Puberty and Secondary Sexual Development PDF

PUBERTY AND SECONDARY SEXUAL DEVELOPMENT Objective 1. Describe and discuss the physiology of puberty, features of abnormal puberty, common problems and their management. 2. Enumerate the causes of precocious puberty. Describe the investigation and management of common causes. 3. Enum...

PUBERTY AND SECONDARY SEXUAL DEVELOPMENT Objective 1. Describe and discuss the physiology of puberty, features of abnormal puberty, common problems and their management. 2. Enumerate the causes of precocious puberty. Describe the investigation and management of common causes. 3. Enumerate the causes of delayed puberty. The physiology of normal puberty Puberty is a period of maturation during which body growth and sexual development change a child into an adult. The HPG axis starts functioning during fetal life, remains active for several months after birth and is then quiescent until puberty. From the age of 8–9 years GnRH is secreted in pulsations of increasing amplitude and frequency.These are initially sleep-related, but as puberty progresses, these extend throughout the day. This stimulates secretion of FSH and LH by the pituitary glands, which in turn triggers follicular growth and steroidogenesis in the ovary. The oestrogen produced by the ovary then initiates the physical changes of puberty. number of factors are known to play a role in the timing of puberty include a) Genetics b) Race c) nutritional status, body weight and exercise the relationship between body fat and the onset of puberty is linked to the release of leptin from adipose sites. The physical changes occurring in puberty  breast development (thelarche).  pubic and axillary hair growth (adrenarche).  growth spurt  onset of menstruation (menarche). The first physical signs of puberty are breast budding and this occurs 2–3 years before menarche. The appearance of pubic hair is dependent on the secretion of adrenal androgens and is usually after thelarche In addition to increasing levels of adrenal and gonadal hormones, growth hormone secretion also increases, leading to a pubertal growth spurt. The mean age of menarche is 12.8 years and it may take over 3 years before the menstrual cycle establishes a regular pattern. Initial cycles are usually anovulatory and can be unpredictable and irregular. The absence of menstruation is called amenorrhoea and may be primary or secondary Pubertal development was described by Tanner and the stages of breast and pubic hair development are often referred to as Tanner stages Genital tract changes during puberty Vulva fat deposition Vagina Elongated , appearance of folds or rouge , decline of vaginal Ph (acidic) Uterus and cervix Prepubertal U/C ration is 1/1 , at puberty become 2/1 Uterus become longer than cervix with pear shape Precocious puberty Definition :the onset of puberty before the age of 8 in a girl or 9 in a boy. Classification 1. central, true or gonadotrophin-dependent 2. peripheral, pseudo or gonadotrophin-independentisolated 3. variants: precocious thelarche, pubarche or menarche. Precocious puberty can be further categorised as either isosexual (where there are secondary sexual characteristics that are appropriatefor the child’s sex) or heterosexual/contrasexual (where secondary sexual characteristics are contrary to the phenotypic sex, i.e. there is virilisation in girls).Central precocious puberty is always isosexual, whereas peripheral precocious puberty can be isosexual or heterosexual. Causes of premature sexual development in girls A. Central precocious puberty Idiopathic Central nervous system pathology/lesion ◦ Hypothalamic hamartoma ◦ Tumour: astrocytoma, glioma, craniopharyngioma, pituitary adenoma ◦ Congenital disorder: hydrocephalus, myelomeningocele,arachnoid cyst ◦ Acquired: central nervous system irradiation, post head trauma, post infection: encephalitis/meningitis, Chemotherapy Secondary to peripheral precocious puberty B. Peripheral precocious puberty Ovarian cause  ◦ Estrogen-secreting: granulosa cell tumour, functional ovarian cyst ◦ Androgen-secreting: Sertoli–Leydig cell tumour, arrhenoblastoma (contrasexual) Adrenal cause ◦ Congenital adrenal hyperplasia (contrasexual) ◦ Cushing syndrome (contrasexual) ◦ Neoplasm: estrogen or androgen-secreting adenoma/carcinoma (isosexual or contrasexual) Exogenous sex hormones: e.g. oral contraceptives, skin cream, anabolic steroid McCune–Albright syndrome Severe long-standing hypothyroidism C. Variants of normal pubertal development Premature thelarche/thelarche variant Isolated premature menarche Premature pubarche/adrenarche (contrasexual) Evaluation of precocious puberty History Age of onset, sequence and progression of pubertal changes Family history: timing of onset of puberty in mother and siblings Neurological symptoms Exogenous sex steroid exposure in food, drugs or cosmetics (e.g. steroid creams, estrogen, anabolic steroids) Social history: history of adoption or child sexual abuse Clinical examination Height and weight measurements plotted using age-specific growth charts Body mass index Pubertal Tanner staging  Neurological examination Examination of eyes including visual fields and fundoscopy Skin lesions (e.g. caf´e au lait spots) Abdominal examination Examination of external genitalia Signs of virilisation: clitoromegaly, deepening of voice, hirsutism Biochemical investigations Serum LH and FSH levels (baseline) GnRH (LHRH) stimulation test (LH and FSH) Estradiol/testosterone levels Adrenal steroids, e.g. 17 OH progesterone, dehydroepiandrosterone sulphate and androstenedione (raised in congenital adrenal hyperplasia and adrenal tumours) Adrenocorticotrophic hormone stimulation test (to identify steroid synthesis defects, e.g. congenital adrenal hyperplasia) Free thyroxine and thyroid-stimulating hormone Serum prolactin levels (may be raised in chronic hypothyroidism, McCune–Albright syndrome or prolactinomas or point towards pituitary stalk compression) Urinary steroid profile (to identify and quantify excess adrenal androgens) Imaging Left wrist X-ray for bone age Cranial magnetic resonance imaging/computed tomography ,CT CT adrenals (adrenal masses) Pelvic ultrasound (size, shape of uterus, endometrial thickness and ovarian morphology) Skeletal survey/bone scan (McCune–Albright syndrome) Treatment The goal of treatment is to:  halt or cause regression of secondary sexual characteristics  prevent early menarche  retard skeletal maturation and improve final height  avoid psychosocial/behavioural sequelae -In the majority of girls with CPP no apparent cause is found, -Treatment of the underlying cause varies with the type of central nervous system lesion involved. Gonadotrophin-releasing hormone analogues (GnRHa) are the mainstay of treatment, The combined use of growth hormone and GnRH agonists is controversial. -GnRH analogues can be administered until such time as the child reaches approximately age 11 Delayed puberty Delayed puberty is usually considered when girls have no secondary sexual characteristics by age 14 years. approximately 50% will have constitutional delay with no explanation and the vast majority will commence the onset of puberty by age 18. couses Hypogonadotrophic hypogonadism This is central and may be constitutional, but other causes must be excluded. These include anorexia nervosa, excessive exercise and chronic illness, such as diabetes or renal failure. Rarer causes include a pituitary tumour and Kallmann syndrome. It is associated with delayed puberty and primary amenorrhoea. Hypergonadotrophic hypogonadism This is caused by gonadal failure. The gonad does not function, despite high gonadotrophins. It is associated with Turner syndrome and XX gonadal dysgenesis. Premature ovarian failure can occur at any age, including prior to pubertal age, and may be idiopathic, but can also be part of an autoimmune or metabolic disorder or following chemo- or radiotherapy for childhood cancer. It is associated with delayed puberty and primary amenorrhoea. It can also occur later in life and will cause secondary amenorrhoea after normal sexual development. Assessment A 12-year-old G0 patient is brought in by her mother for consultation. She is concerned because most of the other girls in her daughter’s class have already started their period. She thinks her daughter has not shown any evidence of going into puberty yet. Knowing the usual first sign of the onset of puberty, the mother should be asked which of the following questions? a. Has your daughter had any acne? b. Has your daughter started to develop breasts? c. Does your daughter have any axillary or pubic hair? d. Has your daughter started her growth spurt? e. Has your daughter had any vaginal spotting? A 9-year-old patient presents for evaluation of cyclic vaginal bleeding. She is healthy and does not take any medications. A careful history reveals she experienced thelarche at age 7 and adrenarche at age 8. Which of the following is the most likely cause of this condition in this patient? a. Idiopathic b. Gonadal tumor c. McCune-Albright syndrome d. Hypothyroidism e. Central nervous system (CNS) tumor