Puberty Lecture Notes PDF

Puberty Dr Samantha Waugh Learning Objectives Describe the important physiological events and triggers of puberty, including precocious and delayed puberty. - Hormonal control of puberty - Physical changes including Tanner stages - Clinical relevance: precocious and delayed puberty Puberty...

Puberty Dr Samantha Waugh Learning Objectives Describe the important physiological events and triggers of puberty, including precocious and delayed puberty. - Hormonal control of puberty - Physical changes including Tanner stages - Clinical relevance: precocious and delayed puberty Puberty Puberty is the process by which complete functional maturation of the reproductive glands and external genitalia occur. Onset of puberty is dictated by activation of the HPG axis and release of gonadotropins stimulating gonadal maturation. pulsatile GnRH Median age of onset has been decreasing. Girls: onset 8-13 years (average 11); complete at age 15-17 varies, girls earlier Boys: onset 10-14 years (average 13); complete 16-17  Pre-puberty - Adrenarche (adrenal gland development) Zona reticularis is zone of androgen release before... True puberty Stages of - Gonadarche (growth and development of puberty the gonads) - Thelarche (breast growth) first sign in females - Pubarche (pubic hair growth) - Menarche (menstruation) - Spermarche (first ejaculation) Puberty Onset Puberty is preceded by adrenarche – an early stage development of the zona reticularis of sexual development that takes place separately to puberty, not involving the HPG axis. Where puberty is the development of the gonads due to release of LH/FSH; adrenarche is the development of the zona reticularis of the adrenal glands and the early release of androgens.for androgen production This precedes TRUE puberty by ~2 years and begins on average between ages 6-8 in girls and 7-11 in roughly around ~7 boys. An initiator has not yet been identified however, biological messengers during the onset of adrenarche are thought to signal in preparation of puberty. Adrenarche During adrenarche, the adrenals secrete weak androgens (DHEA, DHEA-S, and androstenedione). For this reason, adrenarche is sometimes accompanied by the early appearance of axillary and pubic hair (androgen driven). The first androgenic hair resulting from adrenarche can be transient and disappear before the onset of true puberty. Parents and many physicians often infer (incorrectly) the onset of puberty from the first appearance of pubic hair however true puberty begins with growth and development of the gonads (gonadarche) which takes place in response to increasing LH/FSH levels ~2 years from the onset of adrenarche. puberty - growth of gonads adrenarche - development of adrenal gland Hormonal Control in the Initiation of Puberty A critical event in puberty is an increase in the pulsatile secretion of GnRH from the arcuate nucleus of the hypothalamus. Genetics accounts for 50-80% of the variation in pubertal timing, the rest is environmental. other factors can change timing Nutrition, stress, weight, all play a role in the initiation of puberty. Hormones involved: kisspeptin neurons in arcuate nucleus release neurokinin B and dynorphin à these stimulate GnRH release GnRH triggers release of luteinising hormone (LH) and follicle stimulating hormone (FSH) from the anterior pituitary. Hormonal changes in girls: - LH acts on theca cells of the ovary to produce androgens - Granulosa cells convert androgens to oestrogens under FSH influence Hormonal changes in boys: - LH acts on Leydig cells in the testes to produce testosterone FSH - Sertoli cells - spermatogenesis Physical Changes in Girls Thelarche - Breast development with formation of the breast bud and proliferation of the duct and gland epithelium. - The first sign of puberty in girls as gonadarche occurs internally - Main hormones involved: oestrogen, oestradiol, prolactin - Onset: 8-14 years Pubarche - Often the second noticeable pubertal change in girls, within a few months of thelarche. - Hair growth begins along the labia and within 6 months cover the mons and then spreads to the inner thigh. then completes inner thigh at end Menarche - Typically occurs two years after thelarche. - On average, remain anovulatory and irregular for 1-2 years. can be heavy and painful Growth spurt - On average, 2 years earlier in girls than in boys - Approximately 1 year after onset of puberty girls reach oestrogen peak earlier - 3-10cm of growth per year - Release of sex steroids triggers production of GH and IGF-1 - Oestrogen peaks earlier and higher in girls than boys leading to earlier closure of the epiphyseal plates, hence boys tend to have a more prolonged growth spurt and reach taller adult heights. key role in epiphyseal plate closure Internal changes - Vaginal mucosa becomes thicker - Oestrogen increases vaginal glandular secretion - Uterus, ovaries and follicles increase in size Body shape - In response to oestrogen, the pelvis and hips widen - Increased fat distribution to the breasts, hips, buttocks, thighs and pubis - Acne and increased sebum secretion in the skin due to rising androgens  Gonadarche - Puberty in boys begins with enlargement of the testicles and scrotum - Testicular size reaches maximal adult size about 6 years after the onset of puberty. Physical - After the testicles have enlarged for about 1 year, the penis enlarges Changes in Boys - Sperm production also takes place during this time Pubarche - Pubic hair appears shortly after the genitalia begin to grow, first visible at the base of the penis especially in males red blood cell production Tanner Staging A scale that measures the physical sexual development during puberty. There is a tanner staging system for male genital development, female breast development, and pubic hair in both.  Tanner Staging in Girls completion hair increases  Tanner Staging in Boys can occur, regresses  1. Which of the following is the correct order of pubertal development in girls: a. adrenarche-menarche-thelarche b. thelarche-pubarche-menarche B c. thelarche-menarche-pubarche d. gonadarche-menarche-thelarche e. menarche-thelarche-pubarche Practice 2. Which of the following is correct in regard to the onset of puberty: Questions a. Adrenarche is the first stage of puberty and stimulates LH/FSH secretion b. Environmental factors account for 80% of the variation in puberty onset c. An increase in pulsatile GnRH release marks the onset of puberty under the influence of a variety of genetic and environmental factors C d. Adrenarche is often accompanied by the appearance of axillary and pubic hair and marks the onset of true puberty e. Menarche is often the first sign of puberty in girls  Iron deficiency anemia: usually affecting adolescent girls due to menstrual bleeding and insufficient iron intake. heavy periods Gynecomastia: enlargement or swelling of the breast tissue in men, affecting approximately 50% of teenage boys at an average age of 13 years. Gynecomastia is caused by the increased production or action of oestrogens, enhanced breast-tissue Clinical sensitivity to oestrogens, or the decreased production or action of androgens. does regress, not necessarily very large Relevance Acne vulgaris: excess sebum production, follicular colonisation by Cutibacterium acnes and inflammation as a result of excess androgens. especially when boys Dysfunctional uterine bleeding: excessive, prolonged, and/or irregular endometrial bleeding, often seen during the 1st year of menarche. Occurs due to anovulatory cycles as a result of the immature HPG axis, which fails to produce gonadotropins in proper quantities and ratios to induce ovulation. Precocious Puberty secondary sexual characteristics... The appearance of secondary sexual characteristics before the age of 8 years in girls and 9 years in boys (2 SDs below the mean age of puberty). Ten times more common in girls than boys. Central (true) precocious puberty Peripheral precocious puberty Gonadotropin-dependent Gonadotropin-independent In either case, precocious puberty may either be iso-sexual (premature development of secondary sex characteristics appropriate to gender) or heterosexual (masculinisation or girls; feminisation of boys).  Early activation of the HPG axis à elevated GnRH à early development of secondary sex characteristics Central Cause: idiopathic (most common), possibly diet intracranial lesion/trauma/infection, Precocious radiation Puberty Presentation: normal pattern of puberty, occurring earlier than expected. Tend to be shorter when reaching adulthood due to early closure of the epiphyseal plate. Central Precocious Puberty Diagnosis as central - FSH/LH increase - Baseline LH and FSH increased to pubertal levels - GnRH stimulation test (Gold standard): administer GnRH à LH and FSH increase 2-3 fold (hence, GnRH dependent precocious puberty). - Imaging: wrist/hand X-rays allows comparison between bone age and chronological age. If bone age is >2 years from the child’s chronological age, this indicates accelerated bone growth and confirms they have entered puberty. bone age, compare to standard - MRI to rule out intracranial cause Central Precocious Puberty Treatment - GnRH agonist (leuprolide): provides continuous stimulation of GnRH receptors which sensitises the pituitary and eventually reduces LH/FSH release à these hormones are secreted under the influence of pulsatile, not continuous, GnRH release. sensitive and reduces  Early puberty induced by increased peripheral synthesis of or exogenous exposure to sex hormones. No increase in GnRH. as no central role Causes: Peripheral - Increased androgens i.e. congenital adrenal hyperplasia (increased androgen production by adrenal gland - Precocious causes heterosexual precocious puberty in females). Puberty - Increased oestrogen: germ-cell tumours - Exogenous steroid use Clinical features may not follow normal pubertal development pattern (signs of oestrogen or androgen excess) along with signs of underling condition.  Diagnosis as not central stimulation - Serum LH/FSH decreased (prepubertal) - GnRH stimulation test: no increase in LH/FSH with GnRH stimulation Peripheral - Serum testosterone/oestrogen increased - Xray of hand/wrist shows accelerated bone Precocious growth as confirmation Puberty - USS of ovaries/testes Treatment - Dependent on underlying cause i.e. surgical removal of tumours, cortisol replacement in CAH Delayed Puberty Absent or incomplete development of secondary sex characteristics by the age of 14 years in boys or 13 years in girls (specifically, lack of testicular enlargement in boys and breast growth/pubic hair in girls). Most commonly physiological due to familial growth delay. Eventually, these children catch up and complete puberty at a later age. When pathological, may be due to: - Hypergonadotropic hypogonadism à HIGH LH/FSH but no response from gonads due to gonadal pathology. I.e. turners syndrome in girls, klinefelters in boys or due to prior infections, trauma to the gonads, chemo/radiotherapy genetic - XXY, X0 - Hypogonadotropic hypogonadism à LOW FSH/LH due to primary CNS disease i.e. Kallmann syndrome, CNS lesion - Malnutrition (anorexia nervosa) - Chronic disease (IBD, cystic fibrosis) Clinical features consistent with underlying condition. Diagnosis: Kallman - Serum LH/FSH: if high indicates gonadal insufficiency, if low indicates CNS cause - Xray hand/wrist: shows bone age < chronological age - Additional tests depending on suspected cause i.e. prolactin for prolactinoma, karyotyping if suspected Turners/klinefelters, screening for malabsorption (coeliac, IBD) TESTS - PROLACTIN KARYOTYPE Treatment: - Constitutional/familial delay: expectant management, ensure catch-up growth occurs - Treat underlying cause; consider testosterone or oestrogen replacement  1. Which of the following is NOT a recognised cause of central precocious puberty: a. Craniopharyngioma b. Leydig-cell tumour B c. Cranial irradiation d. Hydrocephalus Practice e. Encephalitis Questions 2. In boys with precocious puberty and low LH/FSH, which of the following would be the correct investigation of choice: a. MRI brain b. Field of vision testing c. USS of the testes C d. CT head e. Skeletal survey 3. A 15 year old girl presents with her mother who is concerned that she has not yet shown signs of puberty. She is short in stature, Tanner stage of development of the breasts and pubic hair is 1 and she has not yet started menstruating. Which of the following is a potential cause for her delayed puberty: a. Congenital adrenal hyperplasia b. Turner’s syndrome B c. Dysgerminoma d. Exogenous oestrogen administration e. McCune Albright syndrome