Levothyroxine Absorption Research Articles

SAT-483 Levothyroxine Absorption Test: A Potential Therapeutic Tool for Levothyroxine Malabsorption

INTRODUCTIONPersistent hypothyroidism (PH) even on high doses of levothyroxine is a common clinical problem and it is difficult to treat. Levothyroxine absorption test has been used to distinguish between pseudo-malabsorption and malabsorption as one of its causes. This test uses 1000 mcg of levothyroxine to calculate the percentage of levothyroxine absorbed. We present a case of malabsorption in which we used the levothyroxine absorption test to diagnose as well as treat malabsorption.Case:55-year-old male with history of papillary thyroid cancer status post total thyroidectomy, postsurgical hypothyroidism, recurrent small bowel obstruction, status post jejunal resection, complicated by high output entero-cutaneous fistula, distal high-grade obstruction status post placement of jejunal tube, chronic abdominal pain on narcotics, who initially presented with sepsis and was also found to be hypothyroid.The thyroid stimulating hormone (TSH) level was 45.25 with free thyroxine (FT4) level of 0.54. He was adherent to his levothyroxine (LT4) 175 mcg once daily which is given one hour after tube feeds have been stopped or one hour prior to any administration of other medications.Levothyroxine absorption test was done to distinguish between malabsorption versus pseudo-malabsorption. Three different doses of LT4 were used with results all consistent with malabsorption. The percentage of absorption with 175 mcg, 500 mcg, and 1000 mcg LT4 were 3.4%, 7.2%, and 18% respectively. The formula used to determine the percentage of absorption was (total T4 at 2 hour after LT4 administration - baseline total T4 prior to administration in mcg/L) x plasma volume in liter/dose of administered LT4 in mcg. The final prescription dose of 700 mcg once daily was then derived from the available data, which eventually corrected the patient’s hypothyroidism. Repeat testing after 2 weeks showed TSH of 0.17, FT4 of 1.29 and total T4 of 6.5. The suppressed TSH at this point was attributed to chronic narcotic use but FT4 and total T4 improved appropriately.Conclusion:There is no gold standard protocol for levothyroxine absorption test so we used a different protocol for LT4 dosing compared to the conventional regimen (1000 mcg of LT4). Our patient did show appropriate levothyroxine absorption on the calculated dose. Hence, the Levothyroxine absorption test may be used both as a diagnostic as well as a therapeutic tool for the patients with LT4 malabsorption causing PH.

SAT-503 Levothyroxine Absorption Testing in Three Patients with Severe Hypothyroidism on Adequate Replacement

Background: Levothyroxine (L-T4) absorption is a concern in patients who report appropriate self-administration but remain clinically and biochemically hypothyroid. However, there are no established guidelines for L-T4 absorption testing. Clinical Cases: Two women (A and B) with a history of Graves’ disease and radioactive iodine ablation (RAI) on weight-based L-T4 replacement presented to the hospital with severe fatigue and bilateral leg swelling. A third woman (C) with a history of papillary thyroid carcinoma, total thyroidectomy and RAI, on suppressive doses of L-T4 presented to the clinic with fatigue, constipation and weight gain. All patients reported compliance with taking L-T4 with appropriate technique. They had no known medical problems contributing to a malabsorptive state, and were not taking any medications known to interfere with L-T4 absorption.Initial testing of thyroid function revealed TSH (0.57-3.5 μIU/mL)/Free T4 (0.61-1.18 ng/dL) levels of 10.12/0.249, 45.95/<0.2 and 142/<0.2 in patients A, B and C respectively. Patients A and B tested negative for Helicobacter pylori infection, celiac disease and lactose intolerance. Patient C had been successfully treated for H. pylori infection in the past. Celiac testing was negative, but the patient tested positive for anti-parietal cell antibodies and vitamin B12 deficiency. She was referred to Hematology & GI specialists. None of the patients had clinical evidence of heart failure and had normal echocardiograms.In order to evaluate for poor absorption, all patients underwent L-T4 absorption testing. Based on published data, baseline TSH and Free T4 levels were obtained followed by administration of 1000 mcg of L-T4. Next, free T4 levels were obtained at 2 hours for all patients and at 4, 8 and 24 hours for patient A & B. Patients A and B underwent testing in the inpatient setting, while Patient C was tested in the outpatient clinic.In all cases, a > 50% rise in free T4 levels was observed at 2 hours, suggesting non-adherence or “pseudo-malabsorption”. Patients were counseled extensively regarding proper technique and compliance with L-T4. Patients A and B demonstrated rapid clinical improvement in the hospital, and Patient C reported to her next clinic visit with clinical and biochemical improvement. Conclusions: Though guidelines have not been established for L-T4 absorption testing, case reports exist exhibiting the safety and efficacy of L-T4 absorption challenge with a weekly weight-based dose or 1000 mcg of LT4. Our case series show the success of the latter with meaningful results in as little as 2 hours. Case C demonstrates that this test can be done safely and cost-effectively as an outpatient. Standardization of L-T4 absorption test will be of great utility in the management of this common problem encountered by endocrinologists.

Prevalence of gastrointestinal disorders having an impact on tablet levothyroxine absorption: should this formulation still be considered as the first-line therapy?

In patients with hypothyroidism, levothyroxine (LT4) is the treatment of choice, and tablets are the most commonly prescribed formulation. Despite multiple scenarios being reported in the literature with impaired tablet absorption and likely missed TSH targets, it is yet unclear what the implications are for clinical practice and the role of liquid solution (LS) and soft gel (SG) formulations. We have thus conducted a narrative review evaluating the prevalence within the general population of gastrointestinal disorders impacting tablet LT4 absorption. PubMed and Google Scholar were searched until December 2019 for systematic reviews and meta-analyses on the topic. If they could not be retrieved, other types of manuscripts were searched. Lactose malabsorption and Helicobacter pylori infection represented the most common disorders, with a global prevalence of 68% and 48%, respectively. The prevalence of other conditions, including autoimmune gastritis, bariatric surgery, celiac disease, gastroparesis, giardiasis, liver cirrhosis, or ulcerative colitis, was lower than 20%. Data at regional and country levels were found to be heterogeneous, but at least one in five patients was diagnosed with one disorder. The worldwide prevalence of gastrointestinal disorders associated with tablet LT4 malabsorption, including lactose malabsorption and Helicobacter pylori infection, is high. Interactions with drugs or food can further increase this risk. Considering that all studies investigating the impact of switching patients from tablet to LS or SG found an improved thyroid balance, the latter formulations should be considered as first-line therapy for managing hypothyroidism.

Greetings From the Editor of Clinical Thyroidology

Greetings From the Editor of <i>Clinical Thyroidology</i>

The Levothyroxine Absorption Test: A Four-Year Experience (2015-2018) at The Mayo Clinic.

Background: Levothyroxine (LT4) is the mainstay of therapy for hypothyroidism. Yet, despite physician efforts at dose titration, some patients remain hypothyroid on LT4 doses in excess of weight-based calculations, a condition known as refractory hypothyroidism. The LT4 absorption test (LT4AT) has been proposed to have utility in these patients by enabling distinction of LT4 malabsorption from pseudomalabsorption, a condition of intentional nonadherence. Given its rare use in clinical practice, we reviewed our institution's experience with the LT4AT to assess its impact on management of refractory hypothyroidism. Methods: We reviewed the charts of 16 patients diagnosed with refractory hypothyroidism and who had completed the LT4AT between January 2015 to January 2019. The primary aim was to determine the utility of this test in distinguishing LT4 malabsorption from pseudomalabsorption. Secondary aims were to determine whether the results of this test impacted physicians' management decisions, as well as to report on clinical outcomes at follow-up. Our LT4AT is a six-hour test wherein patients receive a weight-based dose of LT4 followed by serial measurements of total thyroxine (TT4) and thyrotropin (TSH). Percentage absorption is calculated using the following formula, with normal absorption being ≥60%: [Formula: see text] Results: Percentage absorption was calculated in 13 of 16 patients due to lack of TT4 data for 3 patients. Absorption was impaired in one patient (% absorbed = 0), who had known causes of malabsorption. The remaining 12 patients had normal absorption by hour 4 of the test (% absorption 60-158) in conjunction with upward TT4 trends. Clinical follow-up ranged from 1 to 32 months (median 6.5 months), with 11 patients having follow-up data. Six of these had normal or suppressed TSH values at most recent follow-up, and four had improved but persistent TSH elevations. The one said patient with malabsorption improved with intravenous LT4. Conclusions: The LT4AT can provide valuable information for distinguishing malabsorption from pseudomalabsorption. Our findings support the combined use of calculated percentage absorptions with TT4 trends for at least a four-hour time frame when making determinations regarding absorption.

Levothyroxine Absorption Test to Differentiate Pseudomalabsorption from True Malabsorption

Background: The levothyroxine absorption test for evaluation of pseudomalabsorption in patients with primary hypothyroid is not standardised. An individual in whom a workup for malabsorption is warranted remains undefined. Methods: Twenty-five euthyroid, 25 newly diagnosed hypothyroid, 25 treated hypothyroid with normalised TSH, and 25 hypothyroid subjects with elevated TSH despite adequate dose of levothyroxine for more than 6 months, and 10 euthyroid subjects with true malabsorption were administered levothyroxine (10 μg/kg or maximum 600 μg) to study its absorption profile by measuring free T4 level at hourly intervals for 5 h. Results: Free T4 peaked at 3 h with marginal insignificant decline at 4 h in all groups. The increments of free T4 (between baseline and 3 h) of the four groups (except malabsorption) were not statistically different. The mean increment of free T4 in true malabsorption was 0.39 ng/dL (95% CI: 0.29–0.52) and it was 0.78 ng/dL (95% CI: 0.73–0.85) (10.4 pmol/L) for other groups combined together. The cut off of free T4 increment at 3 h from baseline above 0.40 ng/dL had a sensitivity of 97% and specificity of 80% (AUC 0.904, p < 0.001) to exclude true malabsorption. Conclusion: Subjects with elevated TSH on adequate dose of LT4 can be reliably diagnosed to be non-adherent to treatment with levothyroxine absorption test. The incremental value above 0.40 ng/dL (5.14 pmol/L) at 3 h may be useful to identify individuals where workup of malabsorption is unwarranted.

A minimum of two years of undertreated primary hypothyroidism, as a result of drug-induced malabsorption of l-thyroxine, may have metabolic and cardiovascular consequences

ObjectiveCross-sectional studies have reported that TSH above or close to the upper normal limit correlates with unfavorable metabolic and cardiovascular outcomes. Certain medications impair intestinal absorption of levothyroxine (L-T4), resulting in undertreated hypothyroidism (viz. failure of serum TSH to reach target levels, if hypothyroidism is primary).Further to evaluating the magnitude of sub-optimally treated primary hypothyroidism as a result of co-ingestion of those medications, we wished to ascertain whether the above complications would occur during a low number of years under polypharmacy. MethodIn this retrospective study in collaboration with 8 family physicians, we enrolled adults with primary hypothyroidism under L-T4 therapy that, for 2 years minimum, was not associated with those medications (non-exposure, baseline) and that, for another 2 years minimum, it was (exposure). Outcomes were serum levels and proportions of serum TSH levels >4.12 mU/L, and proportions of complications. Complications were aggravation of pre-existing or de novo onset of any of metabolic syndrome, impaired fasting glycemia (IFG), diabetes mellitus, dyslipidemia, hypertension, coronary heart disease (CHD), cerebrovascular disease (CVD). ResultA total of 114 patients were enrolled. Duration of exposure to the interfering medication was 32.1 ± 6.9 months (median 31; range 24–55). Compared with non-exposure, the exposure period resulted in greater TSH levels (2.81 ± 3.62 [median 1.79] vs 1.27 ± 1.34 [median 0.93], P = 2.2 × 10−20) and proportions of values >4.12 mU/L (18.5% vs 4.7%, P = 1.2 × 10−7). Seventy-six patients (67%) had complications, whose rates of TSH >4.12 mU/L were greater than in the 36 complication-free patients (22% vs 11%, P = 0.018). ConclusionDuring a median period of 31 months, there are relevant consequences for L-T4 treated adult hypothyroid patients resulting from hyperthyrotropinemia caused by medications impairing L-T4 absorption. This should be taken into account by future guidelines on hypothyroidism management.

Switch from tablet levothyroxine to oral solution resolved reduced absorption by intestinal parasitosis.

SummaryReduced intestinal absorption of levothyroxine (LT4) is the most common cause of failure to achieve an adequate therapeutic target in hypothyroid patients under replacement therapy. We present the case of a 63-year-old woman with autoimmune hypothyroidism previously well-replaced with tablet LT4 who became unexpectedly no more euthyroid. At presentation, the patient reported the onset of acute gastrointestinal symptoms characterized by nausea, loss of appetite, flatulence, abdominal cramps and diarrhea, associated with increase of thyrotropin levels (TSH: 11 mIU/mL). Suspecting a malabsorption disease, a thyroxine solid-to-liquid formulation switch, at the same daily dose, was adopted to reach an optimal therapeutic target despite the gastrointestinal symptoms persistence. Oral LT4 solution normalized thyroid hormones. Further investigations diagnosed giardiasis, and antibiotic therapy was prescribed. This case report is compatible with a malabsorption syndrome caused by an intestinal parasite (Giardia lamblia). The reduced absorption of levothyroxine was resolved by LT4 oral solution.Learning points:The failure to adequately control hypothyroidism with oral levothyroxine is a common clinical problem.Before increasing levothyroxine dose in a patient with hypothyroidism previously well-controlled with LT4 tablets but no more in appropriate therapeutic target, we suggest to investigate non adhesion to LT4 therapy, drug or food interference with levothyroxine absorption, intestinal infection, inflammatory intestinal disease, celiac disease, lactose intolerance, short bowel syndrome after intestinal or bariatric surgery, hepatic cirrhosis and congestive heart failure.LT4 oral solution has a better absorptive profile than the tablet. In hypothyroid patients affected by malabsorption syndrome, switch of replacement therapy from tablet to liquid LT4 should be tested before increasing the dose of LT4.

Levothyroxine absorption test results in patients with TSH elevation resistant to treatment.

Persistent elevation of thyroid-stimulating hormone (TSH) is common in endocrinology practice in patients undergoing replacement or suppression therapy with levothyroxine sodium (LT4). After examining the causes of this condition, LT4 absorption test is recommended. In this report, we wanted to share our results of LT4 absorption test in patients with elevated TSH levels. The files of patients who presented to our clinic between 2015 and 2018, whose TSH elevation continued despite high-dose LT4 therapy, and who underwent absorption test were reviewed retrospectively. Levothyroxine sodium absorption test was applied to five patients. Absorption test revealed LT4 malabsorption in two patients and pseudomalabsorption in the other three patients. When all published pseudomalabsorption cases were considered, it has been stated that at least 2.5 times increase in basal fT4 level may exclude malabsorption. The formula we used has been implemented by Cleveland Clinic since 2014. In cases where TSH normalization is not achieved despite high doses of LT4 therapy, LT4 absorption test is an easy test for administration and interpretation and prevents unnecessary medical treatments and examinations.

The Effect of the Bariatric Surgery Type on the Levothyroxine Dose of Morbidly Obese Hypothyroid Patients.

Doubts exist about the effect of different bariatric surgery (BS) types on levothyroxine (Lt4) absorption. We compared Lt4 doses and their variation (ΔLt4) in patients with hypothyroidism that underwent malabsorptive (MS) or restrictive (RS) surgery and studied predictors of Lt4 dose change. Retrospective study of morbidly obese hypothyroid patients submitted to BS. We compared RS ("sleeve" gastrectomy or adjustable gastric banding) with MS (Roux-en-Y gastric bypass) patients. We built a multivariable logistic regression and a linear regression model to study predictors of Lt4 dose changes and ΔLt4, respectively. Fifty-seven patients: 35 MS and 22 RS. Mean age 47years; 7% men. Patients submitted to MS had lower BMI at 1year than those submitted to RS. Lt4 dose remained unchanged in 61.4%, increased in 12.3%, and decreased in 26.3% of patients. Initial and 1-year Lt4 dose were not different between surgical groups. Relative Lt4 dose, but not absolute (p = 0.07), increased at 1year (p < 0.001). Neither BS nor BMI variation were predictors of Lt4 dose variation. BMI variation was associated with relative Lt4 dose change independently of initial BMI and BS type: β (95%CI) - 0.03 (- 0.05; 0.00); p = 0.03. There were no differences in Lt4 dose and its variation between restrictive and malabsorptive techniques 1year after surgery. Malabsorptive procedures may not affect Lt4 absorption differently from restrictive ones. Bariatric surgery type was not predictive of Lt4 dose changes. BMI variation is associated with relative Lt4 dose (dose per weight) variation and its association was independent of bariatric surgery type.

Phosphate binders as a cause of hypothyroidism in dialysis patients: practical indications from a review of the literature

BackgroundAlthough fatigue is common in dialysis patients, polypharmacy is seldom listed among its causes. In this report, we describe a dialysis patient who developed severe fatigue due to pharmacological interaction between two commonly prescribed drugs, phosphate binders and levothyroxine.Case PresentationA 65-year old woman, on dialysis for 17 years, complained of fatigue (weight 54 Kg, height 1.55 m, BMI: 23 Kg/m2; malnutrition inflammation index: 10; Charlson index 9). She had been treated with lithium for about 20 years. A heavy smoker, she was obese and diabetic when young, but stopped treatment after weight loss. She had undergone thyroidectomy for papillary carcinoma, left hemicolectomy for colon adenocarcinoma, left quadrantectomy followed by radiotherapy for ductal mammary adenocarcinoma, subtotal parathyroidectomy for tertiary hyperparathyroidism. At the time of this report, she was on thrice-weekly hemodiafiltration (Daugirdas 2 Kt/V: 1.6–1.8). Her recent treatment included spironolactone, amlodipine, perindopril, valproate, lamotrigine, levothyroxine, vitamin D, calcium carbonate, sodium polystyrene and sevelamer. After she questioned her doctor about whether her fatigue might be the result of a drug interaction, levothyroxine interference was identified (TSH, previously normal, increased to 13.07 mU/L, after increasing sevelamer dose, and normalized after change of drug schedule).Literature review: only 5 relevant papers on levothyroxine and phosphate binders on dialysis were found on Pubmed and EMBASE (out of 351 titles retrieved). Information was therefore inferred from studies in normal volunteers or in other diseases.Discussion and conclusionsOur case differs from other reports on lower TSH at diagnosis, underlining the need for awareness of the importance of early diagnosis. Integrating the scant literature on dialysis patients with data available in the general population, some working conclusions can be reached: while all phosphate binders potentially interfere with levothyroxine absorption, interference seems to be highest for sevelamer; interference is limited but not excluded by increasing the intervals between drugs; morning fast is usually indicated but, when clashing with the timing of other drugs, a bedtime dose and liquid preparations may be indicated. In the absence of an agreed control schedule, our case supports close monitoring of TSH (1–3 months if unstable, twice-yearly in stable patients).

Levothyroxine absorption test: a safe help for difficult cases

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Thyroid Hormones Are Transport Substrates and Transcriptional Regulators of Organic Anion Transporting Polypeptide 2B1

Levothyroxine replacement therapy forms the cornerstone of hypothyroidism management. Variability in levothyroxine oral absorption may contribute to the well-recognized large interpatient differences in required dose. Moreover, levothyroxine-drug pharmacokinetic interactions are thought to be caused by altered oral bioavailability. Interestingly, little is known regarding the mechanisms contributing to levothyroxine absorption in the gastrointestinal tract. Here, we aimed to determine whether the intestinal drug uptake transporter organic anion transporting polypeptide 2B1 (OATP2B1) may be involved in facilitating intestinal absorption of thyroid hormones. We also explored whether thyroid hormones regulate OATP2B1 gene expression. In cultured Madin-Darby Canine Kidney II/OATP2B1 cells and in OATP2B1-transfected Caco-2 cells, thyroid hormones were found to inhibit OATP2B1-mediated uptake of estrone-3-sulfate. Competitive counter-flow experiments evaluating the influence on the cellular accumulation of estrone-3-sulfate in the steady state indicated that thyroid hormones were substrates of OATP2B1. Additional evidence that thyroid hormones were OATP2B1 substrates was provided by OATP2B1-dependent stimulation of thyroid hormone receptor activation in cell-based reporter assays. Bidirectional transport studies in intestinal Caco-2 cells showed net absorptive flux of thyroid hormones, which was attenuated by the presence of the OATP2B1 inhibitor, atorvastatin. In intestinal Caco-2 and LS180 cells, but not in liver Huh-7 or HepG2 cells, OATP2B1 expression was induced by treatment with thyroid hormones. Reporter gene assays revealed thyroid hormone receptor α-mediated transactivation of the SLCO2B1 1b and the SLCO2B1 1e promoters. We conclude that thyroid hormones are substrates and transcriptional regulators of OATP2B1. These insights provide a potential mechanistic basis for oral levothyroxine dose variability and drug interactions.

Concurrent Milk Ingestion Decreases Absorption of Levothyroxine.

Levothyroxine is the most commonly prescribed medication in the United States. Many foods and medications, including calcium supplements, can interfere with levothyroxine absorption. No studies have investigated the effect of cow's milk, a common breakfast staple, on the absorption of oral levothyroxine. Cow's milk contains approximately 450 mg of elemental calcium per 12 oz (355 mL) serving. A pharmacokinetic study was conducted in healthy euthyroid subjects to assess levothyroxine absorption with and without concurrent cow's milk consumption. Following an overnight fast, serum total thyroxine (TT4) concentrations were measured at baseline and at one, two, four, and six hours after ingestion of 1000 μg of oral levothyroxine alone or when co-administered with 12 oz (355 mL) of 2% milk. There was a four-week washout period between the two assessments in each subject. Ten subjects (Mage ± SD = 33.7 ± 10.2 years; 60% male) completed the study. The area under the curve (AUC) of TT4 concentrations was significantly lower when levothyroxine was ingested along with 12 oz (355 mL) of 2% cow's milk (M ± SD = 67.3 ± 12.1) compared to that with levothyroxine alone (73.5 ± 17.0; p = 0.02). Also, peak serum TT4 concentrations were significantly lower when cow's milk was co-administered with levothyroxine (M ± SD = 14.1 ± 0.8 μg/dL) than with levothyroxine alone (13.0 ± 0.9 μg/dL; p = 0.04). This is the first study to demonstrate that concurrent cow's milk ingestion reduces oral levothyroxine absorption. The findings support previous literature showing the interference of elemental calcium and food with thyroid hormone absorption. Patients managed with thyroid hormone should be advised to avoid taking their levothyroxine simultaneously with cow's milk.

Treatment of congenital hypothyroidism in a newborn with malabsorption after subtotal ileum resection.

SummaryCongenital hypothyroidism requires prompt treatment to prevent adverse health outcomes. Poor intestinal levothyroxine absorption can complicate management. We present a case of a term female newborn with necrotizing enterocolitis (NEC) requiring subtotal ileum resection. Congenital hypothyroidism was diagnosed by newborn screening. Treatment was complicated by intestinal malabsorption of levothyroxine. Intravenous levothyroxine substitution restored euthyroidism and supraphysiologic PO doses subsequently maintained a euthyroid state. After several months, the required levothyroxine dose was weaned down to typical recommended dosing. In conclusion, small bowel resection secondary to NEC may lead to malabsorption of oral levothyroxine. An intravenous levothyroxine dose of approximately 50% typical PO dosing is effective in providing rapid normalization of free T4 and TSH. High PO doses may be required to maintain euthyroidism. Close thyroid function monitoring and immediate therapy adjustment are essential as the individual absorption may vary widely. Normal absorption levels may be regained due to adaption of the neonatal intestines.Learning points:In neonates with malabsorption after ileum resection intravenous levothyroxine replacement should be used to provide normalization of free T4 and TSH.Very high doses of up to 500% usual oral levothyroxine may be required to maintain euthyroidism. The estimated degree of malabsorption can be used to determine the initial dose.Close thyroid function monitoring and immediate therapy adjustment are essential as the absorption and intestinal adaption may vary widely.

Levothyroxine Absorption Test in the management of a patient with persistent hypothyroidism

Hypothyroidism refers to the common pathological condition of thyroid hormone deficiency. If untreated, it can lead to serious adverse health effects and ultimately death1 . Synthetic thyroxine has been used to treat hypothyroidism successfully since 19272 . The optimal daily dose of 1.6- 1.8 ug/body weight (kg) per day of levothyroxine (LT4) is an appropriate replacement dose1–3. The absorption of oral LT4 occurs mostly in the jejunum and ileum (60–80% of the ingested dose)3–6. It is maximal when the stomach is empty and takes place within the first 3 hours of ingestion2 . For patients who require larger doses of LT4 than expected, the underlying cause can be challenging to determine2 . Several factors must be considered: low patient compliance, reduced LT4 absorption from interfering dietary factors and medications, or gastrointestinal disorders contributing to malabsorption7 . The most common cause of mal-absorption is poor or non-compliance with oral LT4 treatment by the patient8 . Compliance with treatment is the key to good outcomes in medical care.Medical non-compliance is a major public health problem that imposes a considerable financial burden upon modern healthcare systems and is also a source of ongoing frustration to doctors9 . The concept of pseudo-malabsorption of thyroid hormones was first outlined in 1991 when it was described a factitious disorder due to patient non-compliance with the intention to deceive10. An effective way to distinguish nonadherence from mal-absorption is to perform levothyroxine absorption testing (LAT)5 . This article aims describe the LT4 absorption rapid test in a patient with hypothyroidism, highlighting its importance in the diagnosis of LT4 pseudo-malabsorption.

Is Parenteral Levothyroxine Therapy Safe in Intractable Hypothyroidism?

CaseA 32-year old woman was admitted to the hospital due to intractable hypothyroidism refractory to high dose of oral l-thyroxine therapy. She underwent total thyroidectomy and radioactive iodine therapy due to papillary thyroid cancer. After excluding poor adherence to therapy and malabsorption, levothyroxine absorption test was performed. No response was detected. Transient neurologic symptoms developed during the test. She developed 3 attacks consisting of neurologic symptoms during high dose administration. The patient was considered a case of isolated l-thyroxine malabsorption. She became euthyroid after intramuscular twice weekly l-thyroxine therapy. DiscussionThere are a few case reports regarding isolated l-thyroxine. We report successful long term results of twice weekly administered intramuscular l-thyroxine therapy. We also draw attention to neurologic side effects of high dose l-thyroxine therapy.

Coffee and autoimmunity: More than a mere hot beverage!

Coffee is one of the world's most consumed beverage. In the last decades, coffee consumption has attracted a huge body of research due to its impact on health. Recent scientific evidences showed that coffee intake could be associated with decreased mortality from cardiovascular and neurological diseases, diabetes type II, as well as from endometrial and liver cancer, among others. In this review, on the basis of available data in the literature, we aimed to investigate the association between coffee intake and its influence on the immune system and the insurgence of the most relevant autoimmune diseases. While some studies reported conflicting results, general trends have been identified. Coffee consumption seems to increase the risk of developing rheumatoid arthritis (RA) and type 1 diabetes mellitus (T1DM). By contrast, coffee consumption may exert a protective role against multiple sclerosis, primary sclerosing cholangitis, and ulcerative colitis. Concerning other autoimmune diseases such as systemic lupus erythematosus, psoriasis, primary biliary cholangitis and Crohn's disease, no significant association was found. In other studies, coffee consumption was shown to influence disease course and management options. Coffee intake led to a decrease in insulin sensitivity in T1DM, in methotrexate efficacy in RA, and in levothyroxine absorption in Hashimoto's disease. Further, coffee consumption was associated with cross reactivity with gliadin antibodies in celiac patients. Data on certain autoimmune diseases like systemic sclerosis, Sjögren's syndrome, and Behçet's disease, among others, are lacking in the existent literature. As such, further research is warranted.

Levothyroxine absorption test in the management of a patient with persistent hypothyroidism

Levothyroxine absorption test in the management of a patient with persistent hypothyroidism

What is the Clinical Role of Oral Liquid Preparations in the Treatment of Patients With Hypothyroidism?

Fallahi et al ( 1. Fallahi P. Ferrari S.M. Antonelli A. In patients with subclinical hypothyroidism while in therapy with tablet LT4, the liquid LT4 formulation is more effective in restoring euthyroidism. Endocr Pract. 2017; 23: 170-174 Abstract Full Text Full Text PDF PubMed Scopus (22) Google Scholar ) have performed an interesting observational, prospective study assessing the ability of comparable levothyroxine doses of tablet and liquid preparations in lowering serum thyroid-stimulating hormone (TSH) concentration in patients with subclinical hypothyroidism who are not ingesting potentially interfering medications and do not have gastrointestinal disorders that might potentially interfere with levothyroxine absorption. The authors ( 1. Fallahi P. Ferrari S.M. Antonelli A. In patients with subclinical hypothyroidism while in therapy with tablet LT4, the liquid LT4 formulation is more effective in restoring euthyroidism. Endocr Pract. 2017; 23: 170-174 Abstract Full Text Full Text PDF PubMed Scopus (22) Google Scholar ) studied hypothyroid individuals who were taking stable levothyroxine doses and had serum TSH concentrations ≤3 μU/mL on at least two separate determinations within 2 years prior to the study or serum TSH level at least 4 μU/mL or higher (assessed within 1 month prior to the study) in conjunction with normal serum free thyroxine (FT4) and free triiodothyronine (FT3) on two different occasions. They ( 1. Fallahi P. Ferrari S.M. Antonelli A. In patients with subclinical hypothyroidism while in therapy with tablet LT4, the liquid LT4 formulation is more effective in restoring euthyroidism. Endocr Pract. 2017; 23: 170-174 Abstract Full Text Full Text PDF PubMed Scopus (22) Google Scholar ) appropriately excluded patients who had Helicobacter pylori or atrophic gastritis, previous gastric or intestinal surgery, or bariatric surgery. Fallahi et al ( 1. Fallahi P. Ferrari S.M. Antonelli A. In patients with subclinical hypothyroidism while in therapy with tablet LT4, the liquid LT4 formulation is more effective in restoring euthyroidism. Endocr Pract. 2017; 23: 170-174 Abstract Full Text Full Text PDF PubMed Scopus (22) Google Scholar ) did an excellent job of examining and detailing the inclusion and exclusion criteria, even investigating unexplained anemia or dyspepsia and also performed serum antibody measurements to help exclude undiagnosed celiac disease and measured H. pylori antigen in feces. Patients taking medications that are known to interfere with levothyroxine absorption were also excluded.