endocrinology Flashcards
(146 cards)
1
Q
mechanism of action of thionamides
A
stop TPO production so stop T3/4 secretion
2
Q
mechanism of action of KI
A
presumed autoregulatory effect - wolff chaikoff effect
stops iodination of TG
stop TPOH2O2 production so stop thyroid hormone secretion
3
Q
how long does it take for biochemical and for clinical effects of thionamides to show
A
biochemical effects: hours
clinical effects: weeks
4
Q
2 side effects of thionamides
A
agranulocytosis
rashes
5
Q
which hyperthyoid conditions present with pain in gland area
A
viral thyroiditis
toxic nodular goitre (plummers)
6
Q
which cells produce calcitonin
A
thyroid parafollicular cells
7
Q
which hormone in the Vitamin D pathway regulates its own synthesis and how does it do it
A
1,25 (OH)2 cholecalciferol
regulates its own synthesis by decreasing transcription of 1 alpha hydroxylase
8
Q
what effect does vitamin D have on bones
A
increases osteoBlast activity
9
Q
what effect does PTH have on bones
A
increases osteoClast activity - increases calcium mobilisation
10
Q
what effects does PTH have on the kidney
A
1) increases calcium reabsorption
2) increases phosphate excretion –> by inhibiting the Na+/PO4 3- co transporter
3) increases 1 alpha hydroxylase production
–> increases 1,25 (OH)2 cholecalciferol production
–> acts on gut to increase calcium and phosphate absorption
11
Q
what is the role of the Na+/PO4 3- co transporter and which part of the nephron is it
A
increases sodium and phosphate reabsorption / decreases excretion
found in proximal convoluted tubule
12
Q
how does FGF23 regulate phosphate levels
A
inhibits sodium phosphate co transport in the proximal convoluted tubule –> increases phosphate (and sodium) excretion
inhibits calcitriol/vit D –> decreases phosphate absorption in gut
13
Q
give 4 causes of low vitamin D
A
diet
malabsorption
lack of UV light
production issues - renal failure
14
Q
4 causes of low PTH
A
surgical
autoimmune
congenital
Magnesium deficiency
15
Q
what effect does hyeprcalcaemia have on muscles and why
A
atonal muscles
due to reduced neuronal excitability
16
Q
causes of hypercalcaemia
A
1) primary hyperparathyroidism eg parathyroid adenoma
2) malignancy
- bony metastases: factors released activate osteoclasts
- certain cancers eg squamous cell carcinoma release PTH-related peptide
3) vitamin D excess - rare
17
Q
primary hyperparathyroidism
A
parathyroid adenoma - high PTH
calcium rises as a result
but no negative feedback as parathyroid gland is just autonomously secreting high levels of PTH
so end up with high PTH and high Calcium
18
Q
secondary hyperparathyroidism
A
low calcium (usually due to vitamin D deficiency - diet, UV, malabsorption, renal failure) and so PTH levels rise as a result
19
Q
treatment for secondary hypoparathyroidism for someone with and without renal failure
A
without renal failure:
ergocalciferol - 25 hydroxy vitamin D2
cholecalciferol - 25 hydroxy vitamin D3
with renal failure (can’t produce 1 alpha hydroxylase so have to just give them active from of vitamin D):
Alfacalcidol - 1 alpha hydroxycholecalciferol (active vit D analogue)
20
Q
treatment of primary hyperparathyrodism
A
parathyroidectomy
21
Q
treatment of tertiary hyperparathyrodism
A
parathyroidectomy
22
Q
what is tertiary hyperpararthyoidism
A
happens in chronic renal failure
get chronic vitamin D deficiency therefore low calcium
as a result, parathyroid gland secretes more and more PTH, enlarging as a result
the gland hyperplasia causes autonomous PTH secretion, causing hypercalcaemia
(initial part is like secondary hyperparathyroidism, but then get autonomous secretion from gland and high calcium)
23
Q
a patient is suffering from severe vomiting as a result of hypercalcaemia of malignancy, what is the initial treatment plan
A
1) rehydrate with IV fluids - for the vomiting
2) give bisphosphontaes - for the hypercalcaemia
24
Q
what is the diagnosis if PTH is low and calcium is high
A
hypercalcaemia of malignancy
24
what is the diagnosis if PTH is low and calcium is high
hypercalcaemia of malignancy
25
what is the diagnosis if PTH is high, calcium is high and renal function is normal
primary hyperparathyroidism
26
what is the diagnosis if PTH is high, calcium is high and renal function is abnormal
tertiary hyperparathyroidism
27
a patient presents with pain passing urine, haematuria, high PTH, high calcium, normal vit D, low phosphate
what is diagnosis
primary hypoparathyroidism
bc have high PTH and high calcium
--> if vit D was low would have been tertiary hypoparathyroidism
28
what is the name of the neurones carrying AVP and oxytocin to the posterior pituitary, and where do they originate
magnocellular neurones
originate in supraoptic and paraventricular nuclei hypothalamic nuclei
29
contrast the actions of vasopressin when it works on V1 vs V2 receptor
V1: vasoconstriction
V2: increases water reabsorption from collecting duct
30
describe how a haemorrhage would result in less inhibition of VAP
haemorrhage = loss of blood volume
therefore less stretch of/pressure in right atrium
therefore less stimulation of stretch receptors
therefore less inhibition of AVP release via vagal afferents by stretch receptors
31
describe why AVP needs to be released after a haemorrhage
acts on V1 to cause vasoconstriction - increase bp
acts on V2 to increase water reabsorption 0 increase bp
32
what are the two types of stimuli for AVP release
osmotic and non osmotic
33
describe osmotic simulation of AVP release
subfornical organ and organum vasculosum are osmoreceptors
-->they are circumventricular structures meaning that they are highly vascularised, lie around the 3rd ventricle, and do not have a BBB - so can respond to changes in systemic circulation
when there is an increase in extracellular osmolarity/sodium, water leaves the osmoreceptors causing them to shrink
this causes their firing rate to increase
their neurones project to the supraoptic nucleus in the hypothalamic nucleus, so their firing stimulates the release of AVP
34
describe non osmotic stimulation of AVP release
increase in pressure in right atrium is detected by atrial stretch receptors
the atrial stretch receptors inhibit AVP release via vagal afferents to the hypothalamus
35
is glucose normal or abnormal in diabetes insipidus
normal
36
what should you always check in pateints with polyuria, nocturia, polydipsia and thirst - and why
glucose
if its normal it could be diabetes insipidus
if its abnormal it could be diabetes mellitus
37
why do patients with diabetes insipidus feel thirst
they produce large volumes of dilute urine so plasma is hyper osmolar
this is detected by osmoreceptors which stimulate feeling of thirst
38
congenital and acquired causes of nephrogenic diabetes insipidness
congenital: mutations in AVP/AQP2
acquired: drugs - lithium
39
how to distinguish between pschogenic polydipsia and diabetes insipidus
water deprivation test - test osmolarity of urine under water deprivation to see if body is conserving water in body or not
40
cranial DI treatment
desmopressin (like vasopressin but is selective for V2 receptor)
41
distinguishing between cranial and nephrogenic DI
give ddAVP under water deprivation and measure urine osmolarity
42
pt has a BMI of 19 and low FSH and LH, with amenhorrea, what is the diagnosis and treatment
hypogonadotrophic hypogonadism
lifestyle changes
43
what is the treatment for POI to help with fertility
IVF --> stimulates the ovaries using gonadotrophs
44
why would HRT not help with fertility due to POI
HRT is a combination of oestrogen and progesterone
this would help with symptoms but not with infertility as it doesn't contain gonadotrophs LH/FSH --> so does cause ovulation
45
treatment for hyperprolactinaemia
dopamin agonsit: carbergoline
or
surgery
46
what is infertility definition
inability to achieve clinical pregnancy after 12 months or more of unprotected regular (every 2-3 days) sexual intercourse
47
list the post testicular causes of male infertility
obstructive azoospermia
erectile dysfunction
- mechanical
- retrograde ejaculation
- pscyhological
iatrogenic
- vasectomy
congenital
- absence of vas deferent in cystic fibrosis
48
what is cyrptorchidism and what kind of infertility does it cause
undescended testes - causes acquired primary hypogonadism
(bc it doesn't cause hypogonadism straight away, only if left untreated)
49
what is endometriosis and what are the symptoms
endometrial tissue found outside the uterus which responds to progesterone
menstrual pain
deep dyspareunia
infertility
menstrual irregularities
50
what are fibroids
benign tumours of the myometrium which respond to oestrogen
51
list the hypothalamic endocrine causes of male infertility
hyperprolactinaemia
congenital hypogonadotrophic hypogonadism
- anosmic (Kallmans syndrome)
- normosmic
acquired hypogonadotrophic hypogonadism
- stress
- low BMI
- XS exercise
52
give an example of congenital primary hypogonadism in males
Klinefelters syndrome (47XXY)
53
what is the cause of Kallmans syndrome
failure of the GnRH neurones to travel with the olfactory fibres from the olfactory placode to the hypothalamus
resulting in anosmia and infertility + failure of puberty
CAN HAPPEN IN MALES AND FEMALES
54
what is X0 chromosome condition called
turners syndrome
55
symptoms/signs of Klinefelters syndrome
reduced facial and chest hair
female pattern of pubic hair
reduced IQ
small penis and testes
gynaecomastia
narrow shoulders
wide hips
reduced bone density
infertility
tall stature
56
treatment for male infertility
dopamine agonist (cabergoline) for high prolactin
testosterone (for symptoms, not fertility)
gonadotrophins (for infertility)
surgery (micro testicular sperm extraction)
lifestyle
- optimise BMI
- smoking and alcohol cessation
57
blood tests for male infertility
PRL
FSH
LH
morning fasting testosterone
58
POI levels of LH, FSH, oestradiol
LH high
FSH high
Oestradiol low
--> as it is primary hypogonadism
59
diagnostic criteria for POI
FSH > 25 iU/L, 2 times at least 4 weeks apart
60
causes of POI
congenital eg turners syndrome (X0)
autoimmune
cancer treatment
61
anorexia induce amenhorrea levels of FSH , LH, oestradiol
all low
62
PCOS diagnostic criteria
2/3 of
oligomenorrhoea or amenorrhea
high androgens or signs of high androgens eg hirsutism, acne
cysts found on ovarian USS
63
treatment for the different aspects of PCOS
infertility/ irregular menses
- contraceptive pill
- metformin
- IVF
insulin resistance
- lifestyle changes
- metformin
hirsutism
- creams, laser
- anti androgens eg spironolactone
endometrial hyperplasia
- progesterone course
64
hormone levels in PCOS
high LH: FSH ratio
normal E2
high E1
65
symptoms of turners syndrome
shield chest
brown nevi
small fingernails
amenhorrea
infertility
webbed neck
short stature
short 4th metacarpal
elbow deformity
coarcation of part
poor breast development
66
investigation for female infertility
trasnvaginal US
hysterosalpingogram
pituitary MRI
pregnancy test
bloods
- FSH
-LH
-PRL
- mid luteal progesterone
- oestradiol
- androgens
67
what is the name of the tract between the hypothalamus and anterior pituitary
hypothalamic hypophyseal tract
68
what is panhypopituitarism
total loss of anterior and posterior pituitary
69
which hormone does ACTH regulate
cortisol
NOT aldosterone - that is regulated by the renin angiotensin system
70
if a women who has recently delivered a child presents with lethargy, weight loss, inability to breastfeed and her menses haven't returned since pregnancy, what are the likely diagnoses
Sheehans syndrome
anaemia
pituitary tumour
71
what is Sheehans syndrome
post partum haemorrhage --> hypotension --> anterior pituitary infraction --> anterior hypopituitarism
the anterior pituitary enlarges during pregnancy (lactotroph hyperplasia) so is the most vulnerable to infarction
presents with weight loss, lethargy, anorexia, inability to lactate or restarts menses
72
what is pituitary apoplexy
infarction or haemorrhage of the pituitary
presentation is exacerbated by presence of pituitary adenoma - may even be the first presentation of a pituitary adenoma
presents as
severe sudden onset headache
bitemproal hemianopia
if cavernous sinus is involved: diplopia (cn 4/6), ptosis (cn3)
72
what is pituitary apoplexy
infarction or haemorrhage of the pituitary
presentation is exacerbated by presence of pituitary adenoma - may even be the first presentation of a pituitary adenoma
presents as
severe sudden onset headache
bitemproal hemianopia
if cavernous sinus is involved: diaposis (cn 4/6), ptosis (cn 3)
73
how to treat GH deficiency and monitor the response
daily injection
monitor response using quality of life assessment and measure IGF1 levels
74
how does GH deficiency present in adults vs children
adults: reduced quality of life
children: short stature
75
how does ACTH deficiency present
fatigue
NOT salt losing crisis - that do to with the renin angiotensin system and aldosterone
76
how to treat ACTH deficiency
give synthetic steroids
prednisolone - 1 x a day in morning, 3mg a day
hydrocortisone - 3 x a day, 10mg 5mg 5mg
(to represent diurnal rhythm)
77
what are the sick day rules for people with ACTH deficiency, and what are they followed in order to avoid
wear a steroid alert bracelet/necklace
double steroid dose if have fever/intercurrent illness
if cannot take steroids eg are vomiting, inject intramuscularly or go to A&E
in order to avoid adrenal crisis - hypotension, weakness, collapse, death
78
what is primary hypoadrenalism called
Addisons
79
describe radiotherapy induced hypopituitarism
can either be direct or indirect - hypopituitarism induced by radiotherapy targeted at the pituitary eg for an adenoma, or near the pituitary eg for a cns tumour
the higher the total radiotherapy dose, the higher the risk of HPA axis damage
80
which parts of the pituitary is most sensitive to damage from radiotherapy
GH and gonadotrophin
81
what is the best scan to look at pituitary
MRI
82
what medications can precipitate pituitary apoplexy
anticoagulants
83
which two hormones are released from pituitary in response to hypoglycaemia
GH
ACTH
84
what is the numerical cut off for hypoglycaemia
< 2.2 mM
85
what is the difference between a microadenoma and a macroadenoma
micro adenoma < 1cm
macro adenoma > 1cm
86
which receptor does dopamine bind to on anterior pituitary lactotrophs
D2 receptor
87
what medication is used to treat hyperprolactinaemia
cabergoline - dopamine agonist
88
name some drugs which can cause hyperprlocatinaemia
anti psychotics
anti emetics
SSRIs
high dose oestrogen
opiates
89
name some pathological causes of hyperprolactinaemia (other than a prolactinoma)
PCOS
chronic renal failure
primary hypothyroidism
90
name some physiological causes of hyperprolactinaemia (other than a prolactinoma)
stress
pregnancy / breast-feeding
nipple / chest wall stimulation
91
how does GH directly and indirectly stimulate growth
direct: acts on muscles directly
indirect: stimulates liver to produce iGF (insulin like growth factor) which acts on muscles
92
treatment for high GH
transphenoidal pituitary surgery
somatostatin analogue - octreotide
dopamine agonist - cabergoline (there are D2 receptors on GH secreting pituitary tumours)
93
how to measure if cortisol is high
high late night cortisol
high 24 hr urine free cortisol
high cortisol after given oral dexamethasone
94
how to measure if GH is high
high IGF 1
or high GH after given oral glucose load
95
what are the ACTH dependent causes of high cortisol
pituitary corticotroph adenoma
ectopic ACTH (lung cancer)
96
what are the ACTH independent causes of high cortisol
adrenal adenoma
oral steroids
97
difference between cushings disease and syndrome
syndrome = high cortisol
disease = high cortisol due to ACTH secreting corticotrophin adenoma
98
what treatment is used for hyperthyroidism due to graves or plummers
symptom management:
beta blockers - propanolol
reduce thyroxine:
thianomides - carbimazole (CB2), propylthiouracil (PTU)
if thianamodies don't work can try
- radioiodine therapy
- surgery --> KI treatment before to reduce the size of the gland
98
what treatment is used for hyperthyroidism due to graves or plummers
symptom management:
beta blockers - propanolol
reduce thyroxine:
thianomides - carbimazole (CB2), propylthiouracil (PTU)
if thianamodies don't work can try
- radioiodine therapy
- surgery --> KI treatment before to reduce the size of the gland
99
what are some side effects of thionamides
agranulocytosis --> get a sore throat due to reduction in neutrophils and subsequent infection by commensal streptococci
rashes
100
why do you get palpitations, tachycardia etc in hyperthryoidism
you get apparent activation of the sympathetic nervous system
because thyroxine sensitises beta adrenoreceptors to adrenaline and noradrenaline
101
what is plummers
hyperthyroidism due to a benign thyroid adenoma --> toxic nodular goitre
102
difference in presentation of graves, plummers and viral thyroiditis on radio iodine uptake scan
graves - symmetrical shape, all of gland is dark
plummers - only one dark area (the adenoma), not symmetrical
viral - no uptake on scan (gland stops making thyroxine and makes viruses instead)
103
why do you get hyper thryoidism then hypothyroidism in viral thryoiditis
virus attacks gland and uses it to make viruses instead of thyroxine
starts of as hyperthyroidism because gland is over stimulated and releases all of the thyroxine it previously made
then hypo as all the thyroxine stores have been released and its just making viruses now
104
difference in symptoms between graves and plummers
in plummers get no smooth symmetrical goitre, exophthalmus or pretibial, myxoedema
105
what are the symptoms of leptin deficiency
infertility
short stature
reduced
- immune function
- body temp
- energy expenditure
106
what is orlistat
gastric and pancreatic lipase inhibitor
107
side effects of orlistat
fatty and oily stool
oily spotting
facial incontinence and urgency
deficiency of fat soluble vitamins
108
what medications other than orlistat can be used for obesity
liraglutide/saxenda - GLP 1 receptor agonist
semaglutide - long acting GLP1 receptor agonist
terzapetide: GLP 1 and GIP receptor agonist
GLP 1 = glucagon like peptide
GIP = glucose dependent insulinotropic peptide
109
3 types of bariatric surgery
gastric bypass - attach top of stomach to small intestine
gastric band
sleeve gastrectomy - remove part of stomach
110
requirements for being able to get bariatric surgery
BMI
> 40 kg/m2
35 - 40 with comorbidities
30 - 34.9 with newly diagnosed T2DM
111
name the 3 autoantibodies that could be found in type 1 diabetes
insulin autoantibody (IAA)
glutamic acid decarboxylase autoantibody (GADA)
inculinoma-associated-2-autoantibodies (IA2A) - zinc transporter- 8 (Zn8)
112
name some environmental exposures that could stimulate the genetic predisposition for type 1 dm to become a disease
enteroviral infection
cows milk protein exposure
seasonal changes
changes in microbiota
113
which 2 transplants can be done for T1DM
islet cell transplant - from dead donor into hepatic portal vein
pancreas and kidney transplant (works better when together)
114
name some metabolic effects of insulin deficiency
lipolysis
hepatic glucose output (HGO)
proteinolysis
conversion of fatty acyl coA into ketones (fatty acyl coA--> acetoacetate --> acetone + 3OH-B)
115
what are the treatment options for T1DM
insulin pump therapy - short acting insulin, eg novarapid, via a pump, with basal bolus regime
education - DAPHNE course, swap refined carbs for complex carbs
closed loop/artificial pancreas - measures glucose levels of blood and calculates exactly how much insulin is needed
transplant - islet stem cell, kidney and pancreas
116
how is normal insulin release pattern different from the insulin pump therapy release pattern
normal release pattern: prandial peaks with 2 phase (1st and 2nd phase insulin release) - helps make sure have the right amount of insulin
insulin pump therapy - basal bolus regime, release continuous amount of short acting insulin (basal) then larger amounts with meals (bolus)
117
give examples of short and long acting insulin
short
- human insulin eg act rapid
- insulin analogue eg lispro, aspart, glulisine
long
- insulin bound to protamine or zinc eg NPH - neutral protamine Hagedorn
- insulin analogue - glargine, determiner, degludec
118
what are some problems with using HbA1c for glucose measurements
changes with
erythropoiesis
breakdown of erythrocytes
glycation
altered haemoglobin
119
what is the pH, bicarbonate an glucose cut off for diabetic ketoacidosis
pH < 7.3
bicarbonate < 15
glucose >11
120
what is the pH, bicarbonate an glucose cut off for diabetic ketoacidosis
pH < 7.3
bicarbonate < 15
glucose >11
121
what treatments are immediately needed for diabetic ketoacidosis
IV fluids - salien
insulin
anti emetics
122
what are the two types of genetic backgrounds of T2DM
monogenic - single gene mutation: MODY, definitely will get diabetes
polygenic: polymorphisms increasing risk of diabetes: high risk of developing, but its dependent on other factors
123
which type of obesity is worse for causing T2DM
visceral > subcutaneous
124
name 3 conditions which have associations with T2DM
obesity
perturbations in gut microbiota
intra-uterine growth retardation
125
how to diagnose T2DM
one HbA1c reading >= 48 , with symptoms
or
two HbA1c readings >= 48 , without symptoms
126
describe the hyperosmolar hyperglycaemic state that can occur in T2DM
often presents as renal failure
not enough insulin to prevent hyperglycaemia, but enough to stop lipolysis and ketogenesis
127
why is ketoacidosis rare in T2DM
because you still have some insulin, juts not enough to overcome the resistance - have a 'relative deficiency' of insulin
128
which drugs solve the problem of excess hepatic glucose production - T2DM
metformin, reduces hepatic glucose production
129
which drugs solve the problem of insulin resistance - T2DM
metformin + thiozolidinediones, increase insulin sensitivity
130
which drugs solve the problem of insufficient insulin production to counteract the insulin resistance - T2DM
sulphonylureas, GLP1 agonist, DPP4 inhibitors, increase insulin secretion
131
which drugs solve the problem of high glucose in blood - T2DM
alpha glucosidase inhibitor - inhibit carb absorption from gut
SGLT2 inhibitors - inhibit glucose reabsorption from kidneys
132
which 2 things can induce remission of T2DM
sustaining a very low calorie diet
gastric bypass surgery
133
what is metformin contraindicated in
severe liver failure
severe heat failure
moderate renal failure
134
how does metformin reduce insulin resistance
reduces hepatic glucose output
increases peripheral glucose disposal
135
how do sulphonylureas work for T2DM
block the ATP and glucose dependent K+ channel, stimulating insulin release
136
how do SGLT2 inhibitors work for T2DM
inhibit sodium glucose transporter, causing glycosuria
137
how do GLP1 work for T2DM
stimulates insulin, suppresses glucagon
decreases glucose and glucagon
138
why does GLP1 have a short half life
it is rapidly degraded by DPP4 enzyme
139
effects of pioglitazone
peripheral insulin sensitisation
modulation of adipocyte proliferation
peripheral weight gain
140
how is GLP1 produced
transcription of pro glucagon gene in L cell
141
effects of GLP
142
2 enzymes involved in conversion of cholesterol to progesterone
side chain cleavage
3 hydroxysteroid dehydrogenase
143
3 main causes if adrenocortical failure
TB addisons
autoimmune addisons
congenital adrenal hyperplasia
