Primary Hypothyroidism and Hyperthyroidism Flashcards
What is primary hypothyroidism?
What is it?
The clinical and biochemical syndrome resulting from decreased thyroid hormone production. Biochemically, primary hypothyroidism is defined as TSH concentrations above reference range and free T4 and/or T3 levels below reference range.
Hypothyroidism Disease definitions
- Overt Hypothyroidism
a. TSH levels:
b. Free T4 (FT4) levels:
c. symptoms: - Subclinical hypothyroidism
a. TSH levels:
b. FT4 levels:
c. symptoms:
Disease definitions
- Overt Hypothyroidism
a. TSH levels: high
b. Free T4 (FT4) levels: low
c. symptoms: may or may not experience symptoms - Subclinical hypothyroidism
a. TSH levels: high (majority of pts. have btw ULN and 10 mIU/L). if >10, more chance to develop into overt hypothyroidism and having CV events and HF)
b. FT4 levels: normal
c. symptoms: may or may not experience symptoms.
epidiomiology of hypothyroidism
Epidemiology
- occurs in 1.5%-2% of women and 0.2% of men.
- incidence increases with age
clinical representation of hypothyroidism
Clinical Representations
Signs and symptoms
- decreased metabolism
- increase cholesterol
- decreased cardiac output and heart rate
- decrease GI motility/ appetite
- mental slowing, brain fog, slow speech
- decreased muscle tone
- cold intolerance. dry and cold skin
- course hair and skin
- increased weight
with hypothyroidism, what do you treat ?
who to consider treatment for?
Who to Treat?
Treat all:
- Overt Hypothyroidism
- Subclinical if TSH >10.0 mIU/L
- pregnant/ planning pregnancy if TSH >2.5 mIU/L AND (+) TPOAb
Consider treatment
- subclinical if TSH 4.5-10 mIU AND: s/sx ,(+) TPOAb, CAD/CHF or risk factors
- pregnant/planning pregnancy AND not hypothyroid AND
a. TSH 2.5-ULN in 1st trimester/ planning
b. TSH 3.0-ULN in 2nd trimester
hypothyroidism Treatment Goals
Special populations treatment goals
a. Pregnant women:
b. Elderly
Treatment Goals
- biochemically euthyroid
a.TSH anywhere in normal range (0.45-4.12 mIU/L if test does not specify)
ULN increaasewith age
b. t4 and t3 clinical criteria not enough by themselves to guarantee euthyroid - Symptomatic improvement
- avoid oversupplementation (especially in elderly)
Special populations
Pregnant women:
- goal anywhere in trimester specific normal ranges
a. 0.2-2.5 in first trimester
b. 0.3-3.0 in 2nd and 3rd trimesters
c. follow up frequent 1st to 2nd trimester, less frequent 2nd to third trimester
Elderly
1.lower doses usually needed to hit goal
2. avoid over supplementation.
3. reasonable to raise ULN of tarot to 6 mIU/L ???
3.lower incidence of mortality with mildly elevated TSH in subjects subjects aged 85+
3.
hypothyroidism Thyroid Stimulating Hormone
ULN for
general population:
pregnant women:
elderly:
Thyroid Stimulating Hormone
- gold standard and guides decision to treat and therapy adjustments
upper limits of normal
a. 4.12 mIU/L (AACE/ATA)
b. 4.5-5.0 mIU/L (usually lab reference)
c. 2.5 mIU/L (1st trimester of pregnancy)
c. 3.0 mIU/L (2nd and third trimester of pregnancy
d. elderly: 6??
hypothyroidism Pharmacologic Treatment Options in general
their names
content
and clinical pearls
Pharmacologic Treatment Options
- Desiccated Thyroid (Armour Thyroid, Nature-throid, and Westhroid
a. Content: Desiccated pork thyroid gland
b. comments: 4:1 T4:T3 ratio, inexpensive, porcine origin - Levothyroxine (synthroid)
content: synthetic T4
comments: DRUG OF CHOICE, stable, predictable potency, 7 day half life, so daily dosing, available in wide variety of strengths (in IV and PO) - Liothyronine
content: synthetic T3
comments: fast onset of action, short half life, so BID dosing, AE from supernormal T3, can cause cordiotoxicity??. Life threatening hypothyroidism in hospital.
Levothyroxine Dosing
Initial Dosing:
1. otherwise healthy <65y.o:
- otherwise healthy >/= 65 y.o:
- known CAD:
- subclinical hypothyroidism:
dosing changes
Dosing
Initial Dosing: BASED ON IBW, NOT ACTUAL
- otherwise healthy <65y.o: 1.6 mcg/kg/day
- otherwise healthy >/= 65 y.o: 50 mcg/ day
- known CAD: 12.5-25 mcg/ day
- subclinical hypothyroidism: unless compelling argument, avoid. (FOR PURPOSES OF THIS CLASS ONLY)
dosing changes
- Pregnancy: 30% increase dose suggested; changes as soon as 5 weeks gestation.
- severely obese (BMI>40 kg/m^2) may require higher replacement doses
- Autoimmune gastritis, H. Pylori gastritis may require higher replacement doses due to increased acid production, drug break down, and decreased bioavailability.
Hypothyroidism Treatment TimeLine
what to do if switching between LT4 preparations
Treatment TimeLine
- start with appropriate initial LT4 dose for situation
- check TSH in 4-6 weeks
a. if TSH not WNL (0.5- 3.5-4 mIU/L): titrate dose up or down by 12.5-25 mcg/day. recheck in 4-6 weeks
b. if TSH is WNL (0.5- 3.5-4 mIU/L): check TSH again in 4-6 months, then at least yearly or if reason to suspect absorption or metabolism has changed (new drug added, chronic disease, weight change, pregnancy)
Switching Between LT4 Preperations
- obtain new labs after any switch
- avoid switching if possible
Levothyroxine (T4)
brand names:
Class:
Indication:
Mechanism of Action:
Effects of mechanism of Action:
Adverse Effects:
Absolute Contraindications:–
Pregnancy:
Warning/ Precautions: –
Drug-Drug Interactions (DDIs):
Monitoring Parameters:
Pearls:
includes counseling: how to take it?
timing:
Levothyroxine (T4)
brand names: Synthroid, Levoxyl, Tirosint, Unithroid, Mylan (generic)
Class: Thyroid agent
Indication: Replacement or supplemental therapy in congenital or acquired hypoparathyroidism of any etiology. Preferred thyroid preparation.
Mechanism of Action: Levothyroxine )T4) is a synthetic form of thyroxine, an endogenous hormone secreted by the thyroid. T4 is converted to active metabolite T3. thyroid hormones T4 and T3 bind to thyroid receptor proteins in the cell nucleus and exert metabolic effects through DNA transcription and protein synthesis.
Effects of mechanism of Action: involved in normal metabolism, growth, and development, promotes gluconeogenesis, increases utilization and mobilization of glycogen stores, stimulates protein synthesis, increase basic metabolic rate (BMR)
Adverse Effects: Primarily those of hyperthyroidism, anxiety, diarrhea, insomnia, Transient alopecia, allergies (excipients), iatrogenic thyrotoxicosis ( increased bone turnover/ loss, A. fib, caution in cardiac disease)
Absolute Contraindications:–
Pregnancy:can be used
Warning/ Precautions: –
Drug-Drug Interactions (DDIs): metal cations, bile acid sequestrants, sulcrafate, SPS, PPI,/H2RA/orlistat, estrogens/androgens/raloxifene, sertraline/phenobarbital/phenytoin/quetiapine, tyrosine kinase inhibitors , lithium, amiodarone
Monitoring Parameters:
1. TSH:check in 4-6 weeks after initiation, dose change, or switching preparations to check response
Pearls:
- drug of choice for primary hypothyroidism
- decreased risk of cardiac and metabolic diseases
- counseling:
a. take with H2O only and no other meds
b. timing: take 60 minutes before breakfast OR at least 3 hours after evening meal
c. remain consistent
d. if miss a dose, take as soon as remember. if remember next day, patient can actually take 2 doses ??
e. this is a lifelong therapy
f. takes up to 6 weeks to see effect
what is hyperthyroidism?
What is it?
Overproduction of thyroid hormone by the thyroid gland.
Biochemically, primary hyperthyroidism is defined as TSH concentrations below reference range and free T4 and/or T3 levels above reference range.
epidemiology of hyperthyroididm
Epidemiology
- incidence increases with age
- more prevalent in females than males.
clinical representation of hyperthyroidism
Clinical representation
signs and symptoms increased metabolism decreased cholesterol increased cardiac output an heart rate increased GI motility and appetitie CNS symptoms like lack of concentration, poor memory, depression, anxiety, nervousness, irritability increased muscle tone heat intolerance skin/ hair thinning weightloss exophthalmos
Main treatment options for hyperthyroidism
Treatment Options
Any one of the three treatment modalities is equally acceptable. pt-specific factors or desires will impact intimate treatment choice
- Thioamides (Methimazole and Propylthiouriicil)
- Radioactive Iodine (I-131)
- Surgery
Beta Blockade (Propanolol)
- Thioamides (Methimazole and Propylthiouriicil)
I. Factors favoring option:
II. Patient preference factors:
contraindications:
- Thioamides (Methimazole and Propylthiouriicil)
I. Factors favoring option:
a. mild disease
b. increase surgical risk
c. moderate-severe active goiter
d. no access to surgeon
e. previos neck operation/ irradiation
II. Patient preference factors: high value on avidance of lifelong T4 therapy, exposure to radioactivity, and surgery
low value on need for monitoring and possible relapse
contraindications: previous known reactions to anti thyroid drugs
Radioactive Iodine (I-131) I. Factors favoring option:
II. Patient preference factors:
III. contraindications:
- Radioactive Iodine (I-131)
I. Factors favoring option:
a. planning pregnancy > 6 months out
b. increase surgical risk
c. contraindications to anti thyroid drug use
d. no access to surgeon
e. previos neck operation/ irradiation
II.Patient preference factors: high value on definitive control and avoidance of surgery
low value on rapid cure, development of GO,and need for lifelong LT4 replacement
contraindications: pregnancy, lactation, suspected or known cancer, unable to meet safety guidelines, pregnancy 4-6 months out
Surgery
I. Factors favoring option:
II.Patient preference factors:
III.contraindications:
Surgery
I. Factors favoring option:
a. large goiter
b. malignancy suspected
c.planning pregnancy < 6 months out
d. TRAb levels are high
II.Patient preference factors: high value on prompt, definitive control and avoidance of exposure to radioactivity
low value on surgical risk and need for lifelong LT4 replacement
contraindications: substantial comorbidity, pregnancy (surgery option best in 2nd trimester), a surgeon who has not had a high volume of thyroidectomy)
Beta blockade clinical perils in hyperthyroidism
Beta Blockade (Propanolol)
- recommended for all patients with symptomatic thyrotoxicosis, especially if
a. resting HR>90 bpm
b. elderly
c. coexisting CV disease - also blocks conversion of T4-T3
Thioamides
Examples:
Class:
Indication:
Mechanism of Action:
Effects of mechanism of Action:
Adverse Effects:
Absolute Contraindications:–
Pregnancy:
Warning/ Precautions: –
Drug-Drug Interactions (DDIs): -
Monitoring Parameters:
Pearls:
Thioamides
Examples: Methimazole (MMI), Propylthiouricil (PTU)
Class: Thyroid agent
Indication: Treatment of hyperthyroidism in patients with graves disease or toxic multimodal goiter for whom surgery or radioactive iodinee therapy is not appropriate
Mechanism of Action: Inhibits the synthesis of thyroid hormones by inhibiting thyroid peroxidase (TPO). Thereby blocking TPO’s ability to oxidize iodine in the thyroid gland
Effects of mechanism of Action:blocks synthesis of T3 and T4. does not inactivate circulating T3 and T4
Adverse Effects: Serious: agranulocytosis, aplastic anemia, exfoliative dermatitis, hepatitis, leukopenia, pruritic rash, abdominal pain, dark urine, jaundice, echoic stools, fever/ pharyngitis, fatigue
Absolute Contraindications:–
Pregnancy: PTU drug of choice in 1st trimester of pregnancy
Warning/ Precautions: –
Drug-Drug Interactions (DDIs): -
Monitoring Parameters:
1.Consider CBC and liver panel to establish baseline values
2. check FT4, T3 in 2-6 weeks after initiation
3. if patient is euthyroid, check thyroid panels in 4-6 weeks
after tapering dose up or down
4. monitorfor leukopenia, pruritic rash, arthralgia, fatigue
Pearls:
- MMI is preferredthioamide. more potent and longer half life
- TPU also prevents peripheral conversion of T4->T3.
a. rarely used because of greater risk of side effects, especially hepatotoxicity. - tau drug of choice in 1st trimester of pregnancy and in thyroid storm
Thioamide clinical pearls
- MMI is preferredthioamide. more potent and longer half life
- TPU also prevents peripheral conversion of T4->T3.
a. rarely used because of greater risk of side effects, especially hepatotoxicity. - tau drug of choice in 1st trimester of pregnancy and in thyroid storm
Thioamide Dosing
- Typical MMI doses based off of what levels?
startin doses:
Maintenance dose:
Thioamide Dosing
- Typical MMI doses canoe based on FT4
startin doses:
1-1.5x ULN: 5-10 mg/ day (usually qd)
1.5-2x ULN: 10-20 mg/ day (can be QD or BID)
2-3x ULN: 30-40 mg/day (best BID)
Maintenance dose: 30%-50% reduction from initial dose (taper down)
Thioamide treatment algorithm
Thioamide treatment algorithm
- consider abc liver panel to establish baseline values
- start MMI (dose based on FT4 level)
- check FT4, T3 in 2-6 weeks (more often if more sever)
a. if patient is NOT euthryroid: continue therapy and check FT4, T3 in 2-6 weeks
b. if pt. is euthyroid: taper dose down by 30-50% over a few weeks ad repeat thyroid panel (including TSH) in 4-6 weeks - After tapering down dose
a. if patient is NOT euthyroid: increase dose slightly, repeat thyroid panel in 4-6 weeks
b. if patient is euthyroid: continue therapy 12-18 months; monitor thyroid labs q 2-3 months - consider stopping MMI if TSH and TRAb levels are normal
Radioactive Iodine (Na131-I)
Indication:
Mechanism of Action:
Effects of mechanism of Action:
Adverse Effects:
Absolute Contraindications:
Pregnancy:
Warning/ Precautions:
Drug-Drug Interactions (DDIs): -
Monitoring Parameters:
Pearls:
Radioactive Iodine (Na131-I)
Indication: Treatment of hyperthyroidism in patients with graves disease or toxic multimodal goiter, and toxic nodules
Mechanism of Action: beta minus decay destroys bonding of dna and causes cellular damage and cell death. concentrates in the thyroid gland, interrupting hormone synthesis
Effects of mechanism of Action:Decrease T4 nd T3. renders patient hypothyroid
Adverse Effects: transient hyperthyroidism (destruction of cells causes big release of stored thyroid hormone from cells), release of orbital antigen, thyroid tenderness, salivary gland tenderness/ enlargement, dysphagia
Absolute Contraindications:Pregnancy, lactation, suspected or known cancer, unable to meet safety guidelines, pregnancy 4-6 months out.
Pregnancy: DO NOT USE
Warning/ Precautions: Moderate-severe graves eye disease (can be exacerbated by big release of thyroid hormone from cells after destruction)
Drug-Drug Interactions (DDIs): -
Monitoring Parameters:
- post RAI, lab work q 4-6 weeks includes FT4, total T3, and TSH. EARLY MARKER OF TREATMENT SUCCESS IS FT4, NOT TSH (Tsh will be suppressed at least 1 month)
- montor q 4-6 weeks for 6 months
Pearls:
1. counseling
a. avoid high-iodine foods before treatment ( due to Wolff-Chaikoff effect: thyroid rejects the large quantities of iodine and therefor preventing the thyroid from producing large quantities of thyroid hormone). if excess iodine taken before radioactive thyroid treatment, body all prevent radioactive iodine from getting into the thyroid.
b. instructions for outpatient treatment:
I. no contact with kids for 5 days
II. no contact with pregnant women: 10 days
III. no more than 2 hours of contact at a time
IV. bathroom etiquette-> wipe sprinkles of pee because it is excreted in urine
V. avoid bodily fluid contact )4 days. no sharing
Pearls of Radioactive Iodine
Pearls:
1. counseling
a. avoid high-iodine foods before treatment ( due to Wolff-Chaikoff effect: thyroid rejects the large quantities of iodine and therefor preventing the thyroid from producing large quantities of thyroid hormone). if excess iodine taken before radioactive thyroid treatment, body all prevent radioactive iodine from getting into the thyroid.
b. instructions for outpatient treatment:
I. no contact with kids for 5 days
II. no contact with pregnant women: 10 days
III. no more than 2 hours of contact at a time
IV. bathroom etiquette-> wipe sprinkles of pee because it is excreted in urine
V. avoid bodily fluid contact )4 days. no sharing
RAI treatment timeline
RAI treatment timeline
- at dx, pt can be given propranolol for symptom control if necessary
- more severe cases can start MMI to minimize thyroid hormone in thyroid before RAI to prevent big release of thyroid hormone. needs to be stopped 3-7 days before RAI dose
- if female or child bearing potential, give pregnancy test
- RAI therapy. single dose . 10-15 mCi
- if patient had mild active graves opthalmopathy, give steroid (prednisone 0.4-0.4 mg/kg/day 1-3 days after RAI dose.
- 3-7 days after RAI dose, add MMI as needed to decrease complications of release of thyroid hormone from RAI
- after a few weeks of MMI, can taper off and d/c completely
- after 1 month post RAI, can taper propranolol and steroid if being used
- after 3 months, should be completely done with all of the drugs
- if RAI successful (patient hypothyroid) start IBW- based replacement dosing with levothyroxine. monitor and adjust as in hypothyroidism
- if hyperthyroidism persists after 6 months, guidelines suggest another round of RAI therapy
Thyroidectomy
Prep
complications
post surgery
Thyroidectomy
Prep
1. get patient euthyroid and stable before surgery to avoid thyroid storm
a. start MMI 6-8 weeks before surgery. if they get too low, can give lt4 AS NEEDED
B. Start iodide 10-14 days before surgery. decreases thyroid vascularity and decreases blood loss
c. start beta blocker 7-10 days before surgery
d. consider normalizing calcium and vitamin. d since thyroid surgery can sometimes effect parathyroid gland
complications
- transient or permanent hypocalcemia (<2%)
- hyperthyroidism can persists if a sub thyroidectomy (up to 8%)
- vocal cord abnormalities (<5%) (permanent laryngeal nerve injury <1%)
post surgery
- obtain serum calcium, intact PTH levels before discharge. pt may need calcium/calcitriol supplementation
- wean beta blocker
- stop MMI
- start levothyroxine at full IBW replacement dosing (unless elderly)
- obtain TSH in 6-8 weeks
Iodides
examples:
Indication:
Mechanism of Action:
Adverse Effects:
Absolute Contraindications:–
Pregnancy: –
Warning/ Precautions: –
Drug-Drug Interactions (DDIs): -
Pearls:
Iodides
examples: Potassium Iodide (Super saturated potassium iodide (SSKI)), Lugols solution
Indication: Treatment of hyperthyroidism in the immediate preoperative period in patients undergoing thyroidectomy. adjunct to RAI treatment to prevent uptake of radiiodine by the thyroid, reducing the risk of thyroid cancer.
Mechanism of Action: unknown. temporarily inhibits thyroid hormone synthesis and secretion into circulation. also decreases thyroid gland size and vascularity
Adverse Effects: “Iodism”- metallic tate, head cold, burning mouth/throuat, sore teeth/ gums, stomach upset, diarrhea. Hypersensitivity reactions, salivary gland swelling, gynecomastia.
Absolute Contraindications:–
Pregnancy: –
Warning/ Precautions: –
Drug-Drug Interactions (DDIs): -
Pearls:
- not useful in long term treatment of graves disease. body gets used to extra iodine and compensates for it (takes 10 days)
- mainly used for surgery prep, adjunct to RAI treatment
Pearls for Iodides
Pearls:
- not useful in long term treatment of graves disease. body gets used to extra iodine and compensates for it (takes 10 days)
- mainly used for surgery prep, adjunct to RAI treatment
