insensitivity
• Acquired
– Chemotherapy/Radiation/Surgery
– Postinfectious (ie. mumps orchitis, coxsackievirus infection, dengue,
shigella, malaria, varicella)
– Testicular torsion
– Autoimmune/metabolic (autoimmune polyglandular syndromes)
– “Vanishing Testes syndrome”
– “Resistant Ovaries syndomre” (gonadatropin receptor problems)

52. Klinefelter’s Syndrome
• 45 XXY most common (2/3), remainder are mosaic or variant
• Many affected boys will not be identified until adolescence when
puberty is delayed
• Some pubertal development, but testes eventually become fibrotic
– Timing relates to degree of mosaicism in the patient
• Small testicles & gynecomastia
• Also often small phallus size
• 90-100% are infertile
• More female type fat distribution
• Tall in childhood, with euchanoid body habitus
• Have fathered children (particularly those with mosaicism)

54. Turner Syndrome
• 45 XO genotype most common
• Associated with short stature, variable degrees
of puberty, primary amenorrhea & multiple
congenital anomalies
• Often presenting complaint is short stature, but
in others, may present with delayed puberty
• Most have primary ovarian failure
• 50% of patients have some breast develpoment,
some axillary/pubic hair is typical for most
patients
• Associated with SHOX mutations which cause
the short stature

55. Turner syndrome cont’d…
• Residual ovarian function can cause
breast development in 15-25%, menarche
in 5-10% & pregnancy in 1-3%

57. Receptor Defects
• LH gene defects and FSH gene defects
can result in high levels of FSH & LH with
low sex steroids
• Secondary sex characteristics are driven
by LH effects, can have FSH receptor
defect & normal secondary sex
characteristics

58. Eugonadotropic pubertal delay
• Congenital Anatomic Anomalies
– Imperforate hymen
– Vaginal atresia
– Vaginal aplasia
• PCOS
• Hyperprolactinemia

59. • In this case, secondary sex characteristics
are normal
• May have cyclic lower abdominal pain

60. Chronic Illness
• Can affect underlying genetic potential
• May limit adequate nutrition (ie.
inflammatory bowel disease, cystic
fibrosis)
• May be associated with glucocorticoid use,
chemotherapy or radiation

61. Other Endocrine Causes
• Hypothyroidism
– Interferes with gonadotropin secretion (affects
pulsatile secretion of LH)
• Hyperprolactinemia
– Interfere with gonadotropin production
**prolactinomas may not always be visible on
imaging**

62. Investigating Delayed Puberty
• Investigations depend on clinical presentation,
but may include
– Bone age
– Hormone levels (IGF-1, FSH, LH, estradiol,
testosterone, DHEAS, prolactin, TSH)
– Karyotype
– Hormone stimulation tests
• GnRH stimulation test
• GH stimulation test
– Imaging
• MRI if gonadotropins high & no obvious cause of
hypogonadotropic hypogonadism

63. Psychological Distress in Pubertal
Delay
• Much has been written about psychological distress in
males with delayed puberty
• Self-Esteem & Sexuality in girls with Turner Syndrome
has been studied
– Generally had low self-esteem scores (general & social)
– Lifetime sexual experience associated with overall SEI score
– Increasing sexual experience had no effect (all-or-none
phenomenon)
– Ross et al. -> initiation of estrogen therapy associated with
increased self-esteem in girls with Turner syndrome
Psychosocial Adjustment in Turner Syndrome. Journal of Clinical
And Endocriological Metabolism. 2006.

64. Stimulating Puberty in Males
• Should be begun at 12yrs of age
• Multiple indications
• For CDGP
– Indicated in those boys with psychological distress
(who have poor body image, low self-esteem, are
becoming socially withdrawn, or are subjected to
teasing or bullying)
• Time of therapy initiation may vary (if GH
deficiency present, delay starting to optimize
height achievement)
• Testosterone supplementation may help with
bone mineral density

65. • Exogenous testosterone
– Does not increase testicular size (normal puberty continues to
progress)
– Causes virilization (increased phallic size & scrotal rugae)
– Accelerates development of secondary sex characteristics to
avoid psychosocial complications
– Should be used only if bone age is delayed, and introducted
at approx. normal time of development
– Also stimulates growth spurt
– Side effects
• Local discomfort at site of injection
• priapism

66. Androgen Supplementation
• Testosterone
– IM Injections (once puberty has begun)
• Doses of 50-200mg IM using testosterone esters have been
used for periods of 6-12 months
• Depot testosterone like this results in high testosterone peaks &
a duration of action of 2-3 weeks
• Theoretic advantage for negative feedback on HPG axis to be
alleviated with “wearing off” of exogenous testosterone
– Oral
• Associated with more gradual effects
• Testosterone undecanoate 40mg po qdaily
• Oxandrolone 2.5mg po qdaily
– Gels, transdermal patches, etc. have not been
studied as well in boys & dosing is less predictable

67. • hCG
– Can also use to stimulate development of
secondary sexual characteristics
– Increases testicular size
– Can be used to stimulate fertility
– 200-500 units qalt days

68. Stimulating Puberty in Females
• Estrogen Replacement
– Increased gradually to adult replacement
levels (as puberty is normally a slow process)
– Aims:
• Attainment of secondary sexual characteristics
• Attainment of menses
• Stimulation of pubertal growth spurt
• Acquisition of bone mineral mass
• Uterine development

69. Estrogen Replacement in Females
– Initiate replacement at age 10-12 yrs & should continue over
course of normal puberty (approx. 3 yrs)
– Effect of estrogen on growth plate is dose dependent
• Higher doses stimulate epiphyseal growth plate closure
– Once dose of 10-15mcg of ethinyloestradiol has been reached,
breakthrough bleeding becomes apparent – once this occurs,
progesterone should be added on a cyclic basis to prevent
endometrial hyperplasia
– Dosing
• 0.3mg conjugated estrogen daily
• 5mcg of ethinyl estradiol daily
• Transdermal estrogen 25mcg twice weekly
• Increase q6-12 months until maximum (20 mcg)

70. • Suggested dosing increments
– Ethinyloestradiol
• 2mcg/day X 6 months
• 4 mcg/day X 6 months
• 6 mcg/day X 6 months
• 10 mcg/day X 6 months
• 15 mcg/day X 6 months
– 17-estradiol
• 5mcg/day po
• 10 mcg/day po
• 15 mcg/day po
• 20 mcg/day po
– Introduce progesterone once breakthrough bleeding has
occurred, after this point can switch to an oral contraceptive pill

71. Estrogen Side Effects
• Thromboembolism
• Endothelial dysfunction
• Hyperlipidemia
• Increased risk of breast & gynecological
malignancy
• Increased risk of gallstones

72. Achieving Fertility
• May require pulses of GnRH in females
• hCG in males 1-2 times/week helps to
maintain spermatogenesis
– 1200-5000 IU hCG IM 3 times weekly
– 12.5-150 hMG IM 3 times weekly

73. Assessment 1
• Full history of previous growth and
development
• Record timing and sequence of physical
milestones and behavioural changes of
puberty
• Full medical and surgical history
• If underweight: take full nutritional history
• Family hx of early or delayed puberty
• Family hx of any genetic disease

74. Assessment 2
• Plot height, weight, BMI and growth
velocity
• Compare with old measurements if
available
• Examine all systems: endocrine /
neurology NB
• Optic fundi, visual fields, sense of smell
• Genitalia, body habitus, stage of puberty

75. Delayed Puberty:
Hypogonadotrophic
• Constitutional (familial, sporadic)
• Chronic illness (CF, Crohns Disease, Renal failure)
• Malnutrition (Anorexia, CF, coeliac disease)
• Exercise
• PCOS
• Tumours of pituitary/hypothalamus (craniopharyngioma)
• Hypothalamic syndromes (PWS, Laurence-Moon-Biedl)
• Hypothyroidism
• Suppression 20 to hyperthyroidism, hyperprolactinemia,
Cushing Syndrome, CAH
• Panhypopituitarism

76. Delayed Puberty:
Hypergonadotrophic
• Congenital
– Turner Syndrome
– Klinefelters Syndrome
• Acquired
– Irradiation / Chemotherapy
– Surgery
– Testicular torsion, trauma
– Infection
– Autoimmunity

77. Precocious Puberty
• Onset of secondary sexual characteristics
< 8yrs in girls and < 9yrs in boys
• 5 times more common in girls
• Usually benign central process – girls
• Pathological in ~ 50% in boys

78. Precocious puberty
Defined as the onset of secondary sexual
characteristics before 8 yr age in girls and 9 yr
in boys.

79. Classification of precocious puberty
 True precocious puberty ( central or gonadotropin-
dependent = CPP)
 Precocious pseudopuberty ( peripheral,
gonadoptropin independent (PPP)
 Mixed type

80. Conditions causing central precocious
puberty
• Idiopathic
• organic brain lesions
(inflamation, malformation, trauma, chemotherapy,
radiotherapy, brain tumor)
• Hypothyroidism

81. Conditions causing precocious
pseudopuberty in females
• Iso sexual ( feminizing ) conditions
Mc cune – Albrightsyndrome
Autonomous ovarian cyst
Ovarian tumors
Feminizing adrenocortical tumor
Exogenous estrogens
cont

82. • Hetrosexual (masculinizing)
Congenital adrenal hyperplasia
Adrenal tumor
Ovarian tumor
Glucocorticoid receptor defect
Exogenous androgens.

83. Conditions causing precocious
pseudopuberty in males
• Isosexual
congenital adrenal hyperplasia
Adrenocortical tumor
Leydig cell tumor
Familial male precocious puberty
HCG secreting tumor
Teratoma
cont

84. Glucocorticoid receptor defect
Exogenous androgen
• Hertrosexual
Feminizing adrenocortical tumor
Exogenous estrogens

85. Approach to patient with precocious
puberty
• History
(Medication )
(family history of precocious puberty)
• Physical examination
(Wt, Ht, Eye, Thyroid, abdomen, tests)
• paraclinical findings
• bone age
cont

86. • Estradial
• Testosterone
• LH
• FSH
• GnRH stimulation test
(LH/FSH> 1)
(LH>5- 10 IU/L)
• Sonography
(ovaries, Uterus, adrenal glands, testes)
• MRI of brain
(MRI of hypothalamus and hypophysis)
cont

87. The goals of treatment for CPP
1. Improvement of adult height
2. Prevention of social and psychological
problems.

88. Treatment of CPP
GnRH analogues
GnRH antagonist
Aromatize inhibitors

89. Indications for therapy with GnRH
agonist
• True precocious puberty in males
• Rapid progressive CPP in girls
• To stop puberty because of social and
psychological reasons

90. The effect of GnRH agonist therapy on:
• Growth
• Skeletal age
• Pubertal development
• Hormones

91. Treatment is effective if:
1. Serum sex hormone concentration
decrease to prepubertal levels
( testosterone < 20ng/ dL in boys estradial
< 10pg/mL in girls)
1. Serum FSH and LH < 1 IU/L
2. LH/FSH < 1

92. Physiological status after completion
of therapy
• Growth rate
• Bone density
• Pubertal development
• Hormones
• Fertility

93. Premature thelarche / pubarche
• Thelarche – beginning of breast development
• Pubarche – first appearance of pubic hair
– (more common in certain populations e.g asian / afro-caribbean )
• More common than true precocious puberty
• Benign variants
– breast development in girls < 3yrs with spontaneous regression
– Pubic hair in boys and girls < 7yrs due to adrenal androgen
secretion in middle childhood
– NB Examination normal or may be slight advance in growth
curve

94. Precocious Puberty
Gonadotrophin dependant
• Idiopathic (sporadic / familial)
• Congenital (Hydrocephalus)
• Acquired (irradiation/surgery/infection)
• Tumours (hamartomas/gliomas)
• Hypothyroidism
• Russell Silver Syndrome
• Mc Cune Albright Syndrome

95. Precocious Puberty
Gonadotrophin Independant
• Normal pattern of puberty absent
– Virilisation of female (CAH)
– Feminisation of a boy (oestrogen producing
leydig tumour)
– Adrenal Tumour
– Ovarian Tumour

96. Investigations
• Blood Tests (first line)
– FBC
– U&E
– LFT’s
– TFT’s
– FSH/LH
– Oest/Testosterone
– 17 OHP / 11 DOC
– Adrenal androgens
– Prolactin
• Second line
– GnRH assay
– Beta –HCG
– Karyotype if indicated

97. Diagnostic Imaging
• Pelvic USS (ovarian tumours / cysts)
• Testicular USS (tumour)
• Adrenal USS (MRI / CT better if tumour
considered)
• Bone Age (if within 1yr of CA, puberty not
started or only just started; if > 2yrs,
puberty already started)
• Brain MRI in all males and patients with
neurological signs or symptoms)

98. Management
• Treat systemic disease
• Psychological support
• Promote puberty / growth if necessary
– Low dose testosterone
– Ethinyloestradiol

99. Issues
• Treatment of the cause e.g. cranial
neoplasm
• Behavioural difficulties – psychology
• Reduce rate of skeletal maturation (early
growth spurt may result in early epiphyseal
closure and reduced final adult height)
– Halt or slow puberty (GnRH analogue)
– Inhibit action of excess sex steroids

100. Growth and Puberty
• GH plays role in pubertal development
• Amplifies ovarian response to gonadotrophins
• IGF-1 enhances gonadotrophin effect on
granulosa cells
• Isolated GH deficiency associated with pubertal
delay, diminished Leydig cell function and
decreased response to chorionic
gonadotrophins
• GH administration can restore testicular
responsiveness to LH and Leydig Cell
steroidogenesis

101. Growth and Puberty
• Growth hormone-releasing factor (GRF) levels
and GH secretion increase considerably during
puberty, mainly at night
• Amplitude of GH peaks increases in early
puberty – growth spurt
• IGF-1 ►important modulator of growth during
childhood and adolescence
• Adrenal androgens have little physiological role
in normal growth

102. Thelarche
• Absence of a growth
spurt and axillary or
pubic hair
differentiates
thelarche from
precocious puberty

103. Ambiguous genitalia
• Range of presentations
– Inadequately developed male to virilised female
• Most common cause is Congenital Adrenal
Hyperplasia → virilised female
• Urgent identification as can cause adrenal
failure in neonatal period
• Do not ascribe sex immediately
• Identify cause of intersex
• Karyotype does not indicate the sex of rearing
• Family counselling imperative
• Early surgery now less popular

104. Thank You