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      A Case of Refractory Hypothyroidism due to Poor Compliance Treated with the Weekly Intravenous and Oral Levothyroxine Administration

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          Abstract

          Refractory hypothyroidism is caused by decreased gut absorption, increased metabolism, and poor compliance. Previous studies suggested that the weekly oral, suppository, or intramuscular administration of levothyroxine (LT4) is an effective treatment for refractory hypothyroidism. However, limited information is currently available on treatment involving the weekly intravenous administration of LT4. We managed a case of refractory hypothyroidism due to poor compliance, for which, by weekly intravenous LT4 administration, LT4 was intravenously administered weekly at a dose of 300 μg without any adverse effects such as acute ischemic heart diseases or liver dysfunction and effectively maintained the euthyroid status for 14 months. The weekly oral administration of LT4 (700 μg) was also safely performed and was as effective as its intravenous administration. We herein present precise clinical course of the present case including pharmacokinetic data during the weekly intravenous and oral administration of LT4 and discuss the safety and efficacy of the treatments.

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          Most cited references11

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          Hypothyroidism.

          Hypothyroidism is common, potentially serious, often clinically overlooked, readily diagnosed by laboratory testing, and eminently treatable. The condition is particularly prevalent in older women, in whom autoimmune thyroiditis is common. Other important causes include congenital thyroid disorders, previous thyroid surgery and irradiation, drugs such as lithium carbonate and amiodarone, and pituitary and hypothalamic disorders. Worldwide, dietary iodine deficiency remains an important cause. Hypothyroidism can present with nonspecific constitutional and neuropsychiatric complaints, or with hypercholesterolaemia, hyponatraemia, hyperprolactinaemia, or hyperhomocysteinaemia. Severe untreated hypothyroidism can lead to heart failure, psychosis, and coma. Although these manifestations are neither specific nor sensitive, the diagnosis is confirmed or excluded by measurements of serum thyrotropin and free thyroxine. Thyroxine replacement therapy is highly effective and safe, but suboptimal dosing is common in clinical practice. Patient noncompliance, drug interactions, and pregnancy can lead to inadequate treatment. Iatrogenic thyrotoxicosis can cause symptoms, and, even when mild, provoke atrial fibrillation and osteoporosis. We summarise present understanding of the history, epidemiology, pathophysiology, and clinical diagnosis and management of hypothyroidism.
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            Myxedema Coma: A New Look into an Old Crisis

            Myxedema crisis is a severe life threatening form of decompensated hypothyroidism which is associated with a high mortality rate. Infections and discontinuation of thyroid supplements are the major precipitating factors while hypothermia may not play a major role in tropical countries. Low intracellular T3 leads to cardiogenic shock, respiratory depression, hypothermia and coma. Patients are identified on the basis of a low index of suspicion with a careful history and examination focused on features of hypothyroidism and precipitating factors. Arrythmias and coagulation disorders are increasingly being identified in myxedema crisis. Thyroid replacement should be initiated as early as possible with careful attention to hypotension, fluid replacement and steroid replacement in an intensive care facility. Studies have shown that replacement of thyroid hormone through ryles tube with a loading dose and maintenance therapy is as efficacious as intravenous therapy. In many countries T3 is not available and oral therapy with T4 can be used effectively without major significant difference in outcomes. Hypotension, bradycardia at presentation, need for mechanical ventilation, hypothermia unresponsive to treatment, sepsis, intake of sedative drugs, lower GCS and high APACHE II scores and Sequential Organ Failure Assessment (SOFA) scores more than 6 are significant predictors of mortality in myxedema crisis. Early intervention in hypothyroid patients developing sepsis and other precipitating factors and ensuring continued intake of thyroid supplements may prevent mortality and morbidity associated with myxedema crisis.
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              A Review of the Pharmacokinetics of Levothyroxine for the Treatment of Hypothyroidism

              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 levothyroxine. This article will review the pharmacokinetics of levothyroxine in the treatment of hypothyroidism and highlight major concepts that should aid both clinicians and researchers.
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                Author and article information

                Contributors
                Journal
                Case Rep Endocrinol
                Case Rep Endocrinol
                CRIE
                Case Reports in Endocrinology
                Hindawi
                2090-6501
                2090-651X
                2019
                5 February 2019
                : 2019
                : 5986014
                Affiliations
                1Department of Molecular Endocrinology and Metabolism, Graduate School of Medical and Dental Science, Tokyo Medical and Dental University, 113-8510, Japan
                2Department of Preemptive and Metabolism, Graduate School of Medical and Dental Science, Tokyo Medical and Dental University, 113-8510, Japan
                3Department of Endocrinology and Metabolism, Kashiwa Municipal Hospital, 277-0825, Japan
                4Department of Pharmacy, Medical Hospital of Tokyo Medical and Dental University, 113-8510, Japan
                5Department of General Medicine, National Defense Medical College Hospital, 359-0042, Japan
                Author notes

                Academic Editor: Osamu Isozaki

                Author information
                http://orcid.org/0000-0003-1620-7164
                http://orcid.org/0000-0002-3530-689X
                http://orcid.org/0000-0001-8002-4843
                Article
                10.1155/2019/5986014
                6379869
                31c9bc14-3512-450b-b427-76f6f8bb1524
                Copyright © 2019 Yujiro Nakano et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 27 November 2018
                : 29 January 2019
                Funding
                Funded by: Ministry of Health, Labour and Welfare
                Funded by: Japan Society for the Promotion of Science
                Award ID: JP 26461376
                Categories
                Case Report

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