LT4 Absorption Research Articles

Morning exercise affects the absorption of oral levothyroxine: a single center pilot study.

Levothyroxine (LT4) is the first-line hormone replacement therapy for hypothyroidism. Several factors which have an influence on oral LT4 absorption have been previously described; however, the influence of exercise on oral LT4 absorption has not been reported, yet. It was aimed to investigate the possible effect of morning exercise, right after LT4 ingestion, on the absorption of LT4 tablets in this study. Patients with primary hypothyroidism who fulfilled the inclusion criteria were offered to participate in a 6-week morning exercise programme and those who agreed to participate were enrolled in our study. Patients were required to have a walk for 30 min with a regular speed right after taking their daily LT4 treatments and start having breakfast the first hour after LT4 intake. Pre- and post-exercise TSH levels were recorded and TSH percentage change was calculated. All patients had decreased TSH levels after the exercise programme. There was a significant decrease in TSH levels (p < 0.001). A significant positive correlation between TSH percentage change and daily dose of LT4 per kg of body weight was also shown. This is the first study which demonstrates the significant positive effect of morning exercise on the absorption of LT4 tablets. In addition to that, it was also found that as the daily dose of LT4 increases, the percentage decrease of TSH level becomes greater.

Insight of the Biopharmaceutical Implication of Sleeve Gastrectomy on Levothyroxine Absorption in Hypothyroidism Patients.

The growing rate of obesity led to an increased number of bariatric surgeries (BS) as a treatment option for obesity. The gastrointestinal tract (GIT) changes following BS can impact many drugs' absorption. Levothyroxine (LT4) is a synthetic thyroxine (T4) replacement used commonly as tablets to manage hypothyroidism disorder, which is more prevalent among patients with obesity. This study aims to examine the LT4 oral tablet form therapy after sleeve gastrectomy. A retrospective cohort study was conducted in multi-center. The LT4 doses and TSH and T4 levels were compared before and after BS. The post-surgery readings were categorized into three periods: (one to threemonths), (four to sixmonths), and (> six) months after surgery. ANOVA test was used for analysis. A total of 14374 patients who underwent BS from (1/2019 to 3/2022) were screened for eligibility, and n = 101 participants matched the inclusion criteria. The TSH and T4 were not statistically significant differences before and after surgery (P-values of 0.4864 and 0.5970, respectively). However, the doses significantly differed before and after surgery in all the follow-up time point periods (P < 0.002). The LT4 required doses significantly reduced after sleeve gastrectomy, which can be related to the improved endogenous thyroid production in patients with obesity. However, the abnormality of the GIT induced by the sleeve gastrectomy may affect the exogenous LT4 absorption. Using liquid forms of LT4 while monitoring the thyroid function parameters can optimize the treatment after the procedure.

Efficacy of Levothyroxine Sodium Soft Gelatin Capsules in Thyroidectomized Patients Taking Proton Pump Inhibitors: An Open-Label Study.

Background: Treatment with proton pump inhibitors (PPIs) and antacids affects the gastrointestinal absorption of levothyroxine sodium (LT4) tablets. Patients with hypothyroidism taking LT4 and PPIs or antacids, thus, require appropriate monitoring. The objective of this study was to determine whether a soft gelatin capsule of LT4 (Tirosint®) would obviate the effect of PPIs on LT4 absorption. The objective was achieved by assessing the effects of a switch from a conventional LT4 tablet form to the same dose as soft capsules in thyroidectomized patients on treatment with LT4 and PPIs. Methods: Patients with history of hypothyroidism due to total thyroidectomy on stable treatment with LT4 tablets, and with gastrointestinal disease treated with PPIs, were switched to a 12-week treatment with Tirosint at the same dose of the LT4 tablets, while maintaining treatment with PPIs. Serum thyrotropin (TSH) levels were the primary endpoint of the study. Secondary efficacy endpoints were: serum levels of free thyroxine (fT4), total thyroxine (TT4), free triiodothyronine (fT3), total triiodothyronine (TT3), creatine-phosphokinase (CPK), sex-hormone binding globulin, ferritin, angiotensin converting enzyme, and a lipid panel. Results: Forty-seven patients (36 females and 11 males, mean age 55.4 years) were enrolled and 45 of them completed the study (2 patients withdrew consent). During treatment with Tirosint, mean TSH levels demonstrated a statistically significant decrease (mean changes from baseline: -0.32 mIU/L at week 6 and -0.68 mIU/L at week 12) and concomitant increases in thyroid hormone (TH) levels from baseline to week 12, which were statistically significant for fT3 and TT3 (mean changes from baseline: 0.26 pmol/L and 0.10 nmol/L, respectively). Significant decreases of serum low-density lipoprotein, total cholesterol, and CPK levels were observed at week 12. No signs/symptoms arose during the study that could be specifically correlated to either hypo- or hyperthyroidism. Conclusions: In thyroidectomized patients taking PPIs and replacement LT4, a switch from conventional LT4 tablets to LT4 soft capsules at the same dose was associated with a significant decrease in TSH and increase in TH, indicating that LT4 absorption may be less affected by PPIs when given in the form of soft capsules. Clinical Trial Registration: NCT03094416.

Concomitant use of levothyroxine and interacting medications in U.S. ambulatory care visits

BackgroundLevothyroxine (LT4) is the third most commonly prescribed medication in the United States. It is a narrow therapeutic index medication, and thus can be impacted by drug-drug interactions, which are primarily available over-the-counter. The prevalence and associated factors with concomitant interacting drugs with LT4 is limited since over-the-counter products are not routinely captured in many drug databases. ObjectiveThis study aimed to characterize the concomitant use of LT4 with interacting drugs at ambulatory care visits in the United States. DesignA cross-sectional analysis of the National Ambulatory Medical Care Survey (NAMCS) from 2006 to 2018 was completed. Setting and participantsAmbulatory care visits in the United States involving adult patients with a LT4 prescription were included in the analysis. Outcome measuresThe primary outcome was initiation or continuation of a selected concomitant interacting drug which impacts LT4 absorption (e.g., proton pump inhibitor) in a patient visit in conjunction with LT4. ResultsThe authors analyzed 372,942,000 visits (weighted from a sample of 14,880) with a reported LT4 prescription. Concomitant use of interacting drugs with LT4 occurred in 24.4% of visits in which 80% of interacting drugs were proton pump inhibitors. Ages 35-49 years (adjusted odds ratio [aOR], 1.59), 50-64 years (aOR, 2.27), and ≥65 years (aOR, 2.87) compared to 18-34 years, female (aOR 1.37) versus males, and visits in 2014 or later (aOR, 1.27) versus 2006-2009 were associated with increased odds of concomitant interacting drug use in multivariable analysis. ConclusionAt ambulatory care visits between 2006 and 2018, concomitant use of LT4 and interacting drugs impacted one-quarter of patient visits. Increased age, females, and visits later in the study period were associated with increased odds for concomitant interacting drugs. Additional work is needed to identify downstream consequences of concomitant use.

Validity of the Rapid Thyroxine Absorption Test for the Differentiation Between Levothyroxine Non-compliance and Malabsorption in Thyroid-Stimulating Hormone Refractory Hypothyroidism.

Introduction Thyroid-stimulating hormone refractory hypothyroidism is a common problem. This is due to either non-compliance or malabsorption with levothyroxine (LT4). The study aimed to assess the validity of the rapid LT4 absorption test in the differentiation between LT4 malabsorption and non-compliance. Methods A cross-sectional study was done from January to October 2022 at Faiha Specialized Diabetes, Endocrine, and Metabolism Center, in Basrah, Southern Iraq. Twenty-two patients with thyroid-stimulating hormone (TSH) refractory hypothyroidism were evaluated by rapid LT4 absorption test with measurements of TSH before 1000 μg LT4 intake, and free thyroxine (pmol/l) and total thyroxine before (nmol/l) (baseline TT4 and baseline FT4) and two hours after (2-HR TT4 and 2-HR FT4). The findings were compared with the following four-week-long supervised LT4 absorption test results. Results In the rapid LT4 absorption test, patients with (2-HR FT4 minus baseline FT4 ≤1.28 pmol/l (0.1 ng/dl) or 2-HR FT4 minus baseline FT4 1.28-6.43 pmol/l (0.1-0.5 ng/dl) plus 2-HR TT4 minus baseline TT4<72.08 nmol/l (5.6 µg/dl)), eight out of 10 patients were correctly diagnosed with malabsorption. And in those with (2-HR FT4 minus baseline FT4 ≥6.43 (0.5 ng/dl) or 2-HR FT4 minus baseline FT4 1.28-6.43 (0.1-0.5 ng/dl) plus 2-HR TT4 minus baseline TT4≥72.08 (5.6 µg/dl)), 11 out of 12 patients were correctly diagnosed as non-compliant. This criterion showed 88.8% sensitivity, 15.4% specificity, 80% positive predictive value, and 91.6% negative predictive value for diagnosing LT4 malabsorption. Conclusion The rapid LT4 absorption test showed good diagnostic accuracy in differentiating non-compliance from malabsorption when (2-HR FT4 minus baseline FT4) and (2-HR TT4 minus baseline TT4) were used as criteria.

The use of levothyroxine absorption tests in clinical practice.

Although levothyroxine (LT4) is a widely prescribed drug, over 30% of LT4-treated patients fail to achieve the recommended serum level of thyroid-stimulating hormone with a body-weight-based dose of LT4. An LT4 absorption test (LT4AT) is part of the work-up for confirming normal LT4 absorption or diagnosing malabsorption. We searched PubMed with the terms levothyrox*, L-T4, LT4, TT4, FT4, FT3, TT3, test, loading, uptake, absorp*, "absorb*, bioavailab*, bioequiv* malabsorb*, pseudomalabsorb*. 43 full-text publications were analyzed. The published procedures for LT4AT differ markedly in the test dose, formulation, test duration, frequency of blood collection, analyte (total thyroxine (TT4) or free thyroxine (FT4)), metric (absolute or relative peak or increment, or area under the curve) and the threshold for normal absorption. In a standardized LT4AT for routine use, the physician could: advise the patient to not consume food, beverages or medications on the morning of the test; administer 1000 µg of LT4 in the patient's usual formulation as the test dose; ensure that the patient is supervised throughout the LT4AT; perform a 4-hour test, with hourly blood samples; assay FT4; and consider that normal LT4 absorption corresponds to an FT4 increment of more than 0.40 ng/dL (5.14 pmol/L) or a TT4 increment of more than 6 μg/dL (77.23 nmol/L) for a test dose of at least 300 µg, or a percentage TT4 absorption of more than 60%. If the test indicates abnormal LT4 absorption, the physician can increase the LT4 dose, change the formulation or administration route, and/or refer the patient to a gastroenterologist.

Deprescribing in Patients of Hypothyroidism Results in Better Health Outcome: A Case Series

Appropriate levothyroxine (LT4) dosing is essential in hypothyroid patients to maintain biochemical and clinical euthyroidism, but achieving appropriate plasma concentration of LT4 can be complicated by numerous disease states, foods, supplements, and commonly prescribed medications such as calcium supplements, pantoprazole etc. that potentially interfere with intestinal LT4 absorption. About one-third of treated patients are not receiving adequate treatment, leading to decreased quality of life, increased morbidity, and even increased mortality. Hypothyroid patients treated with LT4 must be careful to avoid concomitant ingestion of such medicines or optimal gap must be ensured between ingestions to prevent drug-drug interactions and reduce absorption of LT4. We describe two such real life cases managed in our clinical pharmacology consultation facility to highlight the importance of systematically evaluating the drug-drug interactions of levothyroxine with commonly used concomitant medications and how deprescribing of the same can result in attainment of optimum thyroid replacement with lesser doses of LT4 with better patient outcome.

The performance of levothyroxine tablet is impaired by bariatric surgery

ObjectiveThe aim was to evaluate if bariatric surgery can affect the LT4 performance. The endpoints were the following: 1) difference between LT4 daily dose before and 1 year after surgery, 2) difference between LT4 dose per weight before and 1 year after surgery, 3) difference among LT4 preparations.MethodsThe study period was between January 2018 and May 2022. Inclusion criteria were a) adults undergone bariatric surgery, b) with proven autoimmune hypothyroidism, c) on LT4 therapy before bariatric surgery, d) using any commercialized LT4 preparation. Excluded were patients a) proven to have or suspected for pre-surgical intestinal malabsorption, b) with other potential interfering factors on LT4 absorption; c) with heart, renal, and/or hepatic failure, d) with recent/current infection/inflammation, e) in pregnancy, f) with incomplete data about LT4 therapy.ResultsAccording to the selection criteria, 40 patients were included. Both TSH and LT4 daily doses were not significantly different with respect to baseline values. On the contrary, the LT4 dose per weight was significantly increased, especially in RYGB patients. An increased LT4 dose per weight was observed with the reduction of weight.ConclusionOne year after bariatric surgery 1) the daily dose of LT4 remains unchanged, and 2) despite the significant weight reduction, LT4 dose per weight increases. Most data are referred to LT4 tablet and the performance of LT4 caps should be further investigated.

Levothyroxine malabsorption or pseudomalabsorption? A question in the management of refractory hypothyroidism.

The levothyroxine absorption test (LT4AT) is an important tool for distinguishing hypothyroidism due to malabsorption from 'pseudomalabsorption' conditions. Our aim was to review our institution's LT4AT results and assess its role in the management of patients with refractory hypothyroidism. We performed a retrospective study of all patients evaluated for refractory hypothyroidism who underwent LT4AT in our tertiary center between 2014 and 2020. Its results and the impact on thyroid function management during follow-up were assessed. Ten female patients were included with a mean age of 40 years (min-max: 26-62). Mean weight was 72 kg (min-max: 43-88) and baseline LT4 dosage ranged from 2.5 to 5.3 µg/kg/day. The most common causes of hypothyroidism were postsurgical in 50% (n = 5) and autoimmune in 20% (n = 2). During LT4AT, normal LT4 absorption was found in all but one individual (mean FT4 increase of 231%, min-max: 85-668). The only patient with objective LT4 absorption impairment (maximal increase of 48% by hour 5) presented also Helicobacter pylori gastritis and prior history of 'intestinal surgery' during childhood. No adverse events were reported during any of the LT4ATs. During follow-up (median 11.5 months (IQR 23)), three patients obtained euthyroidism and six had improved their hypothyroidism state. The LT4AT is an effective and safe way to assess refractory hypothyroidism and provides valuable information to distinguish LT4 malabsorption from 'pseudomalabsorption'. Our data suggest that most patients with suspicious LT4 malabsorption perform normally during LT4AT. This test provides relevant information for better management of patients with refractory hypothyroidism.

RF23 | PSAT258 Comparable Bioavailability of a Novel Levothyroxine Solution taken 10 or 30 minutes prior to a High-Fat, High-Calorie Breakfast

Abstract Levothyroxine (LT4) is the recommended treatment for hypothyroidism and the second most prescribed medication in the US. Several formulations are available, however most patients take LT4 tablets. Evidence suggests that absorption of levothyroxine tablets is decreased when taken with food, especially those rich in soy, iodine, and fiber. In order to avoid erratic absorption of LT4, it is recommended that oral formulations are taken on an empty stomach, 30-60 minutes before breakfast. However, compliance with this recommendation is often difficult for patients with busy schedules or on multiple medications, yet important in patients with conditions that are sensitive to changes in TSH levels such as pregnancy and thyroid cancer.There is evidence that oral liquid LT4 formulations that bypass the gastric dissolution phase of absorption may mitigate this food effect. ThyquidityTM (levothyroxine sodium) oral solution has demonstrated bioequivalence to Synthroid® under fasting conditions and allows individualized dosing flexibility. A bioavailability study was conducted to assess the rate and extent of absorption of the oral LT4 solution (100 mcg /5 mL) administered either 10 or 30 minutes before a standardized high-calorie, high-fat breakfast in an open-label, randomized, single-dose, 2-period, 2-sequence, crossover study. A single 600 μg oral dose of LT4 solution (ThyquidityTM, 30 mL) was administered to healthy adults either 10 or 30 minutes before consuming a 950 kcal, high fat (56%) breakfast in each study period and blood was collected for total (bound and free) T4 for 48 hours after drug administration. Treatment periods were separated by a 40-day wash-out period.The ratios of geometric LS means with corresponding 90% confidence intervals were calculated from the exponential of the difference between the LT4 solution administration 10 and 30 minutes prior to the meal for AUC0-48 and Cmax. An absence of food effect (bioequivalence) would be concluded if the baseline corrected 90% confidence intervals of this ratio fell within 80.00% to 125.00% for Ln-transformed AUC0-48 and Cmax.Forty healthy volunteers participated in the trial, 38 were included in the data analysis. There were no serious adverse events or discontinuations due to AEs. The geometric LS mean ratios of AUC0-48 and Cmax for baseline-adjusted LT4 were 88.74% (84.71-92.95%) and 85.07% (81.1-89.33%) respectively. The corresponding 90% CIs were included within the acceptable range for bioequivalence, indicating the absence of a meaningful difference in LT4 absorption when administering at 10 or 30 minutes before a meal.Based on these results, it may be possible to decrease the interval between the administration of Thyquidity (levothyroxine sodium) oral solution to 10 minutes before breakfast, thus offering patients further dosing flexibility. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m., Sunday, June 12, 2022 12:36 p.m. - 12:41 p.m.

RF23 | PSAT365 An Open-Label Therapeutic Efficacy Study of Tirosint (Levothyroxine Sodium) Capsules in Thyroidectomized Patients Taking Proton Pump Inhibitors

Abstract Levothyroxine sodium (LT4) absorption is known to be affected by proton pump inhibitors (PPIs). Normal gastric acid secretion is important for the subsequent intestinal absorption of LT4. A reduced gastric acidity may diminish the dissolution of the LT4 tablet in the stomach and the release of LT4 to the gut. The dissolution profile of LT4 soft capsules has been reported to be less affected by pH than that of tablets. Previous studies in healthy subjects administered with LT4 and PPIs, as well as in hypothyroid patients with atrophic gastritis confirmed little or no impact of increased gastric pH on LT4 absorption when administered in soft capsule formulation. The present study was aimed at evaluating whether LT4 soft capsules may provide better control of thyroid stimulating hormone (TSH) in thyroidectomized patients undergoing chronic replacement therapy with LT4, who were also on chronic use of PPIs.Forty-seven (47) patients were enrolled in this multicenter study. Upon switching to Tirosint capsules at the same previous dose of LT4 tablets and while maintaining the same dose of PPI, TSH (when measured on week 12 of treatment) was significantly reduced from a mean±SD of 1.34±1.51 mIU/L to 0.75±1.08 mIU/L (p&amp;lt;0.0001) in the Intention-To-Treat population analysis on original data. No significant changes were detected in the level of free and total thyroxine (T4), while slight but significant (p&amp;lt;0.05) increases were measured in free and total triiodothyronine (T3). The measured extent of TSH decrease is consonant with the extent of TSH increase previously reported by other authors upon start of PPI therapy in hypothyroid patients treated with LT4 tablets.In conclusion, these data confirm previous reports that LT4 soft capsules absorption is not affected by increased gastric pH due to PPIs. This may be relevant to improve TSH stabilization in patients who take PPIs intermittently or those with gastric pH altered by concomitant pathologies. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m., Sunday, June 12, 2022 1:00 p.m. - 1:05 p.m.

Liquid levothyroxine improves thyroid control in patients with different hypothyroidism aetiology and variable adherence - case series and review.

It is estimated that hypothyroidism treatment may be either suboptimal or excessive in about 32-45% patients treated with L-thyroxine (LT4). There are multiple possible causes of poor control of hypothyroidism, including narrow LT4 therapeutic index, food and drug interactions, comorbidities, and patient non-adherence. Some of these obstacles could possibly be overcome with the novel liquid LT4 formulation. Liquid LT4 reaches maximum blood concentration about 30 minutes faster than the tablet form. Faster pharmacokinetics might lead to more efficient LT4 absorption, as suggested by a recent real-world study in patients with primary and central hypothyroidism. Liquid LT4 treatment led to increased free thyroxine (FT4) and sex hormone binding globulin (SHBG) with decreased low-density lipoprotein (LDL) cholesterol concentration and substantially improved quality of life for the patients. Herein we present a series of 31 patients with hypothyroidism of different aetiologies treated with the novel liquid LT4 formulation in standard clinical care in light of the latest scientific publications on liquid LT4 formula. We observed normalization of thyroid function tests shortly after introduction of liquid LT4, irrespective of concurrent diseases or concomitant medications that could diminish LT4 absorption. In more detail, the treatment with liquid LT4 managed to normalize thyroid-stimulating hormone (TSH) concentrations in patients without any known causes of LT4 absorption disturbances, as well as in those with malabsorption: with gastric bypass, partial small and large intestine resection, scleroderma, gluten intolerance, celiac disease, atrophic gastritis, and polytherapy. In conclusion, considering many factors disturbing LT4 absorption, hypothyroidism therapy with liquid LT4 seems to be a particularly effective option.

Tea consumption affects the absorption of levothyroxine.

Levothyroxine (LT4) is a convenient treatment for hypothyroidism. Coffee, however, prevents the body from efficaciously absorbing LT4. It is unknown whether the intake of tea interferes with LT4 absorption. Thirty-seven hypothyroidism patients with the following types of consumption were recruited: 1) only tea, 2) tea and coffee, and 3) only coffee. The concentrations of thyroid-stimulating hormone (TSH), triiodothyronine (T3), and thyroxine (T4) were recorded before and 3 months after changing the consumption. The patients had reductions in the concentration of TSH to varying degrees after 3 months (p < 0.001 or p < 0.05). The natural logarithms of the differences between the concentrations of TSH before and after the change in the consumption (Δln-TSH) of tea and coffee, only coffee, and only tea were 1.94, 2.00, and 2.18, respectively. Long-term consumption of tea, like coffee, interfered with the absorption of LT4. We believe that avoiding tea when taking LT4 will reduce malabsorption.

A Questionnaire Survey of German Thyroidologists on the Use of Thyroid Hormones in Hypothyroid and Euthyroid Patients: The THESIS (Treatment of Hypothyroidism in Europe by Specialists: An International Survey) Collaborative

To identify the attitudes of German thyroid specialists towards the clinical treatment of hypothyroidism using thyroid hormones (TH). All members of the thyroid section of the German Endocrine Society (DGE) were e-mailed an invitation to participate in a web-based survey about substitution with TH. Out of 206 members of the DGE's thyroid section, 163 (79.1%) responses were received and included in the analysis. Of responding members, 98.6% used levothyroxine (LT4) as the treatment of choice, and 45.4% also prescribed combination therapy with liothyronine (LT4+LT3) in their clinical practice (p<0.001). LT4+LT3 combination was favored in patients with persistent hypothyroidism symptoms despite biochemical euthyroidism on LT4 treatment (p<0.001). Of all respondents, 26.4% never indicated TH therapy for euthyroid patients (p<0.001), while the remainder would consider THs for one or more indications (62.9% for euthyroid infertile women with high anti-thyroid antibody levels (p<0.001), 7.1% in patients with severe hypercholesterolemia, as complementary treatment (p=0.007), and 57.1% in patients with simple goiter (p<0.001)). In conditions that could interfere with LT4 absorption, most respondents still preferred tablets and did not expect a significant difference when switching from one LT4 formulation to another. For German thyroid specialists, LT4 is the treatment of choice for hypothyroidism. Combination therapy with LT4+LT3 was considered for patients with persistent symptoms. Even in conditions that could affect bioavailability, German thyroid specialists prefer LT4 tablets rather than other LT4 formulations, such as liquid or soft-gel capsules. The widespread use of thyroid hormone for non-hypothyroid conditions is not consistent with current evidence and needs further study.

Abstract #1180035: Levothyroxine Absorption Test for Diagnosis of Levothyroxine Pseudomalabsorption: A Six-Year Experience and Proposal of a Cutoff Point

Levothyroxine (LT4) pseudomalabsorption corresponds to a factitious disorder. It should be suspected in subjects with persistently elevated thyroid stimulating hormone (TSH) despite doses ≥1.9 μg/kg per day of LT4. In this scenario, LT4 absorption test (LT4AT) could be performed, this is a non-invasive method to distinguish levothyroxine malabsorption from pseudomalabsorption however, more clinical studies are needed to determine a standard protocol with appropriate cutoffs. The major aim of this study is to estimate the optimal cut point of the free T4 (fT4) delta to determine LT4 pseudomalabsorption.

Abstract #1159800: Levothyroxine (LT4) absorption test in a pregnant patient-safety and efficacy

The safety and efficacy of levothyroxine (LT4) absorption test in pregnant women is yet to be studied. We present a case of a 19-year-old female at 14 weeks of pregnancy who was subjected to LT4 absorption test.

Use of thyroid hormones in hypothyroid and euthyroid patients: A THESIS questionnaire survey of Hungarian physicians

Hypothyroidism has a high prevalence in the adult population. Levothyroxine (LT4) supplementation is considered to be the gold-standard treatment method. In Hungary, LT4 tablets and soft gel capsules are the available formulations. Similarly to the international trends, hypothyroidism is earlier recognised, leading to early LT4 supplementation. Up till now, there has been no survey on the treatment of hypothyroidism among Hungarian endocrinologists. THESIS (Treatment of Hypothyroidism in Europe by Specialists: an International Survey) had been conducted to assess treatment preferences among European endocrinologists. Here we report the results on the use of thyroid hormones in hypothyroid patients and euthyroid individuals in Hungary. An e-mail invitation to participate, containing the link to the online survey was sent to members of the Hungarian Society for Endocrinology and Metabolism. There were 165 responses with full demographics which were included in the analysis. By the majority (99.4%) of them, LT4 was the first treatment of choice. LT4 + LT3 combination was considered an option in patients with persistent symptoms despite biochemical euthyroidism while on LT4 (36,1%). In euthyroid individuals, 60.3% of the respondents would consider starting LT4 in euthyroid infertile women with high antibody levels, which is hardly supported by evidence. In the presence of comorbidities and interfering medications which may hinder LT4 absorption, 66.4% of Hungarian endocrinologist anticipate significant improvement after switching from tablets to soft gel capsules. The treatment of choice for hypothyroidism is LT4 in Hungary. Combination therapy with LT4 + LT3 was considered for patients with persistent symptoms. In the presence of diseases and interfering medications affecting bioavailability, a high number of Hungarian endocrinologists prefer the new LT4 formulation. The administration of LT4 in euthyroid conditions awaits explanation and calls for intensive discussions at local conferences and courses. Orv Hetil. 2022; 163(12): 463-472.

Diagnosis of Levothyroxine Pseudo-malabsorption: The Results of Standardised Testing Protocol.

The levothyroxine absorption test for the assessment of pseudo-malabsorption in patients with refractory hypothyroidism has not been standardised. The aim of this observational study was to describe a protocol for levothyroxine (LT-4) absorption test in patients with refractory hypothyroidism, to report possible side effects and to emphasise the importance of pseudo-malabsorption in the differential diagnosis. The results of 10 patients, who underwent LT-4 absorption tests because thyroid stimulating hormone suppression could not be achieved despite the need for LT-4 >3 mcg/kg/day, were retrospectively analysed. When compared with basal free T4 (fT4), a statistically significant increase in fT4 was observed after the first hour (p=0.012). fT4 reached its peak level and plateau at the 4th hour. The fT4 peak level increased 3.25 times compared to baseline. The shorter LT-4 absorption test with low doses may provide an alternative method to the commonly used longer protocols with higher doses to rule out malabsorption. Key Words: Levothyroxine absorption test, Pseudo-malabsorption, Resistant hypothyroidism.

Levothyroxine Therapy in Thyrodectomized Patients.

Administration of the optimal dose of levothyroxine (LT4) is crucial to restore euthyroidism after total thyroidectomy. An insufficient or excessive dosage may result in hypothyroidism or thyrotoxicosis, either one associated with a number of symptoms/complications. Most literature regarding the LT4 dosage deals with the treatment of primary hypothyroidism, whereas a limited number of studies handle the issue of thyroxin replacement after total thyroidectomy. A literature review was performed focusing on all papers dealing with this topic within the last 15 years. Papers that reported a scheme to calculate the proper LT4 dose were collected and compared to set up a review exploring limits and drawbacks of LT4 replacement therapy in the wide population of patients who had undergone thyroidectomy. Most of the methods for monitoring and adjusting thyroid hormone replacement after thyroidectomy for benign disease use LT4 at an empirical dose of approximately 1.6 μg/kg, with subsequent changes according to thyroid function test results and assessments of the patient’s symptoms. Approximately 75% of patients require a dose adjustment, suggesting that factors other than body weight play a role in the determination of the proper LT4 dose. Hence, several schemes are reported in the literature for the proper initial dose of LT4. An inadequate level of thyroid hormone levels in these patients can be due to several factors. The most common ones that lead to the necessity of LT4 dose adjustments include lack of compliance, changes in LT4 formulation, dosage errors, increased serum levels of T4-binding globulin, body mass changes, and dietary habits. Moreover, concomitant ingestion of calcium supplements, ferrous sulfate, proton-pump inhibitors, bile acid sequestrants, and sucralfate might influence LT4 absorption and/or metabolism. Furthermore, some gastrointestinal conditions and their treatments can contribute to suboptimal LT4 performance by altering gastric acidity and thereby reducing its bioavailability, particularly in the solid form. Beyond the classic tablet form, new formulations of LT4, such as a soft gel capsule and an oral solution, recently became available. The liquid formulation is supposed to overcome the food and beverages interference with absorption of LT4 tablets.

Adequate timing and constant supervision are the keys for successful implementation of levothyroxine or levothyroxine/paracetamol absorption test

BackgroundLevothyroxine (LT4) pseudomalabsorption due to medication non-adherence results in significant costs for Health Service. High dose LT4 or LT4/paracetamol absorption test is used in such cases. Hence, establishment of an optimal test protocol and timing of sample collection is of utmost importance.Case presentationA 34-year old woman was admitted to our Department because of severe hypothyroidism [on admission thyrotropin (TSH) > 100 μIU/ml, free thyroxine (FT4) 0.13 ng/dl (ref. range 0.93–1.7)] despite apparently taking 1000 μg of LT4 a day. Autoimmune hypothyroidism had been diagnosed 4 years before during post-partum thyroiditis. Subsequently, it was not possible to control her hypothyroidism despite several admissions to two University Hospitals and despite vehement denial of compliance problems. There was no evidence of coeliac disease or other malabsorption problems, though gluten-free and lactose-free diet was empirically instigated without success. A combined paracetamol (1000 mg)/LT4 (1000 μg) absorption test was performed in one of these Hospitals. This showed good paracetamol absorption (from < 2 μg/ml to 14.11 μg/ml at 120 min), with inadequate LT4 absorption (FT4 increase from 5.95 pmol/l to 9.92 pmol/l at 0 and 120 min respectively). About 2 years prior to admission to our Department the patient was treated with escalating doses of levothyroxine [up to 3000 μg of T4 and 40 μg of triiodothyronine (T3) daily] without significant impact on TSH (still > 75 μIU/ml, and FT4 still below reference range).After admission to our Department we performed a 2500 μg LT4 absorption test with controlled ingestion of crushed tablets, strict patient monitoring and sampling at 30 min intervals. We observed a quick and striking increase in FT4 from 0.13 to 0.46, 1.78, 3.05 and 3.81 ng/dl, at 0, 30, 60, 90 and 120 min, respectively. Her TSH concentration decreased to 13.77 μIU/ml within 4 days. When informed, that we had managed to “overcome” her absorption problems, she discharged herself against medical advice and declined psychiatric consultation.ConclusionsAdequate patient supervision and frequent sampling (e.g. every 30 min for 210 min) is the key for successful implementation of LT4 absorption test. Paracetamol coadministration appears superfluous in such cases.