Clinical (Week 5 - Calcium and Reproduction) Flashcards Preview

Year 2 - Endocrinology (DP) > Clinical (Week 5 - Calcium and Reproduction) > Flashcards

Flashcards in Clinical (Week 5 - Calcium and Reproduction) Deck (180):
1

Where are oestrogens synthesised?

Ovaries:
- Granulosa
- Theca cells
Corpus luteum

2

What does LH stimulate the granulosa cells to produce?

Pregnenolone

3

What diffuses from the granulosa cells to the adjacent theca cells and what does this cause?

Pregnenolone
Causes theca cells to express:
- 17,20-lyase (also known as 17α-Hydroxylase)
- 3β-HSD

4

What happens when the theca cells express the enzymes in response to pregnenolone?

Pregnenolone is converted to DHEA:
- By 17α-hydroxylase
DHEA is converted to androstenedione:
- By 3β-HSD

5

What other function does 3β-HSD have?

Converts pregnenolone to progesterone

6

What are the three types of naturally occurring oestrogen in the body?

Oestrone (E1)
Oestradiol (E2)
Oestriol (E3)

7

What happens to most androstenedione?

Returns to granulosa cells:
- Converted to oestrone (E1) by aromatase

8

What function does 17β-HSD have?

Converts oestrone (E1) to Oestradiol (E2)
(Also converts Androstenedione to testosterone)

9

What enzymes does FSH increase the expression of?

Aromatase
17β-HSD
(Both from the granulosa cells)

10

Where else can oestrogens be synthesised?

Aromatase is expressed in fat and bone:
- Peripheral production of Oestrone (E1)

11

Where is progesterone synthesised and by what enzyme?

Made from pregnenolone by 3β-HSD in:
- Corpus luteum
- Placenta (during pregnancy)
- Adrenal glands

12

Why is progesterone made in the adrenal glands?

Step in androgen and mineralocorticoid production

13

During the following stages, what products are mainly made from pregnenolone:
- Follicular maturation
- Following ovulation (Luteal phase)

Follicular maturation:
- Oestradiol (E2)
Luteal phase:
- Progesterone

14

What is oligomenorrhoea?

Reduced period frequency to less than 9/year
OR
Having a menstrual cycle > 35 days

15

What is primary amenorrhoea?

Failure of menarche by 16 years of age

16

What is secondary amenorrhoea?

Cessation of periods for >6 months:
- In a woman who previously menstruated

17

What are the two physiological causes of amenorrhoea?

Post-menopausal state
Pregnancy

18

What can cause primary amenorrhoea?

Turner's Syndrome (45, XO)
Kallman's Syndrome

19

A 19 year old woman presents concerned that she hasn't started menstruating. She has also noted that her breasts have hardly developed. On examination you notice she has no sense of smell (anosmia). You decide to test her pituitary hormones and discover a lack of LH and FSH.

Kallman's Syndrome

20

What ovarian problems may cause secondary amenorrhoea?

PCOS
Premature ovarian failure

21

Which of these does not cause hypothalamic dysfunction and therefore does not cause secondary amenorrhoea:
- Weight loss
- Over exercise
- Poor sleep
- Stress
- Infiltrative disease

Poor sleep

22

What pituitary problems can result in amenorrhoea?

Increased PRL
Hypopituitarism

23

Flushing, reduced libido and dyspareunia are signs of what?

Oestrogen deficiency

24

What is dysparenuia?

Difficult or painful sex

25

What are features of PCOS?

Acne
Hirsutism

26

What blood tests should be done in oligo/amenorrhoea?

LH/FSH/Oestradiol

27

What additional investigations can be done if the following are suspected:
- Hirsutism
- Hypothalamic/Pituitary problem
- Primary amenorrhoea or Turner's
- PCOS

Hirsutism:
- Testosterone
Hypothalamic/Pituitary problem:
- Pituitary function tests
- MRI pituitary
Primary amenorrhoea or Turner's:
- Karyotype
PCOS:
- USS

28

What is primary hypogonadism and what can cause it?

An ovarian problem:
- Increased LH/FSH
- Reduced response to gonadotropins
> Hypergonadotropic Hypogonadism
- eg. Premature Ovarian Failure

29

What is secondary hypogonadism and what can cause it?

Problem with hypothalamus and/or pituitary:
- Reduced/Inappropriately normal LH/FSH
> Hypogonadotropic Hypogonadism
- Can be due to
> High PRL
> Hypopituitarism

30

How many times must FSH be high to suggest a diagnosis of premature ovarian failure? What must it be greater than

FSH >30:
- 2 separate occasions -> Greater than 1 month apart

31

What age are patient's suffering from premature ovarian failure?

Women younger than 40

32

What chromosomal abnormalities can cause premature ovarian failure?

Turner's
Fragile X

33

What gene mutations can cause premature ovarian failure?

LH/FSH receptor mutations

34

What autoimmune conditions are associated with premature ovarian failure?

Addison's
Thyroid
APS1/1 (Autoimmune Polyendocrine Syndrome)

35

What iatrogenic causes are there of premature ovarian failure?

Radiotherapy
Chemotherapy

36

What are some hypothalamic causes of secondary hypogonadism?

Functional disorders
Kallman's Syndrome
Idiopathic Hypogonadotropic Hypogonadism (IHH)

37

What are some other causes of secondary hypogonadism?

Prader-Willi (Chromosome 15q11-13 mutations)
Haemochromatosis

38

What are the most common causes of functional hypothalamic amenorrhoea?

Weight change
Stress
Exercise

39

Which of the following is not a sign/symptome of IHH:
- Absent/Delayed sexual development
- Reduced gonadotropins
- Increased sex steroids
- Absence of hypothalamic-pituitary axis defects

Increased sex steroids:
- They are reduced in IHH

40

What underlies IHH?

Inability to activate pulsatile GnRH secretion in puberty

41

What genetic defects may cause IHH?

GnRH neuron migration
GnRH secretion
GnRH action

42

What role does Kisspeptin have and how can this be linked to IHH?

Functions:
- Potent stimulator of GnRH release
- Gatekeeper of puberty
- Regulates male and female fertility
- Influences ovulation and menstruation
Mutations in the KISS1R receptor:
- Prevents Kisspeptin binding
> Reduces GnRH release

43

What would be seen on MRI of a patient with Kallman's syndrome and how does this reflect on one of the symptoms?

Normal pituitary gland
BUT
No olfactory bulb -> Hypo-/Anosmia

44

What is the male:female ratio for Kallman's Syndrome?

4:1

45

What can cause pituitary dysfunction?

Non-functioning pituitary macroadenoma:
- Pressure -> Hypopituitarism
Empty sella
Infarction (Apoplexy)

46

What can cause hyperprolactinaemia?

Prolactinomas
Pituitary pathology
Drugs:
- Antipsychotics
- Dopamine antagonists
Hypothyroidism
Macroprolactin:
- False hyperprolactinaemia

47

What are the Rotterdam criteria for PCOS?

2 of:
- Menstrual irregularity
- Hyperandrogenism
> Hirsutism
> Increased free testosterone
- Polycystic ovaries

48

What are some congenital causes of poor ovarian development?

Absence of uterus
Vaginal atresia
Turner's
Testicular feminisation
CAH

49

What causes hirsutism?

Excess androgen at hair follicle:
- Due to excess circulating androgen
- Peripheral conversion to testosterone at follicle

50

In what populations is familial hirtuism common?

Mediterranean

51

What are the features of these causes of hirsutism:
- PCOS
- Familial
- Idiopathic
- Non-classical CAH

Long histories
Serum testosterone

52

What can cause a short history of hirsutism with signs of virilisation?

Adrenal/Ovarian tumour

53

What testosterone levels are seen in androgen-secreting tumours? What size do these tumours tend to be on MRI

>5nmol/L
>1cm

54

How can PCOS be treated?

Oral contraceptive:
- Regulates cycle
- Reduces ovarian androgens
Anti-androgens:
- Cyproterone acetate
- Efflornithine cream
Cosmesis:
- Electrolysis
- Laser phototherapy

55

How can late onset CAH be treated?

Low does glucocorticoid (reduces ACTH drive)

56

What is the incidence of Turner Syndrome?

1 in 2000 women

57

How many spontaneous abortions is Turner Syndrome responsible for?

15%

58

What are some defining clinical features of Turner Syndrome?

Short stature
Webbed neck
Wide spaced nipples
Cubitus valgus:
- Forearm angled away from body

59

What are some CVS effects of Turner Syndrome?

Aortic coarctation
Bicuspid aortic valve
Hypoplastic left heart

60

What GI problems are patients with Turner Syndrome more likely to have?

Crohn's
UC

61

If a patient has no chromosomal abnormalities, yet absent ovaries, what is this due to?

XX Gonadal Dysgenesis

62

A patient's karyotype is 46 XY, yet they are phenotypically female.

Testicular feminisation:
- Androgen Insensitivity Syndrome
- Pseudohermaphrodites

63

What biochemistry is seen in primary male hypogonadism?

Reduced testosterone
Increased LH/FSH

64

What biochemistry is seen in secondary male hypogonadism?

Reduced testosterone
Reduced/Inappropriately normal LH/FSH

65

What are some congenital causes of primary male hypogonadism?

Klinefelter's
LH/FSH receptor mutations

66

What are some acquired causes of primary male hypogonadism?

Testicular trauma
Haemochromatosis

67

What are some congenital causes of secondary male hypogonadism?

Kallman's
Prader-Willi

68

What are some acquired causes of secondary male hypogonadism?

Hyperprolactinaemia
Pituitary damage

69

What examination signs are relevant in diagnosing male hypogonadism?

Staging of puberty
Testicular volume
Visual fields

70

What level of total testosterone may suggest male hypogonadism?

71

If testosterone is low, what must be done next?

Repeat total testosterone
OR
If SHBG variation suspected:
- Measure free testosterone

72

What free testosterone level suggest male hypogonadism?

73

What does SHBG stand for?

Sex hormone-binding globulin

74

What is the incidence for Klinefelter's Syndrome?

1 in 500 men

75

What is the Karyotype in Klinefelter's?

47, XXY

76

What are the clinical features of Klinefelter's Syndrome?

Reduced testicular volume
Gynaecomastia
Eunuchoidism (Deficiency of sexual development)
Reduced intelligence (in 40%)
Azoospermia

77

What biochemical results are seen in Klinefelter's for each of the following:
- Testosterone
- LH/FSH
- SHBG
- Oestradiol

Testosterone is reduced
LH/FSH are raised
SHBG is raised
Oestradiol is raised

78

What functional causes of secondary male hypogonadism are there?

Exercise
Weight loss
Stress
Illness

79

What infiltrative diseases can cause secondary male hypogonadism?

Sarcoidosis
Haemochromatosis

80

What drugs can cause secondary male hypogonadism?

Anabolic steroids
Opiates

81

When is testosterone replacement offered?

If

82

Will testosterone restore fertility?

No

83

How does testosterone replacement affect the following:
- Sexual function
- Bone health
- Muscle strength

Sexual function:
- Erectile function improved in young men
Bone health:
- Increased hip + spine BMD (IM>Transdermal)
Muscle strength:
- Reduced fat mass
- Increased limb strength

84

What drugs can cause gynaecomastia?

Oestrogens
Testosterone
Spironolactone
Digoxin

85

Why can a germinoma cause gynaecomastia?

Secretes hCG

86

How long does a normal menstrual cycle last?

28-35 days

87

Where is GnRH synthesised?

Hypothalamus

88

What kind of release does GnRH have and what doe sit stimulate the release of?

Pulsatile:
- Low frequency pulses -> FSH
- High frequency pulses -> LH

89

What functions does FSH have?

Stimulates follicular development
Thickens endometrium

90

What functions does LH have?

Its peak stimulates ovulation
Stimulates corpus luteum development
Thickens endometrium

91

What does an ovulation predictor kit detect? How correct is it?

LH
97%

92

When does progesterone peak and why?

After ovulation (Day 21 of cycle)
Produced by corpus luteum

93

When does oestradiol peak?

Before ovulation (Day 12 of cycle)

94

Where is Oestrogen secreted from?

Ovaries
Adrenal cortex
Placenta during pregnancy

95

What functions does oestrogen have?

Thickens endometrium
Produces fertile cervical mucous
High concentrations:
- Inhibit FSH and PRL secretion (-ve feedback)
- Stimulates LH secretion (+ve feedback)

96

What is the main function of progesterone?

Helps maintain early pregnancy

97

What other functions does progesterone have?

Inhibits LH secretion
Produces infertile/thick cervical mucous
Maintains endometrial thickness
Increases basal body temperature
Relaxes smooth muscles

98

How can we confirm ovulation has occurred?

Mid-luteal (Day 21) serum progesterone:
- >30nmol/L
- 2 samples

99

What is the WHO classification of Hypothalamic Pituitary Failure?

Group 1

100

What test can prove oestrogen deficiency?

Negative progesterone challenge test:
- ie No menstruation 5 days after progesterone

101

How can hypothalamic anovulation be managed?

Stabilise weight (BMI>18.5)
Pulsatile GnRH is hypog. hypog.:
- S/C or IV pump (worn continuously)
- Pulse every 90 minutes
OR
FSH/LH daily injections
- Increase multiple pregnancy rate

102

What is WHO group 2?

Hypothalamic Pituitary Dysfunction

103

What WHO group does PCOS belong to?

Group 2

104

How are polycystic ovaries defined?

More than twelve 2-9mm follicles
Increased ovarian volume >10ml
Uni/Bilateral

105

How many PCOS patients are insulin resistant

50-80%

106

What effects does insulin have

Co-gonadotropin to LH:
- Increases LH
Reduces SHBG -> Increased free testosterone
- Hyperandrogenism

107

What criteria must be met before treatment for PCOS?

Weight loss
Smoking cessation
Folic acid (400μg/5mg daily)
Rubella immune
Semen analysis
Patent fallpoian tube

108

What is the 1st line treatment for inducing ovulation in PCOS?

Clomifene citrate:
- 50 to 100 to 150mg
- Days 2-6

109

If a patient is resistant to the 1st line PCOS treatment, what can be tried?

Metformin
FSH injections
Diathermy
IVF

110

What scan findings indicate dichorionic twins and monochorionic twins?

Dichorionic - Lamba Sign
Monochorionic - T Sign

111

What is the pathophysiology behind Twin-Twin Transfusion Syndrome (TTTS)?

Unbalanced vascular connections to placenta
Recipient -> Polyhydramnios
Donor:
- Oliguria
- Oligohydramnios
- Growth restriction

112

How can TTTS be treated?

Laser division of placental vessels
Amnioreduction
Septostomy

113

What are some long-term problems with prematurity?

6 times risk of CP
Impaired sight
Congenital heart disease
Reduced IQ
ADHD

114

What investigation results are seen in hyperprolactinaemia?

Normal FSH/LH
Reduced oestrogen
High PRL:
- >1000iU/L on more than 2 occasions
TFTs normal
MRI

115

How is hyperprolactinaemia treated?

Dopamin agonist:
- Cabergoline twice weekly
- Bromocriptine is conventional

116

Can dopamine agonists be continued during pregnancy?

No

117

What are the FSH levels in ovarian failure?

>30iU/L on more than 2 occasions

118

What WHO group is ovarian failure?

Group 3

119

What are some causes of premature ovarian failure?

Genetic:
- 45, XO
- XX Gonadal agenesis
- Fragile X
Autoimmune
Oophorectomy
Pelvic radiotherapy

120

How is premature ovarian failure treated?

HRT
Egg/Embryo donation

121

When is progesterone tested for?

Day 21 of the menstrual cycle

122

What hormones are tested for on days 2-6 of the menstrual cycle?

FSH/LH/Oestradiol
Testosterone + SHBG
PRL
TSH

123

What is the normal result to a progesterone challenge test?

Menstrual bleed after 5 days:
- Indicated normal oestrogen levels

124

Why is the incidence of infertility increasing?

Older women
Chlamydia infections
Obesity
Male factor infertility

125

What is the definition of infertility?

Failure to achieve a clinical pregnancy after 12 months or more of regular unprotected sex (in absence of known reason) in a couple who has never had a child (WHO definition)

126

What is primary infertility?

Couple has NEVER conceived

127

What is secondary infertility?

Couple previously conceived:
- Pregnancy not successful
> Miscarriage OR
> Ectopic pregnancy

128

At what age are women more likely to conceive?

Younger than 30

129

At what point in the menstrual cycle is conception most likely to occur?

During the 6 days prior to ovulation (particularly two days before)

130

What BMI range is best for conception?

20-30

131

What other lifestyle factors affect the likelihood of conception?

Smoking
Caffeine intake
Use of recreational drugs
Alcohol

132

What are some hypothalamic causes of anovulation?

Anorexia/Bulimia
Over-exercising

133

What are some pituitary causes of anovulation?

High PRL
Tumours
Sheehan Syndrome

134

What is Sheehan Syndrome?

Postpartum hypopituitarism:
- Caused by ischemic necrosis due to blood loss and hypovolemic shock during and after childbirth

135

Loss of hair, increased lanugo hair, low bulse, hypotension and anaemia are signs of what?

Anorexia nervosa

136

What are endocrine features of anorexia?

Low FSH
Low LH
Low oestradiol

137

How does weight affect PCOS?

Exacerbates it

138

What are endocrine features of PCOS?

High free androgens
High LH
Impaired glucose tolerance

139

What are some clinical features of premature ovarian failure?

Hot flushes
Night sweats
Atrophic vaginitis

140

What are endocrine features of premature ovarian failure?

High FSH
High LH
Low oestradiol

141

What are some infective causes of tubal disease?

Pelvic inflammation:
- Chlamydia
- Gonorrhoea
- Other (Anaerobes, Syphilis, TB)
Transperitoneal spread:
- Appendicitis
- Intra-abdominal abscess
Following surgical procedure:
- IUCD
- Hysteroscopy
- HSG

142

What are some non-infective causes of tubal disease?

Endometriosis
Surgical (sterilisation)
Fibroids
Polyps
Congenital
Salpingitis Isthmica Nodosa

143

What is Salpingitis Isthmica Nodosa?

Diverticulosis of the Fallopian tube:
- Nodular thickening of the narrow part

144

What is hydrosalpinx?

Fallopian tube dilated with water

145

How does hydrosalpinx present?

Abdominal/pelvic pain
Fever
Vaginal discharge -> Dyspareunia
Cervical excitation
Menorrhagia
Dysmenorrhoea
Infertility
Ectopic pregnancy

146

What is endometriosis?

Presence of endometrial glands outside uterine cavity

147

What can cause endometriosis?

Retrograde menstruation (commonest)
Altered immunity
Abnormal cellular adhesion molecules

148

How can the uterus appear in endometriosis?

Fixed and retroverted

149

What characteristic cysts are seen on the ovaries in endometriosis?

'Chocolate' cysts

150

What is a varicoele?

Abnormal enlargement of the pampiniform venous plexus in the scrotum

151

What can cause vas deferens obstruction?

Congenital absence (CF)
Vasectomy

152

What can cause erectile dysfunction?

DM
Spinal cord injury
Psychosexual

153

What are some causes of semen disorders?

Globospermia
Kartagener's Syndrome

154

What can cause testicular failure?

47, XXY
Chemotherapy/Radiotherapy
Undescended testes

155

What are some other endocrine causes of male infertility?

Hyperprolactinaemia
Acromegaly
Cushing's
Thyroid disease

156

What are some clinical features of obstructive male infertility?

Normal testicular volume
Normal secondary sexual characteristics
+/- vas deferens absence

157

What investigations results are seen in obstructive male infertility?

Normal LH
Normal FSH
Normal testosterone

158

What are some clinical features of non-obstructive male infertility?

Low testicular volume
Reduced secondary sexual characteristics
Vas deferens present

159

What investigations results are seen in non-obstructive male infertility?

High LH
High FSH
Low testosterone

160

Why would we carry out an endocervical swab in investigating female infertility?

To test for chlamydia

161

What blood tests do we do in an infertile woman?

Rubella immunity
Progesterone level

162

How can we test tubal patency?

Hysterosalpingiogram
Laparoscopy

163

When is a hysterosalpingiogram preferred?

If no know tubal/pelvic problems
Laparoscopy contraindicated

164

What are some contraindications for laparoscopy?

Obesity
Previous pelvic surgery
Crohn's

165

When is laparoscopy preferred for investigating the fallopian tubes?

If history suggests pathology:
- Dysmenorrhoea
- Dyspareunia
If previous pathology:
- Ectopic pregnancy
- Endometriosis
- Appendix rupture

166

Whe is a hysteroscopy carried out?

If suspected/known endometrial pathology:
- Uterine septum
- Adhesions
- Polyps

167

When is a pelvic USS used?

If abnormality felt on examination/seen on HSG

168

How do we carry out semen analysis?

Two samples
Over 6 weeks apart

169

What are the normal levels for each of the following in a semen sample:
- Volume
- pH
- Concentration
- Motility
- Morphology
- WBC

Volume >1.5ml
pH 7.2-7.8
Concentration >15,000,000/ml
Motility >50%
Morphology >4% are normal
WBC

170

If a woman is anovulatory, what should we test?

Early follicular bloods (Days 2-5):
- LH
- FSH
- E2
- Testosterone
- FAI
- PRL
- Thyroid hormones

171

What indicates non-rubella immune?

Rubella IgG antibodies 6U/L

172

If a mother becomes infected with rubella during pregnancy, what can happen to the child?

Microcephaly
PDA
Cataracts

173

What are some short-term complications of chlamydia infection?

Tubo-ovarian abscess
Peritonitis
Fitz-Hugh-Curtis Syndrome

174

What are some long-term complications of chlamydia infection?

Chronic pelvic pain
Infertility
Ectopic pregnancy

175

What are findings in Group 1 WHO ovulatory disorders?

Low FSH
Low oestrogen
Normal prolactin
Negative progesterone challenge

176

What disorders are normogonadotrophic and normoestrogenic?

WHO Group 2 (PCOS)

177

What findings are seen in all variants of ovarian failure and resistant ovary?

High FSH/LH
Low oestrogens

178

How do Letrozole and Anastrozole work? What are they used to treat?

Inhibit ovarian aromatase
PCOS

179

How does Tamoxifen work?

It is an anti-oestrogen

180

How can male infertility be treated?

Surgery to obstructed vas deferens
Intrauterine insemination
Intracytoplasmia sperm injection (ICSI)
Donor insemination