pubertal development dr assunta albanese st george’s hospital london
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PUBERTAL DEVELOPMENT
Dr Assunta AlbaneseSt George’s Hospital
London
PUBERTY
Gonadal maturation with acquisition of secondary sexual characteristics and
associated growth spurt
FERTILITY AND FINAL HEIGHT
PUBERTY
Average age of onset:
• 11.4 years in girls
• 12.0 years in boys
First signs of pubertal maturation:
• breast budding in girls
• increase in testicular volume in boys
TANNER’S STAGING OF PUBERTY IN GIRLS
STAGE BREAST DEVELOPMENT(B)
PUBIC HAIR (PH)
1 Prepubertal; no breast tissue None
2 Areolar enlargement withbreast bud
A few darker hairsalong labia
3 Enlargement of breast andareola as single mound
Curly pigmentedhairs across pubes
4 Projection of areola abovebreast as double mound
Small adultconfiguration
5 Mature adult breast withsingle contour
Adult pubic hairdistribution
OVARIAN REGULATIONOVARIAN REGULATION
HypothalamusHypothalamus
GnRH release
Pituitary glandPituitary gland
FSH LH
OvaryOvary
OestrogenInhibin
Oestrogens produced by ovaries induce/
maintain secondary sexual characteristics
and sustain germ cell production
• Breast development• Libido• Body composition• Bone mineralization
ASSESSMENT OF OVARIAN ASSESSMENT OF OVARIAN FUNCTIONFUNCTION
• Pubertal staging
• Hormone levels (LH, FSH, Oestradiol, Inhibin B, progesterone)
• Pelvic USS
LH, FSH and E2 and PUBERTAL STAGE in GIRLS
Patterns of LH secretion during pubertal development
DIAGNOSTIC VALUE OF PELVIC USS
• Depend on experience of examiner!
• Size and shape of uterus and ovarian volume and appearance are a indicator of the degree of pubertal development
EVALUATION OF OVARIES AT USS
• Shape is oval. If smaller than 1 ml prepubertal. In young adult ~6.5 ml
• Ovarian follicles can be detected from any age of early infancy onward
• Follicles increase progressively in size and number after 8.5 yrs.
• 3-4 small cysts (~ diameter 5 mm) normal at any age
EVALUATION OF UTERUS AT USS
• Shape depends on the age of child:– During neonatal period and infancy drop shaped– By 8 yrs tubular form– During puberty pear shape
• Cervix to corpus ratio: – 2:1 pre-puberty– 1:2 post-puberty
• Angle between corpus and cervix only seen after puberty
• Endometrium thickness not seen in prepuberty
TANNER’S STAGING OF PUBERTY IN BOYS
STAGE GENITALMATURITY (G)
PUBIC HAIR (PH)
1 Prepubertal; testes 2 ml None
2 Enlargement of thetestes 4 ml; reddeningof the scrotum
A few darker hairs at the basisof the penis
3 Lengthening of thepenis; furtherenlargement of testes to6-10 ml
Curly pigmented hairs acrosspubes
4 Broadening of theglands penis; growth oftestis to 10-15 ml
Small adult configuration
TESTICULAR REGULATIONTESTICULAR REGULATION
HypothalamusHypothalamus
GnRH release
Pituitary glandPituitary gland
FSH LH
TestisTestis
TestosteroneInhibin(From the Leyding cells)(From the Sertoli cells)
Testosterone produced by Leyding cells
induces/ maintains secondary sexual
characteristics and sustain germ cell
production
• Virilization of external genitalia• Phallus growth • Pubic, axillary, facial hair • Libido• Erections/ejaculate• Voice change• Body composition• Bone mineralization
ASSESSMENT OF TESTICULAR ASSESSMENT OF TESTICULAR FUNCTIONFUNCTION
• Pubertal staging
• Hormone levels (LH, FSH, testosterone, Inhibin B)
• Sperm count and analysis
LH, FSH and E2 and PUBERTAL STAGE in BOYS
"CONSONANCE" OF PUBERTY
• Close relationship between secondary sexual characteristics and pubertal growth spurt
• In girls the pubertal growth spurt occurs early in puberty, (B2-3)
• In boys the pubertal growth spurt occurs late in puberty, (G3-4, 10 ml testicular volume)
DELAYED PUBERTY
Onset of puberty after:
• 13.4 yrs in girls
• 13.8 yrs in boys
CONCERNS RAISED BY DELAYED PUBERTY
• Possibly sinister underlying cause
• Fear that puberty will never occur
• Emotional and psychosocial upset of immaturity, specially when associated with short stature
• Long term sequelae: ? Reduced bone mineralization
CLASSIFICATION OF DELAYED SEXUAL MATURATION
• CDGP
• Secondary delay: – Chronic systemic illness
– Steroid treatment
– Psychosocial growth disturbance
– Anorexia
• Hypogonadotrophic hypogonadism– Isolated gonadotrophin deficiency– Multiple pituitary hormone deficiency– Secondary to CNS tumours or cranial irradiation
• Hypergonadotrophic hypogonadism– Klinefelter’s and Turner’s Syndromes– Primary or secondary gonadal failure
• Dysmorphic syndromes– Noonan’s syndrome, Prader-Willi, etc
DELAYED PUBERTY
• Absence of a clear pattern of pulsatile gonadotrophin secretion
• Pre-pubertal LH and FSH levels
• Development of secondary sexual characteristics
• Normal "Consonance"
• Bone age delay
• Final height is not impaired except if severe degree of delay
CONCLUSION
• A good understanding of normal puberty is necessary to fully assess disorders of growth and puberty
• The commonest disorders of precocious/delayed puberty are idiopathic
• Psychological disturbances is the commonest indication for intervention
Precocious Puberty
Onset of puberty before:
• 8 yrs in girls
• 9 yrs in boys
Early Puberty
Onset of puberty between:
• 8 - 9 yrs in girls
• 9 - 10 yrs in boys
CLASSIFICATION OF PRECOCIOUS SEXUAL MATURATION
• Gonadotrophin-Dependent (True precocious puberty)
• Gonadotrophin-Independent (Pseudo precocious puberty)
• Variants of Precocious Sexual Maturation
GONADOTROPHIN-DEPENDENT
• Central precocious puberty– Idiopathic
– Secondary to CNS abnormalities
• Congenital anomalies (hydrocephalus)
• Tumours
• Acquired (infections, surgery, irradiation)
• Primary hypothyroidism
CENTRAL PRECOCIOUS PUBERTY
SEXUAL DIMORPHISM
• Usually idiopathic in girls (90% or more)
• Almost always secondary to lesions in CNS in boys
GONADOTROPHIN-DEPENDENT
• Pulsatile gonadotrophin secretion, especially overnight
• LH : FSH ratio > 1
• Gonadal activation with sex steroid production
• Development of secondary sexual characteristics
• Normal "Consonance"
• Bone age acceleration
• Final height impairment
GONADOTROPHIN-INDEPENDENT
• Adrenal disorders • Tumours secreting sex steroids• Congenital adrenal hyperplasia
• Gonadal disorders• Ovarian cyst/tumours secreting sex steroids• Leydig cell tumour
• Exogenous sex steroids• McCune-Albright Syndrome• Testotoxicosis
GONADOTROPHIN-INDEPENDENT
• Sex steroid production from gonads or adrenal gland or exogenous source
• Suppressed LH and FSH levels
• Secondary sexual characteristics or virilization
• Growth acceleration
• Bone age acceleration with final height impairment
McCune - Albright Syndrome
• Fibrous dysplasia of skull and long bone
• "Cafe-au lait" patches with serrated edges • Autonomous endocrine overactivity :
• Precocious puberty• Hyperthyroidism• Hypercortisolism• Pituitary adenomas secreting GH/ PRL• Hyperparathyroidism
McCune - Albright Syndrome
• Precious puberty mainly described in girls
– First phase: intermittent periods of breast development and vaginal bleeding (gonadotrophin independent)
– Second phase: Central precocious puberty (gonadotrophin dependent)
McCune - Albright Syndrome
• Gene mutation for the -subunit of the G
protein, which stimulate cAMP formation
• Activation of receptors that operate with a
cAMP-dependent mechanism
• The somatic mutation occurs early in
embriogenesis
TESTOTOXICOSIS
• Occurs in boys, familiar, Autosomic Dominant
• Normal "Consonance"
• Extreme degree of virilization compared to the testicular enlargement
• Prepubertal values of FSH and LH• Failure to respond to GnRH analogue treatment• Due to a mutation of LH receptor with constant
activation of the G protein even without ligand
VARIANTS OF PRECOCIOUS SEXUAL MATURATION
• Isolated premature thelarche
• Isolated menarche
• Premature adrenarche
• Unclassified forms
ISOLATED PREMATURE THELARCHE
• Isolated cyclic breast enlargement, usually < 2 yrs old
• Absence of other signs of puberty
• Absence of behavioural problems
• Normal growth and bone maturation
• Predominant FSH pulsatility
• Development of follicular ovarian cysts
Features
Central precocious Puberty
Isolated premature Thelarche
Age of onset <8 years Usually < 2 years
Breast development Progressive development Minor, cycling at around 6 week intervals
Pubic and axillary Hair
Progressive development Absent
Menses As in normal puberty Occasionally may occur
Skeletal maturation Advanced Appropriate
Growth velocity Accelerated Normal
PREMATURE PUBARCHE
• Usually begins at around 6-8 years of age
• Early appearance of pubic hair, with or without axillary hair
• Puberty usually occurs at a normal time
• Slight growth spurt and advance in bone maturation
• Final height prognosis is not compromised
PREMATURE PUBARCHE
– Increased adrenal production of sex hormones
– Gonadotrophin secretion is prepubertal
Clitoral virilization in girls and phallic enlargement in boys together with excessive bone age maturation should suggest excessive production of sex hormones due to CAH or an adrenal tumour
DELAYED PUBERTY
Onset of puberty after:
• 13.4 yrs in girls
• 13.8 yrs in boys
CONCERNS RAISED BY DELAYED PUBERTY
• Possibly sinister underlying cause
• Fear that puberty will never occur
• Emotional and psychosocial upset of immaturity, specially when associated with short stature
• Long term sequelae: ? Reduced bone mineralization
CLASSIFICATION OF DELAYED SEXUAL MATURATION
• CDGP
• Secondary delay: – Chronic systemic illness
– Steroid treatment
– Psychosocial growth disturbance
– Anorexia
• Hypogonadotrophic hypogonadism– Isolated gonadotrophin deficiency– Multiple pituitary hormone deficiency– Secondary to CNS tumours or cranial irradiation
• Hypergonadotrophic hypogonadism– Klinefelter’s and Turner’s Syndromes– Primary or secondary gonadal failure
• Dysmorphic syndromes– Noonan’s syndrome, Prader-Willi, etc
DELAYED PUBERTY
• Absence of a clear pattern of pulsatile gonadotrophin secretion
• Pre-pubertal LH and FSH levels
• Development of secondary sexual characteristics
• Normal "Consonance"
• Bone age delay
• Final height is not impaired except if severe degree of delay
CONCLUSION
• A good understanding of normal puberty is necessary to fully assess disorders of growth and puberty
• The commonest disorders of precocious/delayed puberty are idiopathic
• Psychological disturbances is the commonest indication for intervention