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Endocrinology - Rachel Doohan Y5 > ovulation disorders and male hypogonadism > Flashcards

ovulation disorders and male hypogonadism Flashcards

1
Q

oestrogen synthesis

A

oestrogen are a class of steroid hormones which control the development and maintenance of female sex characteristics

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2
Q

glandular oestrogen synthesis occurs in

A

the granulose and theca cells as well as in the corpus lute

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3
Q

granulose cells are stimulated by

A

LH to produce pregnelone, pregneolne then diffuses into adjacent theca cells where it is converted to androstenedione via DHEA.

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4
Q

the androstenedione

A

then returns to the granulose cells where it is converted to oestone via Aromatase and then to estradiol via 17-beta-HSD

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5
Q

expression of aromatase and 17-beta- HSD is controlled by

A

FSH stimulation

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6
Q

extra-glandular synthesis of oestrogen

A

aromatase is also expressed in non-gonadal tissue (one and fat) so in the peripheries aromatisation can occur allowing the conversion of androgens to oestrogen

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7
Q

progesterone is synthesised from

A

pregnelone by the action of 3-beta-HSD in the corpus lute, placenta during pregnancy and the adrenal cortex as a step in androgen and mineralocorticoid synthesis

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8
Q

actions of progesterone are mediated by

A

an intra-cellular progesterone receptor which numbers are increased in the presence of oestrogen

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9
Q

products of the follicular and luteal phase

A

oestradiol is the main production of the follicular phase and progesterone is the main product of the luteal phase

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10
Q

oligomenorrhea

A

reduction in the frequency of an individuals period to less than 9 a year

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11
Q

primary amenorrhoea

A

failure of menarche by the age of 16

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12
Q

secondary amenorrhoea

A

cessation of menarche for more than 6 months in an individual who has previously had periods

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13
Q

physiological causes of amenorrhoea

A
  • physiological: pregnancy and post-menopausal
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14
Q

causes of primary amenorrhoea

A

consider congenital causes such as turners syndrome and kallmans syndrome

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15
Q

causes of secondary amenorrhoea

A
  • ovarian problems; Polycystic ovarian syndrome, premature ovarian failure
  • uterine problems; uterine adhesions
  • hypothalamic dysfunction: caused by excessive weight loss, over-exercise, stress, infiltrative causes
  • pituitary causes: hyperprolactinaemia, hypopituitarism
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16
Q

investigating ammenorrhoea

A
  • in all woman of a child breaking age your first test should always be a pregnancy test measure HcG levels
  • LH, FSH and estradiol levels
  • Thyoird function test, prolactin levels
  • ovarian ultrasound and testosterone levels if PCOS suspected
  • pituitary hormone levels and MRI if pituitary problem suspected
  • Karyotype for those with primary amenorrhoea
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17
Q

next step is too establish

A

if hypogonadism is present, in females hypogonadism is identified by low levels of oestrogen

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18
Q

types of female hypogonadism

A

primar hypogonadism and seondary hypogonaism

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19
Q

primary hypogonadism

A
  • problem is within the ovaries
  • low oestrogen levels but high FSH and LH levels
  • also known as hypergonadotrophic hypogonadism
  • example of primary hypogonadism: premature varian failure
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20
Q

secondary hypogonadism

A
  • problem is within the hypothalamus or the pituitary
  • low oestrogen levels and low FSH and LH levels
  • also known as hypogonadotrophic hypogonadism
  • examples: prolactinoma and hypopituitarism
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21
Q

premature ovarian failure is also known as

A

primary ovarian insufficiency

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22
Q

defintion

A

amenorrhoea, oestrogen fedicient and elevated gonadotrophin in a female before the age of 40 caused by loss of ovarian function

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23
Q

causes

A
  • most commonly is idiopathic
  • chromosomal abnormalities: turners syndrome (missing or structurally altered X chromosome)
  • gene mutation: BRCA 1 gene, fragile X syndrome (expansion of trinucleotide repeat within a gene on the X chromosome)
  • iatrogenic causes: chemotherapy and radiotherapy
  • autoimmune disease: addisons, thyroid disease
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24
Q

50% of females with premature ovarian failure

A

have intermittent ovarian function so may rarely get pregnant this would be impossible in actual menopause

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25
Q

symptoms of premature ovarian failure

A
  • hot flushness
  • night sweats
  • vaginal dryness causing painful sex (dyspareunia)
  • osteoporosis
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26
Q

diagnosis

A

FSH level greater than 30 on 2 occasions more than one month apart

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27
Q

management

A

hormone replacement therapy

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28
Q

turner syndrome is a cause of

A

primary ovarian failure

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29
Q

turners syndrome

A

normally females have two X chromosomes: 46 XX, in turners syndrome one X chromosome is missing: 45 XO (there are other genotypes where the second X chromosome is present but is structurally altered)

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30
Q

clinical features of turners syndrome

A
  • short stature
  • webbed neck
  • underdeveloped ovaries which will eventually fail which causes primary or secondary amenorrhoea depending on when the ovaries fail
  • infertility
  • shield shed chest with nipples that are far apart
  • lymphoedeema
  • coarctation of the aorta
  • elbow deformity
  • shorted metacarpal IV
  • naevi
  • renal malformations: horseshoe shaped kidney
  • cubitus valgus
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31
Q

secondary hypogonadism

A

hypogonadism caused by a problem in the hypothalamus or pituitary (hypogonadotrophic hypogonadism)
- low levels of estradiol and low levels (or inappropriately normal levels) of FSH and LH

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32
Q

causes of secondary hypogonadism

A
  • hypothalamic problem
  • pituitary problem
  • trader will syndrome
  • haemochromatosis
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33
Q

hypothalamic problems causing secondary hypogonadism

A

functional hypothalamic disorders
kallmans syndrome
idiopathic hypogonadotrophic hypogonadism

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34
Q

pituitary problem

A
  • hyperprolactinaemia

- hypopituitarism

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35
Q

functional hypothalamic amenorrhoea is a

A

diagnosis of exclusion

36
Q

what is functional hypothalamic amenorrhoea

A

non-organic reversible disorder where the is loss of pulsatile gonadotrophin releasing hormone secretion from the hypothalamus as a physiological response in order to avoid pregnancy in times of physiological stress

37
Q

3 main types of functional hypothalamic amenorrhoea

A
  • weight loss related (i.e. anorexia)
  • stress related
  • exercise related (extreme exercise)
38
Q

other causes of functional hypothalamic amenorrhoea

A

anabolic steroid abuse, systemic illness, recreational drugs, sarcoidosis

39
Q

idiopathic hypogonadotrophic hypogonadism

A

absent or delayed sexual development associated with inappropriately low levels of gonadotrophin and sex hormone levels in the absence of anatomical or functional defects in the hypothalamic pituitary gonadal axis

40
Q

cause of idiopathic hypogonadotrophic hypogonadism

A

many genes implicated either caused by a mutation in the genres that encode proteins for GnRH neuronal migration or for GnRH secretion

41
Q

mutation of what is linked to idiopathic hypogonadotrophic hypogonadism

A

kisspeptin

42
Q

kallmans syndrome

A

genetic disorder characterised by loss of GnRH secreting and ansomia (loss os sense of smell) or hyposmia (reduced sense of smell)

43
Q

kallamns syndrome is a type of

A

hypogonadotrophic hypogonadism

44
Q

kallmans syndrome is caused by a

A

genetic mutation leading to a defect in the migration of neutrons coming out of the olfactory placed: olfactory neutrons and GnRH neutrons

45
Q

kallmans syndrome is

A

4x more common in males

46
Q

lows levels of

A

sex hormones (testosterone in males ad oestrogen and progesterone in females) leads to failure to start or complete puberty

47
Q

male presentation of kallmans

A
  • small penis and testes
  • improper testicualr descent
  • lack of facial hair
  • low sperm count
  • no deepening of voice
48
Q

female presentation of kallmans

A
  • amenorrhoea or oligomenorrhoea

- lack of breasts and pubic hair

49
Q

in both males and females kallmas can cuase

A

osteoporosis due to the loss of the protective affect of oestrogen and testosterone on bone and infertility

50
Q

pituitary causes of secondary hypogonadism

A
  • any case of hypopituitarism

- hyperproalctinaemia

51
Q

causes of hypopituitarism causing secondary hypogonadism

A
  • non-functioning macro adenoma
  • trauma: road traffic accidents, iatrogenic
  • infection: meningitis
  • infarction: sheehans syndrome, pituitary apoplexy
  • granulomatous causes: sarcoidosis, tuberculosis, histiocytosis X
  • empty sella syndrome
52
Q

causes of hyperprolactinaemia causing secondary hypogonadism

A
  • micro or macro prolactinoma
  • drugs: dopamine antagonists SSRIS
  • hypothyroidism
53
Q

congenital adrenal hyperplasia most common type

A

deficiency of 21-alpha-hydroxylase enzyme

54
Q

steroid biosynthesis pathway

A

draw out diagram

55
Q

congenital adrenal hyperplasia is inherited

A

autosomal recessively

56
Q

in baby girls congenital adrenal hyperplasia presents as

A

ambiguous genitalia caused by virilization

57
Q

in baby boys congenital adrenal hyperplasia presents

A

wishin around one week with salt wasting with dehydration, hyponatrameia, hyperkalaemia and a metabolic acidosis

58
Q

in congenital adrenal hyperplasia the inability to produce cortisol

A

means there is no negative feedback on the hypothalamus or the pituitary gland meaning that ACTH is excessively secreted which causes the excessive production of androgens and hyperplasia of the adrenal glands

59
Q

diagnosis of congenital adrenal hyperplasia

A

serum cortisol levels are always low

the levels of 17-alpha- hydoxyprogesterone are elevated especially after synachtne test

60
Q

non-classical congenital adrenal hyperplasia

A

partial deficiency in 21-alpha- hydorxylase which will present in adolescent or adulthood with normal aldosterone and cortisol levels but causes hirsutism, menstrual disturbance and infertility caused by anovulation

61
Q

androgen secreting tumours

A

tumours secreting male sex steroids that arise in females and cause virilization

62
Q

levels of testosterone in androgen secreting tumours

A

very high usually greater than 5nmol/l

63
Q

androgen secreting tumours can be of the

A

ovaries or the adrenal glands

64
Q

rarer causes pof amennorhoea

A

XX gonadal dysgenesis

androgen insensitivity syndrome

65
Q

XX gondal dysgenesis

A

there is no chromosomal abnormality but the female has no functional ovaries

66
Q

androgen insensitivity syndrome

A

individuals who are genetically male (XY) but phenotypically they are female

67
Q

male hypogonadism

A

primary or secondary

68
Q

primary male hypogonadism

A
  • caused by a problem within the testes
  • also known as hypergonadotrophic hypogonadism
  • low testosterone levels with high FSH and LH levels
  • acquired and congenital causes
69
Q

secondary male hypogonadism

A
  • low levels of testosterone with inappropriately low LH and FSH levels
  • causes are hypothalamic and pituitary disorders
70
Q

congenital causes of male primary hypogonadism

A
  • klinefelters syndrome
  • Y chromosomal micro deletions
  • mutations in Lh and FSH receptors
  • myotonic dystrophy (most common type of muscular dystrophy occurring in adults)
  • cryptorchidism (absence of one or both testes from the scrotum)
71
Q

acquired causes of primary hypogonadism

A
  • testicular trauma/ torsion/ irradiation
  • autoimmune testicular failure
  • haemachromatosis
  • varicocele
72
Q

congenital causes of male secondary hypogonadism

A
  • kallmans syndrome
  • prader willi syndrome
  • mutation in beta subunit of LH and FSH
73
Q

acquired causes of male secondary hypogonadism

A
  • hyperprolactinaemia
  • hypopituatatrism
  • hypothalamic dysfunction
  • idiopathic hypogonadotrophic hypogonadism
74
Q

klinefelters syndrome is the

A

most common congenital cause of primary hypogonadism

75
Q

klinefelters syndrome only affects

A

male

76
Q

klinefelters syndrome is a

A

chromosomal abnormality when there is an extra chromosome: 47 XXY

77
Q

the extra X chromosome results

A

dysfunction of

  • leydig cells: normally LH stimulates the leydig cells convert cholesterol to testosterone
  • sartoli cells: normally FSH and testosterone stimulate the sartoli cells to produce sperme
78
Q

normally due to negative feedback

A

testosterone from the leydig cells acts on the hypothalamus to reduce the release of gonadotrophin releasing hormone and LH secretion and inhibit produced by the sartoli cells inhibits the release of FSH

79
Q

in klinefelters syndrome

A

testosterone is not produced by the leydig cells and inhibit is not produced by the sartoli cells so there is no negative feedback resulting in excessive production of gonadotrophin releasing hormone, FSH and LH

80
Q

low levels of testosterone results in

A

supressed testes maturation and sperm reduction and inhibits the development of male secondary sex characteristics

81
Q

clinical features of klinefelters syndrome

A
  • small penis and testes
  • gynaecomastia
  • infertility
  • intellectual dysfunction
  • reduced secondary sex characteristics
82
Q

secondary male hypogonadism is

A

hypogonadism as a result of hypothalamic or pituitary dysfunction

83
Q

secondary hypogonadism test results

A

low 9am testosterone, low FSH and Low LH

84
Q

hypothalamic causes of male hypogonadism

A
  • idiopathic hypogonadotrophic hypogonadism
  • kallmans syndrome
  • functional hypothalamic disorders
85
Q

pituitary causes of male hypogonadism

A
  • hyperprolactinamia
  • hypopituatatrism
  • haemachromatosis
  • prader will syndrome
86
Q

testosterone replacement

A

in young men with clear evidence of hypogonadism testosterone replacement is indicated

87
Q

benefits of testosterone replacement

A
  • in young men helps with erectile dysfunction

- decreases fat mass and improves limb strength

Endocrinology - Rachel Doohan Y5 (28 decks)

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