Decreased Expression of Ileal Thyroid Hormone Transporters in a Hypothyroid Patient: A Case Report
TL;DR: In this article, the authors present a rare case of a patient exhibiting malabsorption of levothyroxine (LT4) with decreased membranous expression of ileal transporters.
Abstract: Background Malabsorption of levothyroxine (LT4) is a common problem faced in clinical practice. It is usually solved, if there are no complexities including gastrointestinal absorption disorder, by taking medicines on an empty stomach and avoiding foods interfering with LT4. Herein we present a rare case of a patient exhibiting malabsorption of LT4 with decreased membranous expression of ileal transporters. Case The 22-Year-old female presented with sustained hypothyroid status despite medication of 7.8 μg/kg LT4. Medical history and LT4 absorption test (the absorption rate 8.4%) excluded pseudomalabsorption. No organic gastrointestinal disorder was found in the patient by blood chemistry, endoscopies, and abdominal computed tomography scan. The immunohistochemical analysis showed decreased membranous expression of LAT1 and LAT2 in distal ileum and ascending colon in the patient compared to 20 controls who have no thyroid disease. The expression of MCT8 in colon appeared at both nucleus and brush border in the patient, while it was limited to brush border in controls. The expression of other transporters was similar between the patient and controls. Conclusion The changes of the expression of LAT1 and LAT2 in this patient showing LT4 malabsorption might help to understand the role of intestinal transporters in the absorption of LT4 in humans. The functional relevance of the decrement of LAT1 and LAT2 in this patient remains to be elucidated.
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TL;DR: In this article, the impact of patient weight and residual thyroid function on initial levothyroxine dosage and consideration of age, co-morbidities, TSH goal, life stage, and quality of life as Levoyroxine is adjusted can be considered.
Abstract: Hypothyroidism is a common endocrinopathy and levothyroxine is frequently prescribed. Despite the basic tenets of initiating and adjusting levothyroxine being agreed upon, there are many nuances and complexities to consistently maintaining euthyroidism. Understanding the impact of patient weight and residual thyroid function on initial levothyroxine dosage and consideration of age, co-morbidities, TSH goal, life stage, and quality of life as levothyroxine is adjusted can be challenging and continually evolving. As levothyroxine is a life-long medication it is important to avoid risks from periods of overtreatment or undertreatment. For the subset of patients not restored to baseline health with levothyroxine, causes arising from all aspects of the patient's life (co-existent medical conditions, stressors, lifestyle, psychosocial factors) should be broadly considered. If such factors do not appear to be contributing, and biochemical euthyroidism has been successfully maintained, there may be benefit to a trial of combination therapy with levothyroxine and liothyronine. This is not supported by the majority of randomized clinical trials, but may be supported by other studies providing lower quality evidence and by animal studies. Given this discrepancy, it is important that any trial of combination therapy only be continued as long as a patient benefit is being enjoyed. Monitoring for adverse effects, particularly in older or frail individuals, is necessary and combination therapy should not be utilized during pregnancy. A sustained release liothyronine preparation has completed phase 1 testing and may soon be available for better designed and powered studies assessing whether combination therapy provides superior therapy for hypothyroidism.
17 citations
TL;DR: In this article , a review of nanomaterials for the sustained release of levothyroxine to improve patient compliance and reduce costs has been presented, and the efficacy of liquid solutions and soft gel capsules are systematically evaluated.
Abstract: Abstract Although levothyroxine is one of the most prescribed medications in the world, its bioavailability has been reported to be impaired by many factors, including interfering drugs or foods and concomitant diseases, and persistent hypothyroidism with a high dose of levothyroxine is thus elicited. Persistent hypothyroidism can also be induced by noninterchangeability between formulations and poor compliance. To address these issues some strategies have been developed. Novel formulations (liquid solutions and soft gel capsules) have been designed to eliminate malabsorption. Some other delivery routes (injections, suppositories, sprays, and sublingual and transdermal administrations) are aimed at circumventing different difficulties in dosing, such as thyroid emergencies and dysphagia. Moreover, nanomaterials have been used to develop delivery systems for the sustained release of levothyroxine to improve patient compliance and reduce costs. Some delivery systems encapsulating nanoparticles show promising release profiles. In this review, we first summarize the medical conditions that interfere with the bioavailability of oral levothyroxine and discuss the underlying mechanisms and treatments. The efficacy of liquid solutions and soft gel capsules are systematically evaluated. We further summarize the novel delivery routes for levothyroxine and their possible applications. Nanomaterials in the levothyroxine field are then discussed and compared based on their load and release profile. We hope the article provides novel insights into the drug delivery of levothyroxine.
2 citations
01 Jan 2022
TL;DR: The Side Effects of Drugs Annuals as mentioned in this paper is a yearly review of literature that has been published on the adverse effects of drugs, which includes studies, meta-analyses, and case reports on the use of thyroid hormones, thionamides, radioactive iodine, potassium iodine and iodide.
Abstract: The Side Effects of Drugs Annuals are yearly reviews of literature that has been published on the adverse effects of drugs. The Side Effects of Drugs Annuals contributes to the contents of Meyler's Side Effects of Drugs: The International Encyclopedia of Adverse Drug Reactions and Interactions. This literature review includes studies, meta-analyses, and case reports on the use of thyroid hormones, thionamides, radioactive iodine, potassium iodine and iodide published from January 2021 to December 2021.
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TL;DR: TSH and the prevalence of antithyroid antibodies are greater in females, increase with age, and are more in whites and Mexican Americans than in blacks, which needs more research to relate these findings to clinical status.
Abstract: NHANES III measured serum TSH, total serum T(4), antithyroperoxidase (TPOAb), and antithyroglobulin (TgAb) antibodies from a sample of 17,353 people aged > or =12 yr representing the geographic and ethnic distribution of the U.S. population. These data provide a reference for other studies of these analytes in the U.S. For the 16,533 people who did not report thyroid disease, goiter, or taking thyroid medications (disease-free population), we determined mean concentrations of TSH, T(4), TgAb, and TPOAb. A reference population of 13,344 people was selected from the disease-free population by excluding, in addition, those who were pregnant, taking androgens or estrogens, who had thyroid antibodies, or biochemical hypothyroidism or hyperthyroidism. The influence of demographics on TSH, T(4), and antibodies was examined. Hypothyroidism was found in 4.6% of the U.S. population (0.3% clinical and 4.3% subclinical) and hyperthyroidism in 1.3% (0.5% clinical and 0.7% subclinical). (Subclinical hypothyroidism is used in this paper to mean mild hypothyroidism, the term now preferred by the American Thyroid Association for the laboratory findings described.) For the disease-free population, mean serum TSH was 1.50 (95% confidence interval, 1.46-1.54) mIU/liter, was higher in females than males, and higher in white non-Hispanics (whites) [1.57 (1.52-1.62) mIU/liter] than black non-Hispanics (blacks) [1.18 (1.14-1.21) mIU/liter] (P < 0.001) or Mexican Americans [1.43 (1.40-1.46) mIU/liter] (P < 0.001). TgAb were positive in 10.4 +/- 0.5% and TPOAb, in 11.3 +/- 0.4%; positive antibodies were more prevalent in women than men, increased with age, and TPOAb were less prevalent in blacks (4.5 +/- 0.3%) than in whites (12.3 +/- 0.5%) (P < 0.001). TPOAb were significantly associated with hypo or hyperthyroidism, but TgAb were not. Using the reference population, geometric mean TSH was 1.40 +/- 0.02 mIU/liter and increased with age, and was significantly lower in blacks (1.18 +/- 0.02 mIU/liter) than whites (1.45 +/- 0.02 mIU/liter) (P < 0.001) and Mexican Americans (1.37 +/- 0.02 mIU/liter) (P < 0.001). Arithmetic mean total T(4) was 112.3 +/- 0.7 nmol/liter in the disease-free population and was consistently higher among Mexican Americans in all populations. In the reference population, mean total T(4) in Mexican Americans was (116.3 +/- 0.7 nmol/liter), significantly higher than whites (110.0 +/- 0.8 nmol/liter) or blacks (109.4 +/- 0.8 nmol/liter) (P < 0.0001). The difference persisted in all age groups. In summary, TSH and the prevalence of antithyroid antibodies are greater in females, increase with age, and are greater in whites and Mexican Americans than in blacks. TgAb alone in the absence of TPOAb is not significantly associated with thyroid disease. The lower prevalence of thyroid antibodies and lower TSH concentrations in blacks need more research to relate these findings to clinical status. A large proportion of the U.S. population unknowingly have laboratory evidence of thyroid disease, which supports the usefulness of screening for early detection.
3,471 citations
TL;DR: Fifty-two evidence-based recommendations and subrecommendations were developed to aid in the care of patients with hypothyroidism and to share what the authors believe is current, rational, and optimal medical practice for the diagnosis and care of hyp Timothyroidism.
1,319 citations
TL;DR: Cloned rat MCT8 was identified as a very active and specific thyroid hormone transporter and showed high expression in liver, kidney, brain, and heart.
630 citations
TL;DR: Human colon adenocarcinoma (Caco-2) cells, when grown on semipermeable filters, spontaneously differentiate in culture to form confluent monolayers which both structurally and functionally resemble the small intestinal epithelium and may give useful predictions concerning the oral absorption potential of new drug substances.
Abstract: Human colon adenocarcinoma (Caco-2) cells, when grown on semipermeable filters, spontaneously differentiate in culture to form confluent monolayers which both structurally and functionally resemble the small intestinal epithelium. Because of this property they show promise as a simple, in vitro model for the study of drug absorption and metabolism during absorption in the intestinal mucosa. In the present study, the transport of several model solutes across Caco-2 cell monolayers grown in the Transwell diffusion cell system was examined. Maximum transport rates were found for the actively transported substance glucose and the lipophilic solutes testosterone and salicyclic acid. Slower rates were observed for urea, hippurate, and saliylate anions and were correlated with the apparent partition coefficient of the solute. These results are similar to what is found with the same compounds in other, in vivo absorption model systems. It is concluded that the Caco-2 cell system may give useful predictions concerning the oral absorption potential of new drug substances.
578 citations
TL;DR: This meta-analysis provides extensive data on the prevalence and incidence of thyroid dysfunction in Europe and categorizes results into 3 categories: prevalence of undiagnosed thyroid dysfunction, prevalence of Thyroid dysfunction, and incidence.
Abstract: Context: Thyroid dysfunction is one of the leading endocrine disorders. Previous data show that about half of the population with thyroid dysfunction remains undiagnosed. Objective: Our objective was to estimate epidemiologic data on thyroid dysfunction in Europe. Data Sources: PubMed, EMBASE, and SCOPUS databases were searched to identify studies that evaluated the prevalence and/or incidence of thyroid dysfunction in Europe published between 1975 and 2012. Study Selection: Of the 541 identified abstracts examined, 178 were considered for evaluation and 17 were included. Studies were excluded if they included participants with an underlying disease or were limited by age or gender. Data Extraction: Results were grouped into 3 categories: 1) prevalence of undiagnosed thyroid dysfunction, 2) prevalence of thyroid dysfunction, and 3) incidence of thyroid dysfunction. Extraction was conducted independently by 2 investigators. Data Synthesis: An empirical Bayesian random-effects model was used. The prevalence...
464 citations