Puberty

How do hormones cause the changes in girls and boys?

" In boys, LH stimulates testosterone production from the Leydig cells and FSH stimulates the seminiferous tubules and spermatogenesis. The testes volume increases - 90% seminiferous tubules. " Testosterone and dihydrotestosterone produce the secondary male characteristics " In girls, LH and FSH act to stimulate oestrogen and progesterone from theca and granulosa cells. These produce breast development, fat deposition on hips, vaginal secretions etc...

What is the aetiology of precocious puberty?

*Central (gonadotrophin-dependent)* There is early activation of the hypothalamic-pituitary-gonadal axis. Therefore, you will observe a normal sequence of events (in order!) Idiopathic *Intracranial tumours* " Craniopharyngiomas " Astrocytomas " Optic glioma CNS lesions " Hydrocephalus " Traumatic brain injury " Cranial irradiation *Peripheral (Gonadotrophin independent)* This occurs when there is no release of gonadotrophins from the pituitary gland. You will usually see an abnormal sequence of events! Gonadal " McCune Albright " Ovarian tumours " Testicular tumour " Testitoxicosis (an LH receptor activating mutation) Adrenal " Congenital adrenal hyperplasia " Adrenal tumour HCG secreting tumours Iatrogenic " Giving sex steroids exogenously.

What is premature adrenarche? How does it present? How do you diagnose? How do you manage?

Overview Early onset of adrenal androgen secretion Presentation Secondary hair development, acne and body odour Mild height acceleration and increase in bone age Look for signs of: Virilisation, rapid growth. These could be pathological. Investigations DHEA - High Testosterone - normal Management Some woman go on to develop PCOS, consider treating them.

What is puberty?

Puberty is when a sexually immature child becomes a sexually fertile adult'. The process by which this happens revolves around changes in hormone levels, namely LH and FSH. Though the hormonal changes are similar there are differences between sexual maturation in boys and girls

How do you treat precocious puberty?

Central Precocious puberty: " Treat cause - often depends on the predicted adult height " GnRH analogue therapy - inducing downregulation of endogenous GnRH and suppresses pulsatile GnRH secretion. Improves adult height. Independent precocious puberty: " Treat underlying cause

Signs/symptoms of McCune Albright syndrome?

Characterised by: " Skin o Café au Lait spots o hyperpigmented skin " Bone o Bones of head malformed o Bone lesion o Fibrous dysplasia - often confined to one side of the body leading to malformed head, asymmetric growth of long bones, scoliosis " Endocrine o Pituitary adenoma o Obese and Cushing's o Hyperthyroidism o Precocious puberty - More common in girls, although can occur with boys. Bleeding ~ age 2 and development of secondary sexual characteristics.

Give the aetiology for delayed puberty Pituitary Functional Congenital GnRH hormone deficiancy (what causes this?) Primary and secondary hypogonadism

Commonest cause is systemic illness Pituitary/hypothalamic tumours: Adenomas, Germinoma, glioma etc.. causing issue with hormones Infiltrative diseases (Hemochromatosis, histiocytosis) Trauma Pituitary apoplexy Functional deficiency: Anorexia Systemic illness Hyperprolactinaemia Hypothyroidism Congenital gonadotrophin-releasing hormone deficiency: Idiopathic Kallmann's syndrome Others Primary and secondary hypogonadism: (Can be tested by giving gonadotrophins and measuring serum testosterone) Turner's, Klinefelter's Gonadal damage (Trauma/chemo/radio)

What is precocious puberty?

Defined as the onset of secondary sexual characteristics before the age of 8 in girls and 9 in boys Increased growth velocity, advanced bone age and smaller predicted final adult heights due to epiphyseal fusion at an early age. Need to treat early to avoid this fusion. Worth noting that different ethnicities reach puberty earlier - and modern generations are also reaching puberty earlier.

What's the difference between GnRH dependant and independant?

Dependant: Caused by activation of the HPG axis early Pubertal development is consistent with normal puberty with a normal sequence - it's just earlier. The characteristics are also appropriate for the child's gender Independant: This is caused by autonomous endogenous secretion of sex steroids from the gonads or adrenal glands or excess exogenous sex steroids I Development is often not consistent with normal puberty - and deviates from the normal sequence. Moreover, it may not be appropriate for the child's gender

In this circumstance, what tests would you consider?

FBC, UE, LFT, ESR LH,FSH, Oestradiol, testosterone Prolactin Thyroxine and TSH Karyotype Bone age MRI - pituitary/hypothalamus Pelvic/testicular USS

What is McCune-Albright syndrome? What is the genetcis?

Genetic disorder 1:100,000- 1:1000,000 Mutation in GNAS gene Not inherited, random mutation

What is thelarche variant:

This is a middle man between premature thelarche and precocious puberty Patients have breasts, increased growth rate and advanced bone age Sometimes need to treat, sometimes not.

How do you define delayed puberty?

This is defined as the absence or incomplete development of secondary sexual charactoristics by an age in which 95% of children of that sex and culture have initiated sexual maturation In boys: Delayed puberty may be diagnosed when there is no testicular enlargement by age 14 In girls: Delayed puberty may be diagnosed when there is no breast development by age 13

What is premature thelarche?

This is isolated breast development that occurs in females before the age of 2 There is a mild increase in circulating oestrogen which causes the development By ~ age 4/5 the breast enlargement stops *Diagnosis and management:* Raised oestrogen Mildly raised FSH. Low LH Benign condition. Bone maturation, growth and age of menarche unaffected

How do you treat delayed puberty?

Treat underlying cause if treatment required (not in constitutional) In constitutional, you can give a short course of testosterone/oestrogen to kick start growth Other: Boys = Oxandrolone or testosterone Girls = Oestrogen Careful with the closure of the epiphyses too early. If there is a complete gonadotrophin deficiency, testosterone therapy will help, but won't stimulate growth of testosterone. You have to wait until this occurs naturally.

Describe the changes boy's go through during puberty

• Begins age 9-14 (can still be normal even at 16) • Complete between 15 and 173 • Peak height can be achieved as late as 20 • First the testes develop and grow, under influence of FSH (causing proliferation of seminiferous tubules). FSH causes Sertoli cell division and proliferation, which make up the tubules. Induce penis and testicular growth • LH causes interstitial Leydig cells to secrete testosterone and proliferate • After the development of larger testicles you get the penile and pubic hair development. • There is lengthening and development of the larynx = a deepening of voice. Cricothyroid cartilage and laryngeal muscles enlarge to form the Adam's apple.1 • Increased size of prostate, seminal vesicles and epididymis and spermatogenesis (Tanner stage 3) • Development of sebaceous glands and sweat production becomes more smelly as well as the development of a beard.

Describe the changes, both physical and endocrinological that girls go through in puberty

• Starts about 1 year earlier than boys (8-13) • Normally complete by 18 • Peak height is achieved roughly by age 13 (within a year of puberty) • First noted development is 'budding' of the breasts • Menarche (the first time a girl menstruates) is normally between age 11-15 (2 years after onset) • The first 1-2 years of Menarche is characterised by irregular and painful periods. • Oestrogen is responsible for Tanner stages 1-4 (pubic hair growth, fat deposition and proliferation of the ductal system in the breasts, growth of the vagina and maturation of the epithelium and finally growth of the clitoris). • In the final stage, progesterone is needed to cause proliferation of secretory lobules and acini in the breast, finish of vaginal and uterine growth and finally initiate changes to the endometrium as in the menstrual cycle.

Give the different stages of puberty with regards to endocrinology

• The first step in initiation of puberty is the activation of the hypothalamic gonadotrophin-releasing hormone axis and the pulsatile secretion of GnRH (Around age 11). This is gonadarche. • This results in an increase in the plasma concentrations of LH and FSH, and thus testosterone in boys and oestradiol in girls. It takes about a year to have visible effects on the child. • The initial pulsing of GnRH occurs during the night, and as puberty develops it also happens in the day until it reaches the adult pattern of once every 90 seconds • There's also an increase adrenal androgens which is called adrenarche • Adrenarche is defined as pre-puberty and involves higher levels of DHEA, DHEA-s and androstenedione secretion. It happens in children between the ages of 6 and 8 normally. These hormones rise and peak around ages 25-30, after which they decline (andropause). The exact mechanism by which the adrenarche is triggered is unknown.

WHat is the staging we use for measuring puberty?

Tanner staging