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      Assessment of the Adequacy of Thyroid Hormone Replacement Therapy in Hypothyroidism

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          Background: Recent studies identify a significant number of treated hypothyroid patients who express dissatisfaction with their therapy. At present there are sufficient measures of thyroid function to enable the clinician to establish a diagnosis of thyroid disease with a high degree of sensitivity and specificity. The purpose of this study was to quantitate the use of a new and novel assessment of clinically relevant hypothyroid symptoms in the management of patients with thyroid disease and to identify a tool that could help clinicians to assess adequacy of LT 4 treatment.

          Methodology: Unselected outpatients of the Thyroid Clinic of the North Shore University Hospital at Manhasset completed a questionnaire asking them to rate their physical symptoms related to thyroid disease as part of their standard care. This questionnaire consisted of 10 signs and symptoms. The questionnaire was collected from 198 control subjects, 241 subjects with primary hypothyroidism (under treatment), 113 euthyroid subjects (benign nodular thyroid disease), 73 previously hyperthyroid subjects (previously treated), and 27 subjects with thyroid cancer. A repeat questionnaire was obtained from 48 subjects with primary hypothyroidism (20%), 19 euthyroid subjects (17%), and 17 subjects previously hyperthyroid (23%).

          Data Analysis: The mean score for the sum of the signs and symptoms in the primary hypothyroid group with no medication change was 9.62 ± 1.29 for the initial questionnaire, and 10.04 ± 1.32 for the follow up questionnaire (not significant). For the primary hypothyroid patients requiring a medication change, at the time of the initial questionnaire the mean serum TSH was 12.86 ± 2.75 mcU/ml. Concurrently with the normalization of TSH, a statistically significant improvement in the sum of signs and symptoms mean score for this group was noted (16.32 ± 1.93 initial vs. 10.32 ± 1.46 after treatment to normalize TSH).

          Conclusion: The proposed newly devised hypothyroid scale correctly identified subjects with TSH elevation and clinical/subclinical hypothyroidism based on their clinical signs and symptoms. In this particular subset of patients, the hypothyroid symptom scale showed a statistically significant improvement in the sum of the signs and symptoms with the normalization of the subjects' thyroid function.

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          Most cited references 22

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          The molecular basis of thyroid hormone action.

           David A Brent (1994)
          Progress has been made in understanding the molecular basis of a number of clinical manifestations of thyroid disease, yet many questions remain. Why are there two thyroid hormone-receptor genes? Is the function of each of the two receptors indeed unique? How T3 receptors interact with other nuclear proteins and DNA-binding sites and how these interactions are influenced by T3 is incompletely understood. The developmental regulatory role of T3 receptor alpha 1 and its non-T3-binding alpha 2 variant needs to be defined. Most T3-regulated processes, especially those related to metabolism, muscle contraction, and brain development, function in concert with a number of other regulatory factors. The therapeutic applications of knowledge gained about the basic mechanisms of thyroid hormone action should ultimately extend beyond thyroid disease to processes regulated or influenced by T3; these include cardiac function, lipid metabolism, pituitary hormone secretion, and neural development.
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            The syndromes of resistance to thyroid hormone.

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              Replacement therapy for hypothyroidism with thyroxine alone does not ensure euthyroidism in all tissues, as studied in thyroidectomized rats.

              We have studied whether, or not, tissue-specific regulatory mechanisms provide normal 3,5,3'-triiodothyronine (T3) concentrations simultaneously in all tissues of a hypothyroid animal receiving thyroxine (T4), an assumption implicit in the replacement therapy of hypothyroid patients with T4 alone. Thyroidectomized rats were infused with placebo or 1 of 10 T4 doses (0.2-8.0 micrograms per 100 grams of body weight per day). Placebo-infused intact rats served as controls. Plasma and 10 tissues were obtained after 12-13 d of infusion. Plasma thyrotropin and plasma and tissue T4 and T3 were determined by RIA. Iodothyronine-deiodinase activities were assayed using cerebral cortex, liver, and lung. No single dose of T4 was able to restore normal plasma thyrotropin, T4 and T3, as well as T4 and T3 in all tissues, or at least to restore T3 simultaneously in plasma and all tissues. Moreover, in most tissues, the dose of T4 needed to ensure normal T3 levels resulted in supraphysiological T4 concentrations. Notable exceptions were the cortex, brown adipose tissue, and cerebellum, which maintained T3 homeostasis over a wide range of plasma T4 and T3 levels. Deiodinase activities explained some, but not all, of the tissue-specific and dose related changes in tissue T3 concentrations. In conclusion, euthyroidism is not restored in plasma and all tissues of thyroidectomized rats on T4 alone. These results may well be pertinent to patients on T4 replacement therapy.

                Author and article information

                Front Endocrinol (Lausanne)
                Front Endocrinol (Lausanne)
                Front. Endocrinol.
                Frontiers in Endocrinology
                Frontiers Media S.A.
                20 September 2019
                : 10
                1Private Practice , Brooklyn, NY, United States
                2Department of Biological Sciences and Geology, Queensborough Community College, City University of New York , Bayside, NY, United States
                3Department of Medicine, NYU School of Medicine , New York, NY, United States
                Author notes

                Edited by: Jacqueline Jonklaas, Georgetown University, United States

                Reviewed by: Roberto Vita, University of Messina, Italy; Gisah Amaral De Carvalho, Federal University of Paraná, Brazil

                *Correspondence: Sara Danzi saradanzi@ 123456gmail.com

                This article was submitted to Thyroid Endocrinology, a section of the journal Frontiers in Endocrinology

                Copyright © 2019 Brokhin, Danzi and Klein.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                Page count
                Figures: 2, Tables: 3, Equations: 0, References: 22, Pages: 7, Words: 4207
                Original Research

                Endocrinology & Diabetes

                diagnosis of hypothyroidism, treatment, t3, t4, symptom scale


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