Original Endocrinology (main) Flashcards
(199 cards)
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
2
Q
Where are ADH and oxytocin synthesised?
A
Hypothalamus
3
Q
Where are ADH and oxytocin stored?
A
Posterior pituitary
4
Q
What stimulates glucagon?
A
Hypoglycemia
Epinephrine
Cholecystokinin
Acetylcholine
Arginine
Alanine
5
Q
What inhibits glucagon?
A
Somatostatin
Insulin
Uraemia
Increased free fatty acids and keto acids into the blood
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
7
Q
What inhibits TSH?
A
Somatostatin
8
Q
What hormones are produced by the medulla of the adrenals?
A
Epinephrine
Dopamine
Norepinephrine
9
Q
What is produced by the zona glomerulosa?
A
Aldosterone
10
Q
What is produced by the zona fasciculata?
A
Cortisol
11
Q
What is produced by the zona reticularis?
A
Androgens
12
Q
What is a typical FBC finding in Addison’s disease?
A
Eosinophillia and lymphocytosis
13
Q
What hormones does somatostatin inhibit?
A
Insulin
Glucagon
Growth Hormone
Gastrin
Cholecystokinin (CCK)
Secretin
Vasoactive intestinal peptide (VIP)
Gastric inhibitory polypeptide (GIP)
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
15
Q
In what proportion of children does delayed puberty occur?
A
3%
16
Q
What are 2 recognised galactagogues (stimulators of milk production)?
A
- Domperidone
- Metoclopramide
17
Q
What is maternal flow through the uterine artery at term?
A
750ml/min
18
Q
What is flow through the uterine artery when not pregnant?
A
45ml/min
19
Q
What are the 3 types of oestrogen?
A
Estrone (E1)
Estradiol (E2)
Estriol (E3)
20
Q
What is the predominant oestrogen during female reproductive years?
A
Estradiol (except in the early follicular phase when estrone predominantes)
21
Q
What is the predominant oestrogen during pregnancy?
A
Estriol
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
23
Q
What are the ratios of testosterone free:albumin-bound:SHBG-bound?
A
1% free: 19% albumin-bound: 80% SHBG-bound
24
Q
Which cells are responsible for androgen production in the ovary?
A
Theca cells
25
Which cell are responsible for aromatisation of androgens into oestrogen?
Granulosa cells
26
Where are the juxtaglomerular cells located?
Afferent arteriole in the kidney
27
What is leptin release from adipose tissue stimulated by?
Glucocorticoids
High BMI
Long-term hyperinsulinaemia
Excessive food ingestion
28
What is the most common cause of delayed puberty?
Constitutional delay
29
What is the definition of puberty in women?
Physical maturation whereby the women becomes capable of sexual reproduction
30
What is the lifespan of the corpus luteum?
14 days
31
How many hours after the LH surge does ovulation occur?
24-36 hours
32
Where is calcidiol produced?
Liver
33
During pregnancy, from where is bHG produced?
Syncytiotrophoblast
34
At what gestation does the fetal endocrinological system become fully active?
10/40
35
What tumour marker is used for granulosa cell tumours?
Inhibin
36
When does the corpus luteum cease to be essential in maintaining a pregnancy?
6/40
37
What blood abnormalities would you see in Cushing's of different origin, i.e. how do you tell the difference?
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
38
Where does ADH act? And what does it do?
Acts on the distal tubule
Increases water resorption via insertion of aquaporins
39
What are the acquired forms of nephrogenic diabetes insipidus (when the kidney becomes unresponsive to ADH)?
Chronic Renal Failure
Hypokalaemia
Lithium Toxicity
Pregnancy
Hydronephrosis
40
What are the features of hyperaldosteronism?
Hypertension
Hypokalaemia
Alkalosis
41
What are the causes of primary hyperaldosteronism?
Adrenal adenoma (unilateral, common)
Adrenal hyperplasia (bilateral)
42
What is a cause of secondary hyperaldosteronism?
Renal artery stenosis
43
What are the possible causes of Addison's disease?
Primary hypoadrenalism:
Rapidly stopping steroids (drugs)
Bleed, infection, autoimmunity
Secondary: Hypopituitarism
Tertiary: hypothalamic disease
44
What are the laboratory findings in Addison's disease?
Hyperkalaemia
Hyponatraemia
45
How is Addison's disease diagnosed?
Short ACTH stimulation test (i.e. the synacthen test)
46
What is the first catecholamine to be produced in the synthesis of catecholamines?
Dopamine
47
From what are catecholamines derived?
Tyrosine (the amino acid)
48
Into what are catecholamines degraded?
COMT
or
MAO
49
What blood finding is found in phaeochromocytoma?
Hyperglycaemia
50
Diagnosis of phaeochromocytoma is with 24 hour collection of urinary catecholamine - but which one?
Vanillylmandelic acid
51
What is an insulin antagonist?
Somatostatin
52
What are the physiological effects of progesterone?
1. Increased respiratory drive
2. Reduced bowel motility
3. Increased basal body temperature
53
What endocrinological manifestation gives rise to the clinical manifestation of PCOS?
Elevated insulin - it is thought to be the insulin that stimulates androgen secretion
54
What are the stages of female puberty (and order)?
Growth spurt --->
Thelarche (breast development) --->
Adrenarche (pubic hair development) --->
Menarche
55
At what age is menarche considered precocious puberty?
If occurs prior to age 10
56
How frequently does GnRH pulse?
Every 90 minutes
57
What is the overall function of insulin?
Decreased gluconeogenesis
58
What is the function of GH?
Stimulate lipolysis
59
What hormones is GH structurally similar to?
Prolactin
hPL
60
Is plasma iodine concentration reduced or increased during early pregnancy?
Reduced
61
What is the function of hPL?
It enhances amino acid transfer across the placenta
62
How do you diagnose Cushing's syndrome?
Low-dose dexamethasone suppression test
63
What electrolyte imbalance may be seen in Cushing's?
Hypokalaemia (due to excess steroid)
64
To what is extracellular calcium bound?
Bicarbonate
65
What is the action of PTH on bone?
Stimulate osteoclasts, increasing bone resorption and therefore release of calcium
66
What is the action of PTH on kidneys?
Enhances resorption of calcium and magnesium from the distal tubule
Increases excretion of phosphate
67
What is the action of PTH on intestine?
Increases absorption of calcium by increasing vit D (CalciTRIOL) production
68
By what transport mechanism are calcium and phosphate transferred to the fetal circulation?
Active transport
69
When does the fetus begin to produce PTH?
Week 12
70
What happens to maternal PTH/calcitonin level in pregnancy?
PTH reduced
Calcitonin increased
Increases maternal stores
High Ca2+ requirement for foetal growth
71
Which hormones are secreted by the placenta?
1. hCG
2. Oestrogen
3. Progesterone
4. Relaxin
72
What is the function of calcitonin?
Inhibits renal reabsorption of calcium and phosphate;
Inhibits osteoclastic activity in bone
Decreases calcium
Decreases phosphate
73
When does the first cleavage division of the fertilised egg take place?
Approx. 30 hours after fertilisation
74
At what cell stage does the embryo enter the uterus from the fallopian tube?
8 cell stage
75
What are the characteristics of trophoblast cells?
1. Paternal X chromosome inactivation
2. Unmethylated DNA
3. Ability to form multi-nucleated cells
4. Variable expression of MHC1, no MHC2 antigen expression
76
What are the functions of the trophoblast cells?
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
77
What are the three stages of implantation?
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
78
What are the 2 layers of trophoblast?
Outer syncytiotrophoblast - where cellular walls are largely lost
Inner cytotrophoblast - where cell remain recognisibly individual
79
How many lobules are there to each placenta?
200
80
What does each placental lobule contain?
A single primary stem villus
81
Until when does the placenta exceed the weight of the fetus?
Week 17
82
By how many times does blood flow increase through the uterus in pregnancy?
10-15x
83
In humans, where does the placental trophoblast encounter the maternal immune system?
The extravillous cytotrophoblast interacts with uterine tissue (decidua)
The villous syncytiotrophoblast is bathed in maternal blood
84
How many ml of amniotic fluid is present at 8 weeks
15ml
85
Where is the amnion situated?
Between the inner cell mass and the trophoblast (the chorion)
86
How many layers are there to the amnion?
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
How many cells thick is the trophoblast layer?
2-10 cells thick
88
How many layers are there in the chorion?
1. Fibroblasts
2. Reticular layer
3. Basement membrane
4. Trophoblast layer
89
What hormones are hCG structurally similar to?
LH
FSH
TSH
90
At what gestation does hCG peak?
Week 12
91
What is the plasma half life of hPL?
15 minutes
92
At what gestation does plasma concentration peak (and plateau) of hPL?
35/40
93
How much does the pituitary gland weight/measure?
Pituitary gland weight = 0.5g
Pituitary weight dimensions = 10-15mm
94
What are the divisions of the anterior pituitary?
Pars distalis
Pars tuberalis
95
What are the divisions of the posterior pituitary?
Pars nervosa
Infundibular stalk/infundibulum
Median eminence
96
What are the three types of hypothalamic neurosecretory cells?
Magnocellular neurons - release AVP or oxytocin
Hypophysiotropic neurons - release TRH, CRH, somatostatin, GHRH, GnRH and dopamine
Projection neurons
97
What is another name for the anterior pituitary?
Adenohypophysis
98
What is another name for the posterior pituitary?
Neurohypophysis
99
What are the cell types of the adenohypophysis?
Acidophils
Basophils
Chromophobes
100
Which nuclei are magnocellular neurons found in?
Supraoptic or paraventricular nuclei
101
Which nuclei are hypophysiotropic neurons found in?
Paraventricular and arcuate nuclei
102
Which nuclei are projection neurons found in?
Paraventricular and arcuate nuclei
103
What is the embryological origin of the anterior pituitary?
Rathke pouch - an evagination of ectodermal cells of the oropharynx in the primitive gut
104
At what gestation does the anterior pituitary become recognisable?
Weeks 4-5
105
What are craniopharyngiomas?
Tumours that occur when cells of the Rathke persist
106
What is the embryological origin of the posterior pituitary?
Neural crest cells
107
From what cell type is GH synthesised/secreted?
Somatotrophs
108
What inhibits GH secretion?
Somatostatin
109
What is the half life of GH in the circulation?
20 mins
110
How many pulses of GH are secreted in a 24 hour period?
x5/24 hours
111
From what cells type is prolactin synthesised/secreted?
Lactotroph
112
What inhibits prolactin secretion?
Dopamine and somatostatin
113
From what cell type are FSH and LH secreted?
Gonadotrophs
114
What is the earliest sign of puberty in boys?
An increase in testicular volume by 4ml, or 2.5cm
115
When is puberty considered precocious?
In girls, before the age of 8
In boys, before the age of 9
116
What is the most common cause of acromegaly?
GH producing pituitary macroadenoma
117
What is the size of a macroadenoma?
>10mm
118
What is the size of a microadenoma?
<10mm
119
What is central diabetes insipidus?
Decreased secretion of AVP (ADH) from the hypothalamus
120
What is nephrogenic diabetes insipidus?
Resistance to AVP (ADH) in the kidney
121
What is lymphocytic hypophysitis?
An inflammatory/autoimmune condition of the pituitary/pituitary stalk. Its clinical presentation mimics that of a pituitary adenoma
122
What are secondary causes of lymphocytic hypophysitis?
Sarcoidosis
Tuberculosis
Langerhans cell granulomatosis
Wegener's granulomatosis
IgG-IV-related hypophysitis
123
What is the arterial supply of the adrenal glands?
Inferior phrenic artery, renal artery, aorta
124
What are the roles of ACTH in terms of steroid synthesis?
1. Increase in cholesterol esterase
2. Transport of cholesterol into the mitochondria
3. Binding of cholesterol to CYP11A1
125
What is the half-life of catecholamines?
1-2 minutes
126
Catecholamine receptors work by which mechanism?
G-protein-linked membrane receptors
127
What medications are used for Cushing's disease?
Somatostatin analogues - e.g. pasireotide
Adrenal steroid inhibitors
128
What is another name for hyperaldosteronism?
Conn's syndrome
129
How is Conn's syndrome diagnosed?
Random plasma aldosterone/plasma renin activity (PRA) ratio
130
What are the 3 syndromes that are classically associated with pheochromocytoma?
VHL syndrome
MEN2
NF1
131
What is the usual preoperative treatment for pheochromocytoma?
Alpha-adrenergic blockade
132
What hormones are produced by the thyroid?
T3
T4
Calcitonin
133
What causes increased SHBG?
1. OCP
2. Pregnancy
3. Hyperthyroidism
4. Liver cirrhosis
5. Anorexia
6. AEDs
134
What causes decreased SHBG?
1. Androgens
2. PCOS
3. Hypothyroidism
4. Obesity
5. Cushing's
6. Acromegaly
135
What proportion of cases of HTN are caused by pheochromocytoma?
0.1%
136
What causes elevated aldosterone?
Hyperkalaemia
1. Reduced circulating volumes
2. Pregnancy
3. Loop diuretics
4. Conn's syndrome
137
Where in females are androgens produced?
Ovary = 25%
Adrenal glands = 25%
Peripheral conversion of androstenedione = 50%
138
Which is the most active oestrogen of the natural oestrogens?
Estradiol
139
In what form does the kidney excrete oestrogen?
Estriol glucuronide
140
Where in the body is progesterone stored?
Adipose tissue
141
In plasma what does progesterone bind to?
Corticosteroid-binding globulin - CBG
Albumin
142
What are the pre-ovulatory levels of progesterone?
<2ng/ml
143
What are the post-ovulatory levels of progesterone?
5ng/ml
144
What is the term level of progesterone?
100-250ng/ml
145
At term how much progesterone is produced by the placenta?
250mg/day
146
What inhibits lactation, and prevent uterine contraction until term?
Progesterone
147
In whom is SHBG levels higher - males or females?
Females
148
What are the hypothalamic nuclei?
Arcuate nuclei
Pre-optic nuclei
Peri-ventricular nuclei
Paraventricular nuclei
Supraoptic nuclei
149
What hormones are produced in the paraventricular nuclei?
Post pit:
Oxytocin
Ant pit:
CRH (corticotropin - )
TRH (Thyrotropin - )
150
What hormones are produced in the supraoptic and paraventricular nuclei?
ADH (more supraoptic)
Oxytocin (more PV)
151
What hormones are produced in the arcuate nuclei?
Dopamine
GNRH
152
What hormones are produced in the pre-optic nuclei?
GRH
153
What hormone is produced in the peri-ventricular nuclei?
Somatostatin
154
What hormone stimulates the release of prolactin?
TRH - thyrotropin releasing hormone
155
Where are the only place FSH receptors are found?
Granulosa cells
156
Which hormone is responsible for resumption of meiosis by the oocyte?
LH
157
What are the causes of hypoprolactinaemia?
Pharmacological - dopamine agonists
Pathological - Sheehan's syndrome, hypopituitarism, bulimia
158
What are the physiological causes of hyperprolactinaemia?
Pregnancy
Lactation
Exercise
Stress
159
What are the pharmacological causes of hyperprolactinaemia
TRH
Oesotrogen
Dopamine antagonists
Verapamil
Cimetidine
160
What are the pathological causes of hyperprolactinaemia?
Pituitary tumour
Chest wall lesions
Spinal cord lesions
Liver failure
Chronic renal failure
161
How much T4 is produced relative to T3?
20x more
162
What is T3 formed form?
MIT (I2 + tyrosine) + DIT (MIT + I2)
163
What is T4 formed from?
DIT + DIT
164
When does adrenal androgen production begin in males/females?
Males = 7-9 years old
Females = 6-7 years old
165
What are the components of the juxtaglomerular apparatus?
Juxtaglomerular cells of the afferent arterioles
Macula densa (cells of the ascending loop of Henle)
166
What are the functions of angiotensins?
Vasoconstriction
Stimulates aldosterone secretion
167
What are the functions of aldosterone?
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
What antagonises insulin?
Glucagon
Cortisol
GH
Adrenaline
Oestrogen
Thyroid hormone
Prolactin
hPL
169
What are the sizes of a micro-/macro-prolactinoma?
Micro = <10mm
Macro = >10mm
170
When does the growth spurt in boys begin relative to girls?
2 years later
171
When is the bone mineralization in boys/girls respectively?
Boys = 17.5 years old
Girls = 14-16 years old
172
Which tumours secrete hCG
Choriocarcinoma
Germ cell tumour
Hydatiform mole
173
How does the fetus trigger parturition?
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
What is the ferguson reflex?
Neuronal reflex triggered by pressure application to the cervix and vagina
175
When do menses return after pregnancy?
Breastfeeding women = 28 weeks postpartum
Non-breast feeding women = 9 weeks postpartum
176
What are the conditions of lactational amenorrhoea being reliable?
Baby exclusively breast-fed - intervals between feeding no longer than 5 hours
<6/12 postpartum
177
How reliable is lactational amenorrhoea is used correctly?
98%
178
What is colostrum rich in?
Vitmain A
Lactoferrin
IgA
Sodium
179
When is colostrum produced and how much of it?
Secreted for the first 3-5 days at 100ml/day
180
When does steroidogenesis start in the fetus?
7 weeks
181
When are the testes seen in the fetus?
6 weeks
182
When are the ovaries seen in the fetus?
7-8 weeks
183
When does testosterone production begin in the fetus?
10 weeks
184
When does oestrogen production begin in the fetus?
20 weeks
185
In what form does the kidney excrete progesterone?
Pregnanediol glucuronide
186
Which hormones stimulate DUCTAL morphogenesis of the breast?
Oestrogen and GH
187
Which hormones stimulate ALVEOLAR morphogenesis of the breast?
Progesterone, prolactin, hPL
188
In what chromosome are there defects to cause beta or delta thalassaemia?
Chromosome II
189
How does the LH surge at ovulation cause rupture of the mature oocyte?
Acts on theca externa
190
What is the incidence of pheochromocytoma in pregnancy?
1/50,000 pregnancies
191
What is the most common cause of hypothyroidism world-wide?
Iodine deficiency
192
What are the immunological features of Hashimoto's thyroiditis?
Antibodies against thyroid peroxidase and thyroglobulin
193
When is fetal TSH and T4 first detectable?
Week 10
194
What happens if neonatal hypothyroidism is not identified and treated?
Mental and developmental restriction
195
What may be the dose increase of levothyroxine in pregnancy?
30+%
196
In women with thyroid nodules, whom should have FNA?
1. Nodules >1cm
2. Enlarging nodules
3. Nodules associated with palpable cervical lymph nodes
197
What is the molecular weight of insulin?
6000 Dalton
198
What is the early vs. late insulin response to glucose due to?
Early response (w/in 30 mins) = neuronal response
Later response = due to blood concentration
199
What is the receptor for insulin?
Tyrosine kinase - 2 alpha and 2 beta subunits held by a disulphide bond
