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Endocrine disorders and reproduction Flashcards

1
Q

How is GnRH released from the hypothalamus?

A

PULSATILE to cause pulsatile releases from pituitary

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2
Q

What happens if there is a continuous release of GnRH?

A

Downregulates release from pituitary through -ve feedback. This can be used to stop fertilisation in treatments.

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3
Q

What causes a central pathology in the HPG axis?

A
  • Lack of secretion of LH and FSH

- Hypothalamic or pituitary disease

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4
Q

What problems in the gonads affect reproduction?

A
  • Failure of germ cell production

- Lack of sex steroid production

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5
Q

What is oligomenorrhoea?

A

Irregular periods <9 in 1 year or 42 day cycles

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6
Q

What is amenorrhoea?

A

Primary - failure of menarche after 16 years old / never had a period
Secondary - absence of periods for 6 months

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7
Q

What does the frequency of periods suggest?

A

Shows how the HPG axis is functioning and if the reproductive organs are receptive

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8
Q

How does oestrogen deficiency present?

A

Causes premature menopause of hot flushes, poor libido and dyspareunia

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9
Q

What are hirsutism, acne and androgenic alopecia signs of?

A

Dysfunction of HPG axis

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10
Q

What may a galactorrhoea suggest?

A

Prolactinoma

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11
Q

What may be suggested from a women who is underweight?

A

Hypothalamic disease

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12
Q

What may be suggested from a women who is overweight?

A

PCOS

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13
Q

What is the first cause of amenorrhoea that should always be ruled out?

A

Pregnancy

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14
Q

What are the central causes of amenorrhoea?

A

Hypothalamic disease
Pituitary disease e.g. tumour or lactation
Hypogonadotropic hypogonadism = failure of LH and FSH secretion

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15
Q

What may cause hypothalamic disease?

A

Weight loss anorexia, excessive exercise, stress, low fat levels

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16
Q

What are the ovarian causes of amenorrhoea?

A

Turner’s syndrome = streak ovaries
Premature ovarian failure / premature menopause
Polycystic ovary syndrome

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17
Q

What miscellaneous causes of amenorrhoea?

A

Thyrotoxicosis
Chronic disease
Local uterine problems

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18
Q

Which is the most common cause of amenorrhoea after pregnancy?

A

PCOS

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19
Q

What does leptin do?

A

Controls appetite. If a Pt gains weight, their leptin levels increased to reduce appetite.

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20
Q

What is a leptin deficiency caused by?

A

Congential deficiency
Severe obesity
Hyperphagia = excessive desire to eat
Hypogonadotropic hypogonadism

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21
Q

Where is prolactin produced?

A

Synthesised in lactotrophs for production of breast milk

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22
Q

What inhibits prolactin release?

A

Dopamine tonically and constantly inhibits.

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23
Q

What does high levels of prolactin cause?

A

Downregulation of LH and FSH = hypogonadism

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24
Q

What can induce hyperprolactinaemia?

A

Stress and drugs or post seizure.

Easier to identify in premenopausal women than men or postmenopausal

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25
Q

How is prolactin released during pregnancy?

A

Circadian rhythm with levels peaking during sleep.

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26
Q

How does a premenopausal women present with hyperprolactinaemia?

A

Hypogonadism and amenorrhoea
Symptoms of oestrogen deficiency
Galactorrhoea

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27
Q

What are the possible causes of hyperprolactinaemia?

A
  • Prolactinoma
  • Loss of dopamine inhibiton due to pituitary stalk compression or disconnection
  • Dopamine antagonists e.g.TCAs, verapamil, metoclopramide, thiazines
  • Hypothyroidism
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28
Q

What is a prolactinoma?

A

A prolactin secreting tumour of the pituitary.

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29
Q

What is premature ovarian insufficiency?

A

Loss of normal function of ovaries before 40. Inhibited production of normal oestrogen levels = premature menopause

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30
Q

How does a women with POI present?

A

Triad:

  • Amenorrhoea
  • Hypergonadotropism = high LH and FSH
  • Hypoestrogenism = Oestrogen deficiency
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31
Q

What is the congential cause of POI? or What mutations may be present?

A

Turner’s syndrome
Mutation in FSH receptor, FMR1 gene (Fragile X)
Galactossaemia

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32
Q

How does a Pt with Turner’s syndrome present?

A

Short stature, streak ovaries, webbed neck, pronounced angle of elbow, CHD, hypothyroidism, lymphoedema

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33
Q

What is the prognosis for fertility in a Turner’s syndrome Pt?

A

Requires Donor eggs for successful pregnancy

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34
Q

What AI conditions may cause POI?

A

Hashimoto’s thyroiditis
Grave’s disease (thyroid)
Addison’s disease (adrenal) - POI preceeds
DM

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35
Q

What are the iatrogenic causes of POI?

A

Chemotherapy
Radiotherapy
Surgery

36
Q

How does AI cause POI?

A

Inflammatory infiltration of the follicles and production of antiovarian Igs leads to apoptosis and atrophy

37
Q

What is fragile X premutation?

A

Mutations in FMR1 gene increase the risk of fragile X POI. Fx is an inherited X linked dominant pattern.

38
Q

How is POI diagnosed?

A 
FSH and oestrogen levels - multiple readings weeks apart
Karyotyping for Fx and FMR1
Screening for AI
AMH to measure ovarian reserve
DEXA scan for bone density
39
Q

Why is a DEXA scan required?

A

POI increased the risk of osteopenia (reduced mineral content)

40
Q

How is POI managed?

A

Oestrogen replacement

Progesterone given if uterus present to protect against hyperplasia through withdrawal bleeds

41
Q

What is PCOS?

A

Most common endocrine disorder in premenopausal women. It is the growth of cysts on the ovaries and the production of symptoms due to high levels of androgens.

42
Q

How do PCOS pts present?

A

Oligoamenorrhoea
Hirsutism (Excessive body hair)
Obesity
Infertility due to anovulation
Polycystic ovaries on USS
Insulin resistance causes Acanthosis nigricans
Androgenic alopecia (male pattern baldness)

43
Q

What are the hormone levels in PCOS?

A

HYPERANDROGENISM:
High testosterone and DHEA
High LH:FSH ratio
Low oestrogen

44
Q

What has the cause of PCOS been linked to?

A

Insulin sensitivity

45
Q

How is PCOS diagnosed?

A

Requires 2/3 from the triad:

  • Oligo/amenorrhoea
  • Clinical and biochemical hyperandrogenaemia
  • Polycystic ovaries
46
Q

What is the main issue for women with PCOS?

A

Amenorrhoea and infertility

47
Q

What is the risk of pregnancy with PCOS?

A

Increased risk of gestational DM and Pre-eclampsia

48
Q

What is the risk of IVF in PCOS?

A

Risk over ovarian hyperstimulation syndrome leading to the fertilisation of more than 1 egg. Overproduction means low quality eggs and woman feels unwell from the excess follicle stimulation.

49
Q

What is the treatment for obesity induced oligo/amenorrhoea?

A

Metformin to control periods and reduce LH
Lifestyle changes for weight loss
Progesterone for 7 days every 3 months for withdrawal bleed
Weight loss pharmacotherapy e.g. biariatric surgery

50
Q

What is the treatment for anovulation?

A

Metformin and clomiphene

51
Q

What is the treatment for hirsutism?

A

Yasmin, vaniqua cream, cosmetic removal, spironolactone (antiandrogen)

52
Q

What is 21-hydroxylase deficiency?

A

Congenital adrenal hyperplasia caused by a deficiency in 21OH.

53
Q

What is the classical form of CAH 21OH?

A

Detected as a neonate for girls due to ANDROGEN EXCESS causing mascularisation of female and salt wasting from ALDOSTERONE DEFICIENCY causing an adrenal crisis.

54
Q

What is the non-classical form of CAH 21OH?

A

Present late childhood or adulthood due to premature puberty, hirsutism, PCOS, inferitility. ANDROGEN EXCESS but no salt wasting.

55
Q

How is CAH tested for?

A

17OHD

56
Q

How is CAH treated?

A

Steroid replacement

57
Q

What is androgen insensitivity syndrome?

A

Mutations in the androgen receptor causing a spectrum of disorders that can be complete, partial or infertile

58
Q

How does a 46 XY female present?

A

Complete testicular feminisation, female external genitalia, short blinded vagina, no uterus, inguinal hernias from abdominal testes, gynaecomastia

59
Q

What results from 5alpha reductase deficient?

A

46XY females unable to convert testosterone to DHT so lack mascularisation of external genitalia, appearing female. Have abdominal testes and primary amenorrhoea.

60
Q

What happens to testosterone levels with age?

A

Decrease

61
Q

What is the function of inhibin?

A

-ve feedback of FSH

62
Q

What does testosterone -vely regulate?

A

LH and FSH

63
Q

How does hypogonadism present in males?

A

Delayed puberty
Loss of libido, reduced sexual behaviour
Gynaecomastia
Loss of body hair
Reduced muscle mass and female fat distribution
Osteoporosis
Infertility with altered testicular volume

64
Q

What are primary causes of hypogonadism in males?

A

Primary = reduced function of gonads

  • Trauma from surgery of torsion on testes
  • Chemo or radiotherapy
  • Cryptorchidism (undescended testes)
  • Infection, inflammation e.g. mumps
  • Klinefelter’s syndrome 47 XXY
  • Systemic disease e.g. liver cirrhosis, renal failure, thyroid dysfunction
65
Q

What are secondary causes of hypogonadism in males?

A

Secondary = Central causes

  • Pituitary tumour
  • Hyperprolactinaemia
  • Hypothalamic disease
  • Obesity
  • Androgen abuse (Irreversible)
  • Myotonia dystrophy
66
Q

What hypothalamic causes lead to hypogonadism?

A

Craniopharyngioma
Kallaman’s syndrome
GnRH therapy

67
Q

How is hypogonadism in males diagnosed?

A 
Low testosterone (consider age)
FSH and LH levels - determine if primary or secondary
Imaging
Karyotyping
Liver function test
68
Q

What does HIGH LH and FSH mean in regards to the cause of hypogonadism?

A

Primary causes as no -ve feedback on pituitary as no sex steroids produced by gonads

69
Q

What does LOW LH and FSH mean in regards to the cause of hypogonadism?

A

Secondary causes as failure to produce LH and FSH

70
Q

What is Klinefelter’s syndrome?

A

47 XXY, a primary cause of hypogonadism that causes small testes and feminisation leading to azoospermia and gynaecomastia, reduced sexual hair. Osteoporosis.

71
Q

What does Klinefelter increase the risk of?

A

Breast cancer

Behavioural and learning difficulties

72
Q

What is myotonic dystrophy?

A

Autosomal dominant progressive muscular weakness. Causes primary gonadal failure due to disruption of the tissue. Baldness, cataract, myotonia, retardation

73
Q

What is Kallman’s syndrome?

A

Idiopathic hypogonadotropic hypogonadism caused by a failure of migration of GnRH neurones. X linked recessive affecting males>females. Presents with anosmia

74
Q

What genes are affected by Kallman’s?

A

FGF-R1, GnRH-Rec, GPCR54, Kal-1

75
Q

Why does hypogonadotrpoic hypogonadism arise?

A

Due to genetic mutations affecting

  • GnRH neuron migration failure
  • GnRH synthesis and release
  • GnRH action
  • Gonadotropin synthesis
76
Q

How is hypogonadism treated in males?

A

Testosterone replacement

77
Q

How can testosterone be administered?

A

Tablets
Transdermal patches
Subdermal implants for 6mnths
IM monthly or 3mnth (preferred as gives better baseline level)

78
Q

What are the safety issues with testosterone replacement and what does this mean for the Pt?

A

Changes in behaviour and increased risk of prostate cancer so requires annual PSA, FBC, Lipid and BP checks

79
Q

What is the effect of androgen abuse?

A

Causes reduced sperm production as it turns off testosterone production when in excess exogenously.
Affects mood, prostate cancer, infertility, atrophy of tests, CVD, polycythemia

80
Q

How is a Pt who abused androgens treated?

A

Cannot be given fertility treatment, must wait 5 years to see if sperm production restarts. May be irreversible

81
Q

Male infertility as a result of endocrine disorders is rare. What tests can be done to determine the cause?

A

Hx, examination, seminal fluid, FSH, LH and testosterone

82
Q

What does a raised FSH suggest for infertility? How can it be treated?

A

Germ cell failure.

Requires IVF

83
Q

What does a normal FSH suggest for infertility?

A

Obstructive uropathy from injury, vasectomy or CF

84
Q

What does low FSH, LH and testosterone suggest for infertility?

A

Endocrine cause - pituitary or hypothalamic

85
Q

How is endocrine infertility treated?

A

LH replacement with HCG (mimics)
FSH replacement
= mimic pituitary release, sperm production may return <18mths. Aim is to produce enough sperm for IVF.

RED (8 decks)

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