PHAR 555 Thyroid iRAT/tRAT (Review)

What gland secretes thyroid hormones?

thyroid gland (butterfly shaped)

Thyroid hormones influence functions of virtually all organ systems. What are their major clinical effects in…

• Children

• Adults

• Children: Normal growth and development

• Adults: Maintain metabolic stability and homeostasis

  • Cardiovascular effects

  • Thermogenic effects

  • Metabolic effects

What element on the periodic table do thyroid hormones contain?

• Source?

iodine

• Source: Nutritional intake

What are the two different thyroid hormones?

• Triiodothyronine (T₃)

• Tetraiodothyronine, commonly known as thyroxine (T₄)

triiodothyronine (T₃)

• Structure

• Production

• Receptor affinity

• Biological potency to T₄

• Has 3 iodides attached

• Majority from T₄ breakdown in the peripheral tissue (< 20% in the thyroid)

• Has 10-15x affinity than T₄

• 4:1

tetraiodothyronine/thyroxine (T₄)

• Structure

• Production

• Receptor affinity

• Biological potency to T₃

• Has four iodides attached

• Majority in thyroid

• Less than T₃

• 1:4

Describe the steps of the hypothalamic-pituitary-thyroid (HPT) axis.

1. When more thyroid hormones need to be made to achieve “normal”, the hypothalamus releases thyrotropin-releasing hormone (TRH)

2. TRH stimulates pituitary gland (which lies underneath the brain in your skull) to release thyrotropin, more commonly referred to as thyroid-stimulating hormone (TSH)

3. TSH stimulates thyroid to release thyroid hormones T₄ and T₃ into circulation, where they interact with their target organs and the periphery

• While < 20% of T₃ is produced by the thyroid, a majority of T₃ is produced by the breakdown of T₄ in the peripheral tissues, which occurs in the muscles and liver

1. As T₄ and T₃ concentrations increase, the hypothalamus and pituitary gland recognize this and stop producing TRH and TSH, respectively

problem with hyperthyroidism

• Bodily reaction

The thyroid gland produces excessive amounts of T₃ and T₄

• Bodily reaction (more negative feedback loop): The hypothalamus and pituitary gland recognize there’s an excess of thyroid hormones, and respond by reducing the amount of TRH and TSH produced. However, there is something inherently wrong with the thyroid, which continues to produce thyroid hormones

problem with hypothyroidism

• Bodily reaction

The thyroid gland produces too little of T₃ and T₄

• Bodily reaction (less negative feedback loop): The hypothalamus and pituitary gland respond by increasing the levels of TRH and TSH, but something is inherently wrong with the thyroid, which continues to not produce enough T₃ and T₄

thyrotoxicosis

excessive level of thyroid hormone by any cause (e.g., hyperthyroidism)

hyperthyroidism

overproduction of thyroid hormone by the thyroid gland

thyroid storm

sudden release of thyroid hormone by thyroid gland; considered a life-threatening emergency

causes of hyperthyroidism

• Graves’ disease: autoimmune disease in which the body produces thyroid-stimulating antibodies that bind to the thyroid and stimulate production of thyroid hormones

  • Most common cause of hyperthyroidism

• Thyroid adenoma: growth in the thyroid that functions autonomously and produces thyroid hormone

• Excess TSH production by the pituitary gland

• Drug-induced

  • Amiodarone (biggest culprit)

  • Iodinated contrast

  • Lithium

• Interacting drugs with lab assays

  • Biotin (vitamin B7) can result in falsely high levels of T4 and T3 + falsely low levels of TSH, leading to a false diagnosis of hyperthyroidism (Recommendation: STOP biotin for 2 days and then and do/repeat the measurement)

clinical presentation of hyperthyroidism

Helpful hint: Processes speed up

• Heat intolerance

• ↑ Heart rate (HR); palpitations (rapid HR)

• ↑ Blood pressure (BP)

• Bulging eyes (exophthalmos)

  • Seen in Graves’ disease

• Goiter

• Unintentional weight loss

• Increased appetite

• Amenorrhea (scant or no menstrual cycle)

• Anxiety/nervousness

• Diarrhea (frequent stools)

• Fatigue

• Fine hair

• Lid lag

• Clubbed fingers

• Onycholysis (separation of the end of the fingernails from the beds)

• Moist skin

• Pretibial myxedema

  • Seen in Graves’ disease

  • Infiltrative dermopathy

  • Incidence rate: 1-5%

laboratory findings for hyperthyroidism

• TSH levels go down

• T₄ and T₃ go up

goals of therapy for hyperthyroidism

• Desired outcomes

  • Provide symptomatic relief

  • Eliminate excess thyroid hormone

  • Minimize long-term consequences of hyperthyroidism

• Treatment approach

  • Individualize therapy based on:

    • Disease severity

    • Patient gender

    • Patient age

    • Response to previous therapy

treatment options for hyperthyroidism

• Antithyroid drugs (ATD): Thionamides

• Radioactive iodine

• Surgery

thionamides

• MOA

• Role in therapy

• Goal

• Drugs

• MOA: Prevents synthesis (inhibiting peripheral conversion of T₄ → T₃)

• Role in therapy: First-line option for hyperthyroidism

• Goal: Achieve normal thyroid hormone levels (euthyroid)

• Drugs:

  • Methimazole (MMI)

  • Propylthiouracil (PTU)

methimazole (MMI)

• DOC?

• Initial dosing

• Maintenance dose

• DOC due to less hepatic toxicity and other side effects

• Initial dose is based on free T₄ levels (generally 10-30 mg/day)

  • 1-1.5x ULN → 5-10 mg QD

  • > 1.5-2x ULN: 10-20 mg QD

  • > 2x ULN: 20-40 mg/day

• Maintenance dose: 5-10 mg QD

propylthiouracil (PTU)

• DOC?

• Initial dosing

• Maintenance dose

• NOT DOC

• Initial dose: 300-600 mg/day in 3-4 divided doses

• Maintenance dose: 100-150 mg/day in 3 divided doses

expected symptomatic relief for thionamides

• Expected symptomatic relief in 4-8 weeks

  • Titrate doses every 4 weeks

• Maximum response in 4-6 months

• Long-term remission in about 12-24 months

monitoring frequency for thionamides

• TSH, free T₄, and T₃ every 4-8 weeks until euthyroid

• Monitor every 2-3 months once euthyroid

• If euthryoid for 1 year after discontinuation = remission

  • Follow-up after remission about every 6-12 months (due to treatment failures and recurrences)

mild adverse effects of thionamides

• Leukopenia ( < 4,000/mm³)

• GI discomfort and nausea

• Pruritic maculopapular rash

• Fever

• Arthralgias

• Lupus-like syndrome (flu-like symptoms, muscle and joint pain)

severe adverse effects of thionamides

• Monitoring?

• Hepatotoxicity

  • Higher risk with PTU

  • Monitoring: LFTs

• Agranulocytosis (severe decrease in granulocytes)

  • Leads to severe flu-like symptoms (sore throat, fever, fatigue)

  • Rare but life-threatening due to body’s low neutrophil counts = inability to fight infections

  • May occur in MMI doses > 40 mg/day (or PTU-equivalent dose)

  • Treatment: Discontinue therapy

  • Monitoring: CBC (specifically WBC)

counseling points for thionamides

1. If mild adverse effects occur, contact PCP and consider discontinuation of therapy

• Flu-like symptoms (fever/chills, fatigue, sore throat)

2. Contact your doctor if you are or become pregnant due to potential teratogenicity

3. Symptoms should improve in weeks to months

radioactive iodine (¹³¹I)

• Role in therapy

• MOA/Goal

• Role in therapy: Graves’ disease, toxic autonomous nodules, toxic multinodular goiter

• Goal: Destroy (ablate) overactive thyroid cells with emitting beta particles

dosing for and result of radioactive iodine

• Dose: One-time dose of 5-15 mCi

  • Colorless, tasteless liquid

  • Requires adjunctive therapy in the form of iodides to minimize the effect of stored thyroid hormones leaking into circulation from the destroyed thyroid vesicle

• Result: Euthyroid should occur in 6 months to 1 year

  • Can give a second dose after 6 months if euthyroid not achieved

adverse effects of radioactive iodine

• Acute

• Long-term

• Acute:

  • Thyroid tenderness

  • Dysphagia

• Long-term:

  • ↑ risk of small bowel and thyroid cancer

  • ↑ risk of all cause mortality

  • Radiation exposure to family members

Who is contraindicated for radioactive iodine?

• Pregnancy (must defer 6-12 months)

• Lactation

• Inability to adhere to radiation safety guidelines

special radioactive iodine for cardiac disease or elderly

• Give thionamides before and after RAI

  • Stop 4-6 days before RAI

  • Restart 4 days after RAI

• Consider beta blockers

counseling points for radioactive iodine

• For at least 7 days… 📍

  • Sleep in separate bed from another adult

  • Delay return to work

  • Maximize distance from children and women

  • Do not travel by airplane or public transportation

  • Limit time in public spaces

  • Do not prepare food for others

  • Do not share utensils

  • Sit to urinate and flush toilet 2-3 times after use

  • Maintain 6-foot distance from others

types of thyroidectomy

• Subtotal (leaves a little bit of thyroid intact)

• Near-total (takes almost all of the thyroid out)

Consider a thyroidectomy in patients with…

• Enlarged thyroid gland (> 80 g)

• Multinodular goiter (MNG) with cosmetic issues or pressure symptoms

• Severe ophthalmopathy

• Failed therapy with antithyroid drugs

risks for thyroidectomy

• Hyperthyroidism recurrence (subtotal)

• Hypoparathyroidism

• Laryngeal nerve damage

perioperative management for thyroidectomy

• Before surgery: Thionamide + potassium iodide + beta blocker

  • Thionamide (MMI preferred) until patient is euthryoid (~6-8 weeks)

  • Potassium iodide 500 mg/day for 10-14 days before surgery

  • Beta blocker (propranolol preferred) several weeks before surgery, maintaining an HR < 90 BPM

• After surgery: Beta blocker + thyroid replacement therapy

  • Beta blocker (propranolol preferred) 7-10 days after surgery, maintaining an HR < 90 BPM

  • Weight-based dosing of lifelong levothyroxine now that the patient is permanently hypothyroid

adjunctive therapy

• Antiadrenergic therapy

• Iodides

role in therapy for antiadrenergic therapy

Symptomatic management, to minimize risk of further cardiac issues due to severe tachycardia

• Adjunct to antithyroid drugs, radioactive iodine (RAI), or iodides (Graves’ and toxic nodules)

• Preparation for surgery

• Thyroid storm

• Primary management: Thyroiditis

DOC for antiadrenergic therapy

Propranolol (preferred because it helps with both palpitations, as well as anxiety and tremors)

• Initial dose: 10-40 mg 3-4 times daily

• Target: HR < 90 beats/min

contraindications and adverse effects for antiadrenergic therapy

• Contraindications

  • Decompensated heart failure

  • Sinus bradycardia

  • Spontaneous hypoglycemia

  • Concomitant MAOI/TCAs

• Adverse effects:

  • Nausea/vomiting

  • Anxiety

  • Insomnia

  • Lightheadedness

iodides

• Role of therapy

• Result

• Symptom improvement

• Acutely inhibit thyroid hormone release, to help severely thyrotoxic patients with cardiac decompensation and in thyroid storm

  • Prior to surgery in Graves’ disease (7-10 days pre-op)

  • Following radioactive iodine (RAI) to inhibit thyroid hormone release (3-7 days post-op)

• Result: Decreased T₄ and T₃ in several weeks (However, iodides are only good for acute management and not for long-term because, after about 2-4 weeks, the body adapts and thyroid hormone production increases after the initial inhibition)

• Symptom improvement: 2-7 days

iodide options

• SSKI (saturated solution potassium iodide) - Concentrated at 38 mg iodide/drop

• Lugol’s solution - Concentrated at 6.3 mg iodide/drop

contraindications and adverse effects of iodides

• Contraindicated in: Toxic multi-nodular goiter (MNG)

• Adverse effects:

  • Exacerbation of hyperthyroidism (large doses)

  • Hypersensitivity

  • Salivary gland swelling

  • “Iodism” (burning or watery feeling in the mouth; can manifest as a metallic taste, sore teeth and gums, and symptoms of a head cold)

  • Gynecomastia (overdevelopment/enlargement of breast tissue) in men

When are thionamides the preferred treatment option?

• Age > 40 y.o.

• Low T₄:T₃ ratio

• Small goiter

• Disease duration < 6 months

• No history of relapse with antithyroid medications

• Expected therapy duration > 1 year

• Low TSAb titers at baseline or reduced with treatment

When is radioactive iodine the preferred treatment option?

• Graves’ disease

• Toxic nodules

• Toxic multi-nodular goiter

• Female > male

• Low free T₄ levels at diagnosis

When is surgery the preferred treatment option?

• Large goiters

• Patients who refuse RAI

• Failed medication therapy

• Severe ophthalmopathy

What is the preferred treatment option for gestational hyperthyroidism?

Thionamides are preferred

• Specifically PTU because MMI has shown to have higher rates of birth defects when used in the first trimester

For a patient with gestational hyperthyroidism, which thionamide should you give in…

• 1st trimester (+ monitoring?)

• 2nd or 3rd trimester

1st trimester:

• PTU

• (Monitor T₄ and TSH every 4 weeks. Adjust dose to maintain T₄ at ULN or moderately above)

2nd or 3rd trimester:

• PTU

• MMI

What is the preferred option(s) for treating hyperthyroidism in neonates?

• Hyperthyroidism typically presents 7-10 days after birth

• Treat with ATD for 8-12 weeks

• May use iodide as supplementation in the first few days to assist in the transient reduction of thyroid hormones while ATDs take effect

What is the preferred option(s) for treating hyperthyroidism in pediatrics?

• For age < 5 y.o.: Thyroidectomy preferred; avoid RAI

• For age > 5 y.o.: DOC is MMI

subclinical hyperthyroidism

defined as low TSH but normal T₄ and T₃ levels

• Causes are similar to hyperthyroidism, including thyroiditis (from a viral infection, mechanical manipulation, or seen in the postpartum state in women with underlying autoimmune diseases)

treatment approach for subclinical hyperthyroidism (based on patient parameters)

thyroid storm

defined as a sudden, sharp increase in thyroid hormones

• Rare but life-threatening medical emergency

• Precipitating factors:

  • Trauma

  • Infection

  • Withdrawal from ATDs

  • RAI

  • Surgery

clinical features of subclinical hyperthyroidism

• Fever (usually > 103 °F, 29.4 °C)

• Dehydration

• NVD

• Sweating

• Restlessness

• Tachycardia (increased HR)

• Tachypnea (rapid, shallow breathing)

• Heart failure, shock, arrhythmias

• Tremor

• Anxiety

• Hyperreflexia

• Delirium

management for thyroid storm

Thionamides

• Suppresses thyroid hormone synthesis

• Inhibits peripheral conversion of T₄ to T₃ (PTU)

• DOC: PTU

Beta blockers

• Symptomatic management

• DOC: Propranolol

Iodides

• Blocks release of preformed thyroid hormone

• Administer after thionamides

Corticosteroids

• May prevent peripheral conversion of T₄ to T₃

• Prophylaxis against relative adrenal insufficiency

primary (overt) hypothyroidism

elevation in thyroid-secreting hormone (TSH) AND deficiency in T₄/T₃

How can TSH be elevated in a disease of deficiency?

• Normally: In response to a deficiency in thyroid hormones, thyrotropin-releasing hormone (TRH) leaves the hypothalamus and stimulates the anterior pituitary gland to release TSH, the hormone that stimulates the thyroid gland to secrete more T₄. T₄ (think of as the inactive form) is then converted into triiodothyronine (T₃, active form). Once T₃ and T₄ are corrected, this signals the process to stop/shut off (negative feedback loop)

• In hypothyroidism: The thyroid is damaged/dysfunctional, so it can’t adequately respond to TSH and produce more T₄—and these low levels of T4 will keep repeating the process to fruitless results

  • Result: High TSH + low T₄/T₃

subclinial hypothyroidism

ONLY an elevation in TSH

• More common

primary hypothyroidism

• Causes

Primary causes (thyroid gland failure due to chronic autoimmune thyroiditis):

• Iodine deficiency

• Iatrogenic hypothyroidism (can be caused either by exposure to a destructive amount of radiation or surgery, or excessive thionamides in hyperthyroidism treatment)

• Hashimoto’s disease

secondary hypothyroidism

• Causes

• Secondary causes (thyroid gland failure due to pituitary failing to stimulate the thyroid):

  • Disorder of the pituitary gland

  • Hypothalamic hypothyroidism

What medications can cause hypothyroidism?

• Tyrosine kinase inhibitors (TKIs)

• Amiodarone

• Interferon-alpha

• Lithium

Hashimoto’s disease

• An autoimmune-induced hypothyroidism

• Commonly seen in adults without a history of hypothyroidism

• Signs and symptoms:

  • Goiter and mild hypothyroid disorder symptoms (e.g., constipation, excessive/prolonged period, pale and dry skin)

  • Thyroid gland atrophy with more notable alterations to hormones

clinical presentation of hypothyroidism

Helpful hint: Processes slow down

• Symptoms:

  • Cold intolerance

  • Weight gain

  • Constipation

  • Weakness

  • Muscle cramps, myalgias, stiffness

  • Menorrhagia (heavy menses) and infertility

  • Galactosemia (abnormal milk discharged from the breast that is unrelated to normal milk production and breastfeeding)

  • Complaints of:

    • Lethargy

    • Depression

    • Fatigue/weakness

• Signs:

  • Coarse hair and skin

  • Cold or dry skin

  • Slow heart rate (bradycardia)

  • Slow speech and hoarse voice

  • Reversible neurologic syndromes

  • Galactorrhea (in women)

  • Slow relaxation of deep tendon reflexes

laboratory findings for hypothyroidism

goals for treating hypothyroidism

• Resolution of signs/symptoms

• Returning TSH to normal range

• Preventing overtreatment that could lead to hyperthyroidism

treatment options for hypothyroidism

• Levothyroxine (Synthroid)

• Desiccated thyroid (Armour Thyroid)

• Liothyronine (Cytomel)

• Liotrix (Thyrolar)

levothyroxine (Synthroid)

• Content

• Relative dose

• Comments/equivalency

• Synthetic T₄

• 100 mcg

• Comments/equivalency:

  • Stable, predictable potency

  • Generics may be bioequivalent

  • Variable absorption between products

  • Half-life = 7 days (allows for QD)

  • DOC (1st-line agent)

dessicated thyroid (Armour Thyroid)

• Content

• Relative dose

• Comments/equivalency

• Dessicated pork thyroid gland

• 1 grain (equivalent to 74 mcg of T₄)

• Comments/equivalency:

  • High T3/T4 ratio

  • Inexpensive

liothyronine (Cytomel)

• Content

• Relative dose

• Comments/equivalency

• Synthetic T3

• 33 mcg (~100 mcg of T4)

• Comments/equivalency:

  • Uniform absorption

  • Rapid onset

  • Half-life = 1.5 days

  • Rapid peaks and troughs

liotrix (Thyrolar)

• Content

• Relative dose

• Comments/equivalency

• Synthetic T4:T3 ratio

• Thyrolar 1 = 50 mcg of T4 + 12.5 mcg T3

• Comments/equivalency:

  • Stable, predictable

  • Expensive

  • Risk of T3 thyrotoxicosis

levothyroxine (Synthroid)

• MOA

• Clinical advantages

• Clinical disadvantages

• MOA: Replaces T4 to augment available T3 → Reestablishes homeostasis

• Clinical advantages:

  • Relatively inexpensive

  • Active with oral administration

  • Once daily dosing

  • Long half-life, thus making a stable pool of hormone available

• Clinical disadvantages:

  • Avoid therapeutic interchange due to potential effect on thyroid hormone and efficacy of product to stay in therapeutic window

  • Relationship between T4 and TSH concentrations is not linear (e.g., very small changes in T4 can lead to substantial changes in TSH)

  • Absorption concerns when taken with food (must remain consistent)

How to initally dose levothyroxine…

• Typically?

• For CV disease?

• For adults > 50 y.o.?

• For pregnancy?

• Typically: Weight-based (1.6 mcg/kg/day), then adjusted by 12.5-25 mcg/day every 4-6 weeks based on TSH levels

• For CV disease: 12.5-25 mcg/day

  • Need lower starting dose because we don’t want to overcorrect TSH too quickly and risk hypothyroidism, which can have cardiac side effects

• For adults > 50 y.o.: 25-50 mcg/day

  • Need lower starting dose

• For pregnancy: Increase dose by 20-30%

  • Need higher starting dose

Which weight do we use to calculate a levothyroxine dose?

ideal body weight (IBW)

• For males: IBW = 50 kg + 2.3 kg for every inch > 5 ft

• For females: IBW = 45.5 kg + 2.3 kg for every inch > 5 ft

• Multiply by 1.6 mcg/kg/day, and then round to nearest available commercial strength!

• Note: Higher doses than what is recommended from the ideal body weight calculation are required when patients are larger. All-in-all, if you are in the dead center between two commercial levothyroxine strengths, round down for normal-weight people and round up for overweight/obese patients

monitoring parameters for levothyroxine

Monitor TSH 4-6 weeks until euthryoid (following initiation, dosage adjustments, or change in preparation)

• Timeframe needed to achieve steady state

• May also monitor T4

• Increment changes of 12.5-25 mcg/day

• Once an adequate replacement dose has been established, measure TSH at 6 months → then at 12-month intervals or more frequently as clinically indicated (e.g., patient has new symptoms, changes in their health status, new concomitant medications)

drug and food interactions with levothyroxine

All of the folllowing result in LOWER levothyroxine levels → Lower T₄ → Untreated hypothyroid condition:

• Decrease absorption

  • Antacids (e.g., calcium salts)*

  • Bile acid sequestrants (e.g., cholestyramine, colestipol, colesevelam)

  • Ciprofloxacin

  • Ferrous sulfate*

  • Oral bisphosphonates

  • PPI/H2RA (e.g., omeprazole, pantoprazole, famotidine)

  • Phosphate binders (e.g., sevelamer, aluminum hydroxide)

  • Sucralfate

• Increase clearance

  • Carbamazepine

  • Phenobarbital

  • Phenytoin

  • Rifampin

What is a counseling point for levothyroxine with antacids?

* Space levothyroxine out from antacids (calcium- and iron-containing products) by 4 hours

effects of hypothyroidism ON other medications

• Decreased Vd and plasma clearance of digoxin

  • Clinical solution: Lower dose may be required to prevent toxicity

• Delayed degradation of insulin

  • Clinical solution: Lower dose may be required

• Altered clotting factor catabolism (i.e., clotting factor depletes slower) of warfarin

  • Problem: Increased risk of clotting, may unintentionally cause hypoglycemia

  • Solution: Treatment may require increased dose and monitoring to prevent clotting

• Increased O2 retention and precipitation of myxedema with respiratory depressants

  • Avoid use if possible

adverse effects and precautions for levothyroxine

• Excessive doses of thyroid hormone →

  • Heart failure

  • Angina pectoris

  • Myocardial infarction

  • Atrial fibrillation

  • Osteoporosis

• Insufficient doses of thyroid hormone →

  • Signs/symptoms of hypothyroidism

  • Myxedema coma

• Precautions:

  • Do NOT use as a weight-loss product

  • Use with caution and reduce dose in patients with CV disease

patient counseling tips on levothyroxine

• “Take on an empty stomach” (Eating can slow absorption down)

  • Option 1: Administer 30-60 minutes before breakfast and other medications (Note: Separate from antacids by 4 hours)

  • Option 2: Administer 3+ hours after evening meal (no snacking)

• “Consistency is key”

  • Same manufacturer (not bioequivalent)

  • Take at same time each day

• “The process takes time”

  • May take several weeks to see full effects

  • Food decreases levothyroxine absorption → administer on an empty stomach. Then recheck TSH and adjust the levothyroxine dose every 4-6 weeks because TSH takes ~4-6 weeks to reach a new steady state

• “For storage and administration…

  • Store at room temperature away from light and moisture

  • Can be crushed and suspended in water for tube feeds”

dessicated thyroid (Armour Thyroid)

• Origin

• Role in therapy

• In what unit is it dosed?

• Origin: Porcine (pigs)

  • May be problematic in patients who have pork allergies, are vegan, or practice various religions that prohibit consumption of pork

• Role in therapy: Not preferred

  • Primary concern is that the T3 component may be excessive. It has a T4:T3 ratio of 4:1—whereas a normal physiologic T4:T3 ratio is 13:1 or 16:1

• Dosed in “grains”

liothyronine (Cytomel)

• Origin

• Role in therapy

• Origin: Synthetic T3

• Role in therapy: Not preferred

  • Higher incidence of cardiac events

  • Expensive

  • TID dosing

  • Difficult to monitor (has rapid peaks/troughs, the rationale for the frequent dosing → higher potential for missed doses and interruptions in thyroid homeostasis)

liotrix (Thyrolar)

• Origin

• Role in therapy

• Origin: Combination of synthetic T4 and T3

• Role in therapy: Not preferred

  • Expensive

  • Ratio of T4:T3 is greater than that naturally produced by human thyroid gland → can result in thyrotoxicosis if using too much

  • Lack of therapeutic rationale with this agent since most T3 is peripherally converted to T4, so there is no benefit in dosing T3:T4 rather than T4 alone, as you see with levothyroxine

What is the preferred treatment option for pregnant patients with hypothyroidism?

• Monitoring?

• DOC = levothyroxine

  • 20-30% dose increase at start of pregnancy

  • Revert dose back to pre-pregnancy dose 6-8 weeks after delivery

• Target TSH levels:

  • 1st trimester (12 weeks): < 2.5 mIU/L

    • Due to maternal contribution of thyroid hormone in first two months of pregnancy

    • Individuals with preexisting thyroid disorders should be in close contact with their care provider when trying to become pregnant to ensure doses can be adjusted appropriately and in time

  • 2nd and 3rd trimesters: < 3 mIU/L

subclinical hypothyroidism

Prevalence increases with age and is more common in women; has no or few signs/symptoms

• Risks:

  • Cardiovascular disease

  • Reproductive abnormalities

  • Non-fatty liver disease, a complication seen in patients with concomitant obesity and diabetes

treatment for subclinical hypothyroidism

• Levothyroxine is most often initiated when TSH > 10 mIU/L

• Initial dosing is 25-75 mcg/day (not weight-based), and titrated according to response

For hypothyroidism, what is the preferred treatment option(s) for older adults with or without cardiovascular conditions?

• Consider age and cardiovascular disease BEFORE selecting dose

• Older adults should be started at a lower dose and gradually increased. For example:

  • Older adult WITHOUT CV disease: Levothyroxine 25-50 mcg daily, then increase after 4-6 weeks

  • Older adult WITH CV disease: Levothyroxine 12.5-25 mcg daily, then increase by ~25 mcg after 4 - 6 weeks, as necessary

• Cardiovascular abnormalities are common with higher doses of levothyroxine

  • Angina

  • Worsening heart failure

  • Myocardial infarction

myxedema coma

• Life-threatening complication due to inadequate treatment of hypothyroidism

  • 60-70% fatality rate

• Signs/symptoms: Hypothermia, decreased mental status, hypotension, bradycardia, hyponatremia, hypoglycemia, hypoventilation

treatment for myxedema coma

• Correction of this condition requires parenteral (IV) levothyroxine administration due to diminished GI absorption

  • Use lower doses for older adults, smaller patients, and patients with a history of cardiovascular disease/arrhythmias

  • Change patient back to oral therapy after patient has stabilized

• Need to ensure patient has adequate ventilation/stable blood sugar/blood pressure and temperature to prevent complications