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Liothyronine (Monograph)

Brand names: Cytomel, Triostat
Drug class: Thyroid Agents
ATC class: H03AA02
VA class: HS851
CAS number: 55-06-1

Introduction

Synthetic thyroid agent; sodium salt of the l-isomer of 3,3′,5-triiodothyronine (l-T3).a b c e

Uses for Liothyronine

Hypothyroidism

Used orally as replacement or supplemental therapy in congenital or acquired hypothyroidism of any etiology, except transient hypothyroidism during the recovery phase of subacute thyroiditis.a c Specific indications include primary (thyroidal), secondary (pituitary), and tertiary (hypothalamic) hypothyroidism.a c

Generally considered unsatisfactory for long-term use because of potential problems (i.e., wide swings in serum T3 concentrations, possibility of more pronounced adverse cardiovascular effects);a g o however, may be useful when absorption of levothyroxine is questionable, when impairment of peripheral conversion of thyroxine to triiodothyronine is suspected, or in patients allergic to natural thyroid hormone.a b c Levothyroxine is considered drug of choice for replacement therapy.e

For treatment of congenital hypothyroidism (cretinism), levothyroxine is considered drug of choice.a

Used IV for treatment of myxedema coma or precoma.a b c Preferred by some clinicians over levothyroxine when a rapid effect or rapidly reversible effect is desired; however, levothyroxine generally is considered drug of choice for this use.a

Pituitary TSH Suppression

Treatment or prevention of various types of euthyroid goiters, including thyroid nodules, subacute or chronic lymphocytic thyroiditis (Hashimoto’s thyroiditis), and multinodular goiter.a c

Adjunct to radioiodine therapy in the management of thyroid cancer [off-label].o

Diagnosis of Thyroid Disorders

Used diagnostically in suppression tests to differentiate suspected mild hyperthyroidism or thyroid gland autonomy.a c d Use with caution in patients in whom there is a strong suspicion of thyroid gland autonomy because exogenous hormone effects will be additive to endogenous source.c

Liothyronine Dosage and Administration

General

Equivalencies of Thyroid Preparations Based on Clinical Responsed

Thyroid Agent

Approximate Equivalent Dosage

Levothyroxine sodium

100 mcg or less

Liothyronine sodium

25 mcg

Liotrix (levothyroxine sodium/liothyronine sodium)

50 mcg/12.5 mcg (Thyrolar)

Thyroglobulin

65 mg

Thyroid

60–65 mg (1 grain)

Administration

Administer orally or by IV injection.a b c e Do not administer IM or sub-Q.a b

Oral Administration

Administer orally once daily.c

NG Tube

Has been administered orally via NG tube for treatment of myxedema coma; however, IV administration is preferred.a

IV Administration

IV administration may be necessary when oral administration is not feasible or desirable (e.g., in the treatment of myxedema coma, in some neonates, during total parenteral nutrition). Replace with oral therapy as soon as possible.b d

Dosage

Available as liothyronine sodium; dosage expressed in terms of liothyronine.a

Each 25 mcg of liothyronine is approximately clinically equivalent to 60–65 mg of thyroid or thyroglobulin or 100 mcg or less of levothyroxine.a b c (See General under Dosage and Administration.)

Adjust dosage carefully according to clinical and laboratory response to treatment.a c d Avoid undertreatment or overtreatment.d (See Therapy Monitoring under Cautions.)

Initiate at a lower dosage level in geriatric patients, in patients with functional or ECG evidence of cardiovascular disease, and in patients with severe, long-standing hypothyroidism or other endocrinopathies.a

Pediatric Patients

Hypothyroidism
Oral

Initiate therapy as soon as possible after diagnosis of hypothyroidism to prevent deleterious effects on intellectual and physical growth and development.a c d

Recommended initial dosage is 5 mcg once daily.a c Increase by increments of 5 mcg daily at intervals of 3–4 days until desired response is obtained.a c

Maintenance dosage: Infants a few months old may require only 20 mcg daily.c At 1 year of age, 50 mcg daily may be required.c At >3 years of age, full adult daily dosage may be required.c

Adults

Hypothyroidism
Oral

For management of mild hypothyroidism, recommended initial dosage is 25 mcg once daily.a c Increase by increments of 12.5 or 25 mcg daily at intervals of 1–2 weeks until desired response is obtained.a c Usual maintenance dosage is 25–75 mcg daily;a c some patients may require higher or lower dosages.a

For management of severe hypothyroidism (e.g., myxedema), recommended initial dosage is 5 mcg once daily.a c Increase by increments of 5–10 mcg daily at intervals of 1–2 weeks.a c When a dosage of 25 mcg daily is reached, may increase by 5–25 mcg daily at intervals of 1 or 2 weeks until desired response is obtained.c Usual maintenance dosage is 50–100 mcg once daily.a c

Myxedema Coma or Precoma
IV, then Oral

In patients who do not have severe cardiovascular disease, recommended initial dose is 25–50 mcg IV.a b A dosage of ≥65 mcg IV daily in the initial days of therapy reportedly associated with lower mortality; however, clinical experience with dosages >100 mcg daily is limited.a b

Because of potentially wide swings in serum T3 concentrations (possibly precipitating adverse cardiovascular effects), adjust dosage with caution.a b Administer additional doses ≥4 hours apart to allow for adequate assessment of therapeutic response, but no more than 12 hours should elapse between doses to avoid fluctuations in hormone levels.a b

Replace with oral therapy as soon as patient’s condition stabilizes and drug can be given orally.a b

When switching from IV to oral liothyronine therapy, discontinue IV liothyronine, then initiate oral liothyronine at low dosage and increase gradually according to patient’s response.a b

When switching from IV liothyronine to oral levothyroxine therapy, consider delay (several days) in onset of activity of levothyroxine and discontinue IV liothyronine gradually.a b

Pituitary TSH Suppression
Simple (Nontoxic) Goiter
Oral

Recommended initial dosage is 5 mcg daily.a c Increase by increments of 5–10 mcg daily at intervals of 1–2 weeks.a c When a dosage of 25 mcg daily is reached, may increase by 12.5 or 25 mcg daily at intervals of 1–2 weeks until desired response is obtained.a c

Usual maintenance dosage is 75 mcg daily.a c

Diagnosis of Thyroid Disorders
Oral

75–100 mcg daily for 7 days.a c Perform radioactive I 131 uptake test before and after administration of the 7-day course of liothyronine.a c A ≥50% reduction of I 131 uptake after treatment indicates a normal thyroid-pituitary axis and thus rules out thyroid gland autonomy.c

Prescribing Limits

Adults

Myxedema Coma
IV

Limited clinical experience with dosages >100 mcg daily.a b

Special Populations

Patients with Cardiovascular Disease

Hypothyroidism

Initiate therapy at lower dosages than those recommended for patients without cardiovascular disease.c d

Usual initial dosage is 5 mcg daily.c Increase by increments of 5 mcg at intervals of 2 weeks until desired response is obtained.c If cardiovascular disease is aggravated, reduce dosage or temporarily withhold therapy and then cautiously restart therapy at a lower dosage.c d

Myxedema Coma

If liothyronine therapy is clinically indicated, smaller initial IV doses (i.e., 10–20 mcg) may be necessary.b c Titrate dosage gradually.b

Geriatric Patients

Hypothyroidism

Initiate therapy at lower dosages than those recommended for younger patients.b c d

Usual initial dosage is 5 mcg once daily.a Increase by increments of 5 mcg at intervals of 1–2 weeks until desired response is obtained.a If cardiovascular disease is aggravated, reduce dosage or temporarily withhold therapy and then cautiously restart therapy at a lower dosage.c d

Myxedema Coma

Reduced initial IV dose may be appropriate in geriatric patients because of increased risk of cardiovascular disease.b d

Cautions for Liothyronine

Contraindications

Warnings/Precautions

Warnings

Unlabeled Uses

Should not be used for the treatment of obesity or for weight loss either alone or with other therapeutic agents.b c d o In euthyroid patients, doses within the range of daily hormonal requirements are ineffective for weight reduction.b c d Larger doses may produce serious or life-threatening toxicity, particularly when given in conjunction with sympathomimetic amines (e.g., anorectic agents).b c d

Should not be used in the treatment of male or female infertility unless this condition is associated with hypothyroidism.b c d o

Sensitivity Reactions

Hypersensitivity to thyroid hormone is not known to occur.b c However, hypersensitivity reactions to inactive ingredients of thyroid hormone products have been reported and include urticaria, pruritus, rash, flushing, angioedema, abdominal pain, nausea, vomiting, diarrhea, fever, arthralgia, serum sickness, and wheezing.d Allergic skin reactions to liothyronine tablets have been reported rarely.b c

General Precautions

Therapy Monitoring

Thyroid agents have a narrow therapeutic index.d Avoid undertreatment or overtreatment, which may result in adverse effects on growth and development in pediatric patients, cardiovascular function, bone metabolism, reproductive function, cognitive function, emotional state, GI function, and glucose and lipid metabolism.d

Periodically perform appropriate laboratory tests (e.g., serum TSH, total T3) and clinical evaluations to monitor adequacy of therapy.b c e

Preexisting Cardiovascular Disease

Use with extreme caution.b d (See Patients with Cardiovascular Disease under Dosage and Administration.) Potential for cardiotoxicity may be greater than with preparations that do not contain T3.e Patients with CHD should be monitored closely during surgical procedures due to increased risk of arrhythmias.d

Associated Endocrine Disorders

Hypopituitarism, adrenal insufficiency, and other endocrine disorders such as diabetes mellitus and diabetes insipidus are characterized by signs and symptoms which may be diminished in severity or obscured by hypothyroidism.d Thyroid agents may aggravate the intensity of previously obscured symptoms in patients with endocrine disorders, and appropriate adjustment of therapy for these concomitant disorders may be required.b c d

In patients with secondary or tertiary hypothyroidism, consider possibility of additional hypothalamic/pituitary hormone deficiencies and treat if diagnosed.i

Chronic autoimmune thyroiditis may occur in association with other autoimmune disorders (e.g., adrenal insufficiency, pernicious anemia, type 1 diabetes mellitus).g h

Patients with concomitant adrenal insufficiency should be treated with replacement corticosteroids prior to initiation of thyroid agents.b c d Failure to do so may precipitate an acute adrenal crisis due to increased metabolic clearance of corticosteroids when the thyroid agent is initiated.b c d

Patients with diabetes mellitus may require increased dosages of antidiabetic agents when treated with liothyronine.c d

Specific Populations

Pregnancy

Category A.b c

During pregnancy, serum free tetraiodothyronine (thyroxine, T4) levels may decrease and serum TSH levels increase to values outside the normal range.h i Elevations in serum TSH may occur at 4 weeks’ gestation;i monitor TSH levels during each trimester (or every 6 weeks) and adjust liothyronine dosage accordingly.f g o Reduce dosage to pre-pregnancy level immediately after delivery, since postpartum TSH concentrations are similar to preconception levels;i o measure serum TSH concentrations 6–8 weeks postpartum.o

Lactation

Although thyroid hormones are distributed minimally into human milk, exercise caution when administering to a nursing woman.b c However, adequate replacement dosages generally are needed to maintain normal lactation.i

Pediatric Use

Safety and efficacy of IV liothyronine not established in pediatric patients.a b

The goal of treatment in pediatric patients with hypothyroidism is to achieve and maintain normal intellectual and physical growth and development.d Initiate therapy immediately upon diagnosis.c d Maintain therapy for life, unless transient hypothyroidism is suspected.c d

Neonates with suspected hypothyroidism should receive thyroid agent therapy pending results of confirmative tests.d If a positive diagnosis cannot be made on the basis of laboratory findings but there is a strong clinical suspicion of congenital hypothyroidism, initiate replacement therapy to achieve euthyroidism until the child is 1–2 years of age.d During the first 2 weeks of therapy, closely monitor infants for cardiac overload, arrhythmias, and aspiration resulting from avid suckling.d Evaluate infant’s clinical response to therapy about 6 weeks after initiation of thyroid agent therapy and at least at 6 and 12 months of age and yearly thereafter.d

When transient hypothyroidism is suspected, temporarily discontinue therapy for 2–8 weeks to reassess the condition when the child is >3 years of age.c q If the diagnosis of permanent hypothyroidism is confirmed, reinstitute full replacement therapy.d However, if serum concentrations of T4 and TSH are normal, discontinue thyroid agent therapy and monitor carefully;c d repeat thyroid function tests if manifestations of hypothyroidism develop.d

In pediatric patients with transient severe hypothyroidism, reduce replacement dose by half for 30 days to reasses condition.q If, after 30 days, serum TSH is >20 mU/L, consider the hypothyroidism permanent and reinstitute full replacement therapy.q However, if serum TSH has not increased, temporarily discontinue thyroid agent therapy for another 30 days, then repeat serum T4 and TSH measurements.q Reinstitute or discontinue replacement therapy based on laboratory findings.q

Monitor patients closely to avoid undertreatment or overtreatment.d Undertreatment may result in impaired intellectual development, poor school performance (due to impaired concentration and slowed mentation), and reduced adult height.d Overtreatment may result in craniosynostosis in infants and accelerate aging of bones, resulting in premature epiphyseal closure and compromised adult stature.c d q

Treated children may manifest a period of catch-up growth, which may be adequate in some cases to achieve normal adult height.d In children with severe or long-standing hypothyroidism, catch-up growth may not be adequate to achieve normal adult height.d

Pseudotumor cerebri and slipped capital femoral epiphysis have been reported in children receiving thyroid agents.d

Geriatric Use

Because of the increased risk of cardiovascular disease among geriatric patients, liothyronine therapy should not be initiated at the full replacement dose.b c d o (See Geriatric Patients under Dosage and Administration.)

Because of age-related decreases in renal function, may be useful to monitor renal function.b c

Common Adverse Effects

Adverse reactions result from overdosage and resemble manifestations of hyperthyroidism,a c d including fatigue, weight loss, increased appetite, heat intolerance, fever, excessive sweating, headache, hyperactivity, nervousness, anxiety, irritability, emotional lability, insomnia, tremor, muscle weakness, palpitations, tachycardia, arrhythmias, increased heart rate and BP, heart failure, angina, AMI, cardiac arrest, diarrhea, vomiting, abdominal cramps, elevations in liver function test results, hair loss, flushing, decreased bone mineral density, menstrual irregularities, and impaired fertility.b c d

Drug Interactions

Drugs Affecting Hepatic Microsomal Enzymes

Potential increased metabolism of thyroid agent with drugs that induce hepatic microsomal enzymes resulting in increased thyroid agent dosage requirements.d

Drugs That May Decrease T4 5’-Deiodinase Activity

Inhibitors of T4 5’-deiodinase decrease peripheral conversion of T4 to T3, resulting in decreased T3 concentrations.d i u However, serum T4 concentrations usually remain within normal range but may occasionally be slightly increased.d i

Specific Drugs

Drug

Interaction

Comments

Amiodarone

Decreased metabolism of T4 to T3d

Anticoagulants, oral (e.g., coumarins)

Potentiation of anticoagulant activityb c d

Carefully monitor PT and adjust anticoagulant dosage accordingly when thyroid agent therapy is initiatedb c d

Antidepressants (tricyclics, tetracyclics, SSRIs)

Increased risk of cardiac arrhythmias and CNS stimulation when levothyroxine is used with tricyclics or tetracyclicsb c d

Faster onset of action of tricyclicsd

Sertraline may increase levothyroxine requirementsi

Antidiabetic agents (biguanides, meglitinides, sulfonylureas, thiazolidinediones, insulin)

Thyroid agent may cause increased antidiabetic agent or insulin requirementsb c d

Carefully monitor diabetic control, especially when thyroid therapy is initiated, changed, or discontinuedb c d

β-Adrenergic blocking agents (e.g., propranolol hydrochloride dosages >160 mg daily)

Decreased metabolism of T4 to T3d

Impaired antihypertensive effects when hypothyroid patient is converted to euthyroid stated

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

Impaired thyroid agent absorptionc d

Administer liothyronine ≥4 hours apart from these agentsc d

Carbamazepine

Potential increased metabolism of thyroid agentd

May require thyroid agent dosage increased

Cardiac glycosides

Decreased serum digitalis glycoside concentrations in patients with hyperthyroidism or in patients with hypothyroidism in whom a euthyroid state has been achieved; potential for reduced therapeutic effects of digitalis glycosides with thyroid agent used

May need to increase dosage of digitalis glycoside b c

Corticosteroids (e.g., dexamethasone at dosages >4 mg daily)

Decreased metabolism of T4 to T3d

Short-term administration of large doses of corticosteroids may decrease serum T3 concentrations by 30% with minimal change in serum T4 concentrationsd

Estrogen or estrogen-containing oral contraceptives

Possible decreased free T4 concentrationsb c

Patients without a functioning thyroid gland may require liothyronine dosage increaseb c

Ferrous sulfate

Delayed or impaired thyroid absorptiond

Administer thyroid agents ≥4 hours apart from this agentd

Furosemide (at IV dosages >80 mg)

Concomitant use with levothyroxine produces transient increases in serum free T4 concentrations; continued administration results in a decrease in serum T4 and normal free T4 and TSH concentrations, and therefore, patients are clinically euthyroidd

GI drugs (e.g., antacids [aluminum hydroxide, magnesium hydroxide, calcium carbonate], simethicone, sucralfate)

Delayed or impaired thyroid agent absorptiond

Administer liothyronine ≥4 hours apart from these agentsj

Growth hormones (e.g., somatropin)

Excessive use of thyroid agents with growth hormones may accelerate epiphyseal closure; however, untreated hypothyroidism may interfere with growth response to growth hormoned

Heparin

Concomitant use with levothyroxine produces transient increases in serum free T4 concentrations; continued administration results in a decrease in serum T4 and normal free T4 and TSH concentrations, and therefore, patients are clinically euthyroidd

Hydantoins (e.g., phenytoin)

Potential increased metabolism of thyroid agentd

Concomitant use with levothyroxine produces transient increases in serum free T4 concentrations; continued administration results in a decrease in serum T4 and normal free T4 and TSH concentrations, and therefore, patients are clinically euthyroidd

May require thyroid agent dosage increased

Ketamine

Risk of marked hypertension and tachycardiab c d

Use with cautionb c d

NSAIAs (e.g., fenamates, phenylbutazone)

Concomitant use with levothyroxine produces transient increases in serum free T4 concentrations; continued administration results in a decrease in serum T4 and normal free T4and TSH concentrations, and therefore, patients are clinically euthyroidd

Phenobarbital

Potential increased metabolism of thyroid agentd

May require thyroid agent dosage increased

Radiographic agents

Reduced uptake of 123I, 131I, and 99mTcd

Rifampin

Potential increased metabolism of thyroid agentd

May require thyroid agent dosage increased

Salicylates (dosages >2 g daily)

Inhibit binding of T4 and T3 to TBG and transthyretin; initially increases serum free T4, followed by return to normal concentrations with sustained therapeutic serum salicylate concentrations, although total T4 concentrations may decrease by as much as 30%d

Sodium polystyrene sulfonate

Delayed or impaired thyroid absorptiond

Administer liothyronine ≥4 hours apart from this agentd

Sympathomimetic agents

Potentiation of sympathomimetic effects; increased risk of coronary insufficiency in patients with CADd

Observe patient carefully when sympathomimetic agent is administeredd

Xanthine derivatives (e.g., theophylline)

Clearance of xanthine derivatives may be decreased in hypothyroid patients but returns to normal when the euthyroid state is achievedd

Drugs Affecting Thyroid Function or Thyroid Function Tests

Various drugs or concomitant medical conditions (e.g., pregnancy, infectious hepatitis) may adversely affect thyroid function (e.g., alter endogenous thyroid hormone secretion, reduce TSH secretion) resulting in hypothyroidism or hyperthyroidism or interfere with laboratory tests used to assess thyroid function.b c d Consult specialized references for information.

Some drugs may affect transport of thyroid hormones (T3, T4) by affecting serum thyroxine-binding globulin (TBG) concentrations.d i However, free T4 concentrations may remain normal and the patient may remain euthyroid.d i

Drugs Affecting Thyroxine Binding Globulin Concentrationsb c d

Liothyronine Pharmacokinetics

Absorption

Bioavailability

Almost completely absorbed from the GI tract (about 95%).a c e

Onset

More rapid onset of action than levothyroxine.a c Following a single IV dose, metabolic response is detectable within 2–4 hours and peak therapeutic effects occur within 2 days.a b

Duration

Shorter duration of action than levothyroxine.a c

Distribution

Extent

Thyroid hormones do not readily cross the placenta;b c d however, some transfer does occur, as evidenced by levels in cord blood of athyrotic fetuses being approximately one-third maternal levels.i

Minimally distributed into breast milk.b c

Plasma Protein Binding

Circulating thyroid hormones are >99% bound to plasma proteins, including TBG, thyroxine-binding prealbumin (TBPA), and albumin.k T3 is less extensively and firmly bound to TBG and TBPA than T4.b c Only unbound hormone is metabolically active.b c

Elimination

Metabolism

T3 is metabolized principally in the liver through deiodination to diiodothyronine.d i

Elimination Route

Thyroid hormones are primarily eliminated by the kidneys.b c

Half-life

Approximately 1–2 days.a e Plasma half-life is decreased in patients with hyperthyroidism and increased in those with hypothyroidism.a d

Stability

Storage

Oral

Tablets

Tight containers at 15–30°C.a c

Parenteral

Injection

2–8°C.a b

Actions

Advice to Patients

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Liothyronine Sodium

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets

5 mcg (of liothyronine)

Cytomel

King

25 mcg (of liothyronine)

Cytomel (scored)

King

50 mcg (of liothyronine)

Cytomel (scored)

King

Parenteral

Injection, for IV use only

10 mcg (of liothyronine) per mL*

Triostat (with alcohol 6.8%)

King

AHFS DI Essentials™. © Copyright 2024, Selected Revisions July 1, 2008. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

† Off-label: Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

a. AHFS Drug Information 2008. McEvoy GK, ed. Liothyronine Sodium. Bethesda, MD: American Society of Health-System Pharmacists; 2008:3306-7.

b. King Pharmaceuticals. Triostat (liothyronine sodium) injection prescribing information. Bristol, TN; 2007 Jan. From King Pharmaceuticals website. http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?id=15254

c. King Pharmaceuticals, Inc. Cytomel (liothyronine sodium) tablets prescribing information. Bristol, TN; 2004 Mar.

d. AHFS Drug Information 2008. McEvoy GK, ed. Thyroid Agents General Statement. Bethesda, MD: American Society of Health-System Pharmacists; 2008:3298-302.

e. Dong BJ. Thyroid Disorders. In: Koda-Kimble MA, Young LY, eds. Applied therapeutics: The clinical use of drugs. 8th ed. Philadelphia, PA: Lippincott Williams, & Wilkins; 2005:49-1–49-19.

f. Anon. Drugs for hypothyroidism and hyperthyroidism. Treat Guidel Med Lett. 2006; 4:17–24.

g. American Association of Clinical Endocrinologists. Medical guidelines for clinical practice for the evaluation and treatment of hyperthyroidism and hypothyroidism, 2006 amended version. Endocr Pract. 2002; 8:457-69.

h. American College of Obstetricians and Gynecologists (ACOG) Practice Bulletin. Clinical management guidelines for obstetrician-gynecologists, number 37, August 2002: Thyroid disease in pregnancy. Obstet Gynecol. 2002; 100:387-96. http://www.ncbi.nlm.nih.gov/pubmed/12166417?dopt=AbstractPlus

i. Abbott Laboratories. Synthroid (levothyroxine sodium) tablets prescribing information. North Chicago, IL; 2005 Aug. From Abbott website. http://www.rxabbott.com/pdf/synthroid.pdf

o. Singer PA, Cooper DS, Levy EG et al. Treatment guidelines for patients with hyperthyroidism and hypothyroidism. JAMA; 1995; 273:808-12.

q. American Academy of Pediatrics, American Thyroid Association, and Lawson Wilkins Pediatric Endocrine Society. Update of newborn screening and therapy for congenital hypothyroidism. Pediatrics. 2006; 117:2290-303. http://www.ncbi.nlm.nih.gov/pubmed/16740880?dopt=AbstractPlus

u. Talbert RL. Thyroid disorders. In: DiPiro JT, Talbert RL, Yee GC et al, eds. Pharmacotherapy: a pathophysiologic approach. 6th ed. New York: The McGraw-Hill Companies, Inc.; 2005:1369-90.

v. Buckshee K, Kriplani A, Kapil A et al. Hypothyroidism complicating pregnancy. Aust N Z J Obstet Gynaecol. 1992; 32:240-2. http://www.ncbi.nlm.nih.gov/pubmed/1445136?dopt=AbstractPlus

w. Joshi JV, Bhandarka SD, Chadha M et al. Menstrual irregularities and lactation failure may precede thyroid dysfunction or goitre. J Postgrad Med. 1993; 39:137-41. http://www.ncbi.nlm.nih.gov/pubmed/8051643?dopt=AbstractPlus

j. Singh N, Singh PN, Hershman JM. Effect of calcium carbonate on the absorption of levothyroxine. JAMA. 2000; 283:2822-5. http://www.ncbi.nlm.nih.gov/pubmed/10838651?dopt=AbstractPlus

k. Standing Committee on the Scientific Evaluation of Dietary Reference Intakes of the Food and Nutrition Board, Institute of Medicine, National Academy of Sciences. Dietary reference intakes for vitamin A, vitamin K, arsenic, boron, chromium, copper, iodine, iron, manganese, molybdenum, nickel, silicon, vanadium, and zinc. Washington, DC: National Academy Press; 2001.