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

Injectable levothyroxine is for the treatment of myxedema coma or severe hypothyroidism.[2]

Off-label usage includes cadaveric organ recovery.[3]

Levothyroxine (T4) is a synthetic version of one of the body’s natural thyroid hormones: 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). 50% 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.

Once inside the nucleus, thyroid hormones work by directly influencing DNA transcription to increase body metabolism by increasing gluconeogenesis, protein synthesis, the mobilization of glycogen stores, and other more functions.

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.[4]

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.

Capsule: Swallow whole; Do not crush or cut. 

Tablet: May crush into 5 to 10 mL of water and drank 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 for use in the hospital setting in which vital signs can undergo close monitoring.[5][6] 

In cases where the patient can not tolerate anything by mouth due to an underlying problem, the levothyroxine capsules are usable as a suppository and are well absorbed. 

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.[5][6] Pregnant patients with newly diagnosed hypothyroidism should receive initial treatment at 1.8 mcg/kg/day. Adjust dose every four weeks as needed. If a patient has a diagnosis of hypothyroidism before pregnancy, adjust the dose of levothyroxine as needed. After pregnancy, the dose of levothyroxine should decrease to 1.6 mcg/kg/day.[5][6][7]

To treat myxedema coma (IV) or severe hypothyroidism: 200 to 400 mcg initial IV loading dose followed by a daily dose of 1.2 mcg/kg/day with consideration to use 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.[6] The equivalence between intravenous to oral is 0.75 to 1 (for example, 200 mcg IV of levothyroxine is equal to 266 mcg of oral levothyroxine )

For organ recovery from a cadaver (IV):20 mcg IV bolus to the donor, followed by 10 mcg/hour continuous infusion. Given with methylprednisolone, dextrose, and insulin.[8]

Generally, adverse events result from incorrect dosing (excessive dosing) often forms a hyperthyroid-like picture or due to an allergic reaction to the excipient of the levothyroxine tablets. Levothyroxine 50 mcg tablets are white and don't contain any die, so there is a decreased risk for an allergic response.

Adverse effects (frequency undefined) include: angina pectoris, tachycardia, palpitations, arrhythmias, myocardial infarction, dyspnea, anxiety, fatigue, headache, heat intolerance, insomnia, irritability, diaphoresis, skin rash, alopecia, goiter, weight loss, menstrual irregularities, abdominal cramps, diarrhea, emesis, reduced fertility, and decreased bone mineral density (a result of TSH suppression).[5][6]

Levothyroxine is contraindicated in individuals with uncorrected adrenal insufficiency, individuals with acute myocardial infarction, acute myocarditis, pancarditis, active heart arrhythmias, and persons with thyrotoxicosis or hyperthyroidism.[5][6]