PR3152 IC15 + 11(thyroid) Flashcards
physiological functions regulated by thyroid hormone?
overall: increases oxygen consumptions by tissues and increases basal metabolic rate.
- Body temperature
- CNS
- Sleep
- Cardiac function
- GI function
- Muscle strength
- Breathing
- Menstrual cycles
- Skin dryness
- ↑ Lipid metabolism
- ↑ uptake and utilization of glucose
negative feedback involved in thyroid hormone regulation?
when thyroid hormone levels are low,
the hypothalamus detects the low levels and produces TRH (thyrotropin receptor hormones) = binds to pituitary gland, which causes the release of TSH (thyroid stimulating hormones) = act on the thyroid gland to release T3 and T4.
when T3 and 4 levels are sufficiently high, this will induce negative feedback on both hypothalamus and pituitary gland to reduce TRH and TSH production
how will TSH react to hypo and hyperthyroidism?
hypothyroidism:
TH levels are low = detected by the hypothalamus to increase TRH release = stimulate pituitary gland = release more TSH = increase TSH levels
hyperthyroidism
TH levels are high = detected by the hypothalamus to decrease TRH release = stimulate pituitary gland = release less TSH = decrease TSH levels
properties of T3 and T4
include the t1/2
T3:T4 ratio is 1:4
T3 is more potent and 80% is from deionisation of T4 by deiodinase.
Both are highly protein bound
T3 half life 2 days
T4 half life 6-7 days
purpose of unbound T4?
FT4 is used to evaluate thyroid status (together with TSH)
what causes thyroxine-binding globulin to increase
pregnancy and estrogen use will increase TBG, thus reducing the available FT3 and FT4
= hypothalamus will be stimulated to increase TRH = TSH increase by pituitary gland.
what are some autoimmune antibodies related to the thyroid?
include the type of disease that causes these antibodies
ATgA : thyroglobulin antibodies
TPO: thyroperoxidase antibodies
TRAb: thyrotropin receptor IgG antibodies
ATga and TPO found in Graves and Hashimoto
TRAb specific to Graves (confirms)
Indications for screening of thyroid antibodies
1) psychiatric disorders (may be indicative of thyroid abnormalities)
2) history of neck or head radiation due to malignancy
3) presence of autoimmune disease
4) first degree relative to someone with autoimmune thyroid disease
5) amiodarone/lithium (affects thyroid levels)
6) symptoms of hypo or hyperthyroidism
which populations should thyroid antibodies be routinely tested?
all pregnant and pediatric patients to be routinely tested
may cause developmental issues
what are the two classes of hypothyroidism (and their causes)
primary
- iodine deficiency
- hashimoto
- iatrogenic: thyroid resection or RAI ablation
secondary
- central hypothyroidism = related to hypothalamus and pituitary
- drugs = amiodarone, lithium
what are the symptoms of hypothyroidism
weight gain = decrease metabolic function
intolerance to cold = decrease metabolic function
fatigue = decrease metabolic function
slow reflexes
brittle nails, coarse hair
cardiac (bradycardia) = thyroid cathecolamine = increase HR
goiter
menstrual disturbances
periorbital swelling
what are the clinical presentations of hypothyroidism
increased risk of
- miscarriages
- cardiac problems (atherosclerosis, MI)
impaired fetal cognitive development
increased CPK (creatinine phosphokinase)
increased total cholesterol, including TG, LDL
what lab values to track for thyroidism?
TSH and T4
what is the first line drug option for hypothyroidism?
Describe drug admin, monitoring info, goal, counselling
Levothyroxine
Synthetic T4
Dosing
- young healthy adult: 1.6mcg/kg/d
- 50-60 yo: 50mcg OD
- CVS: 12.5-25mcg/d
Dose titration
Dose titration by 12.5-25mcg per day increments (or 10-15% increments)
Counselling
- symptomatic relief in 2-3 weeks
- take 30 min before breakfast or 4h after breakfast (usually higher for high fibre, calcified fortified foods or alkaline water)
- atleast 2h apart from polyvalent ions (antacids)
- treatment is lifelong
Goal
- 0.4-4mIU/L TSH
if central hypothyroidism = use free T4
Monitoring
- assess after 4-8 wks from initiation
- then biannually to annually once euthyroid (NON PREGNANT)
ADR of levothyroxine
ADR:
- hyperthyroidism
- cardiac abnormalities
- increase bone fracture risk
- Reduced appetite, Anxiety, Diarrhea, Difficulty sleeping, Hair loss
- Seizure
what are the PK parameters for levothyroxine
A
F=70-80%
Onset 3-5 days
Absorbed in the duodenum and jejunum (affected by gastric pH and dietary fibre)
D
t1/2 = 7 days
>99% plasma protein bound
M
liver, by glucuronidation and sulphation
E
kidneys excrete t3and4
metabolites excreted via faeces
what does myxedema coma do to levothyroxine?
it is a severe form of hypothyroidism that affects the gut absorption of levothyroxine.
recommended to take IV versions instead.
how to see non adherence to levothyroxine
when the patient TSH is consistently high while there is normalisation in the T4
not enough time to correct the negative feedback loop
what are the different monitoring parameters for levothyroxine if diff thyroid causes (primary vs central
for patients with central hypothyroidism, use free t4 to measure thyroid status as TSH
because TSH will be low due to poor function of the hypothalamus/pituitary gland = unable to increase TSH
in primary hypothyroidism, TSH will increase in response to low T4. Hence TSH can be used as an indicator for thyroid function
what is liothyronine
Describe drug admin, ADR, half life
synthetic T3
25mcg unless patient is elderly or CVD, then 5cmg
high ADR rate
t1/2 = 1-2.5 days
what is the indication for liothyronine
myxedema coma
combination with t4 is patient symptoms unresponsive to T4 monotherapy even though TSH has been normalised
if there is a need to rapidly increase thyroid hormone rate in a medical emergency
effect of maternal hyothyroidism?
1) increased risk of miscarriage, spontaneous abortion
2) congenital defects, cognitive impairment risk
why is TH needed in pregnancy?
TH is provided by the mother for up to 12 weeks until fetus develops his own thyroid glandsw
what are the changes to treatment regimen for levothyroxine in pregnancy (include treatment goals as well) FOR HYPOTHYROIDISM
increase levothyroxine dose by up to 30-50 percent to reach euthyroid state (TBG increases in pregnancy)
goals (per trimester)
1st <2.5
2nd <3.0
3rd <3.5
progressively more tsh so more th production
what is subclinical hypothyroidism?
when TSH is increased despite T4 being at normal levels
could be a sign of early Hashimoto
what are the risks of subclinical hypothyroidism?
> 7 and in older pts = increased CVS risk
10 = increased congestive heart disease
when is treatment indicated in subclinical hypothyroidism (include regimen)?
> 10 = yes
4.5 - 10 + risk factors:
- symptomatic
- risk factors for CVD or current CVD
- TPO antibodies
initiate on levothyroxine 25-75 mcg
patients are to be screened regularly
what are the causes of hyperthyroidism?
graves disease
toxic adenoma (toxic nodule) = single nodule producing T3
toxic multinodular goiter (plummers disease) = multiple nodules producing T3
pituitary adenoma
drug induced (amiodarone, lithium)
subacute thyroiditis = infection, drug induced, hashimoto
= release of thyroid stores
symptoms of hyperthyroidism?
THYROIDISM-E
tremor
hr INCREASE
yawning (fatigue)
restless
oligomenorrhea/amenorrhea
intolerant to heat
diarrhoea
irritability
sweating
muscle wasting/weight loss
exophthalmos
diagnosis for hyperthyroidism?
S/SX
Free T4
TSH = suppressed
antibodies present: ATgA, TPO, TRAb
Biopsy
RAIU (radioactive iodine uptake)
- elevated if adenoma/goiter/graves
- not elevated if thyroiditis/cancer
treatment options for hyperthyroidism? (non phx)
Thyroidectomy
RAI ablation
Surgical resection
Thyroid medication
indications and contraindications for RAI ablation?
indication:
graves
contra:
pregnant
how does RAI ablation work?
radioactive iodine destroys overactive thyroid cells
when is thyroid medication indicated in hyperthyroidism
when awaiting for surgical resection/etc
limited life expectancy
not on surgery/failure to normalise thyroidn
mild disease/small goiter/negative or low antibody titre/ women
thionamides dosing, monitoring?
Carbimazole (1st line for graves) and Propylthiouracil (PTU)
Dosing:
Carbimazole: 15-60mg/day BD-TDS, reduce to 5-15mg once euthyroid
PTU: 50-150mg BD-TDS, reduce to 50mg BD-TDS
Monitoring:
- 4-6 wk onset (long half life of t4+ take time to deplete t4 stores)
- low remission (ie. stopping = normalised t4 and tsh)
- monthly titration (ESP if hypothyroidism, downtitrate once reduced thyroid size and normal TSH) depending on t4 and symptoms (tsh may be suppressed, early in therapy t3 may be a better marker)
thionamid ADR
ADR:
- Hepatotoxicity (higher in PTU, is boxed warning)
- Rash, SJS
- Agranulocytosis in first 3 months (dec neutrophils)
- Fever
- joint pain
- jaundice
(bolded for carbimezole)
thionamides MOA
Carbimazole (1st line for graves) and Propylthiouracil (PTU)
MOA: Acts on TPO to inhibit iodination and synthesis of thyroid hormones.
PTU also blocks conversion of T4 to t3 in the periphery at high doses
what are the PK parameters for carbimazole
A:
- converted to methimazole in serum after absorption
D:
- of methimazole
- t1/2 = 4-6h (clinical effect last 1 day because concentrated in thyroid)
- no binding to plasma proteins
- will stop iodination >90% in 12hours
M:
- CYP450
- FMO
E
- >90% oral excreted as metabolites in urine, rest in faeces (undergoes enterohepatic recirculation)
- around 7% of methimazole excreted unchanged in urine
what happens during hyperthyroidism in pregnancy?
- no weight gain despite good appetite
- bradycardia
- possible fetal loss
use of thionamides in hyperthyroidsm pregnancy (and any dose adjustments)
risk of thionamides in pregnancy causing embroyopathy
decrease to lowest dose possible and keep t4 at upper normal limit
1st trimester: use PTU as carbimazole has risk of congenital malformation
2nd and 3rd trimester: use carbimazole as PTU has risk of hepatotoxicity
what is the MOA and indication for propanolol in hyperthyroidism?
propanolol used to reduce hyperthyroid manifestations
can block t4 to t3 conversion in high doses
indicated for
- symptom relief
- bridging therapy before thionamide symptom relief or before surgery etc
- management of thyroiditis (usually self limiting)
- PRN FOR high risk patients eg CVS and elderly
what is the MOA and indication for iodide in hyperthyroidism?
Lugol’s solution, saturated solution of potassium iodide
MOA: Inhibits the release of stored THs.
Minimal effect on hormone synthesis.
Helps decrease vascularity and size of gland
(usually limited efficacy after 7-14 days due to TH release resume)
Indication
* Before Surgery (7–10 days) to shrink the gland
* After ablative therapy (3–7 days) to inhibit thyroiditis-mediated release of stored TH
* Thyroid storm
contraindications for iodide therapy in hyperthyroidism?
up to 3 days before RAI ablation as it might reduce the uptake of RAI
what is subclinical hyperthyroidism and what are the risks
low to undetectable TSH with normal T4 levels
risks:
- > 60 = increased HF risk
- POSTmenopausal women = increased bone fractures risk
what is the indication and treatment for subclinical hyperthyroidism?
indicated (more compelling) if TSH <0.1mIU/L
(except young patients)
1st line: ablative
2nd line: PO
include BB for HF risk
if untreated
= screen regularly for the overt hyperthyroidism
how does amiodarone cause thyroid disease
Contains iodine in its chemical structure
* Affects iodine uptake, secretion, production; causes thyroiditis
* May cause hypo- or hyperthyroidism
how does lithium cause thyroid disease
Inhibits thyroid hormone secretion and release, thus signaling an increase in
TSH and possible goiter development (hypo)
* Thyroiditis (hyper)
how does interferon alfa cause thyroid disease
Thyroiditis (hyper then hypo)
