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      The impact of Lithium on thyroid function in Chinese psychiatric population

      research-article
      Thyroid Research
      BioMed Central
      Lithium, Thyroid, Subclinical, Hypothyroidism, Psychiatric

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          Abstract

          Background

          Lithium was known to cause thyroid dysfunction and most commonly subclinical hypothyroidism (SCH). The aim of this study is to determine the prevalence of Lithium associated thyroid dysfunction and to identify risk factors associated with development of SCH in patients receiving Lithium.

          Methods

          A retrospective cross-sectional study was conducted. Subjects who developed elated thyroid stimulating hormone (TSH) were compared with those who remained euthyroid with Lithium treatment. Logistic regression and survival analysis were applied to identify the significant factors associated with SCH.

          Results

          The prevalence of Lithium associated with SCH was 31.7 %. The significant risk factors associated with increased risk of SCH included being female, higher serum Lithium level, concomitant use of Valproate Sodium and use of antidepressant. Use of depot injection was associated with decreased risk of SCH.

          Conclusions

          Use of depot and avoidance of Valproate or antidepressant should be taken into account before starting patient on Lithium treatment. Thyroxine replacement should be considered when Lithium associated SCH was identified.

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          Most cited references27

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          The effects of lithium therapy on thyroid and thyrotropin-releasing hormone.

          J Lazarus (1998)
          Lithium is used in the prophylaxis of bipolar depressive disorder in augmentation treatment of depression and in the therapy of some cases of unipolar depression. Lithium affects cell function via its inhibitory action on adenosine triphosphatase (ATPase) activity, cyclic adenosine monophosphate (cAMP), and intracellular enzymes. The inhibitory effect of lithium on inositol phospholipid metabolism affects signal transduction and may account for part of the action of the cation in manic depression. Lithium also alters the in vitro response of cultured cells to thyrotropin-releasing hormone (TRH) and can stimulate DNA synthesis. Lithium is concentrated by the thyroid and inhibits thyroidal iodine uptake. It also inhibits iodotyrosine coupling, alters thyroglobulin structure, and inhibits thyroid hormone secretion. The latter effect is critical to the development of hypothyroidism and goiter. Effects on brain deiodinase enzymes and alterations in thyroid hormone receptor concentration in the hypothalamus are under investigation in relation to the therapeutic effect of lithium. The ion affects many aspects of cellular and humoral immunity in vitro and in vivo. This accounts for a rise in antithyroid antibody titer in patients having these antibodies before lithium administration whereas there is no induction of thyroid antibody synthesis de novo. Goiter, due to increased thyrotropin (TSH) after inhibition of thyroid hormone release, occurs at various reported incidence rates from 0%-60% and is smooth and nontender. Subclinical and clinical hypothyroidism due to lithium is usually associated with circulating anti-thyroid peroxidase (TPO) antibodies but may occur in their absence. Iodine exposure, dietary goitrogens, and immunogenetic background may all contribute to the occurrence of goiter and hypothyroidism during long-term lithium therapy. It is currently unclear whether the reported association of lithium therapy and hyperthyroidism are causal, although there is suggestive epidemiological evidence. Finally, lithium therapy is associated with exaggerated response of both TSH and prolactin to TRH in 50%-100% of patients, although basal levels are not usually high. It is probable that the hypothalamic pituitary axis adjusts to a new setting in patients receiving lithium.
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            Fifteen-year follow-up of thyroid function in lithium patients.

            To study prospectively the course of clinically relevant thyroid dysfunction in a cohort of patients on long-term lithium treatment. Patients (no.=150) who had undergone a cross-sectional evaluation of their thyroid function in 1989, when they were at different stages of lithium treatment, were followed up for thyroid circulating thyroid antibodies, hypothyroidism, hyperthyroidism, and thyroidectomy, during a further period of lithium exposure of up to 15 yr. Annual rates of newly developed circulating thyroid antibodies and hypothyroidism were 1.7 and 1.5%, respectively. Subjects with thyroid antibodies had a higher chance of requiring substitution treatment with levothyroxine for hypothyroidism compared with subjects with no evidence of thyroid antibodies (6.4% annual rate compared to 0.8%; relative risk: 8.4; 95% confidence interval: 2.9-24.0). One case of hyperthyroidism was observed over 976 patient-yr. Three patients underwent thyroidectomy during followup (two for multinodular goiter and one for multicentric papillary carcinoma). Lithium may be associated with hypothyroidism in particular in the presence of circulating thyroid antibodies. Incidence of thyroid antibodies is comparable with that reported for the general population. Hyperthyroidism and thyroid cancer are rare.
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              Lithium-associated clinical hypothyroidism. Prevalence and risk factors.

              Rates of, and risk factors for, lithium-associated clinical hypothyroidism are uncertain. To determine prevalence of and risk factors for clinical hypothyroidism in patients treated with lithium carbonate. Retrospective case-note review of 718 patients who had undergone serum lithium estimation during a 15-month period. Patients on thyroxine had a more detailed review. The prevalence of clinical hypothyroidism during lithium treatment was 10.4%. The main risk factor was female gender (women 14% v. men 4.5%). Women were at highest risk during the first two years of lithium treatment, and women starting lithium aged 40-59 years had the greatest prevalence (> 20%). No equivalent risk factors emerged in men, although, like women, their prevalence of hypothyroidism was substantially higher than community rates. The high rates of clinical hypothyroidism identified may call for a review of the drug information given to women, particularly to those starting lithium in middle age. Consideration should be given to screening for thyroid antibodies before treatment in high-risk cases. Monitoring of thyroid function should take into account gender, age and stage of lithium treatment.
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                Author and article information

                Contributors
                luna-1005@hotmail.com
                Journal
                Thyroid Res
                Thyroid Res
                Thyroid Research
                BioMed Central (London )
                1756-6614
                4 September 2015
                4 September 2015
                2015
                : 8
                : 14
                Affiliations
                Department of Psychiatry, Pamela Youde Nethersole Eastern Hospital, 3 Lok Man Road, Chai Wan, Hong Kong SAR, China
                Article
                26
                10.1186/s13044-015-0026-2
                4558876
                26339294
                c54323a7-d707-4975-acf0-eed3c8227149
                © Tsui. 2015

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 21 July 2015
                : 27 August 2015
                Categories
                Research
                Custom metadata
                © The Author(s) 2015

                Endocrinology & Diabetes
                lithium,thyroid,subclinical,hypothyroidism,psychiatric
                Endocrinology & Diabetes
                lithium, thyroid, subclinical, hypothyroidism, psychiatric

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