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Endocrine disorders and reproduction Flashcards

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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
How is prolactin released during pregnancy?
Circadian rhythm with levels peaking during sleep.
26
How does a premenopausal women present with hyperprolactinaemia?
Hypogonadism and amenorrhoea Symptoms of oestrogen deficiency Galactorrhoea
27
What are the possible causes of hyperprolactinaemia?
- Prolactinoma - Loss of dopamine inhibiton due to pituitary stalk compression or disconnection - Dopamine antagonists e.g.TCAs, verapamil, metoclopramide, thiazines - Hypothyroidism
28
What is a prolactinoma?
A prolactin secreting tumour of the pituitary.
29
What is premature ovarian insufficiency?
Loss of normal function of ovaries before 40. Inhibited production of normal oestrogen levels = premature menopause
30
How does a women with POI present?
Triad: - Amenorrhoea - Hypergonadotropism = high LH and FSH - Hypoestrogenism = Oestrogen deficiency
31
What is the congential cause of POI? or What mutations may be present?
Turner's syndrome Mutation in FSH receptor, FMR1 gene (Fragile X) Galactossaemia
32
How does a Pt with Turner's syndrome present?
Short stature, streak ovaries, webbed neck, pronounced angle of elbow, CHD, hypothyroidism, lymphoedema
33
What is the prognosis for fertility in a Turner's syndrome Pt?
Requires Donor eggs for successful pregnancy
34
What AI conditions may cause POI?
Hashimoto's thyroiditis Grave's disease (thyroid) Addison's disease (adrenal) - POI preceeds DM
35
What are the iatrogenic causes of POI?
Chemotherapy Radiotherapy Surgery
36
How does AI cause POI?
Inflammatory infiltration of the follicles and production of antiovarian Igs leads to apoptosis and atrophy
37
What is fragile X premutation?
Mutations in FMR1 gene increase the risk of fragile X POI. Fx is an inherited X linked dominant pattern.
38
How is POI diagnosed?
``` 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
Why is a DEXA scan required?
POI increased the risk of osteopenia (reduced mineral content)
40
How is POI managed?
Oestrogen replacement | Progesterone given if uterus present to protect against hyperplasia through withdrawal bleeds
41
What is PCOS?
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
How do PCOS pts present?
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
What are the hormone levels in PCOS?
HYPERANDROGENISM: High testosterone and DHEA High LH:FSH ratio Low oestrogen
44
What has the cause of PCOS been linked to?
Insulin sensitivity
45
How is PCOS diagnosed?
Requires 2/3 from the triad: - Oligo/amenorrhoea - Clinical and biochemical hyperandrogenaemia - Polycystic ovaries
46
What is the main issue for women with PCOS?
Amenorrhoea and infertility
47
What is the risk of pregnancy with PCOS?
Increased risk of gestational DM and Pre-eclampsia
48
What is the risk of IVF in PCOS?
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
What is the treatment for obesity induced oligo/amenorrhoea?
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
What is the treatment for anovulation?
Metformin and clomiphene
51
What is the treatment for hirsutism?
Yasmin, vaniqua cream, cosmetic removal, spironolactone (antiandrogen)
52
What is 21-hydroxylase deficiency?
Congenital adrenal hyperplasia caused by a deficiency in 21OH.
53
What is the classical form of CAH 21OH?
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
What is the non-classical form of CAH 21OH?
Present late childhood or adulthood due to premature puberty, hirsutism, PCOS, inferitility. ANDROGEN EXCESS but no salt wasting.
55
How is CAH tested for?
17OHD
56
How is CAH treated?
Steroid replacement
57
What is androgen insensitivity syndrome?
Mutations in the androgen receptor causing a spectrum of disorders that can be complete, partial or infertile
58
How does a 46 XY female present?
Complete testicular feminisation, female external genitalia, short blinded vagina, no uterus, inguinal hernias from abdominal testes, gynaecomastia
59
What results from 5alpha reductase deficient?
46XY females unable to convert testosterone to DHT so lack mascularisation of external genitalia, appearing female. Have abdominal testes and primary amenorrhoea.
60
What happens to testosterone levels with age?
Decrease
61
What is the function of inhibin?
-ve feedback of FSH
62
What does testosterone -vely regulate?
LH and FSH
63
How does hypogonadism present in males?
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
What are primary causes of hypogonadism in males?
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
What are secondary causes of hypogonadism in males?
Secondary = Central causes - Pituitary tumour - Hyperprolactinaemia - Hypothalamic disease - Obesity - Androgen abuse (Irreversible) - Myotonia dystrophy
66
What hypothalamic causes lead to hypogonadism?
Craniopharyngioma Kallaman's syndrome GnRH therapy
67
How is hypogonadism in males diagnosed?
``` Low testosterone (consider age) FSH and LH levels - determine if primary or secondary Imaging Karyotyping Liver function test ```
68
What does HIGH LH and FSH mean in regards to the cause of hypogonadism?
Primary causes as no -ve feedback on pituitary as no sex steroids produced by gonads
69
What does LOW LH and FSH mean in regards to the cause of hypogonadism?
Secondary causes as failure to produce LH and FSH
70
What is Klinefelter's syndrome?
47 XXY, a primary cause of hypogonadism that causes small testes and feminisation leading to azoospermia and gynaecomastia, reduced sexual hair. Osteoporosis.
71
What does Klinefelter increase the risk of?
Breast cancer | Behavioural and learning difficulties
72
What is myotonic dystrophy?
Autosomal dominant progressive muscular weakness. Causes primary gonadal failure due to disruption of the tissue. Baldness, cataract, myotonia, retardation
73
What is Kallman's syndrome?
Idiopathic hypogonadotropic hypogonadism caused by a failure of migration of GnRH neurones. X linked recessive affecting males>females. Presents with anosmia
74
What genes are affected by Kallman's?
FGF-R1, GnRH-Rec, GPCR54, Kal-1
75
Why does hypogonadotrpoic hypogonadism arise?
Due to genetic mutations affecting - GnRH neuron migration failure - GnRH synthesis and release - GnRH action - Gonadotropin synthesis
76
How is hypogonadism treated in males?
Testosterone replacement
77
How can testosterone be administered?
Tablets Transdermal patches Subdermal implants for 6mnths IM monthly or 3mnth (preferred as gives better baseline level)
78
What are the safety issues with testosterone replacement and what does this mean for the Pt?
Changes in behaviour and increased risk of prostate cancer so requires annual PSA, FBC, Lipid and BP checks
79
What is the effect of androgen abuse?
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
How is a Pt who abused androgens treated?
Cannot be given fertility treatment, must wait 5 years to see if sperm production restarts. May be irreversible
81
Male infertility as a result of endocrine disorders is rare. What tests can be done to determine the cause?
Hx, examination, seminal fluid, FSH, LH and testosterone
82
What does a raised FSH suggest for infertility? How can it be treated?
Germ cell failure. | Requires IVF
83
What does a normal FSH suggest for infertility?
Obstructive uropathy from injury, vasectomy or CF
84
What does low FSH, LH and testosterone suggest for infertility?
Endocrine cause - pituitary or hypothalamic
85
How is endocrine infertility treated?
LH replacement with HCG (mimics) FSH replacement = mimic pituitary release, sperm production may return <18mths. Aim is to produce enough sperm for IVF.

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