Puberty - Physiology Disorders - 2023.ppt

Puberty – Physiology & Disorders Dr Dunia Ismail, Paediatrician Module 203 – Jan 2023 Overview  Physiology of Puberty  Disorders of Puberty    Premature Puberty Delayed Puberty Syndromes   Klinefelter Syndrome Turner Syndrome Physiology of Puberty  Definition:   The stage of...

Puberty – Physiology & Disorders Dr Dunia Ismail, Paediatrician Module 203 – Jan 2023 Overview  Physiology of Puberty  Disorders of Puberty    Premature Puberty Delayed Puberty Syndromes   Klinefelter Syndrome Turner Syndrome Physiology of Puberty  Definition:   The stage of physical maturation in which an individual becomes physiologically capable of pro-creation (sexual reproduction) Physical changes    Growth spurt Secondary sex characteristics Menarche/spermatogenesis Physical changes in girls  GROWTH SPURT 8 - 14 yrs 6 - 10 cm / yr peak 2.5 yrs duration  BREAST GROWTH (Thelarche) 8 - 13 yrs ( 11 yrs ) Usually the first sign  PUBIC HAIR (Pubarche) 9 - 13 yrs 1st Pubertal Sign in 25%  AXILLARY HAIR 9.5 - 15 yrs (Adrenarche) May follow menarche  MENSTRUATION10 - 16 yrs ( 13 yrs ) (Menarche) Endocrine changes in puberty    H-P-G synchrony – established in fetal life Until puberty – neural mechanisms suppress GnRH release At 6-9 yrs – pulsatile nocturnal GnRH release Endocrine changes in puberty  Pulsatile GnRH release (nocturnal) every 90-120 min - 6 to 9 y   GnRH leads to  FSH and  LH  Ovaries/testes become sensitized to the effects of FSH and LH  Final phase: development of positive/negative feedback mechanism  ACTH stimulates the adrenals – Pubic & Axillary hair Testes  Production of gametes (sperms)   Production of androgens (Testosterone)    Sertoli cells under FSH control Leydig cells under LH control 95% from testes, 5% from adrenals Testosterone in blood – converted to DHT in the target organs The Ovarian cycle  Follicular phase   Initially E rises (FSH) with LH surge in mid cycle Ovulation occurs The Ovarian cycle  Follicular phase    Initially E rises (FSH) with LH surge in mid cycle Ovulation occurs Luteal phase   Negative feedback after ovulation No further ovulation in the same cycle Normal Ovarian cycle Endometrial cycle Age of Menarche  Related to general health, genetic and nutritional factors  Mean age is falling at a rate of 4 months per decade   Mean age in 1840 = 16.5 y; 1990 = 12.8 y One in 8 girls now reaches menarche while at primary school  Body weight and % fat is also important  Mean weight at menarche is 47.8kg  16-24% fat  Athletes, patients with anorexia – late onset Adrenarche  Adrenal androgens – responsible for axillary and pubic hair   ACTH stimulates zona reticularis of adrenal cortex DHEAS & Androstenedione  Girls – starts by 6, adequate levels by 8  Boys – starts by 8, adequate levels by 10 Chronological Order of puberty  Girls      Growth spurt Breast development Pubic hair Axillary hair Menarche  Boys       Testicular volume Penile length Pubic hair Growth spurt Axillary / Facial hair Deep voice Summary GIRLS BOYS Growth Spurt 10.9 years (8.5-13.3) 12.2 years 11.2 years (9.2-14.2) 13.9 years Years of puberty 2-3 years 3-5 years Menarche/voice deepening 12.9 years (10-15) 14.6 years (12-17) Beginning of puberty Disorders of Puberty  Early or Precocious   Girls – under 8 yrs Boys – under 9 yrs  Delayed   Girls – over 14 yrs Boys – over 14 yrs Arbitrary / conventional cut off points Precocious Puberty   Early or Premature puberty Presence of true pubertal features at an young & inappropriate age  Central or True precocious puberty   Peripheral or Pseudo-precocious puberty   Gonadotrophin dependent Gonadotrophin independent Normal variants   Premature Thelarche Premature Adrenarche Concerns raised by early onset  Possible underlying sinister cause    Boys – upto 80% Emotional & pyscho-social upheaval at an inappropriately young age Early cessation of growth leading to decreased final adult height Hypothalamic hamartoma  Emileigh, 14 months        Blood clots in nappy Bilat breast buds Ht & Wt >97th centile LH 2.2, FSH 3.2, 17β estradiol 432 Uterus – enlarged Bone age – 2.8 yrs MRI scan Precocious puberty Central  Long acting LHRH analog therapy  Sustained supra-physiological LHRH levels Paradoxical cessation of gonadotrophin release  Stops further pubertal progression   Pubertal progression resumes when treatment stopped (at 10-12 yrs) Normal variants  Premature thelarche    Isolated breast development Usually seen in children <2-3 yrs of age Premature adrenarche    Isolated pubic hair development Caution: first sign of puberty in some And . . . Pseudo-precocious puberty  Females  Iso-sexual or feminising   Males  MAS, Ovarian/Adrenal Hetero-sexual or masculinising   CAH, Ovarian/Adrenal Iso-sexual or masculinising   CAH, Adrenal/Leydig cell tumor Hetero-sexual or feminising  Adrenal Exogenous androgens or estrogens Congenital Adrenal Hyperplasia  Mairna, 6 yrs      Obese Pubic hair stage 2 No breast bud LH <1, FSH 1.4, 17β estradiol 32 Steroid profile Steroid biosynthesis Puberty  Early    Girls – under 8 yrs Boys – under 9 yrs Arbitrary or conventional cut off points  Delayed    Girls – over 14 yrs Boys – over 14 yrs Arbitrary or conventional cut off points Delayed puberty     Absence of true pubertal onset at an appropriate age Not necessarily lack of periods in a girl X-files – very important Normal variant  Constitutional growth & pubertal delay Concerns raised by delay     Possible 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 Klinefelter Syndrome  Steven, 16 yrs        No pubertal progress Learning difficulties Tall, 98th centile PH-2, G-2, TV-6ml LH 12, FSH 16, T 40 Bone age – 14.5 yrs Karyotype Klinefelter Syndrome        1 in 1000 male infants 47 XXY / Multiple X Behavioural problems Androgen deficiency Azoospermia / Infertility (Micro genitalia  Sex change) Lifelong testosterone replacement therapy Turner Syndrome  Rosie, 12 yrs        Short Stature No pubertal onset Recurrent ear infections Increased carrying angle Widely spaced nipples LH 56, FSH 95, 17β estradiol 45 Karyotype Turner Syndrome      1 in 2000 live female births Triad - Short stature, streak gonads, primary amenorrhoea Dysmorphic features – Webbing of neck, cubitus valgus Coarctation of aorta, horse shoe kidneys Early clue - Lymphedema  Surprisingly normal !!!  Turner Mosaic Turner Syndrome      Exclude co-existing congenital anomalies Growth Hormone therapy Pubertal induction + ongoing HRT Active monitoring to detect comorbidities Assisted conception Gonadotrophin deficiency  James, 15 yrs         Absent smell sensation PH-1, G-1, AxH-1, TV-2ml each LH <1, FSH 1.2, T 0.8 LHRH stimulation test – peak LH remained <1 HCG stimulation test – min. increase in T MRI scan – Normal Kallman gene analysis – Negative Lifelong Testosterone replacement therapy Normal Variant      Constitutional delayed growth & puberty More common in boys Small & Short in school days Late onset of puberty Bone age delayed slightly  Family history – often present  Normal adult height Pubertal induction – sometimes necessary  Overview  Physiology of Puberty  Disorders of Puberty    Premature Puberty Delayed Puberty syndromes   Klinefelter Syndrome Turner Syndrome Finally . . . 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