Drugs in endocrinology

Question 1

CASE HISTORY - THYROID

i) what does needing additional layers of clothing to stay warm and loss of lateral 1/3 of eyebrow point towards a dx of?
ii) what does hyperpigmentation of palmar creases and buccal mucosa point towards?
iii) what T4/TSH picture is seen in primary hypothyroidism?
iv) what test should be done if hypothyroid symptoms are seen? explain
v) what is the problem with starting levothyroxine straight away if there are a mixture of symptoms

Answer 1

i) hypothyroid
ii) addisons (adrenal insuffic)
iii) primary hypothyroid is low T4 and high TSH
iv) do 9am cortisol to check for adrenal insuffic then if satisfactory start levothyroxine 100mcg daily (schmit syndrome = multiple AI conds cluster together)
v) if patient has adrenal insuff then levothyroxine can increase hepatic steroid metab which causes even lower steroid levels which can cause an addisonian crisis

Question 2

THYROXINE TREATMENT

i) what is schmidt syndrome? how does thyroxine affect this?
ii) what is the drug of choice for hypothyroidism? what actually is it?
iii) why should thyroid drugs be given on an empty stomach?
iv) name two instances patients should be started on a lower dose?
v) what is liothyronine? how quick does it work? who should it be avoided in? why is a downside to this medication

Answer 2

i) addisons and hypothyroid and or T1DM (part of larger polyglandular autoimmune syndrome type 2)
- thyroxine enhances hepatic corticosteroid metab therefore further ppt addisons >crisis

ii) levothyroxine = inactive T4
iii) give levothyrox on an empty stomach to improve absorption (give 30 mins before other meds/coffee/food)

iv) start on a lower dose in frail patients and those with cardiac dysfunc
- start on 24mcg then slowly increase (too much can ppt HF)
- start on 100mcg in fit patients

v) liothyronine is active T3 > has rapid onset
- short half life (24-48hrs) and needs to be avoided in those with cardiac disease (can ppt cardiac events)
- expensive

Question 3

METABOLISM OF THYROID HORMONES

i) by what mechanism are thyroid hormones metabolised?
ii) where is 80% of T3 derived from?
iii) which organ is the major site of degred for T3 and T4?

Answer 3

i) sequential deiodination
ii) 80% of active T3 is dervied from periph T4 by monodeiodination
iii) liver is the major site for degred

Question 4

MYXOEDEMA COMA

i) name five things a patient may present with?
ii) what will thyroid levels be?
iii) what is the correct tx?
iv) what causes it?

Answer 4

i) confused (low GCS), cold, loss of lat 1/3 eyebrow, signif leg oedema, SPB, hypothermic, brady, hypothyroid
ii) hypothyroid

iii) need to warm the patient, give IV T3/T4 and IV hydrocortisone (may be hypoadren)
- give IV levothyrox 300-400mcg then 50 mcg oral daily or give IV liothyronine 20mcg followed by 10mcg 9 hoursly til clinical improvement is seen

iv) caused by profound hypothyroidism untreated for a long time - can be life threatnening

Question 5

HYPOTHYROIDISM AND PREGNANCY

i) what should be done to dose of levothyrox when patient is pregnant? why?
ii) is most T3/T4 bound or unbound? what % is in the free form? which form determines the overall thyroid activity in the body?
iii) what happens to protein binding levels in pregnancy? what does this cause?
iv) when does the fetal thyroid develop? what needs to therefore happen at this time?

Answer 5

i) increase levothyrox dose to 125mcg daily (if usually on 100)
- there is an increase in thyroid binding globulin in pregnancy therefore there is less free T3/4

ii) most T3/4 is bound to proteins (70% ot TBG) and <0.5% is in free form
- the free form is what is measured by assays and is what determines overall thyroid activity in the body

iii) more TBG in pregnancy therefore less free thyroxine available

iv) fetal thyroid dev in 1st trimester > most important to have enough thyroid hormone here so the baby does not go hypothyroid
- need a 20-30% inc in thyroxine dose when finding out pregnant

Question 6

GRAVES DISEASE

i) what is it?
ii) give four symptoms a patient may present with
iii) give three features of graves opthalmopathy
iv) what should be done if a dx of graves is suspected? (5)

Answer 6

i) autoimmune hyperthyroidism > binding of TRAB > overprod thyroid hormone
ii) present with weight loss, palpitations, feeling hot, swelling in neck, grittiness in eyes
iii) proptosis/exopthalmos (bulging eyeballs), lid retraction, swollen conjunctiva

iv) check TSH receptor antibodies
start carbimazole (40 mg OD) and ensure contraception is being used
give beta blockers
refer to endo/opthalmology

Question 7

CARBIMZAOLE

i) how does it work?
ii) name three side effects
iii) what is the most serious side effect? what are the signs of this (3)
iv) what can happen if it is used in pregnancy? what should be used instead?

Answer 7

i) reduces uptake and conc of inorganic iodine by thyroid
- prevents thyroid peroxidase enzyme from coupling and iodinating the tyrosine residues on thyroglobulin therefore reducing prod of thyroid hormones T3 and T4

ii) side effects - GI, hair loss, arthralgia (joint pain)

iii) agranulocytosis is serious SE - low neutrophils > risk of sepsis
- signs = sore throat, mouth ulcer, non spec fever and illness
- need to stop carbimazole and go to A&E > do FBC and if neuts are ok then continue carbimazole

iv) teratogenic > can cause aplasia cutis (skin malformation
- use propylthiouracil instead

Question 8

PROPYLTHIOURACIL

i) how does it work? (2)
ii) name two side effects?
iii) what is the most serious side effect? what must therefore be monitored?

Answer 8

i) inhibits thyroid peroxidase as well as inhibiting conversion of T4 to T3 peripherally (dual effect)
ii) same as carbim > GI, hair loss, arthralgia
iii) fulminant liver failure > monitor LFTs

Question 9

THYROID STORM

i) what is it? give four presenting symptoms
ii) what is treatment directed at?
iii) name four potential treatments? which one is contra indicated in asthma?
iv) what two other things also need to be done

Answer 9

i) hypermetabolic state due to increased release of thyroid hormone
- weight loss, palpipation, fever >38, very tachy

ii) tx directed at thyroid hormone synthesis and secretion from thyroid

iii) carbimazole/propylthiouracil
lugols solution (aq iodine oral solution to decrease thyroid hormone syn)
beta blockers (IV propanolol then oral) - contra indic in asthma, use diliazem
hydrocortisone to decrease T4>3 conversion (and may have co existing hypoadren)

iv) need to determine the ppt cause eg infection
need to give supportive and symptomatic therapy eg resus with o2 and fluid, keep cool, paracetamol

Question 10

ADRENAL INSUFFICIENCY

i) name two presenting features that may be seen? what may these co present with?
ii) name three specific things to be checked in the blood
iii) how is it treated?

Answer 10

i) tanning of skin, hyperpigmentation of palmar creases, post hypotension
- can co present with other AI Diseases such as vitiligo, diabetes and hypothyroid

ii) check cortisol levels, renin levels (will be high as aldo isnt rel from adrenals therefore low BP therefore renin rel to raise it), adrenal cortex antibodies
iii) treat with hydrocortisone and fludrocortisone orally combined (can also just give high dose HC as this also covers MC activity at high doses)

Question 11

STEROIDS

i) name a low, med and high potency steroid? how does half life vary with potency?
ii) what are sick day rules?
iii) name three side effects

Answer 11

i) low = hydrocortisone
med = prednisolone
high = dexamethasone
- inc potency - inc half life

ii) sick day rules - double steroid dose if unwell
- give IM/IV is vomiting

iii) GI symptoms, thin skin/bruising, iatrogenic cushings

Question 12

FLUDROCORTISONE

i) what is it? what does it replace?
ii) what action does it have? (2)
iii) what dose should be started?

Answer 12

i) mineralocorticoid
- replaces endogenous aldosterone

ii) increases sodium reabs and potassium excretion
iii) start at 50-100mcg then titrate according to symptoms

Question 13

PITUITARY APOPLEXY (bleeding of a pit tumour)

i) give four things a patient may present with?
ii) what will blood tests show?
iii) what should be done first in A&E?

Answer 13

i) postural hypotension, visual blurring (bleeding can aff optic chiasm), lethagy, thunderclap headache
ii) low sodium, normal potassium

iii) give IV hydrocortisone 100mg and 0.9% NaCl
- then can do fundoscopy, arrange opthal/endo review

Question 14

DIABETES INCIPIDUS

i) give three things a patient may present with
ii) what will cortisol and sodium levels be?
iii) what should the a&e doctor do? (4)
iv) what does the water deprivation test do? how can this be used to determine the cause of DI?

Answer 14

i) thirst, polyuria, headache, arthralgia, swollen fingers and feet
ii) high sodium and low cortisol

iii) start hydrocortisone and arrange water deprivation test
growth hormone measurement
check TFT/cortisol/PRL
MRI pituitary
visual fields

iv) deprive water and see if they concentrate urine
- if they respond to desmopressin then it means the response is in tact but ADH is not rel from PG therefore cranial DI

Question 15

DESMOPRESSIN

i) what endogenous hormone does it mimic?
ii) why is noting the route of admin so important?
iii) what is the once per week drug holiday? who may this not be suitable for?
iv) what is its mech of action?

Answer 15

i) mimics vasopressin (increases water reabs so patient urinates less)
ii) diff routes of admin have very different dosages eg oral tablet is 100micrograms but IV/subcut is 1 microgram

ii) drug holiday - have a break from the drug once per week
- lets patient urinate as normal to clear excess fluid build up from desmo
- patient needs to have in tact thirst mech therefore not suited to people with traumatic brain injury etc

iv) mech - increases water reabs via AQP2 in the CD
- binds ADH R > aden cyc> cAMP > inc AQP2 transcription therefore more water reabs and patient urinates less

Question 16

TESTOSTERONE THERAPY

i) what LH, FSH, cortisol levels may someone who is hypogondal be?
ii) what is first given to men that are hypogonadal? what may this then progress to
iii) name three things that must be monitored when on testosterone treatment? why?
iv) why do you aim for low levels of normal testosterone?

Answer 16

i) low LH, FSH, cortisol

ii) give testos gel/cream first (monitor 4hrs post admin)
- then can progress to injection (longer lasting) monitor just before next injection

iii) test PSA annually as it can unmask prostate cancer
- FBC as it can increase viscosity of blood so look at haematocrit
- also monitor LFT

iv) aim for low levels of normal as aromatase enzyme will start converting testos to oes if levels are too high

Question 17

DIABETES TX OVERVIEW

i) what tx is given for T1DM/T2DM/MODY/pancreatic diabetes?
ii) at what HbA1c level should metformin be given if lifestyle change has not helped? what can be given if metformin is contrainidcated?
iii) which drug class have proven CVD benefits? (2)
iv) which drugs may reduce HF and or CKD?

Answer 17

i) T1 - insulin
T2 - diet/oral/insulin/GLP1
MODY - no tx/oral eg SU/insulin
panc diabetes - similar to T1DM

ii) HbA1c >48 (T2DM) give metformin
- if met is contrainidc then give DDP-4 inhibitor or an SU

iii) CVD - GLP1 or SGLT2 inhibitor if eGFR is adequate

iv) SGLT2 inhib for HF if eGFR is adequate
- GLP1 if eGFR isnt good enough

Question 18

METFORMIN

i) what two things does it to in tissues?
ii) name three side effects?
iii) which two situaitons should it be avoided in? what can be given instead?
iv) how often should renal function be monitored if RFs or deterioration is suspected?

Answer 18

i) increases periph utilisation of glucose and decreases gluconeogenesis to overall decrease glucode levels
ii) lactic acidosis (rare but serious), GI symp (abdo pain, D+V, nausea), decreased B12 abs, hepatitis

iii) avoid in tissue hypoxia or if GFR<30 (stop temp if dehy or AKI)
- can give linagliptin instead as it is fecally excreted (not renal ex)

iv) monitor renal func at least annually or twice annually

Question 19

SULPHONYUREAS

i) how do they work? why are they only useful in certain situations?
ii) name three side effects
iii) give two cases they should be avoided in

Answer 19

i) increase insulin secretion therefore only useful if you have beta cells (not useful in T1DM or longstanding T2DM)
ii) hypogly, agranulocytosis, liver failure
iii) avoid in liver failure and renal impairment

Question 20

DPP4 INHIBITORS

i) what is their mech of action?
ii) name two side effects
iii) name two situations they should be avoided in? which drugs should they not be used with?

Answer 20

i) inhibit DPP4 to increase insulin secretion and lower glucagon secretion
ii) SE - pancreatitis and steven johnson syndrome (disorder of skin and mucus membranes)

iii) avoid in pancreatitis, renal failure (renally excreted therefore sub with linagliptin)
- dont use with GLP1 agonists

Question 21

GLP1 AGONISTS

i) how do they work?
ii) give three side effects
iii) name four things they should be avoided in? which drugs should they not be used with?
iv) when may they be discontinued?

Answer 21

i) bind to and activate GLP1 receptor to increase insulin secretion
ii) GI SEs (abdo pain, distention, GORD), pancreatitis, alopecia, anapylaxis

iii) avoid in pancreatitus, severe GI disease, elderly, renal impair
- dont use with DPP4 inhibitors

iv) discontinue if HbA1c drops less than 1% or weight drops less than 3% after 6 months of using

Question 22

SGLT2 INHIBITORS

i) how do they work?
ii) name four side effects
iii) name three situaitons they should be avoided in?
iv) why do sick day rules apply here?
v) which two things can these drugs benefit? why?

Answer 22

i) inhibit SGLT2 therefore reduce glucose reabs > glycosyuria
ii) SEs - euglycaemic DKA (wee out lots of glucose so gluc is not high but still hve DKA), genital infection, hypogly, inc risk of amputation
iii) avoid if previous DKA, if unwell (sick day), severe hepatic impair, foot ulcers, elderly
iv) sick day rules > stop medication of patient is sick as they may be dehydrated > ppt DKA

v) can improve BP and CV benefits
- weight loss due to glucose loss, Na loss in urine which decreases BP
- lose more fluid therefore decreased plasma vol and myocardial stretch > CV benefits

Question 23

GLITAZONES

i) what do they do?
ii) name four side effects
iii) give three situations they should be avoided in

Answer 23

i) reduce peropheral insulin resistance
ii) small inc in bladder cancer, increase HF risk, inc bone fractures, liver dysfunc, weight gain
iii) avoid in HF, haematuria/hx of bladder cancer, elderly (as ca risk inc with age)

Question 24

INSULIN

i) what is it the key tx for?
ii) name a short acting and intermed acting version?

Answer 24

i) key tx for T1DM

ii) short - novarapid, actrapid
intermed - humalog

Question 25

CASE HX - DKA

i) what should be given to a T1DM patient that is unconcious with low blood glucose?
ii) what should be given to a patient in DKA? why do they need potassium?
iii) should long acting insulin be omitted when giving fixed rate insulin infusion in DKA?
iv) once DKA is resolved - what should be given if patient is or is not eating and drinking?

Answer 25

i) glucagon 1mg IM

ii) fixed rate influsion of insulin and IV fluids
- need potassium replacement as insulin causes K+ to shift into cells therefore risk of hypokalemia

iii) dont omit long acting ins - just give 20% less when on fixed rate

iv) if not E+D - give variable rate insulin
if yes E+D - give novarapid with meal and stop fixed rate after 30 mins (as novarapid takes 30 min to take effect)