Factors influencing the levothyroxine dose in the hormone replacement therapy of primary hypothyroidism in adults

Abstract

Levothyroxine (LT4) is a safe, effective means of hormone replacement therapy for hypothyroidism. Here, we review the pharmaceutical, pathophysiological and behavioural factors influencing the absorption, distribution, metabolism and excretion of LT4. Any factor that alters the state of the epithelium in the stomach or small intestine will reduce and/or slow absorption of LT4; these include ulcerative colitis, coeliac disease, bariatric surgery, Helicobacter pylori infection, food intolerance, gastritis, mineral supplements, dietary fibre, resins, and various drugs. Once in the circulation, LT4 is almost fully bound to plasma proteins. Although free T4 (FT4) and liothyronine concentrations are extensively buffered, it is possible that drug- or disorder-induced changes in plasma proteins levels can modify free hormone levels. The data on the clinical significance of genetic variants in deiodinase genes are contradictory, and wide-scale genotyping of hypothyroid patients is not currently justified. We developed a decision tree for the physician faced with an abnormally high thyroid-stimulating hormone (TSH) level in a patient reporting adequate compliance with the recommended LT4 dose. The physician should review medications, the medical history and the serum FT4 level and check for acute adrenal insufficiency, heterophilic anti-TSH antibodies, antibodies against gastric and intestinal components (gastric parietal cells, endomysium, and tissue transglutaminase 2), and Helicobacter pylori infection. The next step is an LT4 pharmacodynamic absorption test; poor LT4 absorption should prompt a consultation with a gastroenterologist and (depending on the findings) an increase in the LT4 dose level. An in-depth etiological investigation can reveal visceral disorders and, especially, digestive tract disorders.

Probiotics and Prebiotics in Subclinical Hypothyroidism of Pregnancy with Small Intestinal Bacterial Overgrowth

“…In this study, The TSH of thyroid function in the intervention group was lower than that before treatment, and the level of thyroid function was stable below the target value of treatment.Talebi S et al 9 found that supplementation of probiotics and prebiotics on the basis of levothyroxine could signi cantly reduce the level of TSH, which was consistent with our results.This shows that, for patients with well-controlled thyroid function in the second trimester, the combined application of probiotics and prebiotics is bene cial to maintain the stability of thyroid function. Levothyroxine sodium is absorbed mainly in the small intestine 33 , and as mentioned above, SIBO status disrupts the intestinal barrier, and we hypothesized that probiotics and prebiotics may improve the intestinal barrier and promote the absorption of LT4. Second, gut bacteria can express β-glucuronidase and sulfatase to inactivate thyroid hormones in the liver 9 ,and study has shown that Lactobacillus acidophilus can signi cantly reduce the βglucuronidase activity in feces.…”

Profile of Levothyroxine Replacement Therapy in Graves’ Disease Patients with Hypothyroidism Post-Radioactive Iodine Ablation: Focus on Different Weight-Based Regimens

“…In patients requiring unusually high LT4 doses, investigate other factors apart from compliance and concomitant medications, including gastrointestinal tract malabsorption, concomitant food and drink, and Helicobacter pylori infection. 26 - 28 …”

Seeking optimization of LT4 treatment in patients with differentiated thyroid cancer

“…The most frequently used route of LT4 administration is per os, resulting in intestinal absorption of 60 to 80% of the ingested dose [ 27 ]. Since the absorption is variable and LT4 has a narrow therapeutic index, caution is required in dose individualization and in the mode of ingestion, as well as in ensuring patient compliance [ 24 , 28 ]. However, a long road lies ahead until an optimal LT4 therapeutic target is achieved, which fact has recently been summarized [ 28 ].…”

“…Since the absorption is variable and LT4 has a narrow therapeutic index, caution is required in dose individualization and in the mode of ingestion, as well as in ensuring patient compliance [ 24 , 28 ]. However, a long road lies ahead until an optimal LT4 therapeutic target is achieved, which fact has recently been summarized [ 28 ]. One of the issues specific to thyroidectomized patients is the timing of pharmacologic thyroid homeostasis recovery [ 24 ].…”