Original Endocrinology (main) Flashcards

1
Q

How does pregnancy effect TFTs?

A

In Pregnancy:
Measure free T3 and T4
Total T3 and T4 increased
Free T3 and T4 levels drop (increased binding)
TSH levels are lower

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2
Q

Where are ADH and oxytocin synthesised?

A

Hypothalamus

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3
Q

Where are ADH and oxytocin stored?

A

Posterior pituitary

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4
Q

What stimulates glucagon?

A

Hypoglycemia

Epinephrine
Cholecystokinin

Acetylcholine
Arginine
Alanine

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5
Q

What inhibits glucagon?

A

Somatostatin
Insulin
Uraemia
Increased free fatty acids and keto acids into the blood

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6
Q

What do islet cells produce?

A

Alpha cells secrete glucagon
Beta cells secrete insulin
Delta cells secrete somatostatin
Gamma cells secrete pancreatic polypeptide

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7
Q

What inhibits TSH?

A

Somatostatin

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8
Q

What hormones are produced by the medulla of the adrenals?

A

Epinephrine
Dopamine
Norepinephrine

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9
Q

What is produced by the zona glomerulosa?

A

Aldosterone

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10
Q

What is produced by the zona fasciculata?

A

Cortisol

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11
Q

What is produced by the zona reticularis?

A

Androgens

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12
Q

What is a typical FBC finding in Addison’s disease?

A

Eosinophillia and lymphocytosis

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13
Q

What hormones does somatostatin inhibit?

A

Insulin
Glucagon
Growth Hormone

Gastrin
Cholecystokinin (CCK)
Secretin
Vasoactive intestinal peptide (VIP)
Gastric inhibitory polypeptide (GIP)

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14
Q

Which dopamine agonists may be used to inhibit milk production, and which receptors do they act on?

A

Cabergoline + bromocriptine
Both act on D2 receptors

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15
Q

In what proportion of children does delayed puberty occur?

A

3%

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16
Q

What are 2 recognised galactagogues (stimulators of milk production)?

A
  1. Domperidone
  2. Metoclopramide
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17
Q

What is maternal flow through the uterine artery at term?

A

750ml/min

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18
Q

What is flow through the uterine artery when not pregnant?

A

45ml/min

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19
Q

What are the 3 types of oestrogen?

A

Estrone (E1)
Estradiol (E2)
Estriol (E3)

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20
Q

What is the predominant oestrogen during female reproductive years?

A

Estradiol (except in the early follicular phase when estrone predominantes)

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21
Q

What is the predominant oestrogen during pregnancy?

A

Estriol

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22
Q

Which drugs can cause an increased prolactin?

A

Opiates
Verapamil
Atenolol
H2 antagonists e.g. Ranitidine

SSRI’s e.g. Fluoxetine
Antipsychotics e.g risperidone and haloperidol
Amitriptyline
Methyldopa

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23
Q

What are the ratios of testosterone free:albumin-bound:SHBG-bound?

A

1% free: 19% albumin-bound: 80% SHBG-bound

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24
Q

Which cells are responsible for androgen production in the ovary?

A

Theca cells

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25
Q

Which cell are responsible for aromatisation of androgens into oestrogen?

A

Granulosa cells

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26
Q

Where are the juxtaglomerular cells located?

A

Afferent arteriole in the kidney

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27
Q

What is leptin release from adipose tissue stimulated by?

A

Glucocorticoids
High BMI
Long-term hyperinsulinaemia
Excessive food ingestion

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28
Q

What is the most common cause of delayed puberty?

A

Constitutional delay

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29
Q

What is the definition of puberty in women?

A

Physical maturation whereby the women becomes capable of sexual reproduction

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30
Q

What is the lifespan of the corpus luteum?

A

14 days

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31
Q

How many hours after the LH surge does ovulation occur?

A

24-36 hours

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32
Q

Where is calcidiol produced?

A

Liver

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33
Q

During pregnancy, from where is bHG produced?

A

Syncytiotrophoblast

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34
Q

At what gestation does the fetal endocrinological system become fully active?

A

10/40

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35
Q

What tumour marker is used for granulosa cell tumours?

A

Inhibin

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36
Q

When does the corpus luteum cease to be essential in maintaining a pregnancy?

A

6/40

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37
Q

What blood abnormalities would you see in Cushing’s of different origin, i.e. how do you tell the difference?

A

Adrenal-origin Cushing’s - Cortisol = high, ACTH = low/undetectable
Pituitary-origin Cushing’s - Cortisol = high, ACTH = high
Ectopic ACTH production Cushing’s - Cortisol = high, ACTH = v. high

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38
Q

Where does ADH act? And what does it do?

A

Acts on the distal tubule
Increases water resorption via insertion of aquaporins

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39
Q

What are the acquired forms of nephrogenic diabetes insipidus (when the kidney becomes unresponsive to ADH)?

A

Chronic Renal Failure
Hypokalaemia
Lithium Toxicity

Pregnancy
Hydronephrosis

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40
Q

What are the features of hyperaldosteronism?

A

Hypertension
Hypokalaemia
Alkalosis

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41
Q

What are the causes of primary hyperaldosteronism?

A

Adrenal adenoma (unilateral, common)
Adrenal hyperplasia (bilateral)

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42
Q

What is a cause of secondary hyperaldosteronism?

A

Renal artery stenosis

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43
Q

What are the possible causes of Addison’s disease?

A

Primary hypoadrenalism:
Rapidly stopping steroids (drugs)
Bleed, infection, autoimmunity

Secondary: Hypopituitarism

Tertiary: hypothalamic disease

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44
Q

What are the laboratory findings in Addison’s disease?

A

Hyperkalaemia
Hyponatraemia

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45
Q

How is Addison’s disease diagnosed?

A

Short ACTH stimulation test (i.e. the synacthen test)

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46
Q

What is the first catecholamine to be produced in the synthesis of catecholamines?

A

Dopamine

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47
Q

From what are catecholamines derived?

A

Tyrosine (the amino acid)

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48
Q

Into what are catecholamines degraded?

A

COMT
or
MAO

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49
Q

What blood finding is found in phaeochromocytoma?

A

Hyperglycaemia

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50
Q

Diagnosis of phaeochromocytoma is with 24 hour collection of urinary catecholamine - but which one?

A

Vanillylmandelic acid

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51
Q

What is an insulin antagonist?

A

Somatostatin

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52
Q

What are the physiological effects of progesterone?

A
  1. Increased respiratory drive
  2. Reduced bowel motility
  3. Increased basal body temperature
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53
Q

What endocrinological manifestation gives rise to the clinical manifestation of PCOS?

A

Elevated insulin - it is thought to be the insulin that stimulates androgen secretion

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54
Q

What are the stages of female puberty (and order)?

A

Growth spurt —>
Thelarche (breast development) —>
Adrenarche (pubic hair development) —>
Menarche

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55
Q

At what age is menarche considered precocious puberty?

A

If occurs prior to age 10

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56
Q

How frequently does GnRH pulse?

A

Every 90 minutes

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57
Q

What is the overall function of insulin?

A

Decreased gluconeogenesis

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58
Q

What is the function of GH?

A

Stimulate lipolysis

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59
Q

What hormones is GH structurally similar to?

A

Prolactin
hPL

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60
Q

Is plasma iodine concentration reduced or increased during early pregnancy?

A

Reduced

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61
Q

What is the function of hPL?

A

It enhances amino acid transfer across the placenta

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62
Q

How do you diagnose Cushing’s syndrome?

A

Low-dose dexamethasone suppression test

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63
Q

What electrolyte imbalance may be seen in Cushing’s?

A

Hypokalaemia (due to excess steroid)

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64
Q

To what is extracellular calcium bound?

A

Bicarbonate

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65
Q

What is the action of PTH on bone?

A

Stimulate osteoclasts, increasing bone resorption and therefore release of calcium

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66
Q

What is the action of PTH on kidneys?

A

Enhances resorption of calcium and magnesium from the distal tubule
Increases excretion of phosphate

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67
Q

What is the action of PTH on intestine?

A

Increases absorption of calcium by increasing vit D (CalciTRIOL) production

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68
Q

By what transport mechanism are calcium and phosphate transferred to the fetal circulation?

A

Active transport

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69
Q

When does the fetus begin to produce PTH?

A

Week 12

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70
Q

What happens to maternal PTH/calcitonin level in pregnancy?

A

PTH reduced
Calcitonin increased
Increases maternal stores
High Ca2+ requirement for foetal growth

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71
Q

Which hormones are secreted by the placenta?

A
  1. hCG
  2. Oestrogen
  3. Progesterone
  4. Relaxin
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72
Q

What is the function of calcitonin?

A

Inhibits renal reabsorption of calcium and phosphate;
Inhibits osteoclastic activity in bone

Decreases calcium
Decreases phosphate

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73
Q

When does the first cleavage division of the fertilised egg take place?

A

Approx. 30 hours after fertilisation

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74
Q

At what cell stage does the embryo enter the uterus from the fallopian tube?

A

8 cell stage

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75
Q

What are the characteristics of trophoblast cells?

A
  1. Paternal X chromosome inactivation
  2. Unmethylated DNA
  3. Ability to form multi-nucleated cells
  4. Variable expression of MHC1, no MHC2 antigen expression
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76
Q

What are the functions of the trophoblast cells?

A
  1. Attachment of the placenta to the uterine wall
  2. Transport of nutrients and maternal Ig’s
  3. Elimination of fetal waste
  4. Synthesis/secretion of hormones
  5. Barrier between maternal and fetal circulations
  6. Contact between maternal immune system and conceptus
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77
Q

What are the three stages of implantation?

A
  1. Apposition - when decidualisation takes place
  2. Adhesion - when the zona pellucida is destroyed
  3. Penetration - the trophoblast produces metalloproteases that digest the ECM, facilitating trophoblast invasion into the uterine decidua
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78
Q

What are the 2 layers of trophoblast?

A

Outer syncytiotrophoblast - where cellular walls are largely lost
Inner cytotrophoblast - where cell remain recognisibly individual

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79
Q

How many lobules are there to each placenta?

A

200

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80
Q

What does each placental lobule contain?

A

A single primary stem villus

81
Q

Until when does the placenta exceed the weight of the fetus?

A

Week 17

82
Q

By how many times does blood flow increase through the uterus in pregnancy?

A

10-15x

83
Q

In humans, where does the placental trophoblast encounter the maternal immune system?

A

The extravillous cytotrophoblast interacts with uterine tissue (decidua)
The villous syncytiotrophoblast is bathed in maternal blood

84
Q

How many ml of amniotic fluid is present at 8 weeks

A

15ml

85
Q

Where is the amnion situated?

A

Between the inner cell mass and the trophoblast (the chorion)

86
Q

How many layers are there to the amnion?

A

Inner cell mass
1. Cuboidal epithelium
2. Basement membrane
3. Compact layer
4. Fibroblast layer
5. Spongy layer of mucoid reticular tissue (remnant of extraembryonic coelom)
Chorion

87
Q

How many cells thick is the trophoblast layer?

A

2-10 cells thick

88
Q

How many layers are there in the chorion?

A
  1. Fibroblasts
  2. Reticular layer
  3. Basement membrane
  4. Trophoblast layer
89
Q

What hormones are hCG structurally similar to?

A

LH
FSH
TSH

90
Q

At what gestation does hCG peak?

A

Week 12

91
Q

What is the plasma half life of hPL?

A

15 minutes

92
Q

At what gestation does plasma concentration peak (and plateau) of hPL?

A

35/40

93
Q

How much does the pituitary gland weight/measure?

A

Pituitary gland weight = 0.5g
Pituitary weight dimensions = 10-15mm

94
Q

What are the divisions of the anterior pituitary?

A

Pars distalis
Pars tuberalis

95
Q

What are the divisions of the posterior pituitary?

A

Pars nervosa
Infundibular stalk/infundibulum
Median eminence

96
Q

What are the three types of hypothalamic neurosecretory cells?

A

Magnocellular neurons - release AVP or oxytocin

Hypophysiotropic neurons - release TRH, CRH, somatostatin, GHRH, GnRH and dopamine

Projection neurons

97
Q

What is another name for the anterior pituitary?

A

Adenohypophysis

98
Q

What is another name for the posterior pituitary?

A

Neurohypophysis

99
Q

What are the cell types of the adenohypophysis?

A

Acidophils
Basophils
Chromophobes

100
Q

Which nuclei are magnocellular neurons found in?

A

Supraoptic or paraventricular nuclei

101
Q

Which nuclei are hypophysiotropic neurons found in?

A

Paraventricular and arcuate nuclei

102
Q

Which nuclei are projection neurons found in?

A

Paraventricular and arcuate nuclei

103
Q

What is the embryological origin of the anterior pituitary?

A

Rathke pouch - an evagination of ectodermal cells of the oropharynx in the primitive gut

104
Q

At what gestation does the anterior pituitary become recognisable?

A

Weeks 4-5

105
Q

What are craniopharyngiomas?

A

Tumours that occur when cells of the Rathke persist

106
Q

What is the embryological origin of the posterior pituitary?

A

Neural crest cells

107
Q

From what cell type is GH synthesised/secreted?

A

Somatotrophs

108
Q

What inhibits GH secretion?

A

Somatostatin

109
Q

What is the half life of GH in the circulation?

A

20 mins

110
Q

How many pulses of GH are secreted in a 24 hour period?

A

x5/24 hours

111
Q

From what cells type is prolactin synthesised/secreted?

A

Lactotroph

112
Q

What inhibits prolactin secretion?

A

Dopamine and somatostatin

113
Q

From what cell type are FSH and LH secreted?

A

Gonadotrophs

114
Q

What is the earliest sign of puberty in boys?

A

An increase in testicular volume by 4ml, or 2.5cm

115
Q

When is puberty considered precocious?

A

In girls, before the age of 8
In boys, before the age of 9

116
Q

What is the most common cause of acromegaly?

A

GH producing pituitary macroadenoma

117
Q

What is the size of a macroadenoma?

A

> 10mm

118
Q

What is the size of a microadenoma?

A

<10mm

119
Q

What is central diabetes insipidus?

A

Decreased secretion of AVP (ADH) from the hypothalamus

120
Q

What is nephrogenic diabetes insipidus?

A

Resistance to AVP (ADH) in the kidney

121
Q

What is lymphocytic hypophysitis?

A

An inflammatory/autoimmune condition of the pituitary/pituitary stalk. Its clinical presentation mimics that of a pituitary adenoma

122
Q

What are secondary causes of lymphocytic hypophysitis?

A

Sarcoidosis
Tuberculosis
Langerhans cell granulomatosis
Wegener’s granulomatosis
IgG-IV-related hypophysitis

123
Q

What is the arterial supply of the adrenal glands?

A

Inferior phrenic artery, renal artery, aorta

124
Q

What are the roles of ACTH in terms of steroid synthesis?

A
  1. Increase in cholesterol esterase
  2. Transport of cholesterol into the mitochondria
  3. Binding of cholesterol to CYP11A1
125
Q

What is the half-life of catecholamines?

A

1-2 minutes

126
Q

Catecholamine receptors work by which mechanism?

A

G-protein-linked membrane receptors

127
Q

What medications are used for Cushing’s disease?

A

Somatostatin analogues - e.g. pasireotide
Adrenal steroid inhibitors

128
Q

What is another name for hyperaldosteronism?

A

Conn’s syndrome

129
Q

How is Conn’s syndrome diagnosed?

A

Random plasma aldosterone/plasma renin activity (PRA) ratio

130
Q

What are the 3 syndromes that are classically associated with pheochromocytoma?

A

VHL syndrome
MEN2
NF1

131
Q

What is the usual preoperative treatment for pheochromocytoma?

A

Alpha-adrenergic blockade

132
Q

What hormones are produced by the thyroid?

A

T3
T4
Calcitonin

133
Q

What causes increased SHBG?

A
  1. OCP
  2. Pregnancy
  3. Hyperthyroidism
  4. Liver cirrhosis
  5. Anorexia
  6. AEDs
134
Q

What causes decreased SHBG?

A
  1. Androgens
  2. PCOS
  3. Hypothyroidism
  4. Obesity
  5. Cushing’s
  6. Acromegaly
135
Q

What proportion of cases of HTN are caused by pheochromocytoma?

A

0.1%

136
Q

What causes elevated aldosterone?

A

Hyperkalaemia

  1. Reduced circulating volumes
  2. Pregnancy
  3. Loop diuretics
  4. Conn’s syndrome
137
Q

Where in females are androgens produced?

A

Ovary = 25%
Adrenal glands = 25%
Peripheral conversion of androstenedione = 50%

138
Q

Which is the most active oestrogen of the natural oestrogens?

A

Estradiol

139
Q

In what form does the kidney excrete oestrogen?

A

Estriol glucuronide

140
Q

Where in the body is progesterone stored?

A

Adipose tissue

141
Q

In plasma what does progesterone bind to?

A

Corticosteroid-binding globulin - CBG
Albumin

142
Q

What are the pre-ovulatory levels of progesterone?

A

<2ng/ml

143
Q

What are the post-ovulatory levels of progesterone?

A

5ng/ml

144
Q

What is the term level of progesterone?

A

100-250ng/ml

145
Q

At term how much progesterone is produced by the placenta?

A

250mg/day

146
Q

What inhibits lactation, and prevent uterine contraction until term?

A

Progesterone

147
Q

In whom is SHBG levels higher - males or females?

A

Females

148
Q

What are the hypothalamic nuclei?

A

Arcuate nuclei
Pre-optic nuclei
Peri-ventricular nuclei
Paraventricular nuclei
Supraoptic nuclei

149
Q

What hormones are produced in the paraventricular nuclei?

A

Post pit:
Oxytocin

Ant pit:
CRH (corticotropin - )
TRH (Thyrotropin - )

150
Q

What hormones are produced in the supraoptic and paraventricular nuclei?

A

ADH (more supraoptic)
Oxytocin (more PV)

151
Q

What hormones are produced in the arcuate nuclei?

A

Dopamine
GNRH

152
Q

What hormones are produced in the pre-optic nuclei?

A

GRH

153
Q

What hormone is produced in the peri-ventricular nuclei?

A

Somatostatin

154
Q

What hormone stimulates the release of prolactin?

A

TRH - thyrotropin releasing hormone

155
Q

Where are the only place FSH receptors are found?

A

Granulosa cells

156
Q

Which hormone is responsible for resumption of meiosis by the oocyte?

A

LH

157
Q

What are the causes of hypoprolactinaemia?

A

Pharmacological - dopamine agonists
Pathological - Sheehan’s syndrome, hypopituitarism, bulimia

158
Q

What are the physiological causes of hyperprolactinaemia?

A

Pregnancy
Lactation
Exercise
Stress

159
Q

What are the pharmacological causes of hyperprolactinaemia

A

TRH
Oesotrogen
Dopamine antagonists
Verapamil
Cimetidine

160
Q

What are the pathological causes of hyperprolactinaemia?

A

Pituitary tumour
Chest wall lesions
Spinal cord lesions
Liver failure
Chronic renal failure

161
Q

How much T4 is produced relative to T3?

A

20x more

162
Q

What is T3 formed form?

A

MIT (I2 + tyrosine) + DIT (MIT + I2)

163
Q

What is T4 formed from?

A

DIT + DIT

164
Q

When does adrenal androgen production begin in males/females?

A

Males = 7-9 years old
Females = 6-7 years old

165
Q

What are the components of the juxtaglomerular apparatus?

A

Juxtaglomerular cells of the afferent arterioles
Macula densa (cells of the ascending loop of Henle)

166
Q

What are the functions of angiotensins?

A

Vasoconstriction
Stimulates aldosterone secretion

167
Q

What are the functions of aldosterone?

A

Resorption of Na+ from the DCT and collecting ducts
Excretion of H+ and K+ from the kidneys
Acts on the posterior pituitary to release ADH

168
Q

What antagonises insulin?

A

Glucagon
Cortisol
GH
Adrenaline
Oestrogen
Thyroid hormone
Prolactin
hPL

169
Q

What are the sizes of a micro-/macro-prolactinoma?

A

Micro = <10mm
Macro = >10mm

170
Q

When does the growth spurt in boys begin relative to girls?

A

2 years later

171
Q

When is the bone mineralization in boys/girls respectively?

A

Boys = 17.5 years old
Girls = 14-16 years old

172
Q

Which tumours secrete hCG

A

Choriocarcinoma
Germ cell tumour
Hydatiform mole

173
Q

How does the fetus trigger parturition?

A

Fetal pituitary releases corticotrophin

Corticoptrophin causes fetal adrenals to release cortisol and DHEAS

Fetal cortisol causes increased oestrogen production and formation of oxytocin receptors

DHEAS also leads to increased oestrogen

Increased oestrogen releases prostaglandin F2-alpha, causing myometrial contraction

174
Q

What is the ferguson reflex?

A

Neuronal reflex triggered by pressure application to the cervix and vagina

175
Q

When do menses return after pregnancy?

A

Breastfeeding women = 28 weeks postpartum
Non-breast feeding women = 9 weeks postpartum

176
Q

What are the conditions of lactational amenorrhoea being reliable?

A

Baby exclusively breast-fed - intervals between feeding no longer than 5 hours
<6/12 postpartum

177
Q

How reliable is lactational amenorrhoea is used correctly?

A

98%

178
Q

What is colostrum rich in?

A

Vitmain A
Lactoferrin
IgA
Sodium

179
Q

When is colostrum produced and how much of it?

A

Secreted for the first 3-5 days at 100ml/day

180
Q

When does steroidogenesis start in the fetus?

A

7 weeks

181
Q

When are the testes seen in the fetus?

A

6 weeks

182
Q

When are the ovaries seen in the fetus?

A

7-8 weeks

183
Q

When does testosterone production begin in the fetus?

A

10 weeks

184
Q

When does oestrogen production begin in the fetus?

A

20 weeks

185
Q

In what form does the kidney excrete progesterone?

A

Pregnanediol glucuronide

186
Q

Which hormones stimulate DUCTAL morphogenesis of the breast?

A

Oestrogen and GH

187
Q

Which hormones stimulate ALVEOLAR morphogenesis of the breast?

A

Progesterone, prolactin, hPL

188
Q

In what chromosome are there defects to cause beta or delta thalassaemia?

A

Chromosome II

189
Q

How does the LH surge at ovulation cause rupture of the mature oocyte?

A

Acts on theca externa

190
Q

What is the incidence of pheochromocytoma in pregnancy?

A

1/50,000 pregnancies

191
Q

What is the most common cause of hypothyroidism world-wide?

A

Iodine deficiency

192
Q

What are the immunological features of Hashimoto’s thyroiditis?

A

Antibodies against thyroid peroxidase and thyroglobulin

193
Q

When is fetal TSH and T4 first detectable?

A

Week 10

194
Q

What happens if neonatal hypothyroidism is not identified and treated?

A

Mental and developmental restriction

195
Q

What may be the dose increase of levothyroxine in pregnancy?

A

30+%

196
Q

In women with thyroid nodules, whom should have FNA?

A
  1. Nodules >1cm
  2. Enlarging nodules
  3. Nodules associated with palpable cervical lymph nodes
197
Q

What is the molecular weight of insulin?

A

6000 Dalton

198
Q

What is the early vs. late insulin response to glucose due to?

A

Early response (w/in 30 mins) = neuronal response
Later response = due to blood concentration

199
Q

What is the receptor for insulin?

A

Tyrosine kinase - 2 alpha and 2 beta subunits held by a disulphide bond