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