A Review of the Pharmacokinetics of Levothyroxine for the Treatment of Hypothyroidism.
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SUBMITTER: Colucci P
PROVIDER: S-EPMC6193522 | biostudies-other | 2013 Mar
REPOSITORIES: biostudies-other
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A Review of the Pharmacokinetics of Levothyroxine for the Treatment of Hypothyroidism.
Colucci Philippe P Yue Corinne Seng CS Ducharme Murray M Benvenga Salvatore S
European endocrinology 20130315 1
Thyroxine hormone has been recognised since the early part of the nineteenth century and levothyroxine has been available since the mid-nineteenth century as a replacement for deficient thyroid hormones. While levothyroxine remains the staple treatment for hypothyroidism even to this day, its optimal use can be challenging. As is often the case with older drugs, the pharmacokinetics of levothyroxine is often under-appreciated or misunderstood and many factors influence the optimal dosing of levo ...[more]
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Project description:Subclinical hypothyroidism (SCH) is defined as elevated thyroid stimulating hormone (TSH) with normal levels of free triiodothyronine (FT3) and free thyroxine (FT4). SCH is further classified into a milder condition with TSH levels between 4.0 and 10.0 milli-international units (mIU)/l (mild-SCH) and a severe form with TSH >10.0 mIU/l (severe-SCH). SCH is a common problem (prevalence is greater in women than men), which increases further with increasing age and TSH levels. Even though the risk of progression to overt hypothyroidism is higher in patients with severe-SCH, the risk is also significant in patients having mild-SCH; it has been suggested that every twofold rise in serum TSH would increase the risk from 1 to 4%, which further increases to 38% if thyroid antibodies are positive. Current data have shown increased cardiovascular risk in patients with mild-SCH and have demonstrated some benefits of levothyroxine treatment in reducing these events. However, evidence on the association of mild-SCH and musculoskeletal system, cognitive dysfunction, mood disorders, dyslipidaemia, diabetes and goitre is conflicting. Similarly, the discussion regarding the exact upper limit of normal for serum TSH remains controversial. The data have also shown increased risk of adverse pregnancy outcomes in patient with mild-SCH, with some benefits of thyroxine treatment. The recent available guidelines related to management of patients with serum TSH <10 mIU/l have suggested decisions should be made taking into account the age of the patient, associated risk factors and comorbid conditions. This chronicle review assesses current evidence regarding the risks associated and the recommendations related to benefits of levothyroxine treatment in patients having mild-SCH.
| S-EPMC4740939 | biostudies-literature
Project description:ObjectiveThe purpose of this study was to determine if infants with congenital hypothyroidism (CH) whose initial dose of levothyroxine (LT4) is based on thyroid gland anatomy require fewer dose adjustments in the first 6 months of life than those who were started empirically on LT4.MethodsNewborns with CH who had a thyroid ultrasound performed at diagnosis were eligible for this prospective, historical case-controlled study. The daily LT4 dose prescribed was based on results on the thyroid ultrasound as follows: 15 mcg/kg for athyreosis, 12 mcg/kg for a dysgenetic thyroid, and 10 mcg/kg for an anatomically normal gland. Routine labs according to standard guidelines were obtained, and the number of dose adjustments over the first 6 months of therapy was recorded. Each study participant was matched with 2 historical controls with CH based on sex and thyroid anatomy.ResultsTwenty-two subjects (10 with athyreosis, 4 with dysgenetic glands, and 8 with anatomically normal glands) were matched to 44 controls. There was no significant difference in the overall number of adjustments in the study group compared to controls (P = .74). However, there were significantly fewer adjustments made for undertreatment (P = .03) and significantly more adjustments made for overtreatment (P = .006) in subjects with athyreosis compared to controls.ConclusionTargeted LT4 therapy does not appear to decrease the overall frequency of dose adjustments for infants with CH. However, 15 mcg/kg/day appears to exceed thyroid hormone requirements in infants with CH due to athyreosis.AbbreviationsCH = congenital hypothyroidism LT4 = levothyroxine OT = overtreatment T4 = thyroxine TSH = thyroid-stimulating hormone UT = undertreatment.
| S-EPMC5808429 | biostudies-literature
Project description:IntroductionStudies comparing levothyroxine (LT4) therapy with LT4 + liothyronine (LT3) or desiccated thyroid extract (DTE) did not detect consistent superiority of either treatment. Here, we investigated these therapies, focusing on the whole group of LT4-treated hypothyroid patients, while also exploring the most symptomatic patients.MethodologyProspective, randomized, double-blind, crossover study of 75 hypothyroid patients randomly allocated to 1 of 3 treatment arms, LT4, LT4 + LT3, and DTE, for 22 weeks. The primary outcomes were posttreatment scores on the 36-point thyroid symptom questionnaire (TSQ-36), 12-point quality of life general health questionnaire (GHQ-12), the Wechsler memory scale-version IV (VMS-IV), and the Beck Depression Inventory (BDI). Secondary endpoints included treatment preference, biochemical and metabolic parameters, etiology of hypothyroidism, and Thr92Ala-DIO2 gene polymorphism. Analyses were performed with a linear mixed model using subject as a random factor and group as a fixed effect.ResultsSerum TSH remained within reference range across all treatment arms. There were no differences for primary and secondary outcomes, except for a minor increase in heart rate caused by DTE. Treatment preference was not different and there were no interferences of the etiology of hypothyroidism or Thr92Ala-DIO2 gene polymorphism in the outcomes. Subgroup analyses of the 1/3 most symptomatic patients on LT4 revealed strong preference for treatment containing T3, which improved performance on TSQ-36, GHQ-12, BDI, and visual memory index (VMS-IV component).ConclusionsAs a group, outcomes were similar among hypothyroid patients taking DTE vs LT4 + T3 vs LT4. However, those patients that were most symptomatic on LT4 preferred and responded positively to therapy with LT4 + LT3 or DTE.
| S-EPMC8530721 | biostudies-literature
Project description:Background: A significant number of patients show sub-optimal adherence to levothyroxine (LT4) therapy, mainly because they have to postpone their breakfast by at least 30 min. The aim of this observational cross-sectional study was to assess the therapeutic compliance of patients on LT4 treatment and to verify the preference of a lifetime treatment in tablet or liquid form. Patients and Methods: Ambulatory care patients aged 18 years or older, affected by hypothyroidism and on LT4 treatment (in tablet or liquid form) were administered the eight-item Morisky Medication Adherence Scale (MMAS-8). The MMAS-8 questionnaire was supplemented with 3 further items to specifically evaluate preference between tablet and liquid forms of LT4 for lifetime treatment. Results: A total of 320 patients (272 female), median age 47.9 ± 15.6 years (range, 20-78 years), completed the MMAS-8 questionnaire. Eighty-seven percent of the participants were adhering to their treatment for both tablet and liquid LT4 formulations, although significant differences emerged. Patients on LT4 tablets forgot to take their medication more frequently (p < 0.001), felt hassled about sticking to their treatment plan (p < 0.001), and had difficulty remembering to take all their medication(s) (p < 0.001) than those on liquid LT4 treatment. Conclusions: Adherence to LT4 treatment was high for both tablet and liquid formulations. Taking LT4 at breakfast was the most convenient option for most patients.
| S-EPMC6265311 | biostudies-other
Project description:BACKGROUND:Subclinical hypothyroidism (SHT) may increase the risk of cardiovascular disease. We compared endothelial function between SHT patients and euthyroid individuals, and evaluated the effects of levothyroxine therapy on endothelial function in the patients. MATERIALS AND METHODS:In a quasi-experimental study, flow-mediated dilatation (FMD) and intima-media thickness (IMT) were assessed in SHT patients and healthy controls (n = 25 in each group). Patients then received levothyroxine (50 ?g/day) for 2 months, and the FMD and IMT assessments were repeated. RESULTS:Patients and controls were similar in IMT (0.56 ± 0.09 vs. 0.58 ± 0.08 mm, P = 0.481), but FMD was lower in patients than in controls (4.95 ± 2.02 vs. 6.50 ± 2.57%, P = 0.011). A significant increase was observed in FMD (4.11 ± 2.37%, P = 0.001), but not in IMT (-0.004 ± 0.020 mm, P = 0.327), after levothyroxine therapy among the patients. CONCLUSIONS:Patients with SHT have endothelial dysfunction which responds to levothyroxine therapy. Randomized placebo-controlled trials are needed to confirm these findings.
| S-EPMC4815523 | biostudies-literature
Project description:BACKGROUND AND OBJECTIVE:The possible adverse or positive effects of levothyroxine treatment among patients with atrial fibrillation have been debated. Atrial fibrillation, levothyroxine treatment, and dementia are common among older adults, yet little is known about the effects of levothyroxine on the development of dementia. METHODS:The study population included all adults (n?=?12,057) aged???45 years with a diagnosis of atrial fibrillation at 75 primary care centers in Sweden during 2001-2007 without an earlier recorded dementia diagnosis. Patients with a diagnosis of hypothyroidism and levothyroxine prescription (n?=?756; 180 men and 576 women), or with a prescription without this diagnosis (n?=?415, 100 men and 315 women), were compared to patients without a diagnosis and prescription (n?=?10,886). Cox regression was performed, with hazard ratios and 95% confidence intervals, with outcome defined as dementia of all causes until 31 December, 2010. RESULTS:During a mean 5.7 years (standard deviation 2.4 years) of follow-up, a total of 749 patients with atrial fibrillation (6.2%) were diagnosed with dementia. Women with hypothyroidism and a levothyroxine prescription showed lower hazard ratios (0.61; 0.41-0.90) in adjusted Cox regression models (age, socioeconomic factors, co-morbidity, and warfarin treatment). Levothyroxine prescription without hypothyroidism was non-significant. CONCLUSIONS:We found that women with atrial fibrillation with levothyroxine treatment and hypothyroidism have a lower risk of incident dementia than women with atrial fibrillation without levothyroxine treatment and no hypothyroidism. The results should be confirmed in larger studies.
| S-EPMC6394624 | biostudies-literature
Project description:Subclinical hypothyroidism has been accused for coronary heart disease, lipid metabolism disorders, neuropsychiatric disorders, infertility or pregnancy related problems with various strength of evidence. Currently there is insufficient knowledge about olfaction and taste functions in subclinical hypothyroidism. Aim of the present study is to investigate the degree of smell and taste dysfunction in patients with subclinical hypothyroidism. 28 subclinical hypothyroid patients, and 31 controls enrolled in the prospective study in Istanbul, Turkey. Subclinical hypothyroid patients were treated with L-thyroxine for 3 months. Psychophysiological olfactory testing was performed using odor dispensers similar to felt-tip pens ("Sniffin' Sticks", Burghart, Wedel, Germany). Taste function tests were made using "Taste Strips" (Burghart, Wedel, Germany) which are basically tastant adsorbed filter paper strip. Patients scored lower on psychophysical olfactory tests than controls (odor thresholds:8.1±1.0 vs 8.9±1.1, p = 0.007; odor discrimination:12.4±1.3 vs 13.1±0.9, p = 0.016; odor identification:13.1±0.9 vs 14.0±1.1, p = 0.001; TDI score: 33.8±2.4 vs 36.9±2.1, p = 0.001). In contrast, results from psychophysical gustatory tests showed only a decreased score for "bitter" in patients, but not for other tastes (5.9±1.8 vs 6.6±1.0, p = 0.045). Three month after onset of treatment olfactory test scores already indicated improvement (odor thresholds:8.1±1.0 vs 8.6±0.6, p<0.001; odor discrimination:12.4±1.31 vs 12.9±0.8, p = 0.011; odor identification:13.1±0.9 vs 13.9±0.8, p<0.001; TDI scores:33.8±2.4 vs 35.5±1.7, p<0.001) respectively. Taste functions did not differ between groups for sweet, salty and, sour tastes but bitter taste was improved after 3 months of thyroxin substitution (patients:5.9±1.8 vs 6.6±1.2, p = 0.045). Correlation of changes in smell and taste, with thyroid function test were also evaluated. TSH, fT4 were found have no correlation with smell and taste changes with treatment. However bitter taste found positively correlated with T3 with treatment(r: 0.445, p: 0.018). Subclinical hypothyroid patients exhibited a significantly decreased olfactory sensitivity; in addition, bitter taste was significantly affected. Most importantly, these deficits can be remedied on average within 3 months with adequate treatment.
| S-EPMC4771174 | biostudies-literature
Project description:BackgroundSubclinical hypothyroidism (SCH) is usually treated with levothyroxine, but there is controversy as to whether SCH should be treated, especially for older patients. The aim of the systematic review and meta-analysis was to evaluate whether levothyroxine has a beneficial or harmful effect on older patients with SCH.MethodsDatabases including PubMed, Embase, Cochrane Library, Web of Science, Wanfang, Weipu and China National Knowledge Infrastructure were searched from inception until December 21, 2021. Subjects must be diagnosed with SCH, and older than or equal to 60 years of age. Interventions should be thyroid hormone therapy (e.g. levothyroxine). The literature was independently screened by 2 researchers. Statistical analysis was performed using RevMan5.3 software.ResultsA total of 13 articles were included. Meta-analysis results showed that in older SCH patients, levothyroxine can significantly reduce cholesterol (TC) (p < 0.00001), triglyceride (TG) (p < 0.00001), low-density lipoprotein cholesterol (LDL-C) (p = 0.03) and apolipoprotein B (ApoB) (p < 0.00001). In addition, levothyroxine had no significant effect on bone mineral density, fatigue, hypothyroidism symptoms, quality of life, BMI, cognitive function, depression, blood pressure, etc. in older SCH patients, and also did not significantly increase the incidence of adverse events.ConclusionsAmong older SCH patients, levothyroxine treatment may reduce TC, TG, LDL-C, and ApoB.
| S-EPMC9329610 | biostudies-literature
Project description:ContextThe standard of care for overt hypothyroidism is levothyroxine at doses that normalize serum TSH levels. Whether this approach universally restores thyroid hormone signaling is unknown.ObjectiveTo review studies of overt hypothyroidism in which participants were treated with levothyroxine to normalize serum TSH levels and measured other objective markers of thyroid hormone signaling.DesignDatabases were searched for studies that reported objective markers of thyroid hormone signaling (serum low-density lipoprotein (LDL), total cholesterol (TC), sex hormone-binding globulin (SHBG), creatine kinase and/or ferritin levels; cognition, energy expenditure, and/or renal function) in levothyroxine monotherapy for overt, primary hypothyroidism among nonpregnant adults with normal serum TSH levels. For studies with LDL, TC and SHBG outcomes, data were pooled using random effects meta-analysis.ResultsA total of 99 studies met inclusion criteria, including 65 that reported serum cholesterol data. Meta-analysis showed that levothyroxine-treated hypothyroid participants with normal serum TSH levels had 3.31 ± 1.64 mg/dL higher serum LDL levels (p=0.044) and 9.60 ± 3.55 mg/dL higher serum TC levels (p=0.007) compared to controls. In studies that did not concomitantly assess healthy controls, serum LDL levels were 138.3 ± 4.6 mg/dL (p<0.001) and serum TC levels were 209.6 ± 3.4 mg/dL (p<0.001). Meta-analysis of 2 studies showed no significant difference between SHBG levels of levothyroxine-treated participants and controls.ConclusionsIn studies that utilized levothyroxine monotherapy at doses that normalized the serum TSH for overt, primary hypothyroidism, not all systemic biological markers of thyroid hormone signaling were normalized, including serum LDL and TC levels.
| S-EPMC6226605 | biostudies-literature
Project description:BackgroundSubclinical hypothyroidism (SCH) during pregnancy has been associated with multiple adverse maternal and neonatal outcomes. However, the potential benefits of levothyroxine (LT4) supplementation remain controversial. Variations across studies in diagnostic criteria for SCH may, in part, explain the divergent findings on the subject. This study aimed to assess the effect of LT4 treatment on pregnancy and neonatal outcomes among pregnant women who were diagnosed as SCH based on the most recent diagnostic criteria.MethodsWe conducted a systematic review and meta-analysis of the literature published from inception to January 2020. The search strategy targeted the studies on pregnancy and neonatal outcomes following LT4 treatment in women with SCH based on 2017 American Thyroid Association diagnostic criteria. Pooled effect sizes were estimated using fixed and random effect models, according to the absence or presence of heterogeneity which was assessed using the I-squared statistic. Sources of heterogeneity and the stability of results were evaluated through sensitivity analysis.ResultsOf the 2781 identified references, 306 full-text articles were screened for eligibility. Finally, 6 studies including a total of 7955 participants were retained for analysis. Summary effect estimates indicated that pregnant women with SCH treated with LT4 had a lower risk of pregnancy loss [odds ratio (OR) = 0.55, 95% confidence interval (CI): 0.43-0.71], preterm birth (OR=0.63, 95% CI: 0.41-0.98) and gestational hypertension (OR = 0.78, 95% CI: 0.63-0.97) than those in control group.ConclusionLT4 treatment in pregnant women with SCH may reduce the risk of pregnancy loss, preterm delivery and gestational hypertension.
| S-EPMC8703220 | biostudies-literature