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M2 Endo/Repro > 2/15 Disorders of Puberty - Radovick > Flashcards

2/15 Disorders of Puberty - Radovick Flashcards

1
Q

endocrine system graphic

A
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2
Q

female HPG axis

A

hypothal_GnRH neurons : GnRH

ant pituitary_gonadotropes : FSH & LH

ovaries : P4 (progesterone) & E2 (estradiol)

→→→ endometrium, female phenotype

feedback

  • estradiol has two types of feedback
    • positive feedback at level of GnRH neuron (hypothal) and pituitary → midcycle surge of LH → ovulation
    • negative feedback: high levels of E2 decr levels of GnRH, FSH, LH
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3
Q

male HPG axis

A

hypothal_GnRH neurons : GnRH

ant pituitary_gonadotropes : FSH & LH

testes : T (testosterone)

→→→ male phenotype, spermatogenesis

feedback

  • only one type of feedback
    • negative feedback: high levels of T decr levels of GnRH, FSH, LH
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4
Q

GnRH

A

gonadotropin releasing hormone

decapeptide synth’d via cleavage from pre-pro-GnRH protein in preoptic nuclei

GnRH secretion is PULSATILE

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5
Q

migration of GnRH neurons

disease of non-migration

A

GnRH neurons and olfactory neurons move from olfactory placode through cribriform plate to anterior hypothalamus

**MIGRATION IS CRITICAL

  • no migration? disease

Kallmann Syndrome: hypothalamic hypogonadism (assoc with anosmia)

  • KAL1 protein directs migration (adhesion protein)
  • if mutated? GnRH deficiency → anosmia, hypogonadism
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6
Q

GnRH receptor signaling

A

GnRH hits GnRH receptor in ant pit → FSH, LH synthesis and secretion via stimulation of subunit genes

ALSO stimulates subunit genes

desensitization of GnRH has effects on pulsatility of LH (more) and FSH (some)

  • lack of cytoplasmic tail → reduced receptor desensitization and internalization
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7
Q

pituitary and placental glycoprotein family

A
  1. LH
  2. FSH
  3. TSH
  4. hCG
  • common alpha subunit + hormone-specific beta subunit
  • glycosylation essential for fx
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8
Q

pulsatility of GnRH

A

pulsatility of GnRH → pulstility of LH/FSH secretion

continuous infusion?

no pulsatility of LH/FSH

implication: if you have too much FSH/LH (ex. precocious puberty) and you need to tone it down → cont infusion GnRH is an option → hypogonadism

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9
Q

two cell hypothesis of ovary

A
  1. theca cell: LH receptors
    • LH receptors are Gprotein-coupled → Gs → make adenylyl cyclase → incr cAMP
    • make androstenedione
  2. granulosa cell: FSH receptors
    • FSH receptors are also Gprotein-coupled → make adenylyl cyclase → incr cAMP → conversion of androstenedione from theca cells into E2 (estradiol)
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10
Q

testes

A
  1. Leydig cell: LH receptors
    • make testosterone
  2. Sertoli cell: FSH receptors
    • concentrates testosterone from Leydig cells → req for spermatogenesis
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11
Q

kisspeptin

A

pubertal trigger

  • upstream of GnRH
  • important in triggering puberty and ovulatory surge of gonadotropins
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12
Q

HPG axis summary

A
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13
Q

puberty

definition

puberty: hormones & processes
adrenarche: hormones & processes

A

period of life during which acquisition of secondary sexual characteristics occurs

puberty

hypothal:GnRH → pituitary:FSH/LH → testes/ovaries:testosterone/estradiol

GONADARCHE: incr size of testes (due to testosterone incr)

THELARCHE: onset of breast devpt

adrenarche

pituitary:ACTH → adrenal:DHEA/DHEAS → adrenal androgens

TANNER2-3: PUBIC HAIR

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14
Q

Tanner stage

breasts

A

stage1 : no breast tissue

stage2 : breast bud; elevation under areola (onset ~10y)

stage3: enlargement of breast tissue beyond areola, no separation of contours

stage4 : projection of areola and papilla to form secondary mound above level of breast

stage5 : mature stage

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15
Q

Tanner stage

pubic hair

A

stage1 : no pubic hair

stage2 : sparge growth of long, pigmented hair on labia

stage3 : darker, coarser, curlier hair on pubis

stage4 : adult-type hair, but less quantity

stage5 : adult0type and quantity, inverted triangle

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16
Q

Tanner stage

male genitalia

A

**testicular size is the best way to stage males

stage1 : preadolescent

stage2 : thinning, reddening of scrotum

stage3 : enlargement of penis length, curly pubic hair

stage4 : enlargement of penis length/breadth; development of glans, testes

stage5 : adult size and shape, pubic hair on thigh, adult testicular size

17
Q

females @ time of menarche

males @ time of facial hair

A

female menarche

  • relatively late event in pubertal devpt
  • onset: 12-13yr
    • breasts usually stage 4 (bc started at 10y)
    • occurs significantly after max growth velocity

male facial hair

  • onset: 15yr
    • genital devpt nearly complete
    • occurs after but still close to max growth velocity
18
Q

abnormalities of puberty

A

1. delayed (hypogonadism)

  • CENTRAL : hypogonadotropic
  • PERIPHERAL (primary) : hypergonadotropic
  • females*: no breast devpt by 13, no menses by 16
  • males*: no testicular devpt by 14

2. precocious

  • CENTRAL : gonadotrophic-dependent aka GDPP
  • PERIPHERAL : gonadotropin-indep aka GIPP
  • females:* breast devpt before 8
  • males:* incr testicular size before 9
19
Q

hypogonadism

central vs peripheral

A

central (85%) : inability to make GnRH, LH, FSH

  • constitutional delay of growth, puberty 50
  • fxal hypogonadotropic hypogonadism (20)
    • nutrition, stress, exercise, hyperPRLemia
  • permanent hypogonadotropic hypogonadism (15)
    • genetic, tumors, vascular

peripheral (15%) : increased GnRH, LH, FSH

  • gonadal dysgenesis
    • Turner, Klinefelter
  • gonadal failure
    • autoimmune, chemotx, radiation, torsion
20
Q

Klinefelter Syndrome

A

XXY

  • hypogonadism w very small testes
21
Q

Turner Syndrome

A

XO

small dysfx ovaries → no estrogen produced

elevated FSH/LH

22
Q

tx of delayed puberty

A

females

  • ethinyl estradiol PO or transdermal estradiol
  • progestagen when menstrual bleeding starts

males

  • testosterone IM or transdermal

induction of fertility in hypogonadotropic hypogonadism:

  • pulsatile GnRH
  • combo FSH, hCG tx
23
Q

precocious puberty

A

central (90%) : gonadotropin-dependent → incr in GnRH, LH, GSH, sex steroids

  • idiopathic (most common)
  • general CNS insult
    • radiation, infl, trauma
  • CNS tumors
    • hamartomas

peripheral (10%) : gonadotropin-indep → low LH, FSH; incr sex steroids

  • gonad : sex steroid secreting tumors
  • adrenal : sex steroid secreting tumors, CAH
  • exog estrogen/androgen
  • McCune-Albright syndrome: activating mutation in Galpha-s
  • females : ovarian cysts
  • males : hCG secreting tumors, familial testotoxicosis (activation mutation in LH receptor)
24
Q

tx of central precocious puberty

A
  1. GnRH agonists (analogs) → induce pituitary desensitization
    * can have initial flare (leuprolide + histrelin)
  2. GnRH antagonists (rarely used)
25
Q

summary

M2 Endo/Repro (20 decks)

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