RPA endo Flashcards
1
Q
Diagnosis of diabetes in haemoglobinopathies
A
OGTT
2
Q
what virus is proven to cause T1DM
A
congenital rubella unproven: coxackie, rotavirus, mumps, reovirus, herpes, cows’ milk
3
Q
genetics of T1DM - what chromosome is involved
A
chromosome 6
4
Q
what MHC is involved in beta cell destruction
A
MHC II - on antigen presenting cells
5
Q
what HLA is protective of T1DM
A
DR2 is protective
6
Q
what HLA is a risk factor of T1DM
A
DR3 and DR4 are expressed in 95% of white patients with Type 1 diabetes
7
Q
does the mother or father confer higher risk for T1DM
A
father is 6.1% risk mother is 2.1% risk
8
Q
what antibodies are implicated in T1DM
A
anti GAD anti IA2 zinc transporter 8 first 2 more clinically important
9
Q
which autoantibody is most important for the development of T1DM
A
anti GAD
10
Q
screening for T1DM - what tests to do
A
HLA DR3/DR4 nmeasure anti GAD and anti IA2 ab insulin secreting potential
11
Q
pathogenesis of T2DM
A
insulin resistance but also relative insulin deficiency due to defect glucorecognition
12
Q
does the mother or father confer higher risk for T2DM
A
mothers intrauterine environment is important for the development of type 2 DM
13
Q
what type of genes are affected in T2DM
A
majority relate to beta cell function loss only a small inter related to insulin resistance
14
Q
most important gene for T2DM
A
TCF7L2 - mechanism unknown
15
Q
MODY genetics
A
autosomal dominant single gene defects MODY1-5 enzyme defect - HNF-4alpha, glucokinase (mild hyperglycaemia), HNF-1alpha (very sensitive to sulphonylureas), IPF-1
16
Q
clinical features MODY
A
onset <25 for at least another family member correction of fasting hyperglycaemia for at least 2 years without insulin no ketotic events impaired insulin secretion
17
Q
HNF-1alpha characteristics
A
MODY enzyme defect very sensitive to sulphonylureas
18
Q
glucokinase clinical significance
A
MODY enzyme defect mild hyperglycaemia usually does not require treatment
19
Q
impaired glucose tolerance prevention for diabetes
A
lifestyle - diet, exercise +/- weight loss effects seen without weight loss rosiglitazone reduced new DM by >60% small increase in heart failure however practically lifestyle
20
Q
sulfonylurea MOA, adverse effects
A
stimulates release insulin from the beta cells may have weight gain hypoglycaemia is possible gliceride preferred as metabolites not active and lower risk of hypo CVS impact is neutral on latest study
21
Q
what allergies should avoid for sulfonylureas
A
sulfur allergies
22
Q
biguanides MOA and aderse effects
A
increases insulin action decrease hepatic gluconeogenesis does not cause hypos by itself but can potential hypos in combination with other things lactic acidosis - rare GI side effects start low and go slow
23
Q
metformin eGFR cut off
A
<30
24
Q
metformin contradindications
A
liver damage (pregnancy) nephropathy eGFR <30
25
acarbose MOA and adverse effects
decrease HbA1c by 0.5% at most (very weak agent) AE: flatuence and diarrhoea in 80%! malabsorption
26
TZD - thiazolidinediones
Activates PPAR\_gamma nucleus receptor central to insulin action Tosiglitazone + pioglitazone AE: weight gain, fluid retention/CCF, ?cardiac disease (rose), fractures, ?bladder cancer (pio)
27
incretic mimetics
GIT hormones - GLP-1, GIP GLP-1 analog - exenatides, dulagutide (both weekly injections)
28
what does incretin and GLP1 do
increase insulin release and inhibit glucagon to lower blood glucose
29
what does DPP-4 do
inactivates GLP-1 (so DPP-4 inhibitors increase endogenous GLP-1)
30
GLP-1 analog advantages
potent weight loss ++ low risk of hypos dual/tripe therapy CV outcome studies
31
GLP1 A
expensive injection nausea ++
32
DPP-4 inhibitors
gliptins
33
DPP-4 advantages
tablet otherwise similar to GLP1
34
DPP-4 AE
depends on endogenous production of GLP-1 which is already decreased in T2DM not as potent as GLP-1 no weight loss (As weaker) neutral CV outcome studies
35
what has positive CVS outcome studies
SGLT-2 and GLP-1
36
SGLT-2 transported
transports 90% of glucose out of the tubular lumen
37
pros SGLT-2
relatively potent 0.5-1% HbA1c reduction weight loss lowers BP
38
cons SGLT-2
genital fungal infections euglycaemia DKA
39
SGLT2 eGFR cut off
\<45
40
when does SGLT2 need to be stopped before surgery..procedure or fasting
2-3 days prior
41
lispro insulin, aspart, glulisine vs actrapid
absorbed faster than act rapid
42
what is the next step if someone has good BSL at bedtime but wakes up with high pre breakfast BSL
measure BSL at 3am to see whether it's dawn phenomenon or somogyi effect to see whether it's too little insulin (dawn) or too much (somogyi) causing rebound hyperglycaemia after 3am hypo
43
HbA1C aim T1DM
6.5-7
44
tighter control and weight in T2DM
tighter control = more weight gain
45
good glucose control and micro and macrovascular in T2DM
less micro vascular and maybe macrovascular EDIC showed reduced in major cardiovascular events in group that had initial good HbA1C control (2 groups of good and poor HbA1C but long term both groups had good glucose control but initial good control group early on) so macrovascular outcomes may only be apparent after many years
46
intense glucose control in T2DM
ACCORD study short term outcomes aimed for 6% and lower excessive mortality now we aim for 7% in cardiac disease
47
good glucose control and macrovascular outcomes
improves macrovascular but over long term and need initial good control
48
HBA1C aims T2DM no CV + metformin
\<6%
49
glitazone in CVS
rosiglitazone worsen lipids pioglitazone possibly decreases cardiac outcomes however both should not be used oedema
50
gliptin (DPP4) on CVS
sitaglipin does not increase HF saxagliptin does increase hospitalisation for HF
51
empagliflozin/dapagliflozin none endo effects
3 point MACE heart failure reduced renal composite outcomes note empa has trend towards increased stroke
52
significance of dulagltide for CVS
other studies had populations w established CVS disease the rewind study of dulaglutide included 69% without baseline CV disease so it is showing the dulaglutide as PRIMARY prevention
53
BP lowering DM agents
SGLT2s and GLP1
54
insulinoma testing
prolonged fast when the person gets a hypo, simultaneous c peptide,, insulin insulinoma does not produce hypoglycaemia w OGTT
55
impaired glucose tolerance hypoglycaemia
high-isa C-peptide rapid reactive/postprandial hypoglycaemia
56
c peptide in sulfnoyureas hypoglycaemia
high c-peptide
57
diabetes and VGEF
vgef is the bad guy in pathogenesis in retinopathy
58
treatment of retinopathy
anti-VGEF intravitreal
59
type 2 DM vs type 1 DM - proteinuria and prevention of renal progression
Type 2 DM - ARB Type 1 DM - ACE I
60
bp targets in DM
accord study - no difference SBP 120-140 so aim now 140/80 if microalbuminuria; 140/90 no microalbuminuria
61
fenofibrate in DM
retinopathy add on to statin slow progression of retinopathy does not prevent retinopathy
62
production sites of T4 and T3
T4 soley from the thyroid gland
T3 mainy from the peripheral tissue
63
what happens to TFTs in first trimester of pregnancy, hyperemesis gravidarum, hydatidiform mole
TSH is suppressed
can present like a thyrotoxicosis picture
64
Glucocorticoids TSH
Low TSH
normal T4, low T3
65
TRAb
very high sensitivity and specificity but can occasionally be negative in Graves and occasionally positive in Hashimoto's
66
effect of biotin on TFTs
low TSH
High T3 and T4
TSHRAb positive
(False positive Graves disease picture; normalising after biotin is ceased)
67
Graves disease
68
Multinodular goitre
69
most common cause of Hyperthyroidism
Graves disease
70
clinical dx of graves
symmetrically enlarged thyroid
Graves orbitopathy
mod to severe hyperthyroidism
71
when is scintigraphy contraindicated
pregnancy and lactation
72
what is more elevated (T3 vs T4) in Graves disease
T3 more elevated than T4
73
what BB can blocker T4 to T4 conversion
propanolol
74
what treatment if contraindication in bad graves eye disease
radioactive iodine because it causes an initial rise in TRAb
75
how long to treat with anti-thyroid medications in Graves disease
until TRAb becomes undetectable
76
what treatment for Graves disease has the highest rate of remission
anti-thyroid drugs
77
prevalence of eye disease in Graves' disease
30-50%
5% will develop severe eye disease
78
what is the most common sign of eye disease in Graves?
what is the most specific sign
most common = eyelid retrction of both eyes
most specific - exophthalmos
79
what is the most common eye muscle affected in Graves disease
inferior rectus
80
management of Graves eye orbitopathy
Mild - selenium
Mod-severe - Pulse glucocorticoird
Surgery and orbital decompression
Teprotumumab (IGF-1 receptor inhibitory monoclonal antibody; SE - hyperglyaemia)
81
when to treat subclinical hyperthyroidism
Suppressed TSH \<0.1
\>65 treat
82
amiodarone induced tyroiditis pathophysioogy
37.3% iodine by weight
can induce both hypothyroidism and hyperthyroidism
Type I - Jod-Basedow phenomenon; treated with antithyroid medications
Type II - destructive thyroiditis 5-10% patients, need glucocorticoids
83
treatment of amiodarone induced hyperthyroidism
both carbimazole and prednisolone
84
who to treat for subclinical hypothyroidism
\<70 years of age
AND TSH \>10
between TSH 7-10, treat if there are other high risk factors
85
what's the size cut off for FNA of thyroid nodule
\>1cm
86
USS features of malignancy for thyroid nodule
microcalcification
nodule hypoechogenicity compared with surrounding thyroid/muscle
Irregular margins - infiltrative, microlobuated, spiculated
Taller than wide on a transverse view
cyst more likely to be benign
87
hyperthyroidism and warfarin
hyperthyroidism increases efficacy of warfarin through increasing catabolism of vitamin K dependent clotting factors
88
DIagnosis of diabetes insipidus
water deprivation test (DI patients will continue losing water)
Central DI has response to DDAVP
Peripheral DI does not have response to DDAVP
hypertonic saline insulin test is more sensitive and specific but might not be suitable for use in hypontraemia
Arginine-stimulation and measuring copeptin is aso sensitive/specific
89
gold standard for hypothalamic-pituitary adrenal axis
insulin tolerance test
90
what can insulin tolerance test be used to test
growth hormone and cortisol production
91
pituitary tumour classification
\<1cm microadenoma
\>1cm macroadenoma (has capaticy to compress on the pituitary)
92
acromegaly diagnosis
93
treatment of acromegaly
1. Surgery
2. Radiotherapy
3. Somatostatin receptor ligand
1. octreotide acting on SSTR2
2. Pasireotide acts on 4 somatostatin receptors
1. Hyperglycaemia and diabetes
4. Growth hormone receptor antagonist
1. Pegvisomant - most efficacious (\>90%)
5. Dopamine Agonist
94
screening test for Cushing's syndrome
dexamethasone 1mg suppression test
95
cushing's confirmatory testing
late night salivary cortisol (high sensitivity and specificity)
96
pituitary adenoma treatment
1. Medical therapy first line
1. Cabergoline
2. Visual field
3. Pregnancy
1. Microadeoma - cease treatment during pregnancy
2. Macroadenoma - cont treatment, switch to bromocriptine
3. Visual fields testing once a trimester
97
which immunotherapy is most likely to cause hypophysitis
anti-CTLA4
98
diagnosis of congenital adrenal hyperplasia
basal 17-OHP
confirmation testing with 250mcg of synacthen test and seeing if 17-OHP increases
treatment is not indicated in classical non symptomatic
99
what's the most common cause of primary hyperaldosteronism
bilateral adrenal hyperplasia
100
pathogenesis of obesity
leptin deficiency (long term appetite suppressant)
cholecystokinin (short term satiety factor that regulates meal size)
ghrelin: appetite trigger
Genetic factors:
* MC4R deficiency(causes reduction of appetite; most common monogeneic cause of paediatric obesity)
* FTO - found with GWAS; linked to IRX3 which is another gene which is shown to have an effect of browning white fat; small effect size
101
marker of brown fat
UCP1
browns fat burns energy rather than storing it
102
orlistat
blocks gastrointestinal lipase
causes fatty diarrhoea
-2.75kg over 52 weeks treatment
only works if there is fat consumption
103
phentermine + topiramate
does lead to ~10% weight loss
but note topiramate can cause depression in an already high risk group
104
mean weight loss following bariatric surgery
25% over 12months
105
physiological changes after gastric bypass
increase in GLP-1 and PYY (appetite regulator) (possibly explains sustained weight loss)
106
what outcome has not been demonstrate in bariatric surgery RCTs
mortality diet
(likely because there has not been a long enough follow up)
107
osteocyte - what does it secrete
see slides
108
what is the role of RANK ligand in bone remodelling
rank L are secreted by osteoblasts
they bind to the RANK receptor on the osteoclast
activated RANk causes the osteoclast to be activated and resorb bone
OPG is a decoy receptor that prevents RANK ligant to activate the osteoclast.
109
what happens to RANKL in aging
RANK L goes up
OPG goes down
110
remodlling of bone in aging
cortex thins
holes in the cortex (cortical porosity)
less trabecular bone and loss of connectivity
can lead to skeletal fragility and fracture risk
111
MOA of bisphosphonates and RANK- inhibiter
1. gets uptaken by osteoclasts and kills them
2. stops osteoclast activation
112
what is the z score good at identifying
not as clinically helpful as T scores
but they may be helpful to identify those with underlying accelerated causes of bone loss
113
who to treat for osteoporosis
1. fragility fracture in post menopausal woman or man \>50 years
2. vertebral fractures (loss of weight 20% of front or middle vs back end)
3. No existing fracture but on the basis of risk (but note larger NNT to prevent future fractures). E.g. 70 year olds with low bone density. 20% risk of fracture over 10 years
1. Low BMD
2. Age
3. Previous fracture - HIGHEST RISK
4. iatrogenic
1. Prednisolone: \>7.5mg for 3 months and T score \< -1.5
2. SERM: treat T\<-2 or #
3. Angrogenic dep: treat if T \<2.5 or #
114
steroids and bone
dose dependent but any dose will cause bone loss.
short duration results in reversible bone loss.
occurs very quickly (6-12% in the first year)
inhaled and topical no significant effects
115
HRT in osteoporosis
only if they arehaving sx of menopause and know the risks (increased breast CA and CVS)
116
raloxifene and osteoporosis
useful in people with a persona concern of breast cancer
117
what should be avoided in AF and osteoporosis problem
zolendronic acid
118
what fractures are the most resistance to osteoporosis therapy
non vertebral non hip
| (e.g. humerus, colles)
119
denosumab and discontinuation
rebound fractures due to intense trabeculae remodelling
120
alendronate discontinuation
slow decline in bone density
re-evaluate risk after a few years
121
SE of antiresorptive therapy
1. osteonecrosis of the jaw (bisphosphonates, denosumab)
2. atypical femoral fractures (presents with pain in thigh that occurs months before fracture occurs)
1. Declines with drug holidays
2. Subtrochanteria (no communication, transverse at the lateral cortex, medialslike, diffuse cortiacl thickening, local lateral cortical thickening)
3. Increased by duration of therapy
4.
122
management of atypical fractures
Discontinue anti-resorptive therapy
Consider nail fixation
Consider teriparatide
Monitor the contralateral hip (imagine w XR +/- bone scan or MRI)
123
anabolic therapy
1. PTH
1. Once daily injection
2. stimulate osteoblast and clast - which forms the anabolic window of ~18 months which is where osteoblast activity \> osteoclast
2. New targets - Romosozunab
1. Sclerostin inihibiting mAb
2. LRP5 - a receptor that is important for osteoblast function. LRP5 is inihibited by Sclerostin and DKK
3. TGA but not PBS yet
4. Potent anabolic therapy
124
Paget's pathogenesis
osteoclasc activity is increased
- \> increased bone turn over
- \> weakening of the bone
- \> deformity
- \> fracture
on imaging - alternating areas of lucency
can affect 1 bone or multiple bones
Investigations: ALP, XR, Bone scan
125
paget's treatment
indications fo treatment: high risk of fracture, critical area
## Footnote
zolendronic IV 5mg once every few years
126
hypergonadotropic primary ovarian failure sex hormones
high FSH, low E2
next step - karyotype
127
hypogonadotropic amenorrhoea causes
most commonly functional: weight loss, anorexia, exercise, debilitating disease, psychologic stress
or structural causes
128
amenorrhoea and elevated gonadotropin Ddx
turner syndrome
premature ovarian failure
129
what cardiac diseases to screen for in Turner's
co-arctation and aortic dissection
130
definition of premature ovarian failure
\<40 years amenorrhea
hypergonadotrophic amenorrhea
131
ancillary studies in PCOS
endometrial carcinoma
flucose intolerance
lipids
OSA
132
PCOS fertility tx
1. Weight loss
2. Letrozole
3. Metformin (but not as effective as letrozole)
Clomiphene should be combined with metformin
133
tall, gynaecomastic male
high LH, FSH
features of hypogonadism
Consider kleinfeltter's
XXR
134
MOA of iodine and carbimazole/PTU
iodine: decreases thyroidal iodide uptake, dcreases iodide oxidation and organification and blocks release of thyroid hormones
PTU./carbimazole: prevent synthesis of new thyroid hormone. PTU can also inhibit the conversion of T4 to T4 at high levels
135
waht happens to the thyroid after Iodine I-131
hypothyroidism depending on how much of the thyroid take up radioactive iodine
e.g. in Graves, the patients almost always be hypothyroidism but for a single nodule, the patient woudl be euthyroid
136
Wolff-Chaikoff effect
During the use of a high dose short duration of iodine (usually used as bridge to surgery or to control thyroid storm)
an autoregulatory phenomenon that inhibits organification in the thyroid gland, the formation of thyroid hormones inside the thyroid follicle, and the release of thyroid hormones into the bloodstream
137
Jod-Basedow effect
iodine exposure in uderlying thyroid disease may lead to hypersecretion of thyroid hormones
usually seen in pre-existent thyroid disease or subclinical thyroid disease
138
adrenal crisis w/ hypoNa hyperK+ b/g metastatic melanoma on pembrolizumab - cause?
adrenal metastasis
| (adrenalitis is extremely rare)
139
C-RET
mutation of MEN2A
140
MEN 1
parathyroid
pacnreatic
pituitary
genetic MEN1
141
VHL - Von Hippel-Lindau syndrome
hemangioblastomas
renal cell carcinoma
phaeo
gene (VHL)
inheritance AD
142
cushing's syndrome w normal ACTH
most likely cushing's disease
143
cushing's syndrome confirmed, next step
ACTH
144
pituitary apoplexy first management step
hydrocort
145
what might precipitate addisonian crisis on adrenal replacements
CYP3A4 inducers:henobarbital, phenytoin and rifampicin
146
menopause management
depends if they have the uterus
if no uterus, can give unopposed estrogen
if uterus, then need progesterone
initially estrogen then cyclical progesterone but after 1-2 years can do oral oestrogen and continuous progesterone
also depends if there are risk factors for thromboembolic diseases or if she has hypertriglyceridaemia - use transdermal if possible
also consider non hormonal treatments - 2nd or 3rd line
147
reason for low morning testosterone in obese male
decreased sex hormone inding globulin
148
High Ca2+ and high PTH next step
factional excretion of Ca2+
Familial hypocalciuric hypercalcemia vs primary hyperparathyroidism
149
dumping syndrome
rapid gastric emptying -\> early vs late dumping
after bypass surgery
150
rapid correction of glucose levels adverse effect
retinopathy or neuropathy
151
amyotrophy diabetes
it's a plexopathy
occurs in poorly controlled diabetes
152
T4 elevated and TSH normal
most likely cause
exogenous thyroxine intake
but can also be caused by pituitary thyrotorphy and thyroid homrone resistance and increased heterophile antibodies
