Thyroid Flashcards
What is the difference between T3 and T4
It is the # iodine groups Tri vs Tetra
What is the colloid cells funcitons?
Storage or the thyroid, Iodine, Tyrosine, Thyrogobulin (These are stored in the thyroid)
What are follicular cells?
Responsible for pumping T3/T4 into circulation
What are parafollicular cells?
Calcitonin release, which is responsible for blood serum.
How is T3/T4 made
Combination of mono or di-iodotyrosine (MIT +DIT= T3), DIT + DIT= T4
What is the physiological ration of T4:T3?
13:1 ish, population average that is
Why would the thyroid produce two different thyroid hormones?
Enables more mechanisms for homeostasis. Because T3 is more potent then T4,
Helps with homeostasis generally.
What is the synthesis and secretion of T3 and T4 controlled by
TSH which is controlled by thyrotropin-releasing hormone
Where T4 converted to T3?
Kidney and liver generally
What is the actions of T3/T4 in the Heart
Chronotropic and inotropic
What is the actions of T3/T4 in the Adipose tissue
Catabolic
What is the actions of T3/T4 in the muscle
Catabolic
What is the actions of T3/T4 in the Bone?
Developmental
What is the actions of T3/T4 in the Nervous system
Developmental
What is the actions of T3/T4 in the GUt
Metabolic
What is the actions of T3/T4 in the Other tissues
Calorigenic
What hormone is involved in the production of T3/T4 and is the main drug target?
Thyroid peroxidase
All T4 in circulation is produced in?
Thyroid
How much T3 is produced in thyroid?
Only about 20% as the remainder is converted from T4
How much more potent is T3 then T4?
approx 4x
How much of T4 is converted in the inactive rT3?
45%
What use to be an issue with old T3/T4 tests?
They use to test for all levels (Protein bound and unbound), where protein bound is inactive
How is thyroid hormone production regulated?
Negative feedback loop
How is TSH stimualted?
Low circulating T3/T4 levels and low serum iodide levels
Low serum iodide leads to a state of hypothyroidism
What is hormone release inhibited by?
High circulating T3/T4 levels
Lithium (Because its a molecule that mimics Iodide)
Iodide
What happens if you flood the thyroid with iodine?
Inhibits a process in the thyroid where it decreases T3/T4 production. It will escape that inhibition
It will lead to a temporary inhibition
What percentage of individuals is estimated to live with Hypo/hyperthroidism>?
10%, 50% indiagnosed
Hypothyroidism usually affects ___ more
women 8 out of 10
What is common during pregnancy with thyroid
Hypothyroidism
What are the 4 common causes of hyperthyroidism?
I. Toxic diffuse goiter (Graves disease)
II. Toxic multi-nodular goiter (Plummers disease)
III. Acute phase of thyroiditis
IV. Toxic adenoma
What is a goiter?
Just an enlargement
What is Toxic diffuse goiter
Graves disease
Generally an autoimmune disorder that leads to antibody development of the TSH receptor and secrete t3/t4 unchecked
Because we have antibody binding here too our thyroid negative feedback loop will cause our TSH levels to drop.
This will not do anything because of the antibodies
Leads to enlargement of the cells
What is Toxic multi-nodular goiter
Plummer disease, where the TSH receptors mutate and escapes the negative feedback loop
Iodine deficiency is the most common trigger
What is the general flow chart of Hyperthyroidism as it relates to plummer disease
Iodine deficiency → less T4 production → thyroid cells grow larger (multi-
nodular goiter) → TSH receptors mutate → continually active
What is Acute phase of thyroiditis
Generally trauma, or pregnancy during delivery, only the acute phase would lead to hyperthyroidism
Cells beocme highly permeable and T3/T3 leaks out of colloid.Passive diffusion during this acute phase. and eventually T3/T4 stores depelte and leads to hypothyroidism
Which hyperthyroidism disease can cause hypothyroidism? How?
Acute phase of thyroiditis, depletes stores of T3/T4
What is Toxic adenoma?
Benign tumours growing on thyroid gland and the tumors secretion of T3/T4 but not responding negative feedback loop
What are some side effects related to hyperthyroidism? (The main ones 7)
What is an issue with hyperthyroidism diagnosis?
It is difficult to detect if it is not screened for
If someone have toxic diffuse goiter>
- Exophthalmos (or proptosis)
- Peri-orbital edema- Eye buldging
- Diplopia
- Diffuse Goiter
- Pre-tibial myxedema
What is the toxic nodular goiter specific symptoms?
- Same general hyperthyroidism symptoms
- Individual thyroid nodules may be palpable
What are the general lab values thyroid issues (Sub-clinical hyperthyroidism)
TSH decreased <0.3
Free T3 Normal
Free T4 Normal
What are the general lab values thyroid issues (Toxic Diffuse)
TSH decreased alot <0.1
Free T3 Increased
Free T4 Normal to extremely increased
What are the general lab values thyroid issues (Toxic multi-nodular)
TSH decreased <0.1
Free T3 Increased
Free T4 Increased
What is the issue with toxic diffuse and toxic multi-nodular
They are incredibly hard to differentiate between
Which drug can have a high effect on the thyroid levels?
Amiodarone
When someone starts amiodarone what is typically more common (Hypo or Hyper
Hyper>hypo
What are the main treatment drug classes for hyperthyroidism/
Thioamides
Beta blockers
What are the two anti-thyroid drugs?
Methimazole and Propylthiouracil
What are the indicatiosn for the thioamides?
Toxic diffuse goiter
Toxic multi nodular goiter
Pre-treatment before RAI
What ist he goal of therapy when using a thioamide?
Achieve remission, but know that 30% remain in remission after 1-2 years of therapy (Relpase common)
What is the MOA the thioamides?
Interferes with thyroid peroxidase mediated processes in the production of T3/T4
What does propulthiouracil inhibit that methimazole doesnt”
Conversion of T4 to T3
What is the dosing and administration of thioamides?
We are going to START HIGH!!! (Very different form oridinary meds) and then we are going to lower maintenance doses
When do we decrease dose of thioamides?
Once euthryoid is achieved
When do we titrate the dose of thioamides?
If the TSH and T4 does not imporve in 4-6 weeks
What are the special dosing/administration instructions of thioamides?
None really can take with or without food
What is the onset of effect of thioamides?
Symptom improvement within 1-4 weeks
Euthyroid in 2-3 months
What is Euthyroid?
normal thyroid function that occurs with normal serum levels of TSH and T4.
What is the duration of therapy for thioamides and hyperthyroidism?
12-18 months common, but may taper to D/C and see if relapse eoccurs
What are the common side effects of thioamides?
Gi-upset, rash. arthralgia, abnormal taste/smell
What thioamide is dose dependant with side effects?
MMI (Methimazole) not PTU (Propylthiouracil)
What are some serious side effects of thioamides?
Neutropenia
Hepatotoxicity
Vasculitis
What are some key things patients should watch out for while on this thioamides?
Watch for flu like symptoms and for liver related issues
What are the main drug interactiosn of thioamides?
Warfarin (Decrease in INR), Digoxin (Increase DIG)
What are the monitor parameters usually for thioamide discontinuation?
TSH at 3,6,12, annualy
Within the first 3 months we may see suppressed TSH and normal T4/T3 hence relapse likely
What should be monitored at baseline and 1 week later with thioamide treatment?
CBCs and LFTS
With respect to pregnancy and thioamides which trimester is usually safest to take one of the drugs?
PTU 1st trimester more safe
MMI 2nd and 3rd trimester more safe
What are some other medications that could be used to help in hyperthyroidism?
Beta blockers to reduce the symptoms of hyperthyroidism
Where we would choose propranolol because of short acting nature, we would then recommended atenolol because it is more cardio selective in naturer
What is a more definitive treatment compared to thioamides?
Radioactive Iodine 131 treatement
When should Iodine 131 treatment be used?
Only given mild hyper, downsides it causes permanent hypo, can trigger thyroid storm, worsen exopthalmous
What is Exopthalmous?
a bulging or protruding eyeball or eyeballs
When is radioactive iodine131 CI?
Pregnancy/lactation, severe hyperthyroidism/exopthalmous
What are the ae of iodine131 treatment?
Initial hyperthyroidism, followed by hypothyroidism
While being treated with radioactive iodine what are some special instructions?
When is thryoidectomy and option?
What is considered subclinical hyperthyroidusm?
TSH of 0.1-0.3 and normal FT3/FT4, asymptomatic
What are the management strategies overall for thyroiditis?
Self-limiting
B blockers for symptom
NSAIDS
Course of steroids in some cases
What is thyroid storm?
What is Hashimoto’s disease?
Destruction of the thyroid essentially
Antibodies in some circumstances can interfere with T3/T4 production
What drugs can induce hypothyroidism?
Lithium, amiodarone
What are the clinical presentations of hypothryoidism?
What is the general lab testing results of hypo
What medications cause decreases in TSH?
What medications decrease T4 –> T3 conversion
Amiodarone, beta-blockers, glucocorticoids
What decreases synthesis/release of T3/T4?
Amiodarone, lithium, iodine
What increases T4/T3 metabolismn
What are our options for thyroid replacement hormone?
Desiccated thyroid
Liothyronine
Levothyroxine
Combined T3/T4
What is desiccated thryoid?
COntains T3 and T4, but cuases high peaks of T3
What is a caveate of desiccated thyroid?
Not well standardized batch to batch
What is ratio of T4 to T3 in desiccated thyroid?
4:1, but in our body it should be around 13:1
What is Liothyronine?
Contains T3 and has no effect on T4, Low half life, costly, cardiac events.
What is levothyroxine?
Analogie of T4 and standard 1st line therapy for individuals, this allows our body to convert to T3 which is regulated by the body
What is the half life of levothyroxine?
7 days
What is the dosing/administration we should remember of levothryoxine
Depends on age, weight, cardiac status, and duration of hypothyroidism
What is the average replacement dose of levothyroxine needed?
1.6mcg/kg/d
What should the starting dose range of levothyroxine?
12.5mcg/day to wax wt. based
How is levothyroxine usually given at the start?
12.5-25mcg and titrate up by 12.5-25mcg every 4-6 weeks
What are the potential side effects of levothyroxine?
Hyperthyroidism symptoms
Cardiac risk increase
aggravate existing CVD
BMD reduction
What side effects should people on levothyroxine feel?
None if properly dosed
What should be monitored while on levothyroxine?
TSH aim for low normal value, may take 4-6 weeks to stabilize with each dose change
Free T4 (Normal or slightly elevated)
Free T3 (Normal)
How often should TSH be monitored?
Once stable and symptom free monitor every 6-24 months
What is subclinical hypothyroidism?
TSH of 4.5-10 mIU/L normal T3/T4
Where treatment is controversial
What if treatment of levothyroxine fails?
Adherence
Increased need due to pregnancy, weight gain, or new medications
(Very rare)
Addison’s disease, altered pituitary, insufficient peripheral conversion of T4 to T3