Endocrinology Flashcards
What is the function of insulin?
to drive glucose into cells when not needed
to inhibit ketone production when not needed
what are ketones need for?
to supply energy to brain during periods of hypoglycaema
what occurs during hypoglycaemia / starvation at hormone level
LOW insulin
HIGH glucagon / cortisol etc
this causes GLYCOGEN to be taken out of cells > converted back to GLUCOSE
KETONE production
What will fasting and OGTT tests be in T1DM
Fasting blood glucose >7
OGTT >11.1
what is normal, prediabetes and diabetes HbA1c
Normal: <42
Prediabetes: 42 - 48
Diabetes: >48
what are classical sx of diabetes and why?
TRIAD; fatigue, polyuria,polydipsia
as glucose is an osmotic diuretic, so it pulls out water
what are two classicAL presentations of diabetic neuropathy
Gastroparesis (vagus N neuropathy»_space; erratic BMs, bloating, vomiting)»_space; mx with metoclopramide
Neuropathic pain»_space; mx with amyltryptiline
WHat is diabetic food secondary to?
neuropathy – loss of sensation
Peripheral arterial disease (due to reduced oxygen) – absent foot pulses, intermittent claudication
how do you check for diabetic foot neuropathy
10g monofilament test, done at least annually
how do you check for diabetic NEPHROPATHY
Yearly ACR (albumin : creatinine ratio)
what is the first sign of diabetic nephropathy=
microalbuminuria
what is the effect of ACEi on AKI, CKD and diabetic nephropathy
TOXIC in AKI
PROTECTIVE in CKD and diabetic nephropathy
when must you stop an ACEi
when there is a drop in GFR >20%
what is ACEi’s initial effect of GFR
initial drop due to dilating of the efferent arteriole
How often do you monitor cap glucose in T1 diabetes
4x a day in adults, 5x a day in children
How can you manage T1DM
- BASAL BOLUS REGIMEN (rapid insulin with meal, long acting insulin BD)
OR
- Twice daily BIPHASIC INSULIN (which is a mix of long and short acting)
When is basal bolus regimen most appropriatw
when patients are bale to count carbs and ensure that sufficient insulin is taken per meal
Give examples of short acting insulin
Actrapid
Novorapid
Give exaplines of long acting insulin
lantus
levemir
give example of mixed biphasic insulin
Humulim M3
What HbA1c do you start metforminn for? WHen do you escalate to dual therapy?
Start METFORMIN if HbA1c >48
DUAL THERAPY if HbA1c >58, aim for <53
How do you manage T2DM first line
- Metformin max 2g/day
What is MoA of metformin
increases insulin sensitivity
decreases hepatic gluconeogenesis
side effects of metformin
appetite suppression, diarrhoea, lactic acidosis
what do you do if metformin is causing diarrhoea
change to modified release
when is metformin contraindicated
if eGFR <30
if tissue hypoxia e.g. MI, surgery
When do you upscale to adding another drug to metformin
when HbA1c >58
what classes of drug can you add to metformin
sulphonylurea
thazolidinedione
gliptin
SGLT2 inhibitor
how do sulphonylureas work
by stimulating insulin production in the pancreease
side effects of sulphonylurea
weight gain, HYPOGLYCAEMIA
give examples of sulphonylurea
glibenclamide
gliclazide
what is method of action of gliptins
DPP4 inhibitor – stops the body from destroying incretin, which controls insulin production
give example of gliptin
SITAGLIPTIN
when is a sulphonylurea contraindicated
when patient is already fat
or if ketoacidotis
give example of SGLT 2 inhibitore
Empaglifloxin
What can you give if triple therapy for T2DM?
Metformin + sulphonyluria + other
what can you give for T2DM after triple therapy?
Metformin + sulphonylurea + GLP1 analogue
Why does HHS cause high glucose but not high ketones
because there is insufficient insulin to drive glucose into cells
but still enough insulin to inhibit ketone production
List causes of hyperthyroidism
- Graves disease
- Toxic multinodular goitre
- Toxic adenoma
– these are high uptake on RI scan –
4. Viral thyroiditis , subacute thyroiditis
5. Post partum thyroiiditis
What occurs in Graves disease
Anti TSH R antibodies (igG)
This leads to increased thyroid function and thyroid growth
what are the three key SS of Graves disease
- Diffuse smoothlly enlarged GOITRE
- OPTHAMOPATHY (exomthalmos) (protruding eyes, due to THSr Ab on eye muscles)
- pretibial myxoedema
may also have LID LAG
How do you investigate suspected graves
T4, TSH serum
Anti TSH R Ab
Annti TPO Ab
How do you manage Graves
- Beta blocker PROPANOLOL ( to control sx)
- Anti thyroid drug (e.g. carbimazole, propilthiouracil) with aim of titrating down and stopping
- Radioiodine
- Surgery - last resort
causes of hypothyroidism
- Hashimotos
- Viral thyroiditis, post partum
- Iatrogenic
- Iodine deficiency
- Subclinical thyroiditis
What is Hashmoto’s
AI cause of HYPOTHYROIDsm
due to anti-TBO Ab
Iatrogenic causes of hypothyroidism
Post-graves disease (due to tx)
Drugs (amiodarone, lithium)
How do you manage hypothyroidism
Thyroxine - aim for normal TSH
what will extreme hypothyroidism cause and how does it present
it causes MYXOEDEMA COMA
presents as hypothermia, hyporeflexia, bradycardia, seizures
How do you manaage myxoedema coma
IV tyroxine
IV hydrocortisone
fluids
Where and what hormones are produced by the adrenal
ZG: Mineralocorticoids (ALDOSTERONE)
ZF: Glucocorticoids (Cortisol)
ZR: Androgeens
Medulla: Adrenaline, NA
What triggers production of cortisol
the HPA axis (CRH > ACTH >cortisol)
what is aldosterone produced in respnse to
increased sodium to KIDNEYS
decreaseed perfusion to kidneys
SNS axctivation
what can aldosterone bond to
Mineralocorticoid R
What does aldosterone induce
SODIUM REABSORTPION > WATER REABSORPTION
POTASSIUM EXCRETION
what is the fucntion of glucocorticoids
to regularte glucose balance
What are causes of adrenal insufficiency
PRIMARY: Addison’s (AI) or TB, causing adrenal gland destruction
SECNODARY: Pituitary adenoma / sheehan’s
TERTIARY: brain tumour
How does adrenal insufficiency prsent
fatigue, anorxia, WL
nausea, vomiting, abdo pain
hyperpigmentation (raised ACTH)
low BP (insufficient fluid and salt retention)
How do you investigate adrenal insufficiency
- 9AM cortisol – if LOW: suspect
- adminisrter short synachten test
How do you manage adrenak insufficiency
Hydrocortisone (GC) and fludrocortisone (MC)
+ treat cause
HJow do you manage acute addisonian crisis
- IM hydrocortisone»_space; IV fluid bolus + glucose
What are the two sizes of a pituitary adenoma
microadenoma <1cm
macroadenoma > 1cm
Whayt is the commonest type of pituitary adenoma
PROLACTINNOMA
presentation of prolactinoma
impotence, infertility, decreased libido, galactorrhoea, amenorrhoea, osteoporosis
depletion of hormones > hypopituitarism
headaches
bitemporal hemianopia
prolactinoma mx
Bromocriptine, cabergolien
transnasal hypophysectomy
what is cushings syndrome caused by
EXCESS CORTISOL
Exogenous GC therapy
Endogenous:
- ACTH dependent (Cushings disease, ectopic ACTH production from SCLC)
- ACTH independeenrt (steroids, adrenal adenoma, adrenal carcinoma)
what is CUSHINGS DISEASE
Excess ACTH from pituitary gland, usually due to pituitary tumour
Sx of cushings syndrome
personality changes, irritability
rounded face
interscapular fat pad
gynaecomastia (men )
purple striae, thin skin, easy bruising , petechiae
increaseed susceptibility to infectionn
osteoporosis
PROXIMAL MYOPATHY
Ix for Cushings syndrome
- 11pm salivary cortisol (if low, not cushing’s)
- LDDST
- Inferior petrosal sinus sampling (identifies pituitary disease)
What does LDDST show
after dexamethason:
- if cortisol is low > normal suppression
- if cortisol is still high > confirmed Cushings synsrome, perfomr IPSS
How do you manage pituitary adenoma
surgical removal
How do you manage adrenal mass causing Cushing syndrome
Adrenalectomy + steroid replacement
What is Conns syndrome
Excess ALDOSTERONE ONLY > excess salt and water reabbsorption, excess potassium excretion
causes of Conns syndrome
adrenal adenoma
adrenal hyperplasia (bilateral)
How does Conns present
HTN refractory to tx
hypokalaemia (muslce weakness, parasthesia, tetany)
How do you ix Conns
Plasma aldosterone / renin ratio
What is Plasma aldosterone / renin ratio like in Conns
- result in Conns will be HIGH as very high aldosterone switches off renin production
What is Plasma aldosterone / renin ratio like in RAS
ARR normal
becuase it is the high renin that raises aldosterone
How do you manaage CONNS
spironolactonee / eplerenone > surgery
avoid surgery in elderly
How does PTH control calcum
HIGH PTC causes:
- increased Ca resorption in bone
- increased Ca absorption in GI
- decreaseed Ca excretion in kidney
- increased 1alpha hydroxylase»_space; activates vit D
how does PTH affect vit D
It causes activation of Vit D to 1,25OH2D
by triggering 1a hydroxylase production in kindey
what does 1,25(OH)2D cause
increased Ca absorption in GI
Decreased excretion of Ca in kidney
what must you check first in hypercalcaemia
PTH serum
what does PTH in ypercalacemia tell you
Low PTH: hypercalcaemia of malignancy
- bone mets
- PTH producing Squamous cell carcinoma of lunng
- myeloma
Normal/high PTH: PRIMARY HYPERPARATHYROIDISM
- PT carcinoma
- adenoma
- hyperplasia
Symptoms of hypercalcaemia
Bone pain, fractures
Stones - renal stones
abdo groans - peptic ulcer, constipation, pancreatitis, polyuria, poluyfipssia
psychic moans - depression
How do you treat hypercalcaemA
fluids 3-4 L/day
biphosphonates if bone mets
treat cause
what is secondary hyperparathyroidism and why does it occur
raised PTH due to LOW calcium
caused by:
- chronic renal failure
- vit D deficiency
what is tertiary hyperparathyroidism
continously raised PTH even once calcium normalises / becomes high +
due to end stage renal failure
how do you manage tertiary HPT
parathyroidectomy
what are blood results in pagets
raised ALP
everything lse normal
because this is a disease of excessive bone turnover
causees of B12 deficiency
Pernicious anaemia (AI)
Atrophic gastritis
Gastrectomy
Malnutrition
Signs of B12 deficiiency
Anaemia (lethargy, pallor, dyspnoea)
Neuro (peripheral neuropathy, weakness, ataxia, parasthesia)
Glossitis
Mild jaundicee
Ix for B12 deficiency
FBC (macrocytic anaemia, hypersecomented neutrophils)
b12 level
Anti IF Ab
Anti parital cell antibodies
management B12 deficiency
Severe: IM vitamin B12 (hydroxycobalamin, 3x weekly for 2 weeks, then three monthly injections)
Mild-moderate: PO / IM B12
How does subclinical hypothyroidims present on biochemistry?
High TSH
Normal T4
what do you do with someone presenting with subclinical hypothyroidism
Repeat bloods in 6 weeks
What do you do if repeat TSH is elevated in subclin hypothyroidism?
TSH >10 : levothyroxin
TSH 5-10 + postive autoantibodies : repeat bloods in 1 year
TSH 5-10 and -ve antibodies : repeat bloods in 3-5 years
causes of HYPOCALCAEEMIA
- PTH failure
- Low vit D
- Pancreatitis
- Hypomagnesaemia
How do you investigate a thyroid neck lump that you are concerned about?
- TFT
- thyroid autoaantibodies
- Thryoid USS +- fine needle aspirate
- thyroid uptake scan
how do ytou manage thyroid cancer
hemi thyroidectomy + iodinine
side effect of carbimazole
neutropoenia
what is contraindication of giving radioiodine in graves disease
contraindicated in pregnancy or eye disease
what is complication of surgery to treat Graves
damage to recurrent laryngeal nerve > hoarseness
causes of HYPERNATRAEMIA
DEHYDRATON - LOSS OF WATER
- GI loss
- Sweat loss
- Renal loss (diabetes insipidus, diabetes mellitus)
INCREASE IN SODIUM
- iatrogenic
- high dietary intake
- Conn’s
- RAS
How do you tell apart Conn’s drom RAS
Using aldosterone : renal ratio
in CONNS, ARR is HIGH
In RAS, it is normal
how do you invesrigate HYPERnatraemiia
volume state - physical examination
- serum glucose (exclude diabetes)
- serum K+ (raised > Conn’s. Low > nephrogenic DI)
- plasma and urine osmolarity (hyperaldosteronism: high plasma osmolarity)
- Water deprivation test (diabetes insipidus()
what test can you do for diabetes insipiitdu
water deprivation test
- neurogenic responds to ddavp
- nephrogenic does NOT respond
How do you treat hypernatraemia
Correct water deficit if dehydrated with 1L 5% dextrose IV over 8-10h
treat cause
complications of hypernatraemia
RAPID HYPERnatraemia correction> cerebral oedema
causes of HYPONATRAEMIA (by fluid status)
HYPOVOLAEMIC:
- diarrhoea
- vomiting
- diuretics
EUVOLAEMIC: (E=endocrine)
- SIADH
- Hypothyroid
- Adrenal insufficiency
HYPERVOLAEMIA: (overloaded = organ failure)
- liver failure
- CCF
- renal failure
what occurs physiologically in the kidneys if hypovolaemic and how does it affect sodium concentration?
kidneys increase sodium reeabsorption
this draws in water
this decreases urinary sodium
How can we interpret urinary sodium in the context of hyponatraemia
urinary sodium LOW: this is due to hypovolaemic state (kidneys functioning as normal)
urinary sodium HIGH (above 20): SIADH
what are the two hormones that regulate sodium absorption
aldosterone
ADH
how does aldosterone work
bids to Mineralocorticoid R
Increases NA reabsorption> pulls in water
how does ADH work
inserts aquaporin channels > water reabsorption
what mx required in hyponatraemia?=
HYPOVOLAEMIC: IV fluids (0.9% saline) slowly
Euvolaemic / HYPERvolaemic: fluid restrict + treat cause
SEVERE hyponatraemia <120 : 3% isotonic saline
what do you do if patient is severely hyponatramemiic (<120)
slow 3% salin
what drugs can you give for SIADH
Demeclocycline (induce nephrogenic DI, reducing responsiveness of collecting tubes to ADH )
Tolvaptan (V2 receptor antagonist)
what ix do you do for SIADH
plasma osmolarity and urine osmolarity
plasma will be low, urine will be high
complication of treating hyPOnatraemia too fast
cerebral POntine myelinolysis
Causes of HYPERkalaemia
DECREASED RENAL POTASSIUM EXCRETION
- Low GFR (poor kidney functon> insufficient K excreton)
- Low renin (T24 RTA, NSAIDS)
- ACEi
- ARBs
- Addison’s (no aldosterone > no K+ excretion)
- Aldosterone antagonist (counters aldosterone effect, eg spironolactone)
INCREASED POTASSIUM RELEASE FROM CELLS
- rhabdo
- acidosis
summartise drugs that cause HYPERKALAEMIA
NSAIDS
ACE i
ARBs
Spironolactone
Whhat is presentation of hyperkalaemic pt
muscle weakness and lethargy
fatigue
parasthesia
palpitations
ECG in hyperkalaemia
TALL N TENTED T WAVE
Broad QRS
Flat P wave
Prolonged PR interval
Eventual SINE WAVE > > cardiac arrest
causes of HYPOKALAEMIA
- GI loss (diarrhoea)
- renal loss (loop and thiazide diuretics, excess MR with Conns, Cushings)
- redistribution into cells (insulin / insulinomas, beta agonists, alkalosis)
mx hypokalaemia
K+ >2.5: 2 sandoK tablets TDS for 48h
K+ <2.5 or symptoms /ECG: 3x 1L NaCl with 40mmol KCL over 24h
sick euthyroid cause
acute illness – abnormal thyroidd results but will normalise oncee illness resolves
sick euthyroid biochemistry
Normal or low TSH
low T3 and T4
how do you investigate acromegaly
serum IGF1
to confirm dx, do an OGTT with GH measurement
what do you need to give in refeeding syndrome
phosphate
causes of SIADH
CNS pathology - stroke, haemorrhage, tumour
Lung pathology - pneumonia, pneumothorax
Drugs - SSRI, TCA, carbamazepine, sulphonylurea
Tumour
Surgery
what occurs with SIADH
Excess ADH > increased water retention > increased volume >RAAS suppressed > less aldosterone > less water absorption
So HYPOnatraemia with EUvolaemia
how do you treat MODY
MODY is very sensitive to sulphonylureas
