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      Hypothyroidism.

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          Abstract

          Hypothyroidism is a common condition of thyroid hormone deficiency, which is readily diagnosed and managed but potentially fatal in severe cases if untreated. The definition of hypothyroidism is based on statistical reference ranges of the relevant biochemical parameters and is increasingly a matter of debate. Clinical manifestations of hypothyroidism range from life threatening to no signs or symptoms. The most common symptoms in adults are fatigue, lethargy, cold intolerance, weight gain, constipation, change in voice, and dry skin, but clinical presentation can differ with age and sex, among other factors. The standard treatment is thyroid hormone replacement therapy with levothyroxine. However, a substantial proportion of patients who reach biochemical treatment targets have persistent complaints. In this Seminar, we discuss the epidemiology, causes, and symptoms of hypothyroidism; summarise evidence on diagnosis, long-term risk, treatment, and management; and highlight future directions for research.

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          Most cited references115

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          Clinical practice guidelines for hypothyroidism in adults: cosponsored by the American Association of Clinical Endocrinologists and the American Thyroid Association.

          Hypothyroidism has multiple etiologies and manifestations. Appropriate treatment requires an accurate diagnosis and is influenced by coexisting medical conditions. This paper describes evidence-based clinical guidelines for the clinical management of hypothyroidism in ambulatory patients. The development of these guidelines was commissioned by the American Association of Clinical Endocrinologists (AACE) in association with American Thyroid Association (ATA). AACE and the ATA assembled a task force of expert clinicians who authored this article. The authors examined relevant literature and took an evidence-based medicine approach that incorporated their knowledge and experience to develop a series of specific recommendations and the rationale for these recommendations. The strength of the recommendations and the quality of evidence supporting each was rated according to the approach outlined in the American Association of Clinical Endocrinologists Protocol for Standardized Production of Clinical Guidelines-2010 update. Topics addressed include the etiology, epidemiology, clinical and laboratory evaluation, management, and consequences of hypothyroidism. Screening, treatment of subclinical hypothyroidism, pregnancy, and areas for future research are also covered. Fifty-two evidence-based recommendations and subrecommendations were developed to aid in the care of patients with hypothyroidism and to share what the authors believe is current, rational, and optimal medical practice for the diagnosis and care of hypothyroidism. A serum thyrotropin is the single best screening test for primary thyroid dysfunction for the vast majority of outpatient clinical situations. The standard treatment is replacement with L-thyroxine. The decision to treat subclinical hypothyroidism when the serum thyrotropin is less than 10 mIU/L should be tailored to the individual patient.
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            2013 ETA Guideline: Management of Subclinical Hypothyroidism

            Subclinical hypothyroidism (SCH) should be considered in two categories according to the elevation in serum thyroid-stimulating hormone (TSH) level: mildly increased TSH levels (4.0-10.0 mU/l) and more severely increased TSH value (>10 mU/l). An initially raised serum TSH, with FT4 within reference range, should be investigated with a repeat measurement of both serum TSH and FT4, along with thyroid peroxidase antibodies, preferably after a 2- to 3-month interval. Even in the absence of symptoms, replacement therapy with L-thyroxine is recommended for younger patients ( 10 mU/l. In younger SCH patients (serum TSH 80-85 years) with elevated serum TSH ≤10 mU/l should be carefully followed with a wait-and-see strategy, generally avoiding hormonal treatment. If the decision is to treat SCH, then oral L-thyroxine, administered daily, is the treatment of choice. The serum TSH should be re-checked 2 months after starting L-thyroxine therapy, and dosage adjustments made accordingly. The aim for most adults should be to reach a stable serum TSH in the lower half of the reference range (0.4-2.5 mU/l). Once patients with SCH are commenced on L-thyroxine treatment, then serum TSH should be monitored at least annually thereafter.
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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
                Lancet
                Lancet (London, England)
                Elsevier BV
                1474-547X
                0140-6736
                Sep 23 2017
                : 390
                : 10101
                Affiliations
                [1 ] Academic Centre for Thyroid Disease, Erasmus University Medical Centre, Rotterdam, Netherlands.
                [2 ] Division of Endocrinology and Metabolism, Rush University Medical Center, Chicago, IL, USA.
                [3 ] Division of Endocrinology, Georgetown University, Washington, DC, USA.
                [4 ] Academic Centre for Thyroid Disease, Erasmus University Medical Centre, Rotterdam, Netherlands. Electronic address: r.peeters@erasmusmc.nl.
                Article
                S0140-6736(17)30703-1 NIHMS908127
                10.1016/S0140-6736(17)30703-1
                6619426
                28336049
                75eb31a5-823e-4513-8ca4-2746e7c82d36
                History

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