PUBERTAL DEVELOPMENT Dr Assunta Albanese St George’s Hospital London

FERTILITY AND FINAL HEIGHT PUBERTY Gonadal maturation with acquisition of secondary sexual characteristics and associated growth spurt FERTILITY AND FINAL HEIGHT

PUBERTY Average age of onset: First signs of pubertal maturation: 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

OVARIAN REGULATION Inhibin Oestrogen Hypothalamus GnRH release Pituitary gland FSH LH Ovary Inhibin Oestrogen

Breast development Libido Body composition Bone mineralization Oestrogens produced by ovaries induce/ maintain secondary sexual characteristics and sustain germ cell production Breast development Libido Body composition Bone mineralization

ASSESSMENT OF OVARIAN FUNCTION 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

TESTICULAR REGULATION Hypothalamus GnRH release Pituitary gland FSH LH Testis Inhibin Testosterone (From the Sertoli cells) (From the Leyding 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 FUNCTION 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 Early 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 a-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

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