Puberty and its disorders Flashcards
1
Q
What are the main events of puberty?
A
- transition from non-reproductive state to reproductive state
- Secondary characteristics develop
- Adolescent growth spurt
- Profound physiological and psychological changes
- Gonads produce mature gametes
2
Q
What are the two main endocrine process in puberty?
A
- Adrenarche (pubarche) - maturation of cells in adrenal cortex results in the release of androgens from adrenals
- Gonadarche - follows adrenarche. Driven by HPG axis, LH and FSH activate gonadal function.
3
Q
What are the phenotypic changes due to LH/FSH?
A
- LH causes steroid synthesis, which causes secondary sex characteristics (growth in height, pubic hair and axillary hair
- FSH causes growth of testes, steroid synthesis and folliculogenesis
4
Q
What happens in adrenarche?
A
- Gradual increase in Dehydro-epiandrosterone (DHEA) and DHEA- sulfate (DHEAS) from 6>15 years
- 20 fold increase peaking at 20-25 years
- Decline in DHEA/DHEAS afterwards (adrenopause)
- No change in other adrenal androgens
- no known trigger for adrenarche
5
Q
What is pubarche?
A
- The result of adrenarche
- Appearance of pubic/axillary hair
- Induced by adrenal androgen secretion
- Associated with increased sebum production = acne
- Infection and abnormal keratinisation = acne
- If it is before 8 years (girls) and 9 years (boys) = precocious
6
Q
What is gonadarche?
A
- Several years after adrenarche (~11yrs)
- Reactivation of hypothalamic GnRH
- Activation of gonadal steroid production allowing production of viable gametes and ability to reproduce
7
Q
GnRH
A
- Synthesised and secreted by specialist GnRH neurones in the hypothalamus
- Pulsatile secretion is essential for GnRH function
HPG axis is first activated at 26th week, however is restrained postnatally until ~11yrs, when there is a gradual rise - Changes in the pattern of LH secretion occur during postnatal development
8
Q
How do we measure GnRH secretion?
A
- Cannot measure it directly
- Measure LH as a surrogate as they go hand-in-hand
9
Q
What stimulates the onset of puberty?
A
- Maturational event within the CNS
- Inherent (genetic) maturation of 1-3000 GnRH synthesising hormones?
- Environmental/gentic factors?
- Body fat/nutrition?
- Leptin?
- Other gut hormones
- KISSPEPTIN?
10
Q
How does nutrition and body fat affect GnRH?
A
- link between fat metabolism and reproduction
- Anorexia/ intensive physical training
- reduced response to GnRH
- Decreased gonadotrophin levels
- Amenorrhoea
- Restored when nourished/exercise stopped
- Frisch et al - body fat hypothesis. 17% fat:body weight is necessary for menarche, and 22% to maintain female reproductive ability.
11
Q
How does Kisspeptin affect puberty?
A
- Mutations of GPR54 or the gene coding for kisspeptin–>
- Abnormal development of GnRH neurones. Causes hypogonadotrophic hypogonadism
- Failure to enter puberty
- Hypothalamic hypogonadism
- Activating mutations of kisspeptin receptor. Leads to precocious puberty
12
Q
What is consonance?
A
- The smooth ordered progression of changes
- The order of pubertal changes is uniform
- However the age of onset, pace and duration of changes has wide individual differences
13
Q
What are the Tanner stage of puberty?
A
- A scale of physical measurement of development
- 5 stages
14
Q
5 stages of breast development?
A
1) No breast tissue
2) areolar enlargement, breast bed
3) enlargement of breast and areola as single mound
4) Projection of areola above breast
5) Papilla projections out of areola, forming part of breast contour
15
Q
5 stages of pubic hair development
A
1) none
2) few dark hairs along labia or base of penis
3) curly pigmented hairs across pubes
4) small adult configuration
5) adult configuration with spread onto inner thighs
16
Q
5 stages of male genital development
A
1) prepubertal
2) testis enlarged to 4ml, scrotum larger, skin coarser
3) penis enlarges in length, continued growth of penis and scrotum
4) growth of penis in length and diameter, pigmentation of scrotum
5) testis, scrotum and penis are adult size
17
Q
Which endocrine event leads to which sexual maturation event?
A
- Increased GnRH to increased LH/FSH to increased steroid production
- Oestrogen secretion > breast development
- Testosterone > penile and scrotal development
- FSH > testicular enlargement/follicular development
- Adrenal androgen > pubic and axillary hair
- Sex steroid and GH > growth acceleration
- Oestrogen withdrawal > menarche (anovulatory)
- Induction of LH surge > ovulatory menstrual cycles
18
Q
Male vs female development
A
Males
- initial spurt at around 12. Growth ceases at 16
Females
- Initial spurt at 11. Growth ceases just before 14
19
Q
Give 11 physical changes in girls during puberty
A
- Breasts enlarge (thelarche, first outward sign of oestradiol activity)
- Pubic/axillary hair
- Uterus enlarges, cytology changes, secretions in response to oestradiol
- Uterine tubes
- Vagina
- Cervical changes
- Height - earlier onset than boys, spurt ~12yrs
- Body shape
- HPG axis - increase in ovarian size and follicular growth
- Menarche
- Fertility
20
Q
Give 9 physical changes in boys during puberty
A
- External genitalia - increase in testicular volume >4ml. Growth of penis, scrotum and scrotal skin changes
- Vas deferens - lumen increases
- Seminal vesicles and prostate
- Facial/body/ pubic/ axillary hair
- Larynx - androgens cause larynx to enlarge, Adams apple, voice deepens
- Height - spurt around 14yrs
- Body shape
- Onset of fertility - testosterone from Leydig cells stimulaes meiosis and spermatogenesis in Sertoli cells. Boys are fertile at beginning of puberty
21
Q
What is a Prader orchidometer?
A
- set of beads with specific volumes, represent testicular growth
- 1-3ml childhood
- 4-6ml early puberty
- 8-10ml mid puberty
- 12-15ml late puberty
- 20-25ml adulthood
22
Q
What causes growth spurts?
A
- Complex interaction between GH and oestrogen
- Approximately 2 years earlier in girls
- Low levels of oestrogen give linear growth and bone maturation
- High levels give epiphyseal fusion
23
Q
How do androgens affect the differentiation of pilosebaceous units (PSUs)?
A
- Stmulate sebum secretion, and together with infection, this can cause acne
- induce differentiation of vellus PSUs to terminal PSUs encouraging moustache and beard growth
- induce differentiation of vellus hairs to apo-PSUs encouraging growth in pubic and axilla regions
24
Q
What are 3 psychological changes?
A
- increasing need for independence
- increasing sexual awareness/interest
- Development of sexual personality
25
What is precocious sexual development?
- Development of any secondary sexual characteristic before 8 (girls) and before 9/10 (boys)
- changes are early but still in consonance
26
What are the different types of precious puberty?
Gonadotrophin-dependent (central) - in consonance.
- Excess GnRH secretion (idiopathic or secondary).
- Excess gonadotrophin secretion (pituitary tumour)
Gonadotrophin-independent - loss of consonance.
- Testotoxicosis - activating mutation of LH receptor
- McCune Albright - constitutive activation of adenylyl cyclase causing hyperactivity of signalling pathways and over-production of hormones
- Sex steroid secreting tumour or exogenous steroids
27
What is McCune Albright syndrome?
- Autonomous endocrine function
- most commone gonadotrophin-INdependent precocious puberty
- Get cafe au lait skin pigmentation and fibrous dysplasia
28
What is pseudo-precocious puberty?
- Premature adrenarche/pubarche - precocious development of pubic and/or axillary hairs
- CAH/Cushings
- Premature thelarche - precocious breast development - can be unilateral
29
How do we investigate precocious sexual development?
- Auxology - study all aspects of human growth
- Pubertal staging
- Bone age estimation
- LH, FSH, sex steroid measurements
- LH response to 100ug GnRH (normal for stage of puberty in central, suppressed in testotoxicosis)
- Adrenal steroids - high with tumours, precursors high with CAH
- MRI scans of H-P area
- US scans of pelvis
30
How can you treat precocious sexual development?
- Anti-androgens
- 5-alpha-reductase inhibitor (less DHT)
- Aromatase inhibitor
- Long-acting GnRH analogue (central precocious puberty)
31
What is pubertal delay?
- Absence of secondary sexual maturation by 13 yrs in girls (or absence of menarche by 18yr) or 14 yrs in boys
32
What are the different types of pubertal delay?
Constitutional delay
- affecting both growth and puberty
- Approx 90% of all pubertal delay cases
- 10x more common in boys
- Secondary to chronic illness
Hypogonadotrophic hypogonadism
- Low LH and FSH
- Kallman's syndrme (X-linked KAL gene, GnRH migration)
- Other genetic causes, hypopituitarism
Hypergonadotrophic hypogonadism
- High LH and FSH
- Gonadal dysgenesis, low sex steroid levels
- Congenital - Klinefelters (XXY) 1:500 males, Turner's (XO) 1:3000 girls
- Gonadal dysgenesis with normal karyotype, viral, e.g. mumps
33
How do we investigate delayed puberty?
- Family history, dysmorphic features, anosmia
- Auxology
- Pubertal staging
- Bone age estimation
- LH, FSH, sex steroid measurements
- LH response to 100ug GnRH
- Adrenal steroids - high with tumours, precursors high with CAH
- MRI scans of H-P area
- US scans of pelvis
34
How can we treat delayed puberty?
- Testosterone (males)
- Oestrogens (females)
- Oxandralone (synthetic steroid)
