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      Treatment for primary hypothyroidism: current approaches and future possibilities

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          Abstract

          Primary hypothyroidism is the most common endocrine disease. Although the diagnosis and treatment of hypothyroidism is often considered simple, there are large numbers of people with this condition who are suboptimally treated. Even in those people with hypothyroidism who are biochemically euthyroid on levothyroxine replacement there is a significant proportion who report poorer quality of life. This review explores the historical and current treatment options for hypothyroidism, reasons for and potential solutions to suboptimal treatment, and future possibilities in the treatment of hypothyroidism.

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          Most cited references 103

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          Subclinical thyroid disease: scientific review and guidelines for diagnosis and management.

          Patients with serum thyroid-stimulating hormone (TSH) levels outside the reference range and levels of free thyroxine (FT4) and triiodothyronine (T3) within the reference range are common in clinical practice. The necessity for further evaluation, possible treatment, and the urgency of treatment have not been clearly established. To define subclinical thyroid disease, review its epidemiology, recommend an appropriate evaluation, explore the risks and benefits of treatment and consequences of nontreatment, and determine whether population-based screening is warranted. MEDLINE, EMBASE, Biosis, the Agency for Healthcare Research and Quality, National Guideline Clearing House, the Cochrane Database of Systematic Reviews and Controlled Trials Register, and several National Health Services (UK) databases were searched for articles on subclinical thyroid disease published between 1995 and 2002. Articles published before 1995 were recommended by expert consultants. A total of 195 English-language or translated papers were reviewed. Editorials, individual case studies, studies enrolling fewer than 10 patients, and nonsystematic reviews were excluded. Information related to authorship, year of publication, number of subjects, study design, and results were extracted and formed the basis for an evidence report, consisting of tables and summaries of each subject area. The strength of the evidence that untreated subclinical thyroid disease is associated with clinical symptoms and adverse clinical outcomes was assessed and recommendations for clinical practice developed. Data relating the progression of subclinical to overt hypothyroidism were rated as good, but data relating treatment to prevention of progression were inadequate to determine a treatment benefit. Data relating a serum TSH level higher than 10 mIU/L to elevations in serum cholesterol were rated as fair but data relating to benefits of treatment were rated as insufficient. All other associations of symptoms and benefit of treatment were rated as insufficient or absent. Data relating a serum TSH concentration lower than 0.1 mIU/L to the presence of atrial fibrillation and progression to overt hyperthyroidism were rated as good, but no data supported treatment to prevent these outcomes. Data relating restoration of the TSH level to within the reference range with improvements in bone mineral density were rated as fair. Data addressing all other associations of subclinical hyperthyroid disease and adverse clinical outcomes or treatment benefits were rated as insufficient or absent. Subclinical hypothyroid disease in pregnancy is a special case and aggressive case finding and treatment in pregnant women can be justified. Data supporting associations of subclinical thyroid disease with symptoms or adverse clinical outcomes or benefits of treatment are few. The consequences of subclinical thyroid disease (serum TSH 0.1-0.45 mIU/L or 4.5-10.0 mIU/L) are minimal and we recommend against routine treatment of patients with TSH levels in these ranges. There is insufficient evidence to support population-based screening. Aggressive case finding is appropriate in pregnant women, women older than 60 years, and others at high risk for thyroid dysfunction.
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            The Colorado thyroid disease prevalence study.

            The prevalence of abnormal thyroid function in the United States and the significance of thyroid dysfunction remain controversial. Systemic effects of abnormal thyroid function have not been fully delineated, particularly in cases of mild thyroid failure. Also, the relationship between traditional hypothyroid symptoms and biochemical thyroid function is unclear. To determine the prevalence of abnormal thyroid function and the relationship between (1) abnormal thyroid function and lipid levels and (2) abnormal thyroid function and symptoms using modern and sensitive thyroid tests. Cross-sectional study. Participants in a statewide health fair in Colorado, 1995 (N = 25 862). Serum thyrotropin (thyroid-stimulating hormone [TSH]) and total thyroxine (T4) concentrations, serum lipid levels, and responses to a hypothyroid symptoms questionnaire. The prevalence of elevated TSH levels (normal range, 0.3-5.1 mIU/L) in this population was 9.5%, and the prevalence of decreased TSH levels was 2.2%. Forty percent of patients taking thyroid medications had abnormal TSH levels. Lipid levels increased in a graded fashion as thyroid function declined. Also, the mean total cholesterol and low-density lipoprotein cholesterol levels of subjects with TSH values between 5.1 and 10 mIU/L were significantly greater than the corresponding mean lipid levels in euthyroid subjects. Symptoms were reported more often in hypothyroid vs euthyroid individuals, but individual symptom sensitivities were low. The prevalence of abnormal biochemical thyroid function reported here is substantial and confirms previous reports in smaller populations. Among patients taking thyroid medication, only 60% were within the normal range of TSH. Modest elevations of TSH corresponded to changes in lipid levels that may affect cardiovascular health. Individual symptoms were not very sensitive, but patients who report multiple thyroid symptoms warrant serum thyroid testing. These results confirm that thyroid dysfunction is common, may often go undetected, and may be associated with adverse health outcomes that can be avoided by serum TSH measurement.
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              Thyroid status, disability and cognitive function, and survival in old age.

              Despite the equivocal outcomes of randomized controlled trials, general clinical opinion favors screening and treatment of elderly individuals with subclinical thyroid disorders. To determine whether subclinical thyroid dysfunction should be treated in old age and the long-term impact of thyroid dysfunction on performance and survival in old age. A prospective, observational, population-based follow-up study within the Leiden 85-Plus Study of 87% of a 2-year birth cohort (1912-1914) in the municipality of Leiden, the Netherlands. A total of 599 participants were followed up from age 85 years through age 89 years (mean [SD] follow-up, 3.7 [1.4] years). Complete thyroid status at baseline; disability in daily life, depressive symptoms, cognitive function, and mortality from age 85 years through 89 years. Plasma levels of thyrotropin and free thyroxine were not associated with disability in daily life, depressive symptoms, and cognitive impairment at baseline or during follow-up. Increasing levels of thyrotropin were associated with a lower mortality rate that remained after adjustments were made for baseline disability and health status. The hazard ratio (HR) for mortality per SD increase of 2.71 mIU/L of thyrotropin was 0.77 (95% confidence interval [CI], 0.63-0.94; P = .009). The HR for mortality per SD increase of 0.21 ng/dL (2.67 pmol/L) of free thyroxine increased 1.16-fold (95% CI, 1.04-1.30; P = .009). In the general population of the oldest old, elderly individuals with abnormally high levels of thyrotropin do not experience adverse effects and may have a prolonged life span. However, evidence for not treating elderly individuals can only come from a well-designed, randomized placebo-controlled clinical trial.
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                Author and article information

                Journal
                Drug Des Devel Ther
                Drug Des Devel Ther
                Drug Design, Development and Therapy
                Dove Medical Press
                1177-8881
                2012
                22 December 2011
                : 6
                : 1-11
                Affiliations
                [1 ]Department of Endocrinology, Royal Devon and Exeter Hospital and Peninsula Medical School, Exeter
                [2 ]Endocrine Unit, Royal Victoria Infirmary and Newcastle University, Newcastle upon Tyne, UK
                Author notes
                Correspondence: Bijay Vaidya, MacLeod Diabetes and Endocrine Centre, Royal Devon and Exeter Hospital, Exeter, UK, Tel +44 13 9240 3831, Fax +44 13 9240 3027, Email bijay.vaidya@ 123456pms.ac.uk
                Article
                dddt-6-001
                10.2147/DDDT.S12894
                3267517
                22291465
                © 2012 Chakera et al, publisher and licensee Dove Medical Press Ltd.

                This is an Open Access article which permits unrestricted noncommercial use, provided the original work is properly cited.

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