Current evidence for the treatment of hypothyroidism with levothyroxine/levotriiodothyronine combination therapy versus levothyroxine monotherapy.

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Term Occurence Count Dictionary
hypoparathyroidism 1 endocrinologydiseases
metabolic syndrome 3 endocrinologydiseases
autoimmune thyroiditis 3 endocrinologydiseases
hypothyroidism 62 endocrinologydiseases
liothyronine 1 endocrinologydiseasesdrugs
thyroid carcinoma 1 endocrinologydiseases
thyroiditis 3 endocrinologydiseases
thyrotoxicosis 1 endocrinologydiseases
adrenal insufficiency 1 endocrinologydiseases

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Select Drug Character Offset Drug Term Instance
liothyronine 31433 dose; for combined treatment, daily LT4 dose was reduced by 50 μg and replaced with 10 μg LT3 ( liothyronine )No between‐treatment differences were noted in treatment satisfaction scoresNo significant differences
Select Disease Character Offset Disease Term Instance
adrenal insufficiency 42688 conditions (Table 2), but also serious exacerbation of symptoms or threat to life if, for example, adrenal insufficiency goes unrecognised. Adjustment of the approach to thyroid hormone replacement by adding LT3 for nonspecific
autoimmune thyroiditis 5670 debilitating. In the United States, where iodine deficiency is rare, the most common cause of hypothyroidism is autoimmune thyroiditis .1Our hypothetical patient above fits the typical demographic profile of a patient with hypothyroidism.
autoimmune thyroiditis 23895 particularly good for patients not entirely well with LT4 aloneBunevicius et al, 199944Patients with chronic autoimmune thyroiditis or thyroid cancer (n = 33 completers) treated by near‐total thyroidectomy who were receiving LT4
autoimmune thyroiditis 24690 (P = .001)Bunevicius and Prange, 200045Further analysis of Bunevicius et al, 1999, by diagnostic group (n = 11, autoimmune thyroiditis ; n = 15, thyroid cancer)Randomised, blinded crossover with two 5‐wk periodsLT4 at usual dose or
hypoparathyroidism 18938 not whether they had been told they were cured of their cancer, had a higher BMI, or had developed hypoparathyroidism as a result of the surgery. QoL was also related to the time since their initial diagnosis of thyroid
hypothyroidism 87 Title: International Journal of Clinical PracticeCurrent evidence for the treatment of hypothyroidism with levothyroxine/levotriiodothyronine combination therapy versus levothyroxine monotherapyAlternative
hypothyroidism 835 levels with LT4 monotherapy may have persistent symptoms that patients and clinicians may attribute to hypothyroidism . A long‐standing debate in the literature is whether addition of levotriiodothyronine (LT3) to LT4
hypothyroidism 1250 complaints.MethodsRecent literature indexed on PubMed was searched in March 2017 using the terms “hypothyroid” or “ hypothyroidism ” and “triiodothyronine combination” or “T3 combination.” Relevant non‐review articles published
hypothyroidism 1601 clinical evidence is not sufficiently strong to support LT4/LT3 combination therapy in patients with hypothyroidism . Polymorphisms in deiodinase genes that encode the enzymes that convert T4 to T3 in the periphery may
hypothyroidism 2261 aggressively investigated by the clinician.HennesseyJV, EspaillatR. Current evidence for the treatment of hypothyroidism with levothyroxine/levotriiodothyronine combination therapy versus levothyroxine monotherapy. Int J
hypothyroidism 2598 addition of levotriiodothyronine (LT3) to levothyroxine (LT4) will ameliorate persistent symptoms of hypothyroidism . To explore the evidence for and against LT4/LT3 combination therapy, recent literature was searched
hypothyroidism 2754 LT4/LT3 combination therapy, recent literature was searched using the terms “hypothyroid” or “ hypothyroidism ” and “triiodothyronine combination” or “T3 combination.” In all, 72 relevant non‐review
hypothyroidism 3108 clinicCurrent clinical evidence is insufficient to support LT4/LT3 combination therapy in patients with hypothyroidism . Findings on the effect of LT4/LT3 therapy on clinical symptoms and thyroid‐responsive genes have
hypothyroidism 3650 drugs, and lifestyle.INTRODUCTION1A 53‐year‐old woman presents with a 3‐year history of primary hypothyroidism . She has been receiving a stable dose of levothyroxine (LT4) replacement monotherapy and has had thyroid‐stimulating
hypothyroidism 4423 prevalence of 4.6% was noted in participants ≥ 12 years of age.2 A meta‐analysis of data from hypothyroidism studies conducted in Europe estimated a prevalence of 3.05%.3 The frequency of elevated TSH increases
hypothyroidism 4873 disease, whereas T4 levels remain largely unchanged in the healthy elderly.4In patients with primary hypothyroidism , the thyroid gland is unable to maintain adequate secretion of hormones, triggering the pituitary gland
hypothyroidism 5513 affected as well as the kidneys, skin and connective tissues. The severity of the signs and symptoms of hypothyroidism can range from subclinical to debilitating. In the United States, where iodine deficiency is rare, the
hypothyroidism 5652 subclinical to debilitating. In the United States, where iodine deficiency is rare, the most common cause of hypothyroidism is autoimmune thyroiditis.1Our hypothetical patient above fits the typical demographic profile of a
hypothyroidism 5780 thyroiditis.1Our hypothetical patient above fits the typical demographic profile of a patient with hypothyroidism . However, her continued symptoms, despite seemingly successful normalisation of thyroid function as
hypothyroidism 6926 recent literature indexed on PubMed was searched in March 2017 using the terms “hypothyroid” or “ hypothyroidism ” and “triiodothyronine combination” or “T3 combination.” After limiting the results to the
hypothyroidism 7291 discussion of thyroid replacement therapies, specifically LT4/LT3 combination therapy, in patients with hypothyroidism and are included here.Historical development of treatment for hypothyroidism1.2Initially, thyroid replacement
hypothyroidism 7368 therapy, in patients with hypothyroidism and are included here.Historical development of treatment for hypothyroidism 1.2Initially, thyroid replacement therapies were desiccated thyroid extract preparations of animal origin,
hypothyroidism 8406 patients treated with LT4 monotherapy,12 implying that exogenous LT3 was not required for the treatment of hypothyroidism . A prospective, well‐controlled study by Jonklaas and colleagues compared circulating T3 and T4 levels
hypothyroidism 9216 Despite this, there remains a persistent concept that addition of LT3 has a role in the treatment of hypothyroidism , that is, to improve persistent symptoms.15 Others point to findings that approximately one‐fifth
hypothyroidism 9926 continuing complaints in euthyroid patients receiving LT4.16 Across clinical studies, patients with hypothyroidism who attained normal TSH levels with LT4 treatment had free LT3 levels that were, in general, statistically
hypothyroidism 13693 studies are needed to fully understand the implications of D2 polymorphisms in the treatment of overt hypothyroidism .Associations between thyroid hormone levels and patient‐reported symptoms1.4The patient in our case
hypothyroidism 13947 continued fatigue, hair loss and “brain fog” that she associates with her diagnosis of primary hypothyroidism . What is the evidence that such symptoms are associated with thyroid dysfunction when TSH levels have
hypothyroidism 14239 studies that have evaluated associations between patient‐reported symptoms and the presence of overt hypothyroidism suggest that symptoms, even in newly diagnosed patients, may not reliably signal the existence of the
hypothyroidism 14443 existence of the hypothyroid condition. One study found that, on average, patients newly diagnosed with hypothyroidism (n = 76) reported experiencing 30.2% of symptoms from a panel of 17 traditional hypothyroid symptoms,
hypothyroidism 14808 symptoms that were present, hoarse voice and muscle cramps, remained significantly associated with hypothyroidism in multivariate analysis.33 Patients who reported changes in ≥7 symptoms from a panel of typical traditional
hypothyroidism 15098 likely to be hypothyroid.33 However, it should be noted that many patients newly diagnosed with overt hypothyroidism complain of no or few current or changed symptoms.33 The same investigators demonstrated that the percentage
hypothyroidism 15407 was quite similar, further illuminating the difficulty that clinicians may have in detecting overt hypothyroidism by symptoms alone when confronted with an array of nonspecific complaints.34 Additionally, more than
hypothyroidism 16085 tests before initiating any form of thyroid hormone replacement1, 36 because relying on symptoms of hypothyroidism to generate changes in replacement may be fraught with imprecision.A large questionnaire‐based study
hypothyroidism 16330 psychological well‐being were slightly but significantly lower in 597 patients receiving LT4 to correct hypothyroidism compared with 551 age‐ and sex‐matched controls without thyroid disease (mean GHQ‐12 score, 12.09
hypothyroidism 16816 dysfunction and would have been more likely to have responded to a questionnaire investigating symptoms of hypothyroidism .38 Furthermore, symptoms in some patients may have been due to subclinical hypothyroidism resulting
hypothyroidism 16906 symptoms of hypothyroidism.38 Furthermore, symptoms in some patients may have been due to subclinical hypothyroidism resulting from LT4 under‐treatment; this condition would not have been detected based on the way that
hypothyroidism 17352 study, the association between thyroid hormone levels and QoL measures was assessed in 697 patients with hypothyroidism (84% female [586/697]; mean age, 57.3 years) who had been receiving LT4 at a stable dose for ≥ 3 months.39
hypothyroidism 19268 findings suggested that the nonspecific complaints of fatigue or impaired well‐being in patients with hypothyroidism are not predictably due to a deficiency of circulating T3 and would not be expected to improve by increasing
hypothyroidism 20601 and with age and sex in matched controls.41 The authors concluded that LT4 treatment in patients with hypothyroidism , even when TSH is normalised, does not produce a euthyroid state because (for unknown reasons) BMI is
hypothyroidism 22930 therapyAuthor, YearPatientsStudy designTreatmentsKey findingsSmith et al, 197054Patients treated for hypothyroidism with 200 or 300 μg T4 ≥ 6 mo; judged to be euthyroid (n = 87 completers)Double‐blind crossover
hypothyroidism 25550 patients preferred monotherapy and 2 had no preferenceNygaard et al, 200950Patients with spontaneous hypothyroidism at diagnosis; stable LT4 treatment for ≥ 6 mo and TSH 0.1‐5.0 mIU/L at screening (n = 59 completers)Randomised,
hypothyroidism 26385 by patientsAppelhof et al, 200542Patients receiving adequate LT4 replacement for primary autoimmune hypothyroidism ≥ 6 mo (n = 130 completers)Randomised, controlled, 15‐wk trialLT4 alone (n = 48), LT4:LT3
hypothyroidism 27395 treatment of changes on cognitive testsEscobar‐Morreale 200522Women diagnosed with overt primary hypothyroidism with maintained normal TSH with stable LT4 100 μg for ≥ 1 y (n = 26 completers)Randomised,
hypothyroidism 28861 LT4 monotherapy should remain standard therapyLevitt and Silverberg, 200249Euthyroid patients with hypothyroidism treated with stable LT4 doses, with ≥ 1 persistent symptom of hypothyroidism (n = 59 completers)Double‐blind,
hypothyroidism 28942 200249Euthyroid patients with hypothyroidism treated with stable LT4 doses, with ≥ 1 persistent symptom of hypothyroidism (n = 59 completers)Double‐blind, 3‐6 mo study (outcome was evaluated once TSH levels were normal
hypothyroidism 29570 measuresImprovement in symptoms was correlated with changes in lipidsClyde et al, 200346Patients with primary hypothyroidism receiving stable doses of LT4 for ≥ 3 mo (n = 44 completers)Randomised, double‐blind, placebo‐controlled,
hypothyroidism 30249 significantly different in favour of monotherapySawka et al, 200352Patients with diagnosed primary hypothyroidism receiving a stable dose of LT4 for 6 mo, normal BL TSH, and symptoms of depression (n = 40)Randomised,
hypothyroidism 30837 differences were seen on measures of mood or well‐beingWalsh et al, 200357Patients with primary hypothyroidism diagnosis of ≥ 6 mo, stable LT4 dose of ≥ 100 μg in previous 2 mo, and serum TSH between
hypothyroidism 31830 with treatment at BL, no differences in QoL or cognition were seenSiegmund et al, 200453Patients with hypothyroidism receiving stable long‐term LT4 replacement therapy (100‐175 μg; n = 23 completers)Randomised,
hypothyroidism 34670 favouring LT4/LT3 combination therapyFadeyev et al, 201047Premenopausal women with untreated overt primary hypothyroidism (n = 36)Randomised, controlled, non‐blinded, 6‐mo study20 patients received LT4 1.6 μg/kg; 16
hypothyroidism 35380 and 18 expressed no preferenceKaminski et al, 201648Patients aged 15‐65 y, diagnosed with primary hypothyroidism , receiving stable doses of LT4 in the previous 6 mo (125 or 150 μg/d; n = 32)Randomised, double‐blind,
hypothyroidism 36295 conducted integrated analyses to better discern the role of LT4/LT3 versus LT4 therapy in patients with hypothyroidism . It should be noted that the limited number of available published research articles resulted in a large
hypothyroidism 40106 with LT3 is generally safe although the preponderance of long‐term experience in the treatment of hypothyroidism involves LT4 monotherapy.A common theme of analyses of patients with hypothyroidism is that they have
hypothyroidism 40190 the treatment of hypothyroidism involves LT4 monotherapy.A common theme of analyses of patients with hypothyroidism is that they have poorer overall health relative to matched controls. Although statistical methods may
hypothyroidism 41199 in older patients, addressing these potential sources of symptoms often attributed to recalcitrant hypothyroidism may well be an avenue to clinical improvement.Table 2Potential causes of persistent symptoms in euthyroid
hypothyroidism 42086 failureOpiatesFibromyalgiaAdapted with permission from Okosieme O, Gilbert J, Abraham P, et al. Management of primary hypothyroidism : statement by the British Thyroid Association Executive Committee. Clin Endocrinol (Oxf) 2016; 84:799‐808.LT4,
hypothyroidism 42993 physician seeks the correct underlying cause of the symptom, the patient may require assurance that hypothyroidism is unlikely to be the problem.Guideline recommendations1.7Guidelines for the treatment of patients with
hypothyroidism 43112 unlikely to be the problem.Guideline recommendations1.7Guidelines for the treatment of patients with hypothyroidism consistently recommend LT4 monotherapy as the treatment of choice, recommend against the routine use
hypothyroidism 43527 combination therapy, use of desiccated thyroid extract and the role of genotyping in the treatment of hypothyroidism are presented in Table 3.1, 36, 68, 71, 72, 73 Additionally, these guidelines suggest that the clinical
hypothyroidism 44062 of Clinical Endocrinologists/American Thyroid Association clinical practice guidelines, 20121Primary hypothyroidism (TSH levels > 10 mIU/L) should be treated to the target TSH range (in non‐pregnant women) of 0.45‐4.12 mIU/LPatients
hypothyroidism 44861 have persistent complaintsPatients have already received support to deal with the chronic nature of hypothyroidism Associated autoimmune diseases have been ruled outThyroid extracts should not be used; they may have
hypothyroidism 46906 Endocrinologists guide for clinical practice, 201672Replacement therapy goals Resolution of symptoms/signs of hypothyroidism Normal serum TSH and fasting FT4 levelsQoL improvementLT4 should be the first choice for all hypothyroid
hypothyroidism 47300 problems are ruled outInsufficient safety information exists to support the use of extracts to treat hypothyroidism No recommendationsBritish Thyroid Association statement, 201668Goals are to restore physical and psychological
hypothyroidism 48495 joint task force of the AACE and ATA.1 Regarding the use of LT4 versus LT4/LT3 for the treatment of hypothyroidism , more than 99% of 743 respondents indicated that they would choose LT4 for initial therapy, consistent
hypothyroidism 49639 may be due to factors other than thyroid dysfunction.It is estimated that 5%‐10% of patients with hypothyroidism treated with LT4 with normal TSH levels continue to experience nonspecific symptoms which may be attributed
hypothyroidism 49765 with LT4 with normal TSH levels continue to experience nonspecific symptoms which may be attributed to hypothyroidism .73 Current clinical evidence, however, is not sufficiently strong to support the use of LT4/LT3 combination
hypothyroidism 49913 however, is not sufficiently strong to support the use of LT4/LT3 combination therapy in patients with hypothyroidism . Several genetic polymorphisms have been investigated in an effort to explore potential mechanisms underlying
metabolic syndrome 3515 and autoimmune disorders, haematological conditions, end‐organ damage, nutritional deficiencies, metabolic syndrome s, concomitant drugs, and lifestyle.INTRODUCTION1A 53‐year‐old woman presents with a 3‐year history
metabolic syndrome 13163 thyroid parameters, health‐related quality of life (QoL), cognitive functioning, the presence of metabolic syndrome , or the use of blood pressure or cholesterol‐lowering drugs.32 However, the women receiving LT4 (only
metabolic syndrome 50574 and autoimmune disorders, haematological conditions, end‐organ damage, nutritional deficiencies, metabolic syndrome s, concomitant drugs and lifestyle, is warranted.68DISCLOSURESJ. V. Hennessey received no financial support
thyroid carcinoma 18228 thyroidectomy and postoperative radioactive iodine (131I) remnant ablation for the appropriate treatment of thyroid carcinoma . These individuals had been receiving LT4 suppression at a stable dose for at least the previous 10 weeks
thyroiditis 5681 United States, where iodine deficiency is rare, the most common cause of hypothyroidism is autoimmune thyroiditis .1Our hypothetical patient above fits the typical demographic profile of a patient with hypothyroidism.
thyroiditis 23906 patients not entirely well with LT4 aloneBunevicius et al, 199944Patients with chronic autoimmune thyroiditis or thyroid cancer (n = 33 completers) treated by near‐total thyroidectomy who were receiving LT4
thyroiditis 24701 Prange, 200045Further analysis of Bunevicius et al, 1999, by diagnostic group (n = 11, autoimmune thyroiditis ; n = 15, thyroid cancer)Randomised, blinded crossover with two 5‐wk periodsLT4 at usual dose or
thyrotoxicosis 46697 thyroid extracts is not recommended because it may result in high serum T3 levels, causing symptoms of thyrotoxicosis Evidence currently insufficient for guiding treatmentItalian Association of Clinical Endocrinologists

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