1.1 Puberty

Question 1

How does TRH affects gonadotrophin levels?

Answer 1

high TRH levels): stimulates prolactin production → stimulates dopamine release → inhibits GnRH → limits gonadotrophin (LH, FSH, oestrogen, progesterone) levels

Question 2

Effect of TSH?

Answer 2

Stimulates T3 and T4 production

Question 3

Effect of prolactin?

Answer 3

Stimulates milk production

Question 4

Effect of GH?

Answer 4

Stimulates growth (in children) & maintains bone strength (in adults)

Question 5

Effect of FSH?

Answer 5

Stimulates oestrogen production and oocyte development

Question 6

Effect fof LH?

Answer 6

Stimulates oestrogen and progesterone production

Question 7

Effect of ACTH?

Answer 7

Stimulate cortisol and androgen production

Question 8

Effect of vasopressin?

Answer 8

Regulates osmolality & blood volume

Question 9

Effect of oxytocin?

Answer 9

Triggers uterine contractions during labour

Question 10

Each mature ovarian (Graafian) follicle is formed from an outer ___________ layer, and inner ___________ layer and a fluid-filled central cavity (antrum):
• Theca layer produces androgens which are converted to oestrogens in the granulosa layer (mainly oestradiol and oestrone)

As the secondary follicle grows under the influence of FSH, fluid (follicular liquor) accumulates between the granulosa cells → become confluent and forms the antrum:
• Oocyte becomes surrounded by several layers of granulosa cells, and is attached to the wall of the follicle by the ___________
• Thecal cells outside the basal lamina of the granulosa cells differentiate into the inner theca interna (pale, larger) and outer theca externa (appears like regular stroma)
• Progesterone is only produced later by the corpus luteum (after ovulation)

Answer 10

theca;

granulosa;

cumulus oophoricus;

Question 11

What functions do oestrogens have?

Answer 11

• Stimulate breast development
• Promote growth and maturation of bone and pubertal growth spurt
• Increases binding globulin formation in the liver (e.g. SHBG, TBG)
• Increases HDL and reduces LDL (cardioprotective function)
• High levels stimulate LH production → triggers ovulation

Question 12

What is the function of progesterone?

Answer 12

Progesterone is mainly involved in maintaining the pregnancy:
• Encourages secretory changes in the endometrium and encourages endometrial proliferation
• Thickens the cervical mucus to prevent sperm penetration (after fertilisation)
• Prevents uterine contractions (and other smooth muscles including in the lactiferous glands to prevent lactation during pregnancy)

Question 13

where is oestrogenn synthesized and what is the synthesis mediated by?

Answer 13

• Peripheral conversion of androgens in adipose tissue → mediated by FSH release (in a negative feedback loop)
• Oestradiol synthesis in the ovary requires CYP450 and HSD (hydroxysteroid dehydrogenase) enzyme families

Question 14

where is progesterone synthesized?

Answer 14

Produced by the ovaries, adrenal glands, placenta (from conversion of cholesterol → pregnenolone → progesterone) and stored in the adipose tissues

Question 15

which receptors do progesterone bind to?

Answer 15

intracellular progesterone receptor and mineralocorticoid receptors (with greater affinity than aldosterone and cortisol → strong inhibitor)

Question 16

what does thelarche means?

Answer 16

Start of breast development

Question 17

What does pubarche means?

Answer 17

Development of pubic hair

Question 18

what does adrenarche means?

Answer 18

Development of secondary sexual hair and sebaceous gland formation in the axilla and skin → sweat, body odour and skin oiliness (may cause acne)
• Due to adrenal zona reticularis maturation → androgen production (adrenal source; not gonadal source)

Question 19

What does menarche means?

Answer 19

Onset of menstrual bleeding

Question 20

How is the breast and pubic hair like at stage I puberty in girls?

Answer 20

• breast: only papillae elevated

- no pubic hair

Question 21

How is the breast and pubic hair like at stage II puberty in girls

Answer 21

• Areola and breast elevated as a small mound (areola enlarged)
• Sparse downy, slightly pigmented hair mainly growing along the labia

Question 22

How is the breast and pubic hair like at stage III puberty in girls

Answer 22

• Further enlargement of breast and areola with smooth contours
• Longer coarser hair (mostly curly) over the junction of the labia

Question 23

How is the breast and pubic hair like at stage IV puberty in girls

Answer 23

• Areola and papilla form a contour above the breast tissue

- Pubic hair: Adult in appearance but smaller area covered and no spread to medial surface of thighs

Question 24

How is the breast and pubic hair like at stage V puberty in girls

Answer 24

• Areola flattens in line with breast contour and only papilla elevated
• Pubic hair: Adult in appearance and quantity with spread to medial surface of thigh

Question 25

which stage of puberty does maximal growth spurt occurs?

Answer 25

stages II and III; slower growth (~5cm/year) after the onset of menarche

Question 26

which stage of puberty does menarche occurs?

Answer 26

stage IV

Question 27

what is the definition of preconcious early puberty?

Answer 27

Development of secondary sexual characteristics before 8 (girls) or 9 years (boys):

Question 28

what is the definition of delayed late puberty?

Answer 28

Absent/incomplete development of secondary sexual characteristics by 13 years in girls or 15 years in boys (mostly hypogonadism):

Question 29

what are the causes of central preconcious puberty?

Answer 29

• Central (true/consonant/gonadotrophin-dependent) precocious puberty (CPP) occurs due to the premature activation of the HPG axis
• Causes: idiopathic (90% of girls → boys more likely to have identifiable aetiology), neurological (cerebral tumours, hydrocephalus, meningitis), cranial radiotherapy

Question 30

what are the causes of perioheral preconcious puberty?

Answer 30

sex steroid secretion from gonadal tumours, extragonadal tissues or exogenous administration (e.g. ovarian/adrenal tumours, CAH, oestrogen administration) or genetic (e.g. McCune-Albright syndrome)

Question 31

What is congenital adrenal hyperplasia and what are the signs?

Answer 31

Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive conditions affecting steroid biosynthesis (most commonly 21-hydroxylase deficiency):
• Signs: virilisation of female infants, enlarged penis in male infants, salt-losing crisis 1 – 3 weeks after birth (with poor weight gain, vomiting, lethargy, dehydration), precocious puberty

Question 32

What is Mccune Albright’s syndrome and how does it present?

Answer 32

McCune-Albright syndrome is a complex genetic disorder affecting bone, skin, endocrine systems:
• Due to the unregulated production of sex steroids by the gonads (activating mutation of the G-protein complex)
• Triad of symptoms: ‘café au lait’ spots, fibrous dysplasia (of bone), endocrine hyperfunction

Question 33

what is the hormone profile of central (secondary) hypogonadism?

Answer 33

low GnRH, low LH/FSH, low oestrogen

Question 34

what are the causes of central (secondary) hypogonadism if HPA axis is intact?

Answer 34

• Constitutional delay of growth and puberty
• Chronic illness
• Low BMI (due to malnutrition or anorexia nervosa)

Question 35

what are the causes of central (secondary) hypogonadism if HPA axis is not intact?

Answer 35

• Kallmann syndrome (rare genetic disorder more common in males → isolated GnRH deficiency with anosmia due to impaired migration of GnRH cells and defective olfactory bulb → similar origin)
• Hypothalamic and/or pituitary lesions (e.g. prolactinoma)
• Trauma, tumours, irradiation, hydrocephalus

Question 36

what is the hormone profile of peripheral (primary) hypogonadism

Answer 36

insufficient ovarian production of sex steroids due to gonadal dysfunction
Hormone profile: high GnRH, high LH/FSH (no negative feedback), low oestrogen

Question 37

what are the possible causes for peripheral hypogonadism?

Answer 37

• genetic: Turner syndrome (45X): commonest cause in women
• acquired: Damage to ovarian tissue (e.g. pelvic irradiation, chemotherapy, trauma, surgery, autoimmune, infections (mumps, TB), toxic damage (galactossaemia))

Question 38

What are the features of turner syndrome?

Answer 38

• Common features: ovarian dysgenesis, short stature (presence of SHOX/short stature homeobox gene on X chromosome)
• Less common features (20 – 30%): neck webbing, posteriorly rotated auricles, arrow palate, cubitus valgus, widely spaced nipples
• Associated defects: cardiac (aortic coarctation, bicuspid aortic valve, aortic dilatation), renal, thyroid abnormalities (autoimmune thyroid disease) • Patients with mosaic Turner’s syndrome may have normal puberty and growth

Question 39

How do patients with congenital malformations of the uterus and/ vagina present?

Answer 39

Affected individuals usually present with primary amenorrhoea (no menarche by the age of 16) but otherwise normal pubertal development

Question 40

What is mullerian agenesis?

Answer 40

Absent uterus and vaginal hypoplasia due to failure of development of the Mullerian duct

Question 41

What is imperforate hymen and how does it present as?

Answer 41

Layer of connective tissue forming a transverse septum which obstructs the vaginal opening at the level of the introitus:
• Presentation: primary amenorrhoea, cyclical abdominal pain, urinary retention

Question 42

What is PCOS and how does it present as?

Answer 42

May present with amenorrhoea (accompanied by hirsutism, acne, central obesity)

Question 43

How does preconcious puberty affect growth?

Answer 43

Initially tall then height becomes restricted due to early epiphyseal plate fusion (no more growth)

Question 44

How does delayed puberty affect growth?

Answer 44

Mostly unaffected
Short in Turner syndrome (45XO)
Tall in other conditions (e.g. Klinefelter syndrome 47XXY)