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
