Earn CME/CE in your profession:

Continuing Education Activity

Oral levothyroxine is primarily indicated for treating primary, secondary, and tertiary hypothyroidism. Primary hypothyroidism is when the problem occurs in the thyroid gland. Secondary hypothyroidism is when the problem is in the pituitary gland, and there is a decrease in the production of thyroid-stimulating hormone (TSH). Tertiary hypothyroidism is sporadic. Additionally, levothyroxine has FDA approval for pituitary thyrotropin suppression as an adjunct to surgery and radioiodine therapy to manage thyrotropin-dependent well-differentiated thyroid cancer. This activity covers important information about prescribing levothyroxine, including mechanism of action, pharmacology, adverse event profiles, eligible patient populations, and monitoring, and highlights the interprofessional team's role in managing various forms of hypothyroidism with levothyroxine.


  • Explain the mechanism of action of levothyroxine.
  • Describe the pathophysiology of the three primary forms of hypothyroidism.
  • Outline the contraindications to initiating therapy with levothyroxine.
  • Summarize interprofessional team strategies for improving care coordination and communication to advance levothyroxine and improve outcomes.


Oral levothyroxine is FDA approved for treating primary, secondary, and tertiary hypothyroidism.[1] Primary hypothyroidism is due to a problem in the thyroid gland, with the most common cause being an autoimmune condition (Hashimoto thyroiditis) and iatrogenic hypothyroidism (after thyroidectomy). Secondary hypothyroidism is when the problem is in the pituitary gland (from pituitary adenomas to post-surgical intervention), and there is a decrease in thyroid-stimulating hormone(TSH) production. Tertiary hypothyroidism is rare, and the problem is in the hypothalamus with decreased production of a thyroid-releasing hormone(TRH).[2] 

Additionally, levothyroxine has FDA approval for pituitary thyrotropin suppression as an adjunct to surgery and radioiodine therapy to manage thyrotropin-dependent well-differentiated thyroid cancer.[3] Injectable levothyroxine is FDA approved for the treatment of myxedema coma or severe hypothyroidism.[4] 

Off-label usage of levothyroxine includes cadaveric organ recovery and subclinical hypothyroidism.[5][6] Subclinical hypothyroidism with TSH >10 mIU/L and symptomatic patients should be treated with levothyroxine therapy.[7]

Mechanism of Action

Levothyroxine(T4) is a synthetic version of the body’s natural thyroid hormone: thyroxine(T4). Normally, the hypothalamus secretes thyrotropin-releasing hormone(TRH), which then stimulates the anterior pituitary to secrete thyroid-stimulating hormone(TSH), which subsequently stimulates the thyroid to secrete 80% thyroxine (T4) and 20% L-triiodothyronine(T3). Fifty percent of thyroxine (T4) then gets converted to its active metabolite L-triiodothyronine (T3). The thyroid hormones then work by binding to thyroid receptor proteins contained within the cell nucleus.[8]

Once inside the nucleus, thyroid hormones directly influence DNA transcription to increase body metabolism by increasing gluconeogenesis, protein synthesis, the mobilization of glycogen stores, and other functions.[9] In scenarios where this process is interrupted (as seen in primary, secondary, or tertiary hypothyroidism), levothyroxine(LT4) can mimic the body’s endogenous T4 production by the thyroid.[10]


Absorption: Orally administered levothyroxine is absorbed from the jejunum and upper ileum (40% to 80%). The relative bioavailability of levothyroxine tablets, compared to an equal dose of oral levothyroxine solution, is approximately 93%. Levothyroxine absorption is increased by fasting and is decreased in the presence of food and malabsorption syndromes. Dietary fiber reduces the bioavailability of T4.

Distribution: Thyroid hormones are greater than 99% bound to plasma proteins, including thyroxine-binding globulin (TBG), thyroxine-binding prealbumin (TBPA), and albumin (TBA). T4 has a greater affinity for TBG and TBPA, leading to slower metabolic clearance and a longer half-life of T4 than T3. The free hormone is metabolically active. Many drugs and physiologic conditions alter the binding of thyroid hormones to serum proteins.

Metabolism: Thyroid hormones are primarily metabolized by sequential deiodination. Approximately 80% of T3 derives from peripheral T4. The liver is the primary site of degradation for T4 and T3, with T4 deiodination also occurring at several additional sites, including the kidney. T4 is deiodinated to generate an equal quantity of T3 and reverse T3 (rT3). T3 and rT3 are then deiodinated to diiodothyronine. Thyroid hormones are also metabolized via conjugation and undergo enterohepatic recirculation.

Excretion: The kidneys primarily excrete thyroid hormones. Approximately 20% of T4 is excreted in the stool. Urinary excretion of T4 decreases with age.


Multiple dosage forms of levothyroxine are available, including oral tablets, capsules, solutions, and parenteral dosage forms. Specific instructions for the dosage forms are as below.

  • Oral: Administer levothyroxine on an empty stomach (acidity increases absorption) at least 30 to 60 minutes before breakfast or 3 to 4 hours after dinner. Do not administer levothyroxine within 4 hours of administration of products that may contain iron or calcium. Do not administer levothyroxine in conjunction with antacids or proton pump inhibitors.[11]
  • Capsule: Swallow whole; Do not crush or cut.
  • Tablet: May crush into 5 to 10 mL of water and drink immediately. If swallowing the tablet whole, administer with a full glass of water to prevent dysphagia.
  • Solution: Give either undiluted (directly squeeze contents into the mouth) or diluted in water only (squeeze contents into water, stir, and drink immediately).
  • Intravenous levothyroxine is exclusively used in the hospital setting, where vital signs can undergo close monitoring.
  • If the patient can not tolerate anything by mouth, the levothyroxine capsules are used as a suppository and are well absorbed.[12]

Adult Dosing

  • For the treatment of hypothyroidism (oral): Adults who are healthy and diagnosed with hypothyroidism for a few months should receive an initial dose of 1.6 mcg/kg/day with a 12.5 to 25 mcg/day dose adjustment every 6 to 8 weeks as needed.
  • Adults with cardiac disease or elderly over 65 years old and hypothyroidism should receive an initial dose of 25 mcg/day with a dose adjustment of 12.5 to 25 mcg every 4 to 6 weeks as needed.[13]

Infant and Pediatric Dosing

  • Levothyroxine replacement of 10 to 15 mcg/kg/d should be initiated once newborn screening is positive. Higher doses may be required for infants with severe congenital hypothyroidism. According to product labeling by the FDA following dose of levothyroxine is recommended. The levothyroxine dose is adjusted based on clinical response and laboratory parameters.[14]
  • 0 to 3 months:10 to 15 mcg/kg/day
  • 3 to 6 months: 8 to10 mcg/kg/day
  • 6 to 12 months: 6 to  8 mcg/kg/day
  • 1 to 5 years: 5 to 6 mcg/kg/day
  • 6 to 12 years: 4 to 5 mcg/kg/day
  • Greater than 12 years but growth and puberty incomplete: 2 to 3 mcg/kg/day
  • Growth and puberty complete: 1.6 mcg/kg/day
  • 1-year-old children 4 to 6 mcg/kg/d, adolescents 2 to 4 mcg/kg/d, transition to the average adult dose of 1.6 mcg/kg/d once endocrine maturation is complete.
  • Newborns (0 to 3 months) at risk for cardiac failure: Consider a lower starting dose in newborns at risk for cardiac failure. Based on clinical and laboratory responses, increase the dose every 4 to 6 weeks as needed. 

Myxedema Coma (IV) or Severe Hypothyroidism

  • 200 to 400 mcg initial IV loading dose is followed by a daily dose of 1.2 mcg/kg/day, considering lower doses in patients with a history of cardiac disease, arrhythmia, or older patients. Switch to oral therapy (8 mcg/kg/day) when symptoms resolve. The equivalence between intravenous and oral levothyroxine is 0.75 to 1 (for example, 200 mcg IV of levothyroxine equals 266 mcg of oral levothyroxine).[15]

Organ Recovery from a Cadaver

  • 20 mcg IV bolus to the donor, followed by 10 mcg/hour continuous infusion. Given with methylprednisolone, dextrose, and insulin.[16]

Patients with Hepatic Impairment: There is no information regarding dosage adjustment of levothyroxine in patients with hepatic impairment in the manufacturer's product labeling. 

Patients with Renal Impairment: There is no information regarding dosage adjustment of levothyroxine in patients with renal impairment in the manufacturer's product labeling.

Pregnancy Considerations: Pregnancy may increase levothyroxine requirements. Therefore, clinicians should monitor serum TSH levels and adjust levothyroxine dosage during pregnancy. Pregnant patients with newly diagnosed hypothyroidism should receive initial treatment at 1.8 mcg/kg/day. Adjust the dose every four weeks as needed. If a patient is diagnosed with hypothyroidism before pregnancy, adjust the dose of levothyroxine as needed. After pregnancy, levothyroxine should decrease to 1.6 mcg/kg/day.[17] The American Thyroid Association (ATA) recommends levothyroxine as the treatment of choice for maternal hypothyroidism. Other thyroid preparations, such as T3 or desiccated preparations, should not be used in pregnancy.[18]

Breastfeeding Considerations: Levothyroxine (T4) is a component of human milk. Adequate levothyroxine during lactation may normalize milk production in hypothyroid lactating mothers. The health benefits of breastfeeding should be evaluated, along with the mother's clinical requirement for levothyroxine and possible adverse effects on the breastfed infant from levothyroxine. Exogenous replacement of levothyroxine during breastfeeding has no adverse effects in infants. The American Thyroid Association(ATA) suggests hypothyroidism should be treated with levothyroxine in lactating women. After delivery, levothyroxine should be reduced to the patient's preconception dose. Further thyroid function testing should be performed at approximately six weeks postpartum.[19]

Adverse Effects

Generally, adverse events resulting from incorrect dosing (excessive dosing) often form a hyperthyroid-like picture or an allergic reaction to the excipient of the levothyroxine tablets. Levothyroxine 50 mcg tablets don't contain allergic excipients, so there is a decreased risk for immune reactions.[20] Allergy to the excipients such as dye(tartrazine yellow), lactose, acacia, or even gluten in the levothyroxine tablet may infrequently occur. Hence, allergy or intolerance to levothyroxine can be managed by changing the product, including consideration of gel capsules.[15]Among older persons treated with levothyroxine, levothyroxine at doses more than 75 mcg per day is associated with an increased risk of atrial fibrillation.[21]

Adverse Drug Reactions (According to System Organ Classification)[22]

Cardiovascular Adverse Drug Reactions

  • Angina pectoris
  • Tachycardia
  • Palpitations
  • Arrhythmia
  • Myocardial infarction[23]
  • Atrial fibrillation[15]

Neuropsychiatric Adverse Drug Reactions

  • Anxiety
  • Insomnia(advise the patient to take levothyroxine in the morning)

Gastrointestinal Adverse Drug Reactions

  • Weight loss
  • Fatigue
  • Diarrhea
  • Emesis

Dermatological Adverse Drug Reactions

  • Skin rash
  • Alopecia
  • Diaphoresis

Endocrine Adverse Drug Reactions

  • Goiter
  • Menstrual irregularities
  • Heat intolerance
  • Decreased bone mineral density (a result of TSH suppression)[13][15]

Hepatic Adverse Drug Reactions

  • Increased liver enzymes(hepatocellular or mixed pattern)
  • Immunoallergic hepatitis(with eosinophilia)[24]

Drug Interactions

  • Calcium carbonate, ferrous fumarate, and sevelamer bind to levothyroxine and reduce the absorption of levothyroxine. Administer levothyroxine 4 hours apart from the medications mentioned above. Bile acid sequestrants (e.g., colesevelam, cholestyramine, colestipol) and ion exchange resins, e.g., polystyrene sulfonate, reduce levothyroxine absorption. Administer levothyroxine at least 4 hours before these drugs and monitor TSH levels. Monitor patients treated concomitantly with levothyroxine and orlistat for changes in thyroid function due to reduced absorption. Gastric acidity is a prerequisite for adequate absorption of levothyroxine. Sucralfate, antacids, and proton pump inhibitors can cause hypochlorhydria and decrease levothyroxine absorption.[15]
  • Furosemide inhibits the protein binding of T4 to thyroid binding globulin(TBG), leading to an increase in free T4; it also competes for T4-binding sites on TBG, so a single high dose of furosemide can acutely lower the total T4 level. Phenytoin and carbamazepine decrease the protein binding of levothyroxine, and total and free T4 may be reduced by 20% to 40%. However, most patients have normal TSH levels and are clinically euthyroid. Therefore, clinicians should closely monitor thyroid hormone parameters. Drugs that increase serum TBG include estrogen, tamoxifen, clofibrate, opioids, mitotane, fluorouracil, and capecitabine. Estrogen treatment in postmenopausal women is associated with an increase in mean TSH concentration. Rapid estrogen increase is associated with increased TBG and TSH values in treated hypothyroid women. Androgens have the opposite effect and reduce the serum TBG concentrations, thus requiring a decrease in levothyroxine dose. Propranolol and amiodarone, reduce the conversion of T4 to T3. Carbamazepine, phenobarbital, and rifampin induce liver microsomal enzymes, increase levothyroxine metabolism, and decrease serum concentration. Drugs such as dopamine, glucocorticoids, and octreotide can reduce TSH concentration, while lithium, iodine, and sulphonamides interfere with thyroid hormone synthesis.[15][25]
  • Patients treated with immune checkpoint inhibitor therapy (ICPi- pembrolizumab, nivolumab, ipilimumab) may develop hypothyroidism due to immune-related adverse events (IRAE), which may require discontinuation of ICPi.[26]
  • The absorption of levothyroxine can be impaired by soybean, papaya, and grapefruit.[25]


  • Acute myocardial infarction
  • Uncorrected adrenal insufficiency
  • Acute myocarditis, pancarditis
  • Active cardiac arrhythmias
  • Thyrotoxicosis
  • Hyperthyroidism[13][15]

Boxed Warning: Levothyroxine or other thyroid hormones, alone or with other therapeutic drugs, should not be used to treat obesity or promote weight loss. In euthyroid patients, levothyroxine dose in the range of daily hormonal requirements is ineffective for weight loss. In addition, larger doses of levothyroxine may lead to serious and life-threatening manifestations, especially when combined with sympathomimetic amines like phentermine used for anorectic effects.


In adults, monitor TSH levels approximately 6 to 8 weeks after initiating treatment with levothyroxine. Upon achieving the correct dosing of levothyroxine, monitor TSH levels after 4 to 6 months and then every 12 months. Patients should receive education about the symptoms of hyperthyroidism and contact their clinician for medication dose decrease if those symptoms appear.[13][15] It is important to consider that TSH is unreliable in patients with secondary or tertiary hypothyroidism, and the best indicator to adjust dosing will be the free T4 or total T4.[27] The clinician should counsel the patient to use the same levothyroxine brand because of the narrow therapeutic index.[28]

Oral semaglutide (GLP-1 analog) increases total T4 exposure when given levothyroxine. In addition, levothyroxine pharmacokinetics is influenced by co-administration with oral semaglutide. Therefore, thyroid function tests should be monitored, and the clinician should adjust the levothyroxine dose.[29]


Levothyroxine toxicity is rare; however, it is most likely to occur in the setting of accidental ingestion by children or older adults. Thyroxine (T4) and triiodothyronine (T3) levels rise within 1 to 2 hours of ingestion. In the initial stage of overdose (6 to 12 hours post-ingestion), the common signs of toxicity would be tremulousness, tachycardia, hypertension, anxiety, and diarrhea. Rarely convulsions, thyroid storms, acute psychosis, arrhythmias, and acute myocardial infarction may occur. Laboratory workup usually reveals elevated serum total T4 and T3, suppressed serum TSH, and elevated Free T4 and Free T3.

Employ the following treatment approach in acute levothyroxine overdose. 

  • Administer activated charcoal to prevent the absorption of levothyroxine.
  • Cholestyramine binds thyroxine and enhances its elimination. The dose used is 4 grams orally every 8 hours.[30]
  • Beta-blockers are beneficial to alleviate the metabolic effects of thyroid hormone, mainly on the cardiac system (controlling tachycardia, preventing arrhythmias). Propranolol also blocks the peripheral conversion of T4 to T3.
  • Glucocorticoids such as (Dexamethasone 4 mg orally) can reduce the conversion of LT4 to T3, the active hormone.
  • Propylthiouracil can be used to prevent the conversion of T4 to T3.
  • Hemodialysis is utilized in severe cases, but it is of limited benefit since T3 and T4 are primarily protein-bound. 
  • Hemoperfusion utilizing activated charcoal is a complex but efficient procedure for reducing thyroxine levels. Therefore, reserve it for adult patients with severe intoxication.[31] 
  • The severe cases of intoxication leading to a thyroid storm require treatment in a MICU.[32]

In summary, it is essential to note that there is no antidote to treat levothyroxine overdose. Treatment options include gastric lavage, activated charcoal, cholestyramine, glucocorticoids, beta-blockers, propylthiouracil, and supportive measures.[33]

Enhancing Healthcare Team Outcomes

Upon first prescribing levothyroxine, medication adjustment should occur every 6 to 8 weeks until the patient reaches a steady state. Clinicians should also evaluate the response to levothyroxine by using a validated questionnaire, such as thyroid-related quality of life (ThyPRO) and the underactive thyroid treatment satisfaction questionnaire (ThySRQ).[34][35] If the patient has symptoms of hyperthyroidism, advise the patient to contact the clinician to determine if these are side effects of the medication. A clinician should then order TSH and free T4 levels immediately. If the free T4 comes back elevated, the clinician should decrease the dose of levothyroxine to prevent cardiac complications and other symptoms of hyperthyroidism. Finally, clinicians should refer the patient to an endocrinologist if hypothyroidism is due to central causes. In all the scenarios mentioned above, pharmacists should ensure proper dosing and report to the clinician if there is any potential drug-drug interaction or if supplies may dictate a change to a different formulation. 

In an acute overdose of levothyroxine, emergency department physician and triage nurses stabilize the patient, focusing on maintaining a patent airway, breathing, and circulation. Critical care physicians play an essential role in managing thyroid storms. In the case of extreme overdose where hemoperfusion or hemodialysis is planned, a nephrologist referral is required.[31] In such cases, nursing will play a crucial role in monitoring the patient, administering medication, and reporting any patient status changes to the clinician. As described above, multiple healthcare professionals take care of the patient prescribed levothyroxine for various indications. An interprofessional team-based approach involving clinicians (MDs, DOs, NPs, PAs), specialists, nurses, pharmacists, and other healthcare providers achieves maximum efficacy. It minimizes the adverse drug reactions associated with levothyroxine therapy which translates to improved patient outcomes. [Level 5]



Ricardo Correa


8/28/2023 9:59:11 PM



Cooper DS, Halpern R, Wood LC, Levin AA, Ridgway EC. L-Thyroxine therapy in subclinical hypothyroidism. A double-blind, placebo-controlled trial. Annals of internal medicine. 1984 Jul:101(1):18-24     [PubMed PMID: 6428290]

Level 1 (high-level) evidence


Chaker L, Bianco AC, Jonklaas J, Peeters RP. Hypothyroidism. Lancet (London, England). 2017 Sep 23:390(10101):1550-1562. doi: 10.1016/S0140-6736(17)30703-1. Epub 2017 Mar 20     [PubMed PMID: 28336049]


Haugen BR, Alexander EK, Bible KC, Doherty GM, Mandel SJ, Nikiforov YE, Pacini F, Randolph GW, Sawka AM, Schlumberger M, Schuff KG, Sherman SI, Sosa JA, Steward DL, Tuttle RM, Wartofsky L. 2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer: The American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer. Thyroid : official journal of the American Thyroid Association. 2016 Jan:26(1):1-133. doi: 10.1089/thy.2015.0020. Epub     [PubMed PMID: 26462967]


Ono Y, Ono S, Yasunaga H, Matsui H, Fushimi K, Tanaka Y. Clinical characteristics and outcomes of myxedema coma: Analysis of a national inpatient database in Japan. Journal of epidemiology. 2017 Mar:27(3):117-122. doi: 10.1016/j.je.2016.04.002. Epub 2017 Jan 5     [PubMed PMID: 28142035]


Salim A, Vassiliu P, Velmahos GC, Sava J, Murray JA, Belzberg H, Asensio JA, Demetriades D. The role of thyroid hormone administration in potential organ donors. Archives of surgery (Chicago, Ill. : 1960). 2001 Dec:136(12):1377-80     [PubMed PMID: 11735863]


Calissendorff J, Falhammar H. To Treat or Not to Treat Subclinical Hypothyroidism, What Is the Evidence? Medicina (Kaunas, Lithuania). 2020 Jan 19:56(1):. doi: 10.3390/medicina56010040. Epub 2020 Jan 19     [PubMed PMID: 31963883]


Khandelwal D, Tandon N. Overt and subclinical hypothyroidism: who to treat and how. Drugs. 2012 Jan 1:72(1):17-33. doi: 10.2165/11598070-000000000-00000. Epub     [PubMed PMID: 22191793]


Feingold KR, Anawalt B, Blackman MR, Boyce A, Chrousos G, Corpas E, de Herder WW, Dhatariya K, Dungan K, Hofland J, Kalra S, Kaltsas G, Kapoor N, Koch C, Kopp P, Korbonits M, Kovacs CS, Kuohung W, Laferrère B, Levy M, McGee EA, McLachlan R, New M, Purnell J, Sahay R, Shah AS, Singer F, Sperling MA, Stratakis CA, Trence DL, Wilson DP, Rousset B, Dupuy C, Miot F, Dumont J. Chapter 2 Thyroid Hormone Synthesis And Secretion. Endotext. 2000:():     [PubMed PMID: 25905405]


Anyetei-Anum CS, Roggero VR, Allison LA. Thyroid hormone receptor localization in target tissues. The Journal of endocrinology. 2018 Apr:237(1):R19-R34. doi: 10.1530/JOE-17-0708. Epub 2018 Feb 12     [PubMed PMID: 29440347]


Fish LH, Schwartz HL, Cavanaugh J, Steffes MW, Bantle JP, Oppenheimer JH. Replacement dose, metabolism, and bioavailability of levothyroxine in the treatment of hypothyroidism. Role of triiodothyronine in pituitary feedback in humans. The New England journal of medicine. 1987 Mar 26:316(13):764-70     [PubMed PMID: 3821822]


Ianiro G, Mangiola F, Di Rienzo TA, Bibbò S, Franceschi F, Greco AV, Gasbarrini A. Levothyroxine absorption in health and disease, and new therapeutic perspectives. European review for medical and pharmacological sciences. 2014:18(4):451-6     [PubMed PMID: 24610609]

Level 3 (low-level) evidence


Kashiwagura Y, Uchida S, Tanaka S, Watanabe H, Masuzawa M, Sasaki T, Namiki N. Clinical efficacy and pharmacokinetics of levothyroxine suppository in patients with hypothyroidism. Biological & pharmaceutical bulletin. 2014:37(4):666-70     [PubMed PMID: 24694613]


Garber JR, Cobin RH, Gharib H, Hennessey JV, Klein I, Mechanick JI, Pessah-Pollack R, Singer PA, Woeber KA, American Association of Clinical Endocrinologists and American Thyroid Association Taskforce on Hypothyroidism in Adults. Clinical practice guidelines for hypothyroidism in adults: cosponsored by the American Association of Clinical Endocrinologists and the American Thyroid Association. Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists. 2012 Nov-Dec:18(6):988-1028     [PubMed PMID: 23246686]

Level 1 (high-level) evidence


Clarke N, Kabadi UM. Optimizing treatment of hypothyroidism. Treatments in endocrinology. 2004:3(4):217-21     [PubMed PMID: 16026104]


Jonklaas J, Bianco AC, Bauer AJ, Burman KD, Cappola AR, Celi FS, Cooper DS, Kim BW, Peeters RP, Rosenthal MS, Sawka AM, American Thyroid Association Task Force on Thyroid Hormone Replacement. Guidelines for the treatment of hypothyroidism: prepared by the american thyroid association task force on thyroid hormone replacement. Thyroid : official journal of the American Thyroid Association. 2014 Dec:24(12):1670-751. doi: 10.1089/thy.2014.0028. Epub     [PubMed PMID: 25266247]


Nath DS, Ilias Basha H, Liu MH, Moazami N, Ewald GA. Increased recovery of thoracic organs after hormonal resuscitation therapy. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation. 2010 May:29(5):594-6. doi: 10.1016/j.healun.2009.12.001. Epub 2010 Mar 6     [PubMed PMID: 20207554]


Alexander EK, Marqusee E, Lawrence J, Jarolim P, Fischer GA, Larsen PR. Timing and magnitude of increases in levothyroxine requirements during pregnancy in women with hypothyroidism. The New England journal of medicine. 2004 Jul 15:351(3):241-9     [PubMed PMID: 15254282]


Alexander EK, Pearce EN, Brent GA, Brown RS, Chen H, Dosiou C, Grobman WA, Laurberg P, Lazarus JH, Mandel SJ, Peeters RP, Sullivan S. 2017 Guidelines of the American Thyroid Association for the Diagnosis and Management of Thyroid Disease During Pregnancy and the Postpartum. Thyroid : official journal of the American Thyroid Association. 2017 Mar:27(3):315-389. doi: 10.1089/thy.2016.0457. Epub     [PubMed PMID: 28056690]


. Levothyroxine. Drugs and Lactation Database (LactMed®). 2006:():     [PubMed PMID: 30000062]


Choi YH, Choi WY, Kang HC, Koh YI, Bae EH, Kim SW. Drug rash induced by levothyroxine tablets. Thyroid : official journal of the American Thyroid Association. 2012 Oct:22(10):1090. doi: 10.1089/thy.2011.0462. Epub 2012 Sep 10     [PubMed PMID: 22962862]


Gong IY, Atzema CL, Lega IC, Austin PC, Na Y, Rochon PA, Lipscombe LL. Levothyroxine dose and risk of atrial fibrillation: A nested case-control study. American heart journal. 2021 Feb:232():47-56. doi: 10.1016/j.ahj.2020.09.016. Epub 2020 Oct 3     [PubMed PMID: 33022231]

Level 2 (mid-level) evidence


Bousquet C, Lagier G, Lillo-Le Louët A, Le Beller C, Venot A, Jaulent MC. Appraisal of the MedDRA conceptual structure for describing and grouping adverse drug reactions. Drug safety. 2005:28(1):19-34     [PubMed PMID: 15649103]


Mustafa C, Ozgül U, Zehra GC, Hülya C. Transient ST-segment elevation due to iatrogenic hyperthyroidism in a patient with normal coronary arteries. Internal medicine (Tokyo, Japan). 2011:50(15):1595-7     [PubMed PMID: 21804288]


. Thyroid Hormone. LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. 2012:():     [PubMed PMID: 31643816]


Colucci P, Yue CS, Ducharme M, Benvenga S. A Review of the Pharmacokinetics of Levothyroxine for the Treatment of Hypothyroidism. European endocrinology. 2013 Mar:9(1):40-47. doi: 10.17925/EE.2013.09.01.40. Epub 2013 Mar 15     [PubMed PMID: 30349610]


Brahmer JR, Lacchetti C, Schneider BJ, Atkins MB, Brassil KJ, Caterino JM, Chau I, Ernstoff MS, Gardner JM, Ginex P, Hallmeyer S, Holter Chakrabarty J, Leighl NB, Mammen JS, McDermott DF, Naing A, Nastoupil LJ, Phillips T, Porter LD, Puzanov I, Reichner CA, Santomasso BD, Seigel C, Spira A, Suarez-Almazor ME, Wang Y, Weber JS, Wolchok JD, Thompson JA, National Comprehensive Cancer Network. Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: American Society of Clinical Oncology Clinical Practice Guideline. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2018 Jun 10:36(17):1714-1768. doi: 10.1200/JCO.2017.77.6385. Epub 2018 Feb 14     [PubMed PMID: 29442540]

Level 1 (high-level) evidence


Persani L. Clinical review: Central hypothyroidism: pathogenic, diagnostic, and therapeutic challenges. The Journal of clinical endocrinology and metabolism. 2012 Sep:97(9):3068-78. doi: 10.1210/jc.2012-1616. Epub 2012 Jul 31     [PubMed PMID: 22851492]


Wartofsky L. Levothyroxine: therapeutic use and regulatory issues related to bioequivalence. Expert opinion on pharmacotherapy. 2002 Jun:3(6):727-32     [PubMed PMID: 12036412]

Level 3 (low-level) evidence


Hauge C, Breitschaft A, Hartoft-Nielsen ML, Jensen S, Bækdal TA. Effect of oral semaglutide on the pharmacokinetics of thyroxine after dosing of levothyroxine and the influence of co-administered tablets on the pharmacokinetics of oral semaglutide in healthy subjects: an open-label, one-sequence crossover, single-center, multiple-dose, two-part trial. Expert opinion on drug metabolism & toxicology. 2021 Sep:17(9):1139-1148. doi: 10.1080/17425255.2021.1955856. Epub 2021 Aug 31     [PubMed PMID: 34289755]

Level 3 (low-level) evidence


de Luis DA, Dueñas A, Martin J, Abad L, Cuellar L, Aller R. Light symptoms following a high-dose intentional L-thyroxine ingestion treated with cholestyramine. Hormone research. 2002:57(1-2):61-3     [PubMed PMID: 12006723]


Kreisner E, Lutzky M, Gross JL. Charcoal hemoperfusion in the treatment of levothyroxine intoxication. Thyroid : official journal of the American Thyroid Association. 2010 Feb:20(2):209-12. doi: 10.1089/thy.2009.0054. Epub     [PubMed PMID: 20151829]


Chiha M, Samarasinghe S, Kabaker AS. Thyroid storm: an updated review. Journal of intensive care medicine. 2015 Mar:30(3):131-40. doi: 10.1177/0885066613498053. Epub 2013 Aug 5     [PubMed PMID: 23920160]


Feingold KR, Anawalt B, Blackman MR, Boyce A, Chrousos G, Corpas E, de Herder WW, Dhatariya K, Dungan K, Hofland J, Kalra S, Kaltsas G, Kapoor N, Koch C, Kopp P, Korbonits M, Kovacs CS, Kuohung W, Laferrère B, Levy M, McGee EA, McLachlan R, New M, Purnell J, Sahay R, Shah AS, Singer F, Sperling MA, Stratakis CA, Trence DL, Wilson DP, Medeiros-Neto G. Thyroxine Poisoning. Endotext. 2000:():     [PubMed PMID: 25905265]


Watt T, Cramon P, Hegedüs L, Bjorner JB, Bonnema SJ, Rasmussen ÅK, Feldt-Rasmussen U, Groenvold M. The thyroid-related quality of life measure ThyPRO has good responsiveness and ability to detect relevant treatment effects. The Journal of clinical endocrinology and metabolism. 2014 Oct:99(10):3708-17. doi: 10.1210/jc.2014-1322. Epub 2014 Jul 8     [PubMed PMID: 25004246]

Level 2 (mid-level) evidence


Quinque EM, Villringer A, Kratzsch J, Karger S. Patient-reported outcomes in adequately treated hypothyroidism - insights from the German versions of ThyDQoL, ThySRQ and ThyTSQ. Health and quality of life outcomes. 2013 Apr 23:11():68. doi: 10.1186/1477-7525-11-68. Epub 2013 Apr 23     [PubMed PMID: 23618009]

Level 2 (mid-level) evidence