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03-02-2025 | Original Article

Thyroxine overuse and clinical indices guiding successful treatment withdrawal

Authors: Sarantis Livadas, Nicholas Angelopoulos, Anastasios Kollias, Rodis D. Paparodis, Ioannis Androulakis, Panagiotis Anagnostis, Anastasios Boniakos, Dimitrios Askitis, Djuro Macut, Juan C. Jaume, Leonidas Duntas

Published in: Journal of Endocrinological Investigation

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Abstract

Purpose

Levothyroxine (LT4) is commonly prescribed, but there is evidence strongly suggesting that a significant proportion of these patients are on treatment without solid evidence of hypothyroidism. Small trials on treatment discontinuation, did not detect any predictors of success. Therefore, we conducted this study in an attempt to identify predicting factors for successful LT4 withdrawal.

Methods

In 802 consecutive patients (83% females, mean age 48 ± 16 years) on LT4 treatment for 8.8 ± 7.3 years without a solid diagnosis of hypothyroidism, therapy was abruptly discontinued. A total of 387 persons were followed up for up to 4 months (group A) and 415 individuals who were euthyroid at 4 months post LT4 discontinuation, were followed up for up to 60 months (group B). Recurrent hypothyroidism was defined if thyrotropin (TSH) level exceeded 4.5mIU/L.

Results

Among the entire cohort, 182 patients (23%) became hypothyroid, 40% of group A and 7% of group B (p < 0.001). The Τhyroid treatment Discrimination Index (T4RxDI), the product of TSH levels multiplied by the daily LT4 dose divided by BMI, was calculated. In group A, successful LT4 withdrawal was strongly indicated by a T4RxDI value < 2.78 (72% sensitivity, 66% specificity), while in group B, the corresponding value was 3.75 (100% sensitivity, 48% specificity).

Conclusions

Our findings reveal considerable overuse of LT4 and propose a T4RxDI product of < 3 as a valuable predictive factor of recurrent hypothyroidism, justifying a treatment discontinuation trial. If hypothyroidism does not resume within 4 months, the risk of developing long-term hypothyroidism is likely to be minimal.
Literature
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go back to reference Gharib H, Papini E, Garber JR, AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS, AMERICAN COLLEGE OF ENDOCRINOLOGY, AND ASSOCIAZIONE MEDICI ENDOCRINOLOGI MEDICAL GUIDELINES FOR CLINICAL PRACTICE FOR THE DIAGNOSIS AND MANAGEMENT OF THYROID NODULES–2016 UPDATE (2016) Endocr Pract 22:622–639. https://doi.org/10.4158/EP161208.GLCrossRefPubMed Gharib H, Papini E, Garber JR, AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS, AMERICAN COLLEGE OF ENDOCRINOLOGY, AND ASSOCIAZIONE MEDICI ENDOCRINOLOGI MEDICAL GUIDELINES FOR CLINICAL PRACTICE FOR THE DIAGNOSIS AND MANAGEMENT OF THYROID NODULES–2016 UPDATE (2016) Endocr Pract 22:622–639. https://​doi.​org/​10.​4158/​EP161208.​GLCrossRefPubMed
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go back to reference Koutras DA, Alevizaki M, Tsatsoulis A, Vagenakis AG (2003) Greece is iodine sufficient. Lancet 362:405–406CrossRefPubMed Koutras DA, Alevizaki M, Tsatsoulis A, Vagenakis AG (2003) Greece is iodine sufficient. Lancet 362:405–406CrossRefPubMed
Metadata
Title
Thyroxine overuse and clinical indices guiding successful treatment withdrawal
Authors
Sarantis Livadas
Nicholas Angelopoulos
Anastasios Kollias
Rodis D. Paparodis
Ioannis Androulakis
Panagiotis Anagnostis
Anastasios Boniakos
Dimitrios Askitis
Djuro Macut
Juan C. Jaume
Leonidas Duntas
Publication date
03-02-2025
Publisher
Springer International Publishing
Published in
Journal of Endocrinological Investigation
Electronic ISSN: 1720-8386
DOI
https://doi.org/10.1007/s40618-025-02543-2

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