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Year 2 - Endocrine > Week 5 > Flashcards

Week 5 Flashcards

1
Q

Where does glandular synthesis of oestrogen occur?

A

Granulosa and theca cells of the ovaries as well as the corpus luteum

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2
Q

Where does extra-glandular synthesis of oestrogen occur?

A

Aromatase is expressed in non-gonadal sites and facilitates peripheral aromatisation of androgens to estrone (e.g. in fat and bone)

This is why overweight men can develop breast tissue

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3
Q

Briefly describe the sequence of steps that results in oestrogen synthesis

A

LH stimulates the granulosa cells in the ovaries to release pregnenolone, which then passes into the theca cells

Pregnenolone is converted in the theca cells to androstenedione via DHEA

Most androstenedione returns to the granulosa cells and is converted to oestrone by aromatase, and then converted to oestradiol by 17beta-HSD

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4
Q

What is progesterone synthesised from?

A

Pregnenolone by 3beta-HSD in the corpus luteum, by the placenta during pregnancy and by the adrenals

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5
Q

What are the two phases of the menstrual cycle?

What is the main hormonal product of each phase?

A

Follicular phase - oestradiol

Luteal phase - progesterone

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6
Q

Define the following terms

  • oligomenorrhoea
  • primary amenorrhoea
  • secondary amenorrhoea
A

Oligomenorrhoea - reduction in the frequency of periods to less than 9 in a year

Primary amenorrhoea - failure of menarche by the age of 16

Secondary amenorrhoea - cessation of periods for >6 months in someone who has previously menstruated

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7
Q

What are some physiological causes of amenorrhoea?

A

Pregnancy

Menopause

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8
Q

Primary amenorrhoea - causes

A

Consider congenital causes e.g. Turner’s syndrome, Kallman’s syndrome

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9
Q

Secondary amenorrhoea - causes

A

Ovarian problem - PCOS, Premature Ovarian Failure

Uterine problem - uterine adhesions

Hypothalamic dysfunction - stress, excessive exercise, weight loss

Pituitary - high PRL, hypopituitarism

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10
Q

What investigations do all patients presenting with amenorrhoea have done?

A

(hCG if age-appropriate)

LH, FSH and Oestradiol

Thyroid function and PRL

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11
Q

How is female hypogonadism identified?

What is the difference between primary and secondary hypogonadism?

A

Hypogonadism in females = low levels of oestrogen

Primary

  • problem is with the ovaries
  • High LH/FSH but low oestradiol - “hypergonadotrophic hypogonadism”
  • e.g. Premature Ovarian Failure

Secondary

  • problem is with the hypothalamus or the pituitary
  • Low LH/FSH and low oestradiol - “hypogonadotrophic hypogonadism”
  • e.g. high PRL, hypopituitarism
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12
Q

How is Premature Ovarian Failure defined?

How is it diagnosed?

A

Amenorrhoea, low oestrogen and elevated LH/FSH before the age of 40

Measure FSH >30 on two separate occasions, more than a month apart

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13
Q

What would be lost if the cause of amenorrhoea was due to the hypothalamus?

A

There would be no pulsatile release of GnRH, meaning no release of LH/FSH

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14
Q

Mutations in what receptor have recently been identified as a cause of idiopathic hypogonadotrophic hypogonadism (IHH)?

What is the ligand for this receptor? How does it affect GnRH secretion?

A

The G-Protein Coupled Receptor KISS1R

Kisspeptin is the ligand for KISS1R and has been noted to be a potent stimulator of GnRH secretion - treatments with kisspeptin may be able to help restore menstruation

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15
Q

What genetic disorder can cause hypothalamic hypogonadism?

What are the symptoms?

A

Kallman’s syndrome - loss of GnRH secretion

Presents with infertility and anosmia (loss of olfactory bulbs)

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16
Q

What drugs can cause hyperprolactinaemia?

A

Dopamine antagonists e.g. metoclopramide, domperidone

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17
Q

What criteria is used to determine if a patient has Polycystic Ovary Syndrome?

What does this criteria consist of?

A

The Rotterdam Criteria

2/3 to diagnose PCOS…

  • Menstrual irregularities
  • Hyperandrogenism (hirsutism, acne, elevated free testosterone)
  • Polycystic ovaries
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18
Q

PCOS is an ovarian cause of amenorrhoea. What other ovarian causes are there?

A

Ovarian failure (POF)

Congenital problems - absence of uterus/vaginal atresia, Turner syndrome, CAH etc.

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19
Q

If a woman presented with signs of hirsutism that developed over a short period of time, is this cause for concern?

A

Potentially - could indicate adrenal or ovarian tumour

PCOS and other causes of hirsutism in women typically occur over a longer period of time

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20
Q

How is Congenital Adrenal Hyperplasia inherited?

What is the difference between Classical and Non-Classical CAH?

A

Autosomal recessive

Classical CAH - typically diagnosed in infancy with virilism and salt-wasting

Non-Classical CAH - partial deficieny in 21alpha-hydroxylase and presents in adolescence/adulthood with hirsutism, menstrual disturbances and infertility

21
Q

How is Non-Classical CAH tested for clinically? What is used as a marker?

A

Synacthen test is used

Following ACTH stimulation, an increase in 17-OH progesterone is seen

22
Q

PCOS - treatment

A

Oral contraceptive pill - regulates cycle and decreases androgens

Can also use anti-androgens - cyproterone acetat

Cosmesis to treat virilism

23
Q

Late-onset (i.e. Non-Classical) CAH - treatment

A

Low dose glucocorticoids to suppress ACTH (hydrocortisone)

24
Q

Turner’s Syndrome only affects women - true or false

What are the clinical features?

A

True, patients are 45 XO

Clinical features

  • short stature
  • webbed neck
  • “shield-like chest” with wide-spaced nipples
  • failure to progress through puberty
25
Q

What is the biochemical difference between primary and secondary hypogonadism in males?

A

Primary - low testosterone, high LH/FSH (congenital and acquired)

Secondary - low testosterone, low LH/FSH (hypothalamic/pituitary disease)

26
Q

Congenital and acquired causes of primary hypogonadism in males

A

Congenital

  • Kleinfelter’s
  • Y-chromosome microdeletions
  • LH/FSH receptor mutations
  • Myotonic dystrophy

Acquired

  • Trauma/torsion/radiation to testicles
  • Orchitis
  • Chemotherapy
  • Infiltrative disease
  • Varicocele
  • Cirrhosis/excessive alcohol intake
27
Q

Congenital and acquired causes of secondary hypogonadism in males

A

Congenital

  • Kallman’s
  • Prader-Willi

Acquired

  • Hyperprolactinaemia
  • Damage to pituitary
  • Excessive exercise
  • Acute illness
  • Medications etc. etc.
28
Q

Klinefelter’s - clinical presentation

A

Reduced testicular volume

Gynaecomastia

Eunuchoidism

Intellectual dysfunction in 40%

Karyotype is XXY

Low testosterone, high LH/FSH

29
Q

What is the mean duration of the menstrual cycle?

What is the range?

A

Mean duration = 28 days

Range = 21-35 days

30
Q

What is the range of duration of menses (period)?

What day does ovulation typically occur?

A

Range of menses = 3-8 days

Ovulation typically occurs around day 14

31
Q

In the follicular stage of the menstrual cycle, at what point is the oocyte released?

A

Approx 24-36 hours after the LH surge

32
Q

At what point in the mestrual cycle are progesterone levels at their peak?

A

1 week after ovulation

33
Q

Which part of the hypothalamus produces GnRH?

A

The arcuate nucleus

34
Q

LH acts on ____ cells

FSH acts on ____ cells

A

LH acts on theca cells

FSH acts on granulosa cells

35
Q

What are the actions of…

  • Inhibin
  • Activin
A

Inhibin - negative feedback on pituitary FSH secretion and locally enhances LH-induced androstenedione production

Activin - stimulates FSH-induced oestrogen production

36
Q

In the male, LH acts on ____ cells and FSH acts on ____ cells

A

LH - Leydig cells

FSH - Sertoli cells

37
Q

What process must occur for the sperm to be able to fertilise the egg?

What occurs after this proces?

A

Capacitation

2 parts to the process, 1) the acrosomal head membrane of the sperm destabilises and 2) chemical changes occur in the tail of the sperm giving it a greater degree of motility

Occurs in the female genital tract

Following capacitation, an acrosome reaction occurs that allows the sperm to penetrate the egg (triggered by zona pellucida ZP3)

38
Q

Low frequency pulses of GnRH cause release of _____

High frequency pulses of GnRH cause release of _____

A

Low frequency pulses = FSH release

High frequency pulses = LH release

39
Q

What are the main actions of FSH?

A

Stimulates follicular development

Thickens endometrium

40
Q

What are the main actions of LH?

A

Stimulates ovulation and corpus luteum development

Also thickens endometrium (like FSH)

41
Q

What triggers the beginning of the next menstrual cycle?

A

Fall in progesterone

42
Q

What feedback mechanisms is oestrogen involved in regarding ovulation?

What type of mucus is oestrogen responsible for?

A

High oestrogen concentrations inhibit secretion of FSH and prolactin (negative feedback) and stimulate secretion of LH (positive feedback)

Responsible for fertile cervical mucus

43
Q

What effects does progesterone have?

What type of mucus is it responsible for?

A

Inhibits LH secretion

Maintains thickness of endometrium (as does oestrogen)

Increases basal body temp and relaxes smooth muscle

Responsible for thick, infertile cervical mucus

44
Q

How is ovulation assessed?

A

If regular cycles, highly likely that ovulation is normal

Assess by measuring progesterone at mid-luteal phase (day 21)

45
Q

What other endocrine sign is seen in 50-80% of women with PCOS?

A

Insulin resistance

However, they have a normal pancreatic reserve, resulting in hyperinsulinaemia

46
Q

What are the 3 approaches that could be taken in inducing ovulation in someone with PCOS (after pre-treatment interventions i.e. weight loss, smoking cessation etc.)?

A
  1. Give clomifene citrate - stimulates LH and FSH to drive ovulation, 70% ovulate and 40-60% conceive
  2. Daily gonadotrophin injections with recombinant FSH, 80% ovulate and 60-70% conceive
  3. Laparoscopic ovarian diathermy, 80% ovulate
47
Q

What other drug can be given alongside lifestyle modifcations that restores menstruation and ovulation, and may improve chances of conception in PCOS?

A

Metformin

Improves insulin resistance and reduces the amount of androgen produced

48
Q

What medication can be given in hyperprolactinaemia?

A

Dopamine agonists e.g. cabergoline

49
Q

Woman presents with dysmenorrhoea, dysparenuia, menorrhagia, painful defaecation, chronic pelvic pain, infertility and “chocolate cysts” are seen on ovary.

What’s the diagnosis?

A

Endometriosis (presence of endometrial glands outside of uterine cavity)

Year 2 - Endocrine (8 decks)

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