Endocrinology Flashcards
How do you calculate the Insulin Sensitivity Factor ?
100/Total Daily Dose
What does the insulin sensitivity factor tell you?
The amount your BSL will drop with 1 unit Insulin
How do you calculate your meal ratio?
500/TDD
What does your meal (carbohydrate) ratio mean?
How many units of Carbs 1 unit of Insulin will cover
What is someone’s usual daily requirement of exogenous insulin?
0.5u/kg
What % of your daily insulin is basal vs. prandial
50% each
What cell mediates the development of T1DM?
T1DM is a T cell mediated process
What HLA types increase the risk of T1DM
DR3/DQ2 and DR4/DQ8
What is the most common Ab in T1DM?
Anti-GAD
What are the other Antibodies in T1DM?
IAA, IA-2A/2B, ZnT8
What is the risk of T1DM if you have 2 Abs?
60%
What are the 3 criteria for LADA?
> 30 years old, 1+ Abs, No Insulin for the first 6/12
Having which parent affected by T1DM gives you a higher risk of having T1DM?
Father >Mother
What HLA type protects from T1DM development?
HLA-DR2
Risk of developing T1DM if offspring of affected mother vs. affected father vs. both parents affected vs. non-twin sibling vs. monozygotic twin
3% vs. 6% vs. 30% vs. 5% vs. 50% life time risk
Ethnicities that get T1b DM
African and Asian
Drug that prevented T1DM development in those w. multiple autoAbs and IGT
Teplizumab
What is an islet cell transplant good for?
hypoglycaemic unawareness
Best bariatric surgery procedure
Roux-en-Y
Most common MODY mutation
HFN1a
Most common type of MODY
MODY 3
MODY 3 rx
Sulphonylurea
MODY 2 rx
Only in Pregnancy, otherwise not needed
In gestational diabetes what could hypoglycemia indicate?
failing placenta
Placenta effect on insulin
Increases insulin resistance
Are TSHrAbs stimulating or blocking?
Usually stimulating, can block/be both in same pt
Medication that can falsely lower TSH and elevate T4
Biotin
T1 Amiodarone thyroid dysfunction is from? U/S finding? onset? mgmt
Increased iodine causes hyperthyroidism (JBasedow), U/S normal or increased, usually within 3 months, anti-thyroid meds
T2 Amiodarone thyroid dysfunction is from? U/S finding? onset? mgmt
directly toxic causing thyroiditis, reduced vascularity on U/S, usually 2-3 years, steroids or surgery
Endocrinopathies with lithium, there are four
Nephrogenic DI, hypothyroidism, hyperparathyroidism, distal RTA
When do you treat subclinical hyperthyroidism?
Age >65, TSH <0.1
When to treat subclinical hypothyroidism?
TSH >10
Which anti-thyroid drugs to use/when in pregnancy?
PTU 1st trimester (less placental t/f and otherwise risk of aplasia cutis/choanal/oesophageal atresia), CBZ in 2nd/3rd (hepatitis risk from PTU late)
TSH levels in pregnancy
BHCG acts like TSH, so elevated hormones and low TSH
Concerning thyroid nodules
taller than wide, >2cm, solid, hypoechoic, irregular margins, central microcalcification, no halo
mgmt of thyroid follicular neoplasm undetermined significance
hemithyroidectomy
Thyroid cancer most common type
papillary
worst thyroid ca prognosis
anaplastic
thyroid ca familial links
medullary
Medullary thyroid ca marker
calcitonin
Mgmt of thyroid ca
thyroidectomy, thyroxine to suppress TSH, RAI
sick euthyroid hormone changes
T3 always low or normal. Others do anything
Adrenal anatomy outer to inner
Glomerulosa, fasciculata, reticularis (GFR)
adrenal zone hormone production outer to inner
Mineralocorticoid, Glucocorticoid, Androgen
CAH enzyme deficiency
21-hydroxylase
CAH screening test
17-OH progesterone
Ab causative for AI adrenal insufficiency
21-OH Ab
If PAI but 21-OH Ab -ve, then which further 2 tests are required? and why?
CT adrenals and VLCFA. Adrenoleukodystrophy and e.g. adrenal haemorrhage/infiltration/necrosis
Primary aldosteronism confirmatory test after ARR is?
Seated saline suppression test
drug that causes the most false +ves in Aldo:renin is…
Beta blockers
Adrenal adenoma features
<3cm, smooth, round, homogenous, <10HU, not vascular, high washout, <1cm/year growth
Biochemical Ix of adrenal tumour, 3 tests are:
1mg DST, ARR, plasma metanephrines
rx of adrenal ca
mitotane
glucocorticoid receptor antagonist drug for cushing’s
mifeprestone
action of metyrapone
11 beta hydroxylase inhibitor, prevents steroid synthesis, use in cushing’s
PCOS needs 2/3 of:
oligo/anovulation, clinical/biochem hyperandrogenism, PCOvaries on imaging
Most important rx for PCOS
weight loss
primary ovarian insufficiency w. FHx. of same or evidence of retardation/tremor/ataxia, need to test for
fragile X: FMR1 gene, CGG triple repeat, >55 repeats are affected
hypogonadotrophic hypogonadism w. anosmia =
Kallman’s
what does being overweight do to testosterone levels in males and why?
overweight -> low T because Insulin -> reduced sex HBG -> lower total T
low anti-mullerian hormone implies…
reduced ovarian reserve
What do thiazides do to ca?
reduce urinary ca excretion, hypercalcaemia
FHH due to mutation in:
CaSR
primary hyperpara should get surgery if…
<50 yrs of age, eGFR <60, Ca>2.8, T score < -2.5, previous asymptomatic vertebral fracture, nephrolithiasis/calcinosis
tubular maximal reabsorption of phosphate is an indicator of…
renal responsiveness to PTH
pseudohypoparathyroidism is due to…
resistance of action of PTH
finger changes in pseudohypoparathyroidism
4th and 5th MCP shortening
Ca and PO4 in pseudohypoparathyroidism…
Low Ca and high PO4
Hypophosphataemic Rickets is due to…
mutation in FGF23 -> unable to be cleaved
rx of hypoparathyroidism
ca carbonate + calcitriol. Calcium citrate if on PPI
what location are atypical femoral #s w. bisphosphonates?
subtrochanteric
define ONJ
exposed bone in maxfax region that doesn’t heal within 8 weeks
MOA of Romosozumab
Sclerostin inhibitor
Who to start on osteoporosis therapy if on steroids
Previous #, age >70, pred >7.5mg/day
Which bone cells does PTH act on?
Osteoblasts -> RANKL -> osteoclassts
Hungry bone rx
aggressive Ca replacement until bones are full, and vitamin D
PTH effect on PO4 and mechanism
phosphaturic, impairs tubular reabsorption
Is primary or secondary adrenal insufficiency more severe?
primary
alkylating agent for aggressive pituitary tumours?
Temozolamide
What is copeptin?
cleaves in making ADH, correlates w. ADH production
What causes of hypopit are assoc. w. pregnancy?
post-partum lymphocytic hypophysitis, Sheehand’s
Pan hypopit replacement drugs/dose
Glucocorticoids 10mg/m2 e.g. 20-30mg hydrocortisone/day; thyroxine; Men T gel or IM, Females COCP or HRT
Central DI due to issues in which anatomical location in brain?
hypothal
how do you confirm central vs. nephrogenic DI?
DDAVP response (central respond to it)
Mgmt of DI
intranasal DDAVP +/- oral, titrate to serum Na
Hyperprolactinaemia is usually due to…
stalk compression -> no dopamine inhibition
Hyperprolactinaemia causes what sx?
galactorrhoea, hypogonadism
mgmt of hyperprolactinaemia
dopamine agonists (e.g. Cabergoline), secondary might do surgery if smaller
Best screening for acromegaly
IGF-1
Usual cause of acromegaly is…
pituitary tumour, therefore should MRI
Mgmt of acromegaly
transsphenoidal tumour resection, RTx or medical
medical mgmt of acromegaly includes…
octreotide, pevisomant (GH receptor antagonist), cabergoline if hyper PRL
Top 3 causes of cushing’s in order:
iatrogenic, pit adenoma, adrenal adenoma/ca
If ACTH INdependent cushing’s, next test is…
CT adrenals
If suspect pituitary or ectopic Cushing’s, you can do a…
high dose dex, which will suppress if pit; or do a CRH stim
If pit cushing’s suspected, do 2 tests:
MRI and BIPSS (2:1 basal ACTH central:peripheral
Mx options for Cushing’s
surgery, RTx, medical- ketoconazole, pasireotide (somatostatin analogue)
If you perform a bilateral adrenalectomy, you need to…
irradiate the pit due to risk of Nelson’s syndrome
5 drugs for weight loss
phentermine, topiramate, naltrexone/bupropion, metformin, liraglutide, SGLT2
Denosumab must be followed up by…
bisphosphonate
Denosumab mechanism:
RANKL inhibitor, which usually promotes osteoclast maturation; secreted by osteoblasts
What does WNT normally do?
causes osteoblast proliferation
What inhibits WNT?
Sclerostin
4 meds that can cause ONJ
Bisphosphonates, Denosumab, Sunitinib, Bevacizumab
Raloxifene prevents
vertebral # only
teriparatide DOES NOT protect against
hip #
Dumping syndrome test
mixed meal
weight loss reduction surgery does not improve
mortality
DPP4-I that should not be used in heart disease
Saxagliptin
MOA and side effect of Pasireotide
high somatostatin receptor affinity as antagonist; for rx of refractory acromegaly and cushing’s disease; hyperglycaemia
growth hormone replacement in adults is recommended in GH deficiency because of:
body composition, exercise capacity and bone and CV health
cabergoline MOA and side effect
dopamine receptor agonist; compulsive behaviours e.g. gambling, spending
alternative test to water deprivation test for diabetes insipidis
hypertonic saline stimulated plasma copeptin (precursor derived surrogate of arginine vasopressin); greater diagnostic accuracy than water deprivation test
Drug that improves PFS in radioiodine refractory differentiated TC
lenvatinib (MKI against VEGFR1, 2 and 3)
Promising/improving drug for locally advanced/ metastatic medullary thyroid ca
Vandetanib- TKi against RET
Primary target cell of PTH in bone
Osteoblast
What is the sequence of physiological responses to hypoglycaemia in a non-diabetic
reduced insulin -> increased glucagon -> adrenaline -> growth hormone and cortisol
additional effects of glucagon
increases lipolysis, fatty acid oxidation and ketogenesis, satiety, thermogenesis and energy expenditure, bile acid synthesis; decreases food intake
what effect does amiodarone have on the thyroid?
inhibits conversion of T4 to T3; transiently inhibits iodine transport and thyroid hormone synthesis.
What can artificially increase serum thyroglobulin assays and seem as if there is a recurrence of cancer?
Anti-thyroglobulin antibodies
Best recognised alternation in maternal thyroid physiology
increase in TBG in the first trimester, persisting until shortly after delivery
increased concentration of TBG in pregnancy triggers a concomittant increase in
maternal thyroid synthesis, elevation of total thyroxine and T3.
Causes of increased TBG
Oestrogen, methadone, heroin, tamoxifen/raloxifene, hepatitis
Causes of low TBG
Cushing’s, acromegaly, androgens, nephrotic syndrome
