Changes in subtypes of overt thyrotoxicosis and hypothyroidism following iodine fortification.

OBJECTIVE: To investigate the impact of mandatory iodine fortification (IF) on the incidence of nosological subtypes of overt thyrotoxicosis and hypothyroidism. DESIGN: We identified and scrutinized all possible new cases of overt thyrotoxicosis and hypothyroidism in an open cohort in Northern Jutland (n = 309 434; 1 January 1997) during the years 2014-2016. Individual medical history was evaluated to verify and detail the incidence of overt thyroid dysfunction and for classification into nosological subtypes. A number of cases were excluded during final verification due to spontaneous normalization of thyroid function, as they had no medical history suggesting a known condition, which could transiently affect thyroid function (subacute/silent thyroiditis, PPTD and iatrogenic thyroid dysfunction). An identical survey was conducted in 1997-2000 prior to mandatory IF of salt (13 µg/g) that was in effect from year 2001. RESULTS: The standardized incidence rate (SIR) of verified overt thyrotoxicosis decreased markedly from 97.5/100 000/year in 1997-2000 to 48.8 in 2014-2016 (SIRR: 0.50 [95% CI: 0.45-0.56]). This was due to a distinct decrease in the SIR of multinodular toxic goitre (SIRR: 0.18 [0.15-0.23]), solitary toxic adenoma (SIRR: 0.26 [0.16-0.43]) and to a lesser degree Graves' disease (SIRR: 0.67 [0.56-0.79]). SIR for overt hypothyroidism was unaltered by 2014-2016 (SIRR: 1.03 [0.87-1.22]). However, age distribution shifted with more young and fewer elderly cases of verified overt hypothyroidism. CONCLUSION: Mandatory IF caused a substantial reduction in SIR of verified overt thyrotoxicosis (especially of nodular origin) while avoiding an increase in SIR of verified overt hypothyroidism.

L-carnitine supplementation for the management of fatigue in patients with hypothyroidism on levothyroxine treatment: a randomized, double-blind, placebo-controlled trial.

Hypothyroid patients experience fatigue-related symptoms despite adequate thyroid hormone replacement. Thyroid hormone plays an essential role in carnitine-dependent fatty acid import and oxidation. We investigated the effects of L-carnitine supplementation on fatigue in patients with hypothyroidism. In total, 60 patients (age 50.0 ± 9.2 years, 3 males, 57 females) who still experienced fatigue (fatigue severity scale [FSS] score ≥ 36) were given L-carnitine (n = 30, 990 mg L-carnitine twice daily) or placebo (n = 30) for 12 weeks. After 12 weeks, although neither the FSS score nor the physical fatigue score (PFS) changed significantly, the mental fatigue score (MFS) was significantly decreased by treatment with L-carnitine compared with placebo (from 4.5 ± 1.9 to 3.9 ± 1.5 vs. from 4.2 ± 1.8 to 4.6 ± 1.6, respectively; P < 0.01). In the L-carnitine group, 75.0%, 53.6%, and 50.0% of patients showed improvement in the FSS score, PFS, and MFS, respectively, but only 20.0%, 24.0%, and 24.0%, respectively, did so in the placebo group (all P < 0.05). Both the PFS and MFS were significantly improved in patients younger than 50 years and those with free T3 ≥ 4.0 pg/mL by treatment with L-carnitine compared with placebo. Additionally, the MFS was significantly improved in patients taking thyroid hormone after thyroid cancer surgery. These results suggest that L-carnitine supplementation may be useful in alleviating fatigue symptoms in hypothyroid patients, especially in those younger than 50 years and those who have hypothyroidism after thyroidectomy for thyroid cancer (ClinicalTrials.gov: NCT01769157).

Thyroid status, insulin sensitivity and glucose tolerance in overweight and obese adults before and after 36 weeks of whey protein supplementation and exercise training.

UNLABELLED: Research suggests that subclinical hypothyroidism (SHT) influences insulin sensitivity and glucose tolerance. Reductions in thyroid stimulating hormone (TSH) concentrations are associated with exercise training (ExTr), which improves insulin sensitivity and glucose uptake. PURPOSE: A secondary analysis of previously published data was conducted to examine the relationship between SHT, TSH and glucose homeostatic control at baseline and to assess the impact of ExTr on thyroid status and how SHT affects changes in insulin sensitivity after ExTr. MATERIALS AND METHODS: Data were obtained from a 36-week ExTr and whey protein supplementation intervention trial. Subjects (n = 304, 48 ± 7 years, females = 186) were randomized to a specific whey protein group (0, 20, 40, or 60 g per day) and all subjects participated in a resistance (2 d/wk) and aerobic (1 d/wk) training program. Testing was conducted at baseline and post-intervention. RESULTS: At baseline, 36% (n = 110) and 12% (n = 35) of subjects were classified with SHT based on the TSH ≥ 3 µIU/L or TSH ≥ 4.5 µIU/L cut-offs, respectively. No association was found between baseline TSH and baseline measures of glucose homeostatic control. Whey protein supplementation did not influence intervention outcomes. Post-intervention (n = 164), no change was observed in TSH. SHT did not affect changes in insulin sensitivity following ExTr. CONCLUSION: These results support that the health benefits of ExTr for the management of insulin resistance (IR) are not blunted by SHT.

[Assessment of the using effectiveness of iodine containing additives in development of meat products for child nutrition].

The effectiveness of iodine containing additives on the basis of whey protein and milk protein casein compared to iodized salt in the composition of meat minced semi-finished products for child nutrition was examined in the experiment on laboratory animals. Four variants of the semi-finished products were investigated: 1 - control; 2 - enriched with iodine containing milk protein casein; 3 - enriched with iodine containing whey proteins; 4 - enriched with iodized salt. The semi-finished products were enriched at the level of 15% of the daily norm of iodine requirement for children at the age of 7-12 years. Iodine content in 100 g of product was 20 µkg. Rats (initial body weight 140±20 g, n=80) were divided into five groups (control, intact and three experimental groups). Groups 1 and 5 included the animals fed with a standard vivarium diet throughout the experiment. The rats from groups 2-4 were fed with the iodine enriched diet: group 2 received diet containing semi-finished products No. 2; group 3 sample No. 3 and group 4 - sample No. 4. The first stage of the experiment was aimed at accumulation of iodine in tissues and organs of animals consumed the tested iodine containing additives in the composition of semi-finished products. The second stage of the experiment consisted in simulation of the mercazolilum-induced (50 mg/kg b.w.) hypothyroidism (iodine deficiency) and detection of preventive effects of iodine containing meat semi-finished products in a model of experimental hypothyroidism in rats. The data obtained upon the end of the experiment suggest that the highest effect for correction of iodine deficiency was achieved when using the culinary products enriched with iodine containing whey proteins (sample No. 3): the level of thyroxine (T4) was restored by 98.7% in the animals from group 3 compared to the indices of the intact group, Т3 by 100%, TSH - by 89.3%. This effect was confirmed by the hematological and biochemical blood indexes, as well as the dynamics of their weight change: the level of white blood cells was significantly lower by 28%, granulocytes by 44%, monocytes by 42% compared to control rats; the weight gain of the animals of the 3 group was 20.3%, closer to that of intact animals - 26.4%, while in the control group it was 2.6 %.

Diphenyl diselenide modulates gene expression of antioxidant enzymes in the cerebral cortex, hippocampus and striatum of female hypothyroid rats.

INTRODUCTION: Cellular antioxidant signaling can be altered either by thyroid disturbances or by selenium status. AIMS: To investigate whether or not dietary diphenyl diselenide can modify the expression of genes of antioxidant enzymes and endpoint markers of oxidative stress under hypothyroid conditions. METHODS: Female rats were rendered hypothyroid by continuous exposure to methimazole (MTZ; 20 mg/100 ml in the drinking water) for 3 months. Concomitantly, MTZ-treated rats were either fed or not with a diet containing diphenyl diselenide (5 ppm). mRNA levels of antioxidant enzymes and antioxidant/oxidant status were determined in the cerebral cortex, hippocampus and striatum. RESULTS: Hypothyroidism caused a marked upregulation in mRNA expression of catalase, superoxide dismutase (SOD-1, SOD-3), glutathione peroxidase (GPx-1, GPx-4) and thioredoxin reductase (TrxR-1) in brain structures. SOD-2 was increased in the cortex and striatum, while TrxR-2 increased in the cerebral cortex. The increase in mRNA expression of antioxidant enzymes was positively correlated with the Nrf-2 transcription in the cortex and hippocampus. Hypothyroidism caused oxidative stress, namely an increase in lipid peroxidation and reactive oxygen species levels in the hippocampus and striatum, and a decrease in nonprotein thiols in the cerebral cortex. Diphenyl diselenide was effective in reducing brain oxidative stress and normalizing most of the changes observed in gene expression of antioxidant enzymes. CONCLUSION: The present work corroborates and extends that hypothyroidism disrupts antioxidant enzyme gene expression and causes oxidative stress in the brain. Furthermore, diphenyl diselenide may be considered a promising molecule to counteract these effects in a hypothyroidism state.

Obesity and Obesity-Related Thyroid Dysfunction: Any Potential Role for the Very Low-Calorie Ketogenic Diet (VLCKD)?

PURPOSE OF REVIEW: This review aims to explore in-depth the different aspects of the association between very low-calorie ketogenic diet (VLCKD), obesity and obesity-related thyroid dysfunction. RECENT FINDINGS: The VLCKD, proposed as a non-pharmacological strategy for the management of certain chronic diseases, is becoming increasingly popular worldwide. Initially used to treat epilepsy, it has been shown to be effective in controlling body weight gain and addressing various pathophysiological conditions. Research has shown that a low-calorie, high-fat diet can affect thyroid hormone levels. Weight loss can also influence thyroid hormone levels. Studies have suggested that long-term use of VLCKD for refractory epilepsy may be related to the development of hypothyroidism, with an effect seen in various populations. In particular, women with obesity following VLCKD tend to have reduced T3 levels. We propose further research to unravel the underlying mechanisms linking VLCKD to obesity and obesity-related thyroid dysfunction.

Investigation of iodine deficient state and iodine supplementation in patients with severe motor and intellectual disabilities on long-term total enteral nutrition.

Iodine concentrations of enteral nutrition (EN) formulae available in Japan are very low and long-term total EN (TEN) might result in hypothyroidism due to iodine deficiency (HID). Our aim of this study was to determine the degree of iodine deficiency (ID) and need for iodine supplementation (IS) in patients with severe motor and intellectual disabilities (SMID) on long-term TEN. Thyroid function including urinary iodine concentration (UIC) was monitored, and powdered kelp was provided as a source of iodine supplement. Thirty-five SMID on TEN participated in our study. UIC less than 100 µg /L, representing ID, were detected in 97 % of them. Their TSH ranged from 0.5 to 90 µIU/mL. IS using powdered kelp raised their UIC to the normal range. Thyroid function also recovered in the five hypothyroidism cases, which were diagnosed as HID, was also detected. In Japan, there must be many cases with ID associated with long term TEN. We also discuss the regulation of thyroid function in the iodine deficient state.

Influences of hypertonic and hypovolemic treatments on vasopressin response in propylthiouracil (PTU) induced hypothyroid rat and effect on supplementation with L-thyroxine.

This study was performed to investigate the effects of L-thyroxine treatment on plasma vasopressin (AVP) levels in rats with hypothyroidism induced by propylthiouracil (PTU). Animals were separated into three groups each having 6 rats: control, PTU, PTU+L-thyroxine groups. Then, the groups were further divided into 3 sub-groups including 6 rats (a; basal, b; hypertonic stimulated and c; hypovolemic stimulated). At the end of the experiments all rats were decapitated in order to obtain plasma samples for analysis in terms of Hct, osmolality, TT 3 , TT 4 and vasopressin. Haematocrit (Hct) levels were the highest in hypovolemic stimulated sub-group (P < 0.001). Osmolality levels were higher in hypertonic stimulated sub-groups (P < 0.001). Total T 3 and T 4 values were the lowest in the PTU group and the highest in the L-thyroxine treated group (P < 0.001). Plasma AVP levels were reduced by hypothyroidism. However, L-thyroxine treatment after the hypothyroidism prevented this reduction (P < 0.001). Vasopressin responses to basal, hypovolemic and hypertonic stimulations were the lowest in the PTU group (P < 0.001). The results of the present study show that basal and stimulated plasma vasopressin levels are reduced in PTU-induced hypothyroidism. However, L-thyroxine treatment following hypothyroidism prevents this reduction.

A Lifestyle (Dietary) Intervention Reduces Tiredness in Children with Subclinical Hypothyroidism, a Randomized Controlled Trial.

PURPOSE: Subclinical hypothyroidism (SH) in children and adults is a subject for discussion in terms of whether to treat it or not with respect to the short-term clinical implications and consequences of SH and in the long term. If treatment with thyroxine supplementation is not indicated, no other treatment is available. We investigated whether a lifestyle (dietary) intervention improves or normalizes SH or decreases the presence of Thyroid Stimulating Hormone (TSH) and/or tiredness. Methods: We randomized children aged 1-12 years with SH to the control group (standard care = no treatment) or intervention group (dietary intervention). The dietary intervention consisted of green vegetables, beef, whole milk and butter for 6 months. The rest of the diet remained unchanged. We measured TSH, FreeT4, Lipid profile, Body Mass Index (BMI) and Pediatric Quality of Life (PedQL) multidimensional fatigue scale scores. Results: In total, 62 children were included. After 6 months, TSH decreased in both groups without a significant difference between the groups (p = 0.98). PedQL fatigue scores for sleep (p = 0.032) and total fatigue scores (p = 0.039) improved significantly in the intervention group, compared to the control group. No unfavorable effects occurred in the lipid profile or BMI. Conclusion: The lifestyle (dietary) intervention did not normalize SH and TSH levels, but it significantly reduced tiredness. These results suggest that children's well-being can be improved without medication.

Constant iodine intake through the diet could improve hypothyroidism treatment: a case report.

Currently, hypothyroidism is usually treated only with drugs; patients are never told that they could regulate their levels of iodine with dietary recommendations in a complementary way. The objective of this work was to explore the effect of a constant iodine intake through the diet in a postmenopausal woman with subclinical grade II hypothyroidism, who also had mild hypercholesterolemia and obesity. Baseline anthropometric nutritional, pharmacological, and habit data were obtained, then the woman was scheduled for 1 month a diet in which she was provided food naturally containing iodine, so that the recommended requirements (iodine 150 µg/day) were met. All the information about which foods contain this mineral was supplied and explained to the patient. This diet was also designed to help her to gradually lose weight, and was more balanced and closer to the nutritional recommendations. The results obtained in this work were satisfactory, having achieved improved blood levels of thyroid-stimulating hormone (1.78 µIU/mL) and reduced total cholesterol levels (198 mg/dL). Statement of hypercholesterolemia was demoted. In addition, a significant improvement in relation to weight and body volume was reached (body mass index fell from 30.13 to 28.5 kg/m2), an important fact since it has impacted the overall well-being of the patient. In conclusion, it was demonstrated that a constant iodine intake through the diet for this patient with grade II hypothyroidism was very effective, and therefore, this aspect should be also considered during hypothyroidism treatment.

[Efficiency evaluation of the iodine-containing dietary supplements in the experiment].

The article presents the results of medical and biological studies, performed in animals of influence of food supplements "Jodium-elastin" and Jodium-active" as well as pharmacopeia preparation "KJ" on the level of thyroid hormones TT4, TT3 and TTG in blood serum at experimental hypothyrosis, caused by thyreostatic merkazolil. Of all the used products, food supplement "Jodium-elastin" turned out to be the most effective. It completely normalized the level of the studied hormones in animals at experimental hypothyrosis.

Caloric restriction does not alter thyrotropin secretion in hypothyroidism.

The effect of caloric restriction, as a model of nonthyroid illness, on serum thyroid hormone and TSH concentrations in hypothyroid patients was studied to determine if pituitary-thyroid function is altered in such patients, as it is in euthyroid subjects. Serum T4, T3, and TSH concentrations and serum TSH responses to TRH were measured in 5 untreated hypothyroid patients and 10 hypothyroid patients receiving T4 replacement therapy before and after restriction of caloric intake to 500 cal daily for 7 days. In 5 untreated hypothyroid patients, the mean serum T3 concentration declined 17%, from 75 +/- 14 (+/- SE) to 62 +/- 11 ng/dl. The mean basal serum TSH concentrations were 154 +/- 67 (+/- SE) microU/ml before and 161 +/- 75 microU/ml at the end of the period of caloric restriction, and the serum TSH responses to TRH were similar on both occasions. In 10 T4-treated hypothyroid patients, the mean serum T3 concentration declined 35%, from 110 +/- 8 to 71 +/- 8 ng/dl. In this group, mean basal serum TSH concentrations were 17 +/- 5.1 microU/ml before and 18.2 +/- 7.0 microU/ml at the end of the period of caloric restriction, and as in the untreated hypothyroid patients, the serum TSH responses to TRH were similar on both occasions. Mean serum T4 concentrations and serum free T4 index values did not change in either group. These results indicate that caloric restriction in both untreated and T4-treated hypothyroid patients is accompanied by 1) reduced serum T3 concentrations, as it is euthyroid subjects, and 2) no alterations in basal or TRH-stimulated TSH secretion.

Effect of iodine restriction on thyroid function in subclinical hypothyroid patients in an iodine-replete area: a long period observation in a large-scale cohort.

BACKGROUND: Excessive iodine intake is related to a higher prevalence of hypothyroidism, including subclinical hypothyroidism (SCH), in iodine-replete areas. This study aimed to evaluate the effect of iodine restriction on thyroid function in SCH patients in an iodine-replete area and analyze the relationship between serum thyrotropin (TSH) levels and iodine intake. METHODS: The study consisted of 146 consecutive patients who were diagnosed with SCH at the Samsung Medical Center between 2010 and 2012. Urinary iodine concentration (UIC) was measured in 82 patients. Of these, 20 patients with UIC < 300 µg/L were excluded, and 62 patients with UIC ≥ 300 µg/L were educated about the restriction of iodine-rich foods. Following the first follow-up visit, these patients were divided into two groups based on the UIC level: group A (well-controlled iodine intake, UIC < 300 µg/L, n = 40), and group B (poorly controlled iodine intake, UIC ≥ 300 µg/L, n = 22). The remaining 64 patients did not restrict iodine rich foods (group C). The 82 patients with measured UICs were reevaluated every 3-6 months, and the median follow-up was 13 months (range 3-32 months). Thyroid function and UIC were measured at each visit. The correlation between serum TSH level and UIC was determined for the 82 patients in whom UIC was measured. RESULTS: Following 3-6 months of iodine restriction, the serum TSH levels significantly decreased in group A (from 9.0 mU/L to 4.7 mU/L; p < 0.01). In addition, the serum free thyroxine (T4) levels in group A significantly increased (from 1.11 ± 0.23 ng/dL to 1.18 ± 0.17 ng/dL; p < 0.05). However, there were no significant changes in serum TSH or free T4 levels in groups B and C. Serum TSH levels significantly correlated with UIC (r = 0.33, p < 0.01). CONCLUSION: Iodine restriction may normalize or, at the very least, decrease serum TSH levels in SCH patients, and serum TSH levels are strongly correlated with UIC. Therefore, restriction of iodine intake could be a primary treatment option in SCH patients in an iodine-replete area.

Diphenyl diselenide supplemented diet reduces depressive-like behavior in hypothyroid female rats.

Hypothyroidism has been associated to psychiatric disorder development and tissue oxidative damage. In this study, we evaluated the effect of diphenyl diselenide supplementation on depressive-like behavior triggered by methimazole exposure in female rats. Additionally, thiobarbituric acid reactive substances (TBARS), reactive oxygen species (ROS) and non-protein thiol (NP-SH) levels were analyzed in cerebral cortex, hippocampus and striatum structures of rats. Monoamine oxidase (MAO) activity was evaluated in total brain. Firstly, female rats received methimazole (MTZ) 20mg/100ml in the drinking water for 30days and were evaluated in open-field and forced swimming tests (FST). In this set of experiments, the rats exposed to MTZ presented a depressive-like behavior, which was evidenced by a significant increase in the immobility time when compared to control group. Thereafter, MTZ-induced hypothyroid rats received either a standard or a diet containing 5ppm of diphenyl diselenide, and then they were evaluated monthly in open-field and FST tests during 3months. No alteration on the locomotor performance was observed among the groups. The depressive-like behavior of hypothyroid rats was blunted by diphenyl diselenide supplementation during all experimental periods. The levels of thyroid hormones remained low in MTZ exposed groups until the end of experimental period. The MTZ group had an increase in TBARS and ROS levels that were restored by diphenyl diselenide supplementation. NP-SH content of cerebral structures was not modified by MTZ exposure and/or diphenyl diselenide supplementation. Diphenyl diselenide supplementation restored the MAO B activity that was decreased in MTZ group. In summary, our results show that hypothyroidism induced by MTZ methimazole triggers a depressive-like behavior in female rats and that dietary diphenyl diselenide was able to reduce this effect.

Iodine contributes to thyroid autoimmunity in humans by unmasking a cryptic epitope on thyroglobulin.

CONTEXT: The mechanisms linking thyroid autoimmunity and iodine use in humans are unknown. OBJECTIVE: Our aim was to correlate iodine intake, thyroid autoimmunity, and recognition of thyroglobulin (Tg) epitopes after implementation of iodine prophylaxis. SETTING: The general community living in an Italian village was evaluated. MAIN OUTCOME MEASURES: Thyroglobulin autoantibodies (TgAb), thyroperoxidase autoantibodies (TPOAb), and urinary iodine excretion were assessed in 906 iodized salt users (IS-users) and 389 nonusers (IS-nonusers). Ultrasound (US) was performed to identify thyroid hypoechogenicity, suggestive of Hashimoto thyroiditis (HT). TgAb epitope pattern in 16 IS-users and 17 IS-nonusers was evaluated by an inhibition binding assay to Tg, using human monoclonal TgAb-Fab directed to A, B, C, and D epitopes on Tg. RESULTS: Median urinary iodine excretion was slightly higher in IS-users than in IS-nonusers (112.0 µg/L vs 86.5 µg/L; P < .01). TgAb, and not TPOAb, was more frequent in IS-users (18.9% vs 13.6%, P = .02). HT-US was found in 87 subjects, among whom both positive TgAb (58.4% vs 31.8%, P = .03) and TPOAb (61.5% vs 45.4%. P = .04) were more frequent in IS-users. In this group significantly higher serum levels of TgAb (median 108 U/mL vs 30 U/mL; P = .02), but not of TPOAb, were present. Iodized salt use had no effect on the 1208 non HT-US subjects. TgAb directed to the epitope B of Tg were more frequent in IS-users than in IS-nonusers (27.5% vs 3.0%, P = .047). CONCLUSIONS: Iodine-induced thyroid autoimmunity is related to TgAb and the unmasking of a cryptic epitope on Tg contributes to this relationship in humans.

Desiccated thyroid extract compared with levothyroxine in the treatment of hypothyroidism: a randomized, double-blind, crossover study.

CONTEXT: Patients previously treated with desiccated thyroid extract (DTE), when being switched to levothyroxine (L-T4), occasionally did not feel as well despite adequate dosing based on serum TSH levels. OBJECTIVE: Our objective was to investigate the effectiveness of DTE compared with L-T4 in hypothyroid patients. DESIGN AND SETTING: We conducted a randomized, double-blind, crossover study at a tertiary care center. PATIENTS: Patients (n = 70, age 18-65 years) diagnosed with primary hypothyroidism on a stable dose of L-T4 for 6 months were included in the study. INTERVENTION: Patients were randomized to either DTE or L-T4 for 16 weeks and then crossed over for the same duration. OUTCOME MEASURES: Biochemical and neurocognitive tests at baseline and at the end of each treatment period were evaluated. RESULTS: There were no differences in symptoms and neurocognitive measurements between the 2 therapies. Patients lost 3 lb on DTE treatment (172.9 ± 36.4 lb vs 175.7 ± 37.7 lb, P < .001). At the end of the study, 34 patients (48.6%) preferred DTE, 13 (18.6%) preferred L-T4, and 23 (32.9%) had no preference. In the subgroup analyses, those patients who preferred DTE lost 4 lb during the DTE treatment, and their subjective symptoms were significantly better while taking DTE as measured by the general health questionnaire-12 and thyroid symptom questionnaire (P < .001 for both). Five variables were predictors of preference for DTE. CONCLUSION: DTE therapy did not result in a significant improvement in quality of life; however, DTE caused modest weight loss and nearly half (48.6%) of the study patients expressed preference for DTE over L-T4. DTE therapy may be relevant for some hypothyroid patients.

The influence of lactose intolerance and other gastro-intestinal tract disorders on L-thyroxine absorption.

The preferred treatment for hypothyroidism is oral levothyroxine (LT4) ingestion, in doses that ensure a sustained state of hormonal balance. Many different factors may significantly influence the absorption of LT4, including: interval between the ingestion of the drug and the last meal, eating habits, and different functional and organic pathologies of the gastro-intestinal tract. The main purpose of this paper is to review and systematise the available literature on the subject of the influence of different malabsorption syndromes on the effectiveness of LT4 preparations. The need to use high LT4 doses in the substitutional treatment of hypothyroidism is often the very first sign of one of the pathologies that are connected with malabsorption syndrome, which might have been asymptomatic and undiagnosed previously. Patients who require more than 2 µg/kg body weight of LT4 per day, with constantly increased thyrotropin level, should be diagnosed with the suspicion of pseudomalabsorption or real absorption disorder. An LT4 absorption test, using high doses of LT4, may be useful in the diagnosis of pseudomalabsorption. After excluding non-compliance, the differential diagnosis should include such disorders as lactose intolerance, coeliac disease, atrophic gastritis, Helicobacter pylori infection, bowel resection, inflammatory bowel disease, and parasite infection. Where there is a diagnosis of lactose intolerance, both a low lactose diet and a lactose-free LT4 preparation should be administered to restore euthyroidism or make it possible to decrease the dose of the LT4 preparation. In coeliac disease, a gluten-free diet usually allows a normalisation of the need for LT4, as do eradication of the H. pylori infection or parasite colonisation. In cases of atrophic gastritis or inflammatory bowel disease, treating the underlying diseases and regaining the state of remission may improve the absorption of LT4. In patients after gastro-intestinal tract surgery, a dose of LT4 higher than that typically used is needed to restore euthyroidism.