Levothyroxine Users Research Articles

Levothyroxine use and longitudinal changes in thigh muscles in at-risk participants for knee osteoarthritis: preliminary analysis from Osteoarthritis Initiative cohort

BackgroundWe examined the association between levothyroxine use and longitudinal MRI biomarkers for thigh muscle mass and composition in at-risk participants for knee osteoarthritis (KOA) and their mediatory role in subsequent KOA incidence.MethodsUsing the Osteoarthritis Initiative (OAI) data, we included the thighs and corresponding knees of participants at risk but without established radiographic KOA (baseline Kellgren-Lawrence grade (KL) < 2). Levothyroxine users were defined as self-reported use at all annual follow-up visits until the 4th year and were matched with levothyroxine non-users for potential confounders (KOA risk factors, comorbidities, and relevant medications covariates) using 1:2/3 propensity score (PS) matching. Using a previously developed and validated deep learning method for thigh segmentation, we assessed the association between levothyroxine use and 4-year longitudinal changes in muscle mass, including cross-sectional area (CSA) and muscle composition biomarkers including intra-MAT (within-muscle fat), contractile percentage (non-fat muscle CSA/total muscle CSA), and specific force (force per CSA). We further assessed whether levothyroxine use is associated with an 8-year risk of standard KOA radiographic (KL ≥ 2) and symptomatic incidence (incidence of radiographic KOA and pain on most of the days in the past 12 months). Finally, using a mediation analysis, we assessed whether the association between levothyroxine use and KOA incidence is mediated via muscle changes.ResultsWe included 1043 matched thighs/knees (266:777 levothyroxine users:non-users; average ± SD age: 61 ± 9 years, female/male: 4). Levothyroxine use was associated with decreased quadriceps CSAs (mean difference, 95%CI: − 16.06 mm2/year, − 26.70 to − 5.41) but not thigh muscles’ composition (e.g., intra-MAT). Levothyroxine use was also associated with an increased 8-year risk of radiographic (hazard ratio (HR), 95%CI: 1.78, 1.15–2.75) and symptomatic KOA incidence (HR, 95%CI: 1.93, 1.19–3.13). Mediation analysis showed that a decrease in quadriceps mass (i.e., CSA) partially mediated the increased risk of KOA incidence associated with levothyroxine use.ConclusionsOur exploratory analyses suggest that levothyroxine use may be associated with loss of quadriceps muscle mass, which may also partially mediate the increased risk of subsequent KOA incidence. Study interpretation should consider underlying thyroid function as a potential confounder or effect modifier. Therefore, future studies are warranted to investigate the underlying thyroid function biomarkers for longitudinal changes in the thigh muscles.

Association of maternal levothyroxine use during pregnancy with offspring birth and neurodevelopmental outcomes: a population-based cohort study

BackgroundThe influence of maternal levothyroxine treatment during pregnancy remains unclear. This study aimed to evaluate the associations of maternal levothyroxine treatment during pregnancy with the birth and neurodevelopmental outcomes in offspring.MethodsThis population-based cohort study was conducted among pregnant women using the Hong Kong Clinical Data Analysis and Reporting System. Mother-child pairs in Hong Kong from 2001 to 2015 were included and children were followed up till 2020. We defined the exposure group as mothers who were exposed to levothyroxine during pregnancy. Preterm birth and small for gestational age (SGA) were included as birth outcomes. Attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) were included as neurodevelopmental outcomes. Odds ratios (OR) or hazard ratios (HRs) with a 95% confidence interval (CI) were evaluated to assess the association of gestational levothyroxine use with offspring birth and neurodevelopmental outcomes respectively, using propensity score fine-stratification weighting and a Cox proportional hazards regression model.ResultsAmong 422,156 mother-child pairs, 2125 children were born from mothers exposed to levothyroxine during pregnancy. A significantly increased risk of preterm birth was observed in children with maternal levothyroxine exposure during pregnancy, when compared to mothers who had no history of thyroid-related diagnoses or prescriptions (weighted OR [wOR]: 1.22, 95% CI: 1.07, 1.39). Similarly, an increased risk of preterm birth was found among children of gestational levothyroxine users, when compared to children of mothers who had used levothyroxine before but stopped during pregnancy (wOR: 2.16, 95% CI: 1.09, 4.25). Sensitivity analysis, by excluding mothers exposed to psychotropic or antiepileptic medications before or during pregnancy, also indicated a similar increased risk of preterm birth regarding the gestational use of levothyroxine (wOR: 1.26, 95% CI: 1.10, 1.45). No significant association was observed for the risk of SGA, ADHD, and ASD.ConclusionsThere is no evidence that gestational use of levothyroxine is associated with SGA, ADHD, or ASD in offspring. Gestational levothyroxine treatment is associated with a higher risk of preterm birth. Such risk might be confounded by the underlying maternal thyroid disease itself, however, we cannot completely exclude the possible effect of gestational L-T4 treatment on offspring preterm birth. Our findings provided support to the current guidelines on the cautious use of levothyroxine treatment during pregnancy.

ODP514 Safety of Inactivated and mRNA COVID-19 Vaccination among Patients Treated for Hypothyroidism: a Population-based Cohort Study

Abstract Background Thyroiditis and Graves’ disease have been reported after COVID-19 vaccination. Patients with hypothyroidism due to various etiologies may be at risk of thyroid-specific outcomes. We aimed to evaluate the risks of thyroid-specific outcomes and adverse events after COVID-19 vaccination among patients treated for hypothyroidism. Methods In this population-based cohort from Hong Kong Hospital Authority electronic health records with Department of Health vaccination records linkage, levothyroxine users were categorized into unvaccinated, vaccinated with BNT162b2 (mRNA vaccine) or CoronaVac (inactivated vaccine) between 23 February and 9 September 2021. Propensity score (PS) weighting with inverse probability of treatment weighting (IPTW) was applied to balance the baseline characteristics among the three groups, which included age, sex, history of COVID-19, health care utilization, comorbidities, baseline thyroid-stimulating hormone (TSH) level (within the 6 months before the index date), and recent use of medications including anti-hypertensive, anti-diabetic and lipid-lowering agents. Study outcomes were dosage reduction or escalation in levothyroxine, emergency department visit, unscheduled hospitalization, adverse events of special interest (AESI) according to World Health Organization's Global Advisory Committee on Vaccine Safety, and all-cause mortality. Results In total, 47,086 levothyroxine users were identified (BNT162b2: n=12,310; CoronaVac: n=11,353; unvaccinated: n=23,423). After PS weighting, all baseline characteristics had standardised differences of less than 0.2, implying a balance of covariates among the three groups. COVID-19 vaccination was not associated with increased risks of levothyroxine dosage reduction (BNT162b2: HR=0.971, 95% CI 0.892–1. 058; CoronaVac: HR=0.968, 95% CI 0.904–1. 037) or escalation (BNT162b2: HR=0.779, 95% CI 0.519–1.169; CoronaVac: HR=0.715, 95% CI 0.481–1. 062). Besides, COVID-19 vaccination was not associated with a higher risk of emergency department visits (BNT162b2: HR=0.944, 95% CI 0.700-1.273; CoronaVac: HR=0.851, 95% CI 0.647-1.120) or unscheduled hospitalization (BNT162b2: HR=0.905, 95% CI 0.539-1.520; CoronaVac: HR=0.735, 95% CI 0.448-1.207). There were two (0. 016%) deaths and six (0. 062%) AESI recorded for BNT162b2 recipients, and one (0. 009%) and three (0. 035%) for CoronaVac recipients, respectively. Sensitivity analyses were performed by stratifying the groups according to age, sex and pre-vaccination thyroid status. The results were largely consistent with the main analysis. Conclusion BNT162b2 or CoronaVac vaccination is not associated with unstable thyroid status or an increased risk of adverse outcomes among patients treated for hypothyroidism. These reassuring data should encourage them to get vaccinated against COVID-19 for protection from potentially worse COVID-19-related outcomes. Presentation: No date and time listed

Safety of Inactivated and mRNA COVID-19 Vaccination Among Patients Treated for Hypothyroidism: A Population-Based Cohort Study.

Background: Thyroiditis and Graves' disease have been reported after coronavirus disease 2019 (COVID-19) vaccination. We evaluated the risks of adverse events after COVID-19 vaccination among patients treated for hypothyroidism. Methods: In this retrospective population-based cohort study of Hong Kong Hospital Authority electronic health records with the Department of Health vaccination records linkage, levothyroxine (LT4) users were categorized into unvaccinated, vaccinated with BNT162b2 (mRNA vaccine), or CoronaVac (inactivated vaccine) between February 23, 2021, and September 9, 2021. Study outcomes were dosage reduction or escalation in LT4, emergency department (ED) visit, unscheduled hospitalization, adverse events of special interest (AESI) according to the World Health Organization's Global Advisory Committee on Vaccine Safety, and all-cause mortality. Inverse probability of treatment weighting for propensity score was applied to balance baseline patient characteristics among the three groups. Hazard ratios (HR) were estimated using Cox regression models. Patients were observed from the index date until the occurrence of study outcome, death, or censored on September 30, 2021, whichever came first. Results: In total, 47,086 LT4 users were identified (BNT162b2: n = 12,310; CoronaVac: n = 11,353; and unvaccinated: n = 23,423). COVID-19 vaccination was not associated with increased risks of LT4 dosage reduction (BNT162b2: HR = 0.971 [confidence interval; CI 0.892-1.058]; CoronaVac: HR = 0.968 [CI 0.904-1.037]) or escalation (BNT162b2: HR = 0.779 [CI 0.519-1.169]; CoronaVac: HR = 0.715 [CI 0.481-1.062]). Besides, COVID-19 vaccination was not associated with a higher risk of ED visits (BNT162b2: HR = 0.944 [CI 0.700-1.273]; CoronaVac: HR = 0.851 [CI 0.647-1.120]) or unscheduled hospitalization (BNT162b2: HR = 0.905 [CI 0.539-1.520]; CoronaVac: HR = 0.735 [CI 0.448-1.207]). There were two (0.016%) deaths and six (0.062%) AESI recorded for BNT162b2 recipients, and one (0.009%) and three (0.035%) for CoronaVac recipients, respectively. Conclusions: BNT162b2 or CoronaVac vaccination is not associated with unstable thyroid status or an increased risk of adverse outcomes among patients treated for hypothyroidism in general. These reassuring data should encourage them to get vaccinated against COVID-19 for protection from potentially worse COVID-19-related outcomes.

Quantitative Ultrasound of Phalanx in Primary and Secondary Osteoporosis: Mini-review and Practical Experience

Objective: Dual x-ray absorptiometry (DXA) is gold standard of bone densitometry, but quantitative ultrasound (QUS) of bone is less expensive and portable. This study was designed to assess its usefulness in secondary osteoporosis diagnosis. Materials and Methods: There were 200 secondary osteoporosis cases (rheumatoid arthritis, hemodialysis, kidney transplant patients, and levothyroxine users) and of those, their phalanx QUS results were compared with normal controls. Also, the QUS and DXA results were compared to find any correlation of these methods for diagnosing osteoporosis. Results: There was not significantly different results compared with normal controls, except for those of hemodialysis patients ( P = .00). Also, the comparison of QUS with DXA results showed no significant correlation except in hemodialysis patients, in both spinal and femoral regions ( P = .023 and .21, respectively), as well as the levothyroxine group’s spinal region ( P = .005). Conclusion: These results suggest that QUS of phalanx may be useful in screening secondary osteoporosis but for establishment of diagnosis, DXA measurements are still needed.

LEVOTHYROXINE USE MAY BE ASSOCIATED WITH LONGITUDINAL QUADRICEPS ATROPHY AND SUBSEQUENT KNEE OA RISK: PRELIMINARY ANALYSIS FROM OAI COHORT

Levothyroxine, the primary treatment for hypothyroidism, is prescribed for more than 7% of Americans. Levothyroxine use, or the underlying hypothyroidism can be associated with musculoskeletal symptoms; however, no prior work has investigated this association using sensitive biomarkers. We examined the association between levothyroxine use and longitudinal MRI biomarkers for thigh muscle mass and composition in participants at-risk of knee OA and their mediatory role in subsequent knee OA radiographic and symptomatic incidence. Thighs and knees of OAI participants without established radiographic knee OA were included. Levothyroxine users were defined as self-reported use at all annual follow-up visits until the 4th-year and were matched with nonusers for potential confounders using 1:2/3 propensity-score (PS) matching. We developed and validated a deep learning method for automated thigh segmentation and assessed the association between levothyroxine use and 4-year longitudinal changes in muscle mass, including cross-sectional area (CSA) and muscle composition biomarkers including intramuscular adipose tissue (intra-MAT), contractile percentage, and specific force (force per CSA). We further assessed whether levothyroxine use is associated with an 8-year risk of standard knee OA radiographic and symptomatic incidence. Finally, we assessed whether the association between levothyroxine use and knee OA incidence is mediated via muscle changes. We included 1485 matched thighs/knees (387:1098 users:non-users; age: 62±9 years, female/male:3.1). Levothyroxine use was associated with decreased quadriceps CSAs (mean difference, 95%CI:-15.46mm2/year, -25.11– -5.82) but not thigh muscles’ composition biomarkers. Levothyroxine use was also associated with an increased 8-year risk of radiographic (hazard ratio (HR):1.59, 1.15–2.20) and symptomatic knee OA incidence (HR:1.60, 1.12–2.29). A decrease in quadriceps CSA partially mediated the increased risk of knee OA incidence associated with levothyroxine use. Our exploratory analyses suggest that levothyroxine users might have increased risk of thigh muscle atrophy and subsequent knee OA. Study interpretation should consider underlying thyroid function as a potential confounder or effect modifier and therefore, future studies are warranted to investigate the underlying thyroid function biomarkers for longitudinal thigh muscles atrophy and associated knee OA incidence risk. NIH National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) under Award Number R01AR079620-01. AG reported receiving funding from Merck Serono, AstraZeneca, Galapagos, Pfizer, Roche, TissueGene (for consultation), and Boston Imaging Core Lab (as the president and stockholder). SD reported that he received funding from Toshiba Medical Systems (for consultation) and grants from GERRAF and Carestream Health (for a clinical trial study). Authors acknowledge OAI staff and team. CORRESPONDENCE ADDRESS: sdemehri1@jhmi.edu .

Prevalence and factors associated with chronic use of levothyroxine: A cohort study

Levothyroxine prescriptions are rising worldwide. However, there are few data on factors associated with chronic use. To assess the prevalence of chronic levothyroxine use, its rank among other chronic drugs and factors associated with chronic use. To assess the proportion of users outside the therapeutic range of thyroid-stimulating hormone (TSH). Cohort study (CoLaus|PsyCoLaus) with recruitment from 2003 to 2006. Follow-ups occurred 5 and 10 years after baseline. A random sample of Lausanne (Switzerland) inhabitants aged 35-75 years. We evaluated the prevalence of chronic levothyroxine use and we then ranked it among the other most used chronic drugs. The ranking was compared to data from health insurance across the country. We assessed the association between each factor and chronic levothyroxine use in multivariable logistic regression models. The proportion of chronic levothyroxine users outside the usual TSH therapeutic range was assessed. 4,334 participants were included in the analysis (mean±SD age 62.8±10.4 years, 54.9% women). 166 (3.8%) participants were chronic levothyroxine users. Levothyroxine was the second most prescribed chronic drug after aspirin in the cohort (8.2%) and the third most prescribed when using Swiss-wide insurance data. In multivariable analysis, chronic levothyroxine use was associated with increasing age [odds ratio 1.03, 95% confidence interval 1.01-1.05 per 1-year increase]; female sex [11.87 (5.24-26.89)]; BMI [1.06 (1.02-1.09) per 1-kg/m2 increase]; number of concomitant drugs [1.22 (1.16-1.29) per 1-drug increase]; and family history of thyroid pathologies [2.18 (1.37-3.48)]. Among chronic levothyroxine users with thyroid hormones assessment (n = 157), 42 (27%) were outside the TSH therapeutic range (17% overtreated and 10% undertreated). In this population-based study, levothyroxine ranked second among chronic drugs. Age, female sex, BMI, number of drugs and family history of thyroid pathologies were associated with chronic levothyroxine use. More than one in four chronic users were over- or undertreated.

Levothyroxine use and the risk of colorectal cancer: a large population-based case-control study.

ObjectiveWhether an association between oral levothyroxine use, leading to supraphysiological exposure of the colon to thyroid hormones, and risk of colorectal cancer exists in humans is unclear. We therefore aimed to assess whether the use of levothyroxine is associated with a reduced risk of colorectal cancer in a linked cohort of pharmacy and cancer data.DesignPopulation-based matched case–control study.MethodsA total of 28,121 patients diagnosed with colorectal cancer between 1998 and 2014 were matched to 106,086 controls. Multivariable logistic regression was used to estimate the association between levothyroxine use and occurrence of colorectal cancer, adjusted for potential confounders. Results were stratified by gender, age, tumour subtype, and staging, as well as treatment duration and dosing.ResultsA total of 1066 colorectal cancer patients (4%) and 4024 (4%) controls had used levothyroxine at any point before index date (adjusted odds ratio 0.95 (0.88–1.01)). Long-term use of levothyroxine was seen in 323 (30%) colorectal cancer patients and 1111 (28%) controls (adjusted odds ratio 1.00 (0.88–1.13)). Stratification by tumour subsite showed a borderline significant risk reduction of rectal cancer, while this was not seen for proximal colon cancer or distal colon cancer. There was no relationship with treatment duration or with levothyroxine dose.ConclusionsIn this study, no reduced risk of colorectal cancer was seen in levothyroxine users. When stratifying by tumour subsite, a borderline significant risk reduction of rectal cancer was found and may warrant further research.

Risk of cancer in long-term levothyroxine users: Retrospective population-based study.

Levothyroxine is a widely prescribed medication for the treatment of an underactive thyroid. The relationship between levothyroxine use and cancer risk is largely underdetermined. To investigate the magnitude of the possible association between levothyroxine use and cancer risk, this retrospective case‐control study was conducted using Taiwan’s Health and Welfare Data Science Center database. Cases were defined as all patients who were aged ≥20 years and had a first‐time diagnosis for cancer at any site for the period between 2001 and 2011. Multivariable conditional logistic regression models were used to calculate an adjusted odds ratio (AOR) to reduce potential confounding factors. A total of 601 733 cases and 2 406 932 controls were included in the current study. Levothyroxine users showed a 50% higher risk of cancer at any site (AOR: 1.50, 95% CI: 1.46‐1.54; P < .0001) compared with non–users. Significant increased risks were also observed for brain cancer (AOR: 1.90, 95% CI: 1.48‐2.44; P < .0001), skin cancer (AOR: 1.42, 95% CI: 1.17‐1.72; P < .0001), pancreatic cancer (AOR: 1.27, 95% CI: 1.01‐1.60; P = .03), and female breast cancer (AOR: 1.24, 95% CI: 1.15‐1.33; P < .0001). Our study results showed that levothyroxine use was significantly associated with an increased risk of cancer, particularly brain, skin, pancreatic, and female breast cancers. Levothyroxine remains a highly effective therapy for hypothyroidism; therefore, physicians should carefully consider levothyroxine therapy and monitor patients’ condition to avoid negative outcomes. Additional studies are needed to confirm these findings and to evaluate the potential biological mechanisms.

Epidemiology of thyroid disorders in the Lifelines Cohort Study (the Netherlands).

Thyroid hormone plays a pivotal role in human metabolism. In epidemiologic studies, adequate registration of thyroid disorders is warranted. We examined the prevalence of thyroid disorders, reported thyroid medication use, thyroid hormone levels, and validity of thyroid data obtained from questionnaires in the Lifelines Cohort Study. We evaluated baseline data of all 152180 subjects (aged 18-93 years) of the Lifelines Cohort Study. At baseline, participants were asked about previous thyroid surgery and current and previous thyroid hormone use. At follow-up (n = 136776, after median 43 months), incident thyroid disorders could be reported in an open, non-structured question. Data on baseline thyroid hormone measurements (TSH, FT4 and FT3) were available in a subset of 39935 participants. Of the 152180 participants, mean (±SD) age was 44.6±13.1 years and 58.5% were female. Thyroid medication was used by 4790 participants (3.1%); the majority (98.2%) used levothyroxine, and 88% were females. 59.3% of levothyroxine users had normal TSH levels. The prevalence of abnormal TSH levels in those not using thyroid medication was 10.8%; 9.4% had a mildly elevated (4.01-10.0 mIU/L), 0.7% had suppressed (<0.40 mIU/L), while 0.7% had elevated (>10.0 mIU/L) TSH levels. Over 98% of subjects with TSH between 4 and 10 mIU/L had normal FT4. Open text questions allowing to report previous thyroid surgery and incident thyroid disorders proved not to be reliable and severely underestimated the true incidence and prevalence of thyroid disorders. Undetected thyroid disorders were prevalent in the general population, whereas the prevalence of thyroid medication use was 3.1%. Less than 60% of individuals using levothyroxine had a normal TSH level. The large group of individuals with subclinical hypothyroidism (9.4%) offers an excellent possibility to prospectively follow the natural course of this disorder. Both structured questions as well as linking to G.P.'s and pharmacists' data are necessary to improve the completeness and reliability of Lifelines' data on thyroid disorders.

Hypothyroidism and the increased risk of preeclampsia – interpretative factors?

ABSTRACT Objective To evaluate the causes behind the association between hypothyroidism and the risk of preeclampsia. Methods Checking of individual hospital and birth records from 149 levothyroxine users among 2,508 women in the preeclampsia case–control study (2002-2016). Results There were significant association between levothyroxine medication and preeclampsia (OR 1.48, 95th CI 1.06–2.07; p ≤ 0.022). The presence of comorbid diseases was associated with a significantly higher risk for the development of preeclampsia in women using levothyroxine. Conclusion Levothyroxine use during pregnancy was associated with 1.5-times higher risk for preeclampsia, but it is also linked to the other comorbid risk factors.

First-trimester placental function in levothyroxine-using pregnant women: a case-control study

We aimed to compare the pregnancy-associated plasma protein-A (PAPP-A) and the uterine artery pulsatility index (UtA PI) levels of euthyroid pregnant women using levothyroxine vs. a control group of uncomplicated pregnancies and to evaluate the effects of different levothyroxine dosages on pregnancy outcomes. We retrospectively evaluated 206 levothyroxine-using pregnant women by looking at their basic placental function markers and obstetric outcomes. A sample of 449 women whose pregnancies concluded with uncomplicated term deliveries composed of our control group. To examine the relationship between the levothyroxine dosages and the frequency of pregnancy complications, levothyroxine users were divided into different groups according to the 75, 100, and 150 mcg cutoffs. The median PAPP-A MoM levels of levothyroxine users were significantly lower at 0.94 vs. 1.11 (p < .001) and the median mean UtA PI was significantly higher than the control group at 2.08 vs. 1.74 (p < .0001). The median birth weight was significantly lower for the levothyroxine users’ group at 3292 g vs. 3427 g (p < .0001). Using 75, 100, and 150 mcg dose cutoffs, PAPP-A MoM, mean UtA PI and obstetric complication frequencies were not significantly different among levothyroxine users. Significant changes in placental function markers have been observed in euthyroid levothyroxine-using pregnant women during the first trimester. However, the frequency of obstetric complications does not appear to be dose dependent.

Levothyroxine Replacement in Obese Adults: The Role of Metabolic Variables and Aging on Thyroid Testing Abnormalities.

General rates of over- and underreplacement in levothyroxine (LT4) users with primary hypothyroidism are variably high. No information on LT4 adequacy exists in obesity. We explored rates and factors relating to LT4 adequacy in obese patients with primary hypothyroidism. Tertiary care center. Among 4954 consecutive obese patients admitted between 2011 and 2014, 691 hypothyroid patients receiving LT4 therapy and 691 body mass index (BMI)-, age-, and sex-matched euthyroid controls underwent analysis of thyroid function, glucolipid profile, body composition, and indirect calorimetry. LT4 users were classified into low TSH (<0.27 mU/L), euthyroid (0.27 to 4.2 mU/L), and high TSH (>4.2 mU/L). LT4 users constituted 13.9% of the incident population. TSH was low in 7.5%, high in 17.2%, and normal in 75.2% of LT4 users. Overtreatment decreased with aging and more LT4 users ≥65 years of age had normal TSH than those <65 years of age (P < 0.05). Compared with the euthyroid obese group, LT4 users showed higher adiposity, similar insulin resistance, but a healthier lipid profile. In multivariable analyses, LT4 dose was predicted by fat-free mass, hypothyroidism cause, and sex (P < 0.0001 to < 0.05). Risk of LT4 overreplacement increased with younger age (OR 0.96; 95% CI 0.94 to 0.99), higher LT4 dose (OR 2.98; 95% CI 1.44 to 6.14), and lower BMI (OR 0.93; 95% CI 0.88 to 0.99). Male sex increased the likelihood of LT4 underreplacement (OR 2.37; 95% CI 1.10 to 5.11). Obesity is associated with milder rates of inadequate LT4 treatment compared with nonobese populations. LT4 adequacy increases with aging. Age, body composition, and sex are main determinants of LT4 requirements in obesity.

Treatment pattern and frequency of serum TSH measurement in users of different levothyroxine formulations: a population-based study during the years 2009-2015.

Several conditions can modify the intestinal absorption of levothyroxine tablets, with potential consequences on their therapeutic effect. Pre-dosed ampoules and oral drops have been recently made available to overcome this limitation. To describe the pattern of use of different formulations of levothyroxine in a general population of Southern Italy and to perform an exploratory analysis investigating the effect of switching from levothyroxine tablets to oral liquid formulations. Data were extracted from the Caserta Local Health Unit database. All patients receiving at least one levothyroxine prescription during the years 2009-2015 were identified. 1-year incidence of use of formulation-specific levothyroxine was calculated. Switchers between levothyroxine tablets and oral liquid formulations were identified and the frequency of thyroid-stimulating hormone measurement within 2 years prior and after the switch date was explored. Overall, 56,354 levothyroxine users were included in the study. Of these, 55,147 patients received at least one prescription for tablets (97.9%), 1867 pre-dosed ampoules (3.3%) and 1550 oral drops (2.8%). The proportion of levothyroxine users receiving oral liquid formulations slightly increased over time. Patients switching from tablets to oral liquid formulations showed a statistically significant reduction in the number of thyroid-stimulating hormone measurements after switching from tablets, especially in presence of drugs interacting with levothyroxine potentially altering its absorption. Use of levothyroxine oral liquid formulations is increasing over time even though their use is still limited in a general population of Southern Italy. Our exploratory analysis showed that the frequency of thyroid-stimulating hormone measurement was reduced in patients switching from levothyroxine tablet to new formulations.

Levothyroxine Use Is Associated with Poor Health-Related Quality of Life (HR-QoL), but HR-QoL and Executive Function Do Not Differ by D2-Thr92Ala Allele Polymorphism Status Among Levothyroxine Users or the General Population

Clinical ThyroidologyVol. 28, No. 12 SummariesLevothyroxine Use Is Associated with Poor Health-Related Quality of Life (HR-QoL), but HR-QoL and Executive Function Do Not Differ by D2-Thr92Ala Allele Polymorphism Status Among Levothyroxine Users or the General PopulationElizabeth N. PearceElizabeth N. PearceSearch for more papers by this authorPublished Online:1 Dec 2016https://doi.org/10.1089/ct.2016;28.376-378AboutSectionsView articleView Full TextPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail View articleFiguresReferencesRelatedDetails Volume 28Issue 12Dec 2016 InformationCopyright 2016 American Thyroid Association, Inc.To cite this article:Elizabeth N. Pearce.Levothyroxine Use Is Associated with Poor Health-Related Quality of Life (HR-QoL), but HR-QoL and Executive Function Do Not Differ by D2-Thr92Ala Allele Polymorphism Status Among Levothyroxine Users or the General Population.Clinical Thyroidology.Dec 2016.376-378.http://doi.org/10.1089/ct.2016;28.376-378Published in Volume: 28 Issue 12: December 1, 2016PDF download

Drug interactions with levothyroxine therapy in patients with hypothyroidism: observational study in general practice.

Several drugs may interact with levothyroxine and reduce its bioavailability. The aim of this study was to analyse the Italian general practice patients with hypothyroidism from 2002-2011, in terms of variation of thyroid-stimulating hormone (TSH) levels, number of levothyroxine prescriptions and dose of levothyroxine before and during potential drug-drug interactions (DDIs). Data were extracted from the Italian general practice Health Search CSD Longitudinal Patient Database (HSD). Analysis was limited to individuals aged 18 years and older with at least one levothyroxine prescription from 2002 to 2011 and at least one year of clinical history recorded in HSD. A quasi-experimental pre-post analysis was carried out using a self-controlled study design, on an intention-to-treat basis. Overall, 5,426 levothyroxine users (7.5 % of population in HSD) were included in the study. The incidence rate ratio comparing the TSH trend before and during the period of exposure to potential DDI showed a significant increase of TSH levels during initial exposure to potential DDI, which decreased over time. The number of prescriptions and dose of levothyroxine decreased before the potential DDI and increased symmetrically during the period of exposure to potential DDI. The co-prescription of levothyroxine and potentially interacting drugs results in an increased use of levothyroxine. Clinicians should carefully consider adjusting levothyroxine therapy in presence of concomitant drugs, such as proton-pump inhibitors, which may reduce levothyroxine bioavailability.

Thyroid hormone replacement: current status and challenges

Introduction:Correction of hypothyroidism with synthetic levothyroxine is simple, effective and safe. In most cases levothyroxine restores well-being and normalizes serum thyrotropin (TSH) concentrations. However, up to 30 – 50% of levothyroxine users do not achieve adequate biochemical euthyroidism. Also, a small proportion of hypothyroid individuals remain dissatisfied with treatment even with normal TSH concentrations.Areas covered:This review addresses strategies for achieving optimal thyroid hormone replacement based on a systematic search of the literature for controlled trials, cohort studies or systematic reviews published on the topic since 1960.Expert opinion:Careful attention to factors that affect levothyroxine availability such as medication adherence, drug interactions and co-morbidities should improve the adequacy of therapy, but these factors are challenging to manage in practice. The case for combined therapy with levothyroxine and triiodothyronine (T3) is compelling but is not supported by current evidence from randomized controlled trials. Recent studies of common genetic variations in deiodinase and thyroid hormone transport proteins offer fresh insights in understanding the variable response to thyroid hormone therapy and future research may clarify whether subsets of patients will benefit from combined therapy. Despite significant challenges, opportunities abound for improving therapeutic outcomes.

Levothyroxine dose and risk of fractures in older adults: nested case-control study

Objective To quantify the effect of levothyroxine dose on risk of fractures in older adults.Design Nested case-control study.Setting Population based health databases, Ontario, Canada.Participants Adults aged 70 or more prescribed...

Adequacy of thyroid hormone replacement in a general population

Suboptimal thyroid hormone replacement may carry harmful health consequences. Our objectives were to determine the prevalence and factors associated with inadequate replacement in patients receiving treatment with levothyroxine. Retrospective general practice audit. We identified levothyroxine users through electronic searches of primary care records in all 11 practices within a county borough. The adequacy of thyroid hormone replacement was determined from the current serum, serum thyrotropin (TSH) as: (i) adequate replacement (normal TSH; 0.4-4.0 mU/l); (ii) over replacement (low TSH; <0.4 mU/l); and (iii) under replacement (high TSH; >4.0 mU/l). Out of a registered patient population of 58 567, we identified 1037 patients who were first included in the hypothyroidism disease register between January 2004 and December 2009 (mean age 62.4 ± 15.9 years; female 85.9%, male 14.1%). Inadequate replacement was seen in 385 patients (37.2%), comprising 205 patients (19.8%) with over replacement and 180 patients (17.4%) with under replacement. Step-wise logistic regression showed that the factors associated with under replacement were male gender [odds ratio (OR) 2.85, confidence interval (CI) 1.86-4.38; P < 0.001 and younger age (OR 0.88, CI 0.80-0.98; P = 0.02 per 10 year increase in age) while longer duration of treatment was associated with over-treatment (OR 1.06, CI 1.01-1.10). A thyroid function test was performed in the preceding 12 months in 914 patients (88.1%) and appropriate dose adjustments had been made in 81.0% (312/385) of patients with abnormal results. Despite frequent monitoring and dose adjustment activities, inadequate thyroid hormone replacement remained a problem in over a third of levothyroxine users in this population.

Prevalence of hypothyroidism in Finland—a nationwide prescription study

The aim of this study was to estimate the 1-year prevalence of levothyroxine-treated hypothyroidism in Finland. Data on all individuals who had regularly purchased levothyroxine sodium tablets during 2007 were retrieved from the nationwide Finnish Drug Prescription Database. The prevalence rates and 95% confidence intervals were calculated per 100 individuals assuming a Poisson distribution. In total, 189,027 individuals (84% female) were identified as using levothyroxine tablets, which translated into a 1-year prevalence of hypothyroidism of 3.6%. The disease was notably more common in females (5.9%) than in males (1.2%), with a gender prevalence rate ratio (PRR) of 4.5. Prevalence increased with age. A comparison of five university hospital districts revealed that the prevalence rates were fairly stable regionally, with the lowest rate being 3.1% and the highest 4.4%; the regional PRR was 1.3. To the best of our knowledge, this nationwide prescription study includes the largest population of reported levothyroxine users to date. This comprehensive data justifies estimating the gender- and age-specific prevalence of hypothyroidism in Finland.