Levothyroxine tablet replacement or suppression therapy is one of the widely used therapeutic drugs for patients with thyroid disorders. Familiarity with the absorption and metabolic characteristics of the drug and mastering the timing, indications and dose adjustment methods are among the clinical skills that endocrinologists need to master on an individual basis.
Levothyroxine tablets (trade name Eugenol, L-T4) is one of the commonly used drugs for patients with clinical thyroid diseases. Despite its widespread use, some patients, and even physicians, are unable to fully grasp the proper use and dose adjustment of this medication, resulting in patients not receiving proper treatment and even developing pharmacogenic hyperthyroidism or pharmacogenic hypothyroidism.
With regard to the use of this drug, the following points require clinical attention.
1. Understanding the absorption of L-T4 and the factors affecting it
L-T4 is a chemically synthesized levate of the natural hormone thyroxine (T4), whose chemical properties and physiological characteristics are identical to those of natural T4. After oral administration, it is absorbed in the small intestine (mainly in the duodenum and jejunum), but gastric acid affects its absorption, and usually the higher the gastric acid, the lower the absorption. In healthy individuals, the blood concentration peaks about 2 hours after dosing, with a bioavailability of 60-80% and a volume of distribution of 11.5 liters. In hypothyroid patients, the peak blood concentration time is extended to 3 hours, the bioavailability is increased, and the volume of distribution is up to 14.7 liters.
Meals can significantly affect the absorption of L-T4, and it is generally recommended to take it 1 hour before meals. Pay particular attention to dietary fiber, grapes, soy, papaya, and coffee can reduce its absorption. The absorption and metabolism of L-T4 are also affected by proton pump inhibitors, anti-epileptic drugs, sunitinib and other anti-tumor drugs.
2. Indications for L-T4 treatment and estimation of measurement
(1) Primary hypothyroidism is the main indication for L-T4 replacement therapy. Most of them are chronic lymphocytic thyroiditis, some of them are postpartum thyroiditis and the less common De Quervain’s thyroiditis. Others include hypothyroidism following surgical removal or radiation therapy for benign or malignant thyroid lesions, and hypothyroidism following lithium, amiodarone, or other iodine-containing agents.
(2) Central hypothyroidism, which is secondary to hypothalamic pituitary lesions or injury. The application of L-T4 can directly correct the levels of target hormones and improve clinical symptoms.
(3) Whether subclinical hypothyroidism (subthyroidism) requires L-T4 therapy is still controversial, but most scholars advocate L-T4 replacement therapy for subthyroidism with positive thyroid autoantibodies and high serum TSH levels (>10mIU/L). In recent years, subthyroidism in pregnancy has received increasing attention due to the possible potential adverse effects on the pregnant woman and the fetus. L-T4 replacement therapy is recommended in most clinical practices to bring maternal TSH to the pregnancy-specific reference range.
(4) The use of L-T4 in benign thyroid nodules is also inconclusive. Studies in mildly iodine-deficient areas have shown that administration of inhibitor doses of L-T4 can help reduce the size of benign thyroid nodules, but studies in iodine-sufficient areas do not support the use of the drug. Combined with the results of the meta-analysis, most currently recommend L-T4 for the treatment of benign thyroid nodules in iodine-deficient areas.
(5) L-T4 is usually given after thyroidectomy and/or radiation therapy for differentiated thyroid cancer to achieve suppression of TSH levels and reduce the risk of tumor recurrence.
Treatment with L-T4 in non-thyroidectomy is usually started at 50 μg/d, or halved or even started at 12.5 μg/d if the patient has cardiovascular risk, and the dose is gradually adjusted according to the response to treatment and the results of thyroid function monitoring, usually to maintain TSH at 2 mIU/L. In most hypothyroid patients, a replacement dose of 1.6 μg/kg.d is considered adequate, equivalent to 100-125 μg of L-T4 per day for patients weighing less than 60-75 kg. For post-thyroidectomy patients, L-T4 is mostly calculated according to the patient’s body weight and is generally estimated to be 1.3-1.6 μg/kg.d. Depending on the risk of distant tumor recurrence, different levels of TSH suppression are determined Different TSH suppression levels are determined according to the different risks of tumor long-term recurrence, among which high-risk patients should be treated with L-T4 to make TSH <0.1 mIU/L, while TSH control at 0.1-0.5 mIU/L is sufficient for low-risk patients. Monitor TSH after applying L-T4 and gradually adjust the dose to reach the standard.
3, L-T4 dose adjustment instructions
(1) Since L-T4 is mainly absorbed in the small intestine, the dose should be increased for patients with dissection syndrome who have had their small intestine surgically removed.
(2) In patients with hypothyroidism diagnosed before pregnancy, the thyroid gland development in the first trimester of pregnancy is completely dependent on the thyroid hormone provided by the mother because the fetal thyroid function is not yet established.
(3) Although the dose of L-T4 therapy is weight dependent, the dose should be increased in infants and pediatric patients compared to adults.
(4) Premenopausal women usually receive higher doses of L-T4 than men and postmenopausal women due to higher circulating levels of thyroid hormone-binding globulin.
(5) Since one of the main physiological effects of thyroid hormone is heat production, season and region also have an impact on its physiological requirements. Some researchers have found that the dose of L-T4 increases in colder regions and in winter compared to tropical regions and summer.
(6) Patients require different doses of thyroid hormone replacement in different physiological and pathological states. In particular, as hormone metabolism slows with increasing age, the dose of L-T4 should usually be reduced as appropriate.
(7) Physicians should educate patients about the clinical symptoms that may occur with drug overdose or underdose, ensure that all patients have regular thyroid function testing, and adjust the L-T4 dose when appropriate to truly achieve individualized and appropriate treatment.