5 - Thyroid Flashcards
What gender is more affected?
women
Describe the negative feedback loop of the endocrine system
- Hypothalamus secretes TRH
- Stimulates pituitary gland to secrete TSH
- Thyroid secretes T4 and T3
- T4 and T3 send a message to the hypothalamus to stop secreting the stimulating hormones
*negative feedback loop
What do thyroid hormones do in children?
Important for normal growth and development
What do thyroid hormones do in adults?
Maintain metabolic stability
- regulate normal growth and maturation
- thermoregulation (T4 increases in cold environments)
- cognitive and peripheral nervous function
- cardiac function (high level of T4 increase cardiac output and HR)
Is T4 or T3 produced exclusively by the thyroid gland?
T4
Where else is T3 produced?
by deiodination of T4 (I think this happens in liver ???)
The thyroid gland manufactures and stores T3 and T4 in _________ - a protein that both synthesizes and stores the hormone
thyroglobulin
You need ____ for the synthesis of thyroid hormones and the source is from your diet (seafood, diary, iodinated salt).
iodine
How much T4 is produced per day?
80-100 mcg
How much T3 is produced per day?
30-40 mcg
____ T4 and T3 determine hormone biologic activity
Free
Most T4–>T3 happens in the periphery by _________
5’-deiodinase
What are some binding proteins that are ensuring the serum T3 and T4 remain within normal limits?
- TBG (thyroxine-binding globulin)
- TTR (transthyretin)
- albumin
T4 or T3:
Longer half life and less potent?
T4
T4 or T3:
Shorter half life and more potent?
T3
List the 4 types of general thyroid disorders
1) Hypothyroidism
- Primary
- Central
2) Subclinical hypothyroidism
3) Hyperthyroidism
4) Subclinical hyperthyroidism
What are some causes of primary hypothyroidism?
- Autoimmune thyroiditis (Hashimoto’s)
- Congenital
- Iodine deficiency
- Intrafiltrative disease (viral or bacterial)
- Latrogenic (thyroid surgery, radioiodine, neck irradiation)
- Drugs (lithium, amiodarone, interferon, tyrosine kinase inhibitors)
What are some causes of central hypothyroidism?
Problem with the hypothalamus and/or pituitary
Briefly list a few hypothyroidism symptoms
Think about metabolic rate slowing down:
- weight gain
- bradycardia
- fatigue and weakness (in hyper too)
- dry skin
- cold extremities
Briefly list a few hyperthyroidism symptoms
Think about metabolic rate speeding up:
- weight loss
- tachycardia
- hyperactivity, irritability
- fatigue and weakness (in hypo too)
- diarrhea
- warm skin
What lab results would you see for primary hypothyroidism?
TSH = high T4 = low T3 = low (or normal)
What lab results would you see for subclinical hypothyroidism?
TSH = high T4 = normal T3 = normal
What lab results would you see for hyperthyroidism?
TSH = low T4 = high T3 = high
What lab results would you see for subclinical hyperthyroidism?
TSH = low T4 = normal T3 = normal
Goals of therapy for thyroid conditions ?
- Achieve euthyroid state and manage symptoms
- Recognize which patients with loiter or thyroid nodules require treatment
- Ensure appropriate management of thyroid conditions in pregnancy
What are risk factors for thyroid disease?
- Personal or strong family Hx of thyroid disease
- Diagnosis of autoimmune disease
- Past history of neck irradiation
- Drug therapies such as lithium and amiodarone
- Women over age 50
- Elderly
- Women who are pregnant or post partum
What does hyperthyroidism refer to ?
overproduction of thyroid hormone by the thyroid gland
What is the most common cause of hyperthyroidism in adults?
Graves’ disease
What is Grave’s disease?
- Autoimmune disease
- Thyroid stimulating antibodies (TSAb) –> thyrotropin receptor on the surface of thyroid cell
- Immunoglobulins activate the enzyme adenylate cyclase in the same manner as TSH
- Results in hormone synthesis/release
look at slide 22
prob won’t but okay dude
Goals of therapy for hyperthyroidism?
1) Minimize or eliminate symptoms, improve quality of life
2) Minimize long term damage to organs (heart disease, arrhythmias, sudden cardiac death, bone demineralization, fractures)
3) Normalize fT4 and TSH concentrations
What are treatment options for hyperthyroidism?
1) Ablation with radioactive iodine or surgery
2) Thionamides
3) Non-selective Beta blocker
4) Iodine
What is Ablation?
- Often the treatment of choice for Grave’s disease, toxic nodule, multinode goiter
- Ablative therapy often leads to HYPOthyroidism
- Note patients will be asked to stop their medications weeks before radioactive ablation therapy
What will cause a higher uptake of radioactive iodine?
Higher TSH level
List 2 thionamides
Methimazole (MMZ)
Prophylthiouracil (PTU)
What is the MOA of Methimazole ?
Inhibits the synthesis of thyroid hormones by blocking the oxidation of iodine in the thyroid gland: blocks the synthesis of thyroxine and T3; does not inactivate the circulating T3 and T4
When would you use methimazole?
Preferred agent for Grave’s disease
If pregnant do you use methimazole?
Use PTU in the first trimester, switch to MMZ in second trimester (risk of embryopathy)
SE of methimazole?
rash, arthralgias, lupus-like symptoms, fever, agranulocytosis early in therapy
What should we monitor while on methimazole?
baseline CBC, and then may repeat if patient becomes febrile or develops pharyngitis
When will you see an effect with methimazole?
Slow onset in reducing symptoms (weeks). Maximal effect may take 4-6 months
MOA of prophylthiouracil
Inhibits the synthesis of thyroid hormones by blocking conversion of thyroxine to T3 in peripheral tissues; does not inactivate circulating T3 and T4
When do we use PTU ?
- If tolerant to MMZ, cannot have had agranulocytosis
- If pregnant use PTU in first trimester
SE of PTU
rash, arthralgias, lupus-like symptoms, fever, agranulocytosis early in therapy
*HEPATOTOXICITY
Monitoring of PTU
baseline CBC, and then may repeat if patient becomes febrile or develops pharyngitis
Efficacy of PTU
Slow onset in reducing symptoms (weeks). Maximal effect may take 4-6 months.
PTU may cause severe ____ injury
liver
*this is idiosyncratic
What 4 things are part of monitoring thionamide (MMZ or PTU) therapy ?
1) TSH
- Every 4-6 weeks until stable
- Can remain suppressed for months. May use fT4 initially
2) fT4
- Every 4-6 weeks until stable
- In 4-12 weeks most are euthyroid
3) Symptom improvement
- should improve in a few days-weeks
- adjust to maintenance dose once euthyroid
4) Toxicity
- Baseline CBC
- Educate patients to report pharyngitis
- Baseline LFT
- Patients should be monitoring for signs of hepatotoxicity (pruritic rash, jaundice, light stools, dark urine, tiredness, nausea, anorexia, joint point or abdominal pain or feel ill)
MOA of Beta blockers
Beta blockade to mitigate the beta-adrenergic manifestation of hyperthyroidism
What is the role of BB in hyperthyroidism?
used for severe symptoms while awaiting onset of thiourias (palpitation, anxiety, tremor, heat intolerance)
What type of BB do we choose for hyperthyroidism and why?
Non-selective (non ISA)
-easier to titrate and withdraw
Choose: Propranolol
AE of BB?
fatigue, lethargy, peripheral coldness, dizziness, vertigo, bradycardia
MOA of iodines and iodides ?
Inhibits the release of stored thyroid hormone. Minimal effect on the hormone synthesis. Helps to decrease the vascularity and the size of the gland before surgery.
What is the iodine solution called ?
Lugols suolution (6.3-8mg iodide per drop)
SE of Lugols solution (iodine)?
Hypersensitivity, metallic taste, soreness or burning in the mouth or tongue
*May reduce uptake of radioactive iodine therapy - do not take on the days prior to ablation
Describe the efficacy of Lugols solution (iodine)
- Effective for 7-14 days
- Usual role is 7-10 days prior to surgery
- Can be used after ablative therapy x 3-7 days
- Role in stopping thyroiditis mediated release of stored hormone
- Acute role in thyroid storm
What is a thyroid storm?
-Severe and life-threatening decompensated thyrotoxicosis. Mortality rate may be as high as 20%
What are some precipitating causes of a thyroid storm?
Trauma, infection, antithyroid agent withdrawal, severe thyroiditis, post ablative therapy (especially if inadequate pretreatment).
Describe the presentation of a thyroid storm
Fever, tachycardia, vomiting, dehydration, coma, tachypnea, delirium
What is the treatment for a thyroid storm?
PTU or MMZ Idide Beta blocker Steroid Antipyretic (want to use tylenol over NSAIDs because NSAIDs can cause a displacement of protein bound thyroid)
What treatment options are available for hypothyroidism?
1) Desiccated thyroid (T3/T4)
- Porcine source
2) Liothyronine (T3)
- Cytomel
3) Levothyroxine (T4)
- Eltroxin
- Synthroid
MOA of levothyroxine
Synthetic T4 supplement
Why is levothyroxine the drug of choice for hypothyroidism ?
Easier to titrate that desiccated thyroid or liothyronine - allows for body to fine tune itself by converting exogenous Lt$ to the more biologically active T3 or inert rT3 in target tissues
List some AE from levothyroxine that usually occur from overtreatment
- palpitations
- alopecia, sweating, excessive
- weight loss
- diarrhea
- insomnia
- anxiety, nervousness
- fatigue
When should levothyroxine be taken?
Best absorption on an empty stomach - so take it 30-60 mins prior to breakfast or at bedtime (4h after meal)
Describe Liothyronine (T3) for treating hypothyroidism.
- Essentially no role in thyroid replacement
- Short t1/2, need multiple doses
- Rapid absorption causes high Cpeak immediately after dosing
- Increased incidence of CV side effects
- More difficult dose titration
- Increased cost
- Only plays a role in patients who insist or lack of response to T4 ?
Describe desiccated thyroid (T3/T4) for treating hypothyroidism.
Natural product with varying potencies depending on batch/lot#
- Allergic reactions
- Rapid absorption causes high Cpeak immediately after dosing
- More difficult dose titration
When and what are we monitoring after initiating thyroid therapy?
monitor TSH q4-8 weeks until normal, then q6-12 months
When and what are we monitoring after changing thyroid therapy?
monitor TSH q6-8 weeks
In pregnancy, requirements ______
increase
What is the most accurate indication of thyroid status in pregnancy?
TSH (total T4 recommended also)
How often do we monitor TSH in pregnancy?
every 4 weeks during 1st half of pregnancy, then 1 additional time between week 26-32
How do we adjust LT4 (levothyroxine) dose in pregnancy?
by 25-50 mpg to achieve TSH target
When should therapy be considered for pregnant women?
if TSH is greater than the upper limits of TSH ranges for each trimester
After delivery, what dose of levothyroxine do we give?
Pre-conception dose, and then test TSH again in 6-8 weeks
Who do we treat for subclinical hypothyroidism?
- Elevated THS with normal T4. Often the result of early Hashimoto’s disease
- Treatment is controversial as risk reduction has been seen only in the elderly
Treat for TSH between 4.5-10 AND:
- symptoms of hypothyroid
- antithyroid peroxidase antibodies present
- Hx CVD, HF or risk factors
What is a Myxedema coma?
-Severe and life-threatening decompensated hypothyroidism
What are some precipitating causes of Myxedema coma?
Trauma, infections, heart failure, medications (sedatives, narcotics, anesthesia, lithium, amiodarone)
What is the presentation of a Myxedema coma?
Coma is not required and is uncommon despite terminology; altered mental state (very common); diastolic hypertension, hypothermia, hypoventilation
What is the treatment for Myxedema coma?
- Thyroid hormone replacement IV
- Antibiotic therapy
- Steroid
