{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,24]],"date-time":"2025-09-24T00:07:33Z","timestamp":1758672453333,"version":"3.44.0"},"reference-count":26,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T00:00:00Z","timestamp":1758585600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:p>Physicians demonstrate differing attitudes about the management of hypothyroid patients on optimal replacement with thyroxine (T4) who have persisting symptoms. The use of liothyronine (T3) as combination therapy (T4+T3) has been promoted, and some patients demonstrate a compelling benefit. They can be identified by delayed relaxation of tendon reflexes, that is, a positive Woltman\u2019s sign. This is specific for T3 responders. A generation of Endocrinologists has neglected this useful clinical sign. Patients with autoimmune symptoms and elevated anti-thyroid peroxidase (anti-TPO) antibodies show improvement after total thyroidectomy, but with the risk of significant postoperative complications. This discrete subgroup tends to be disregarded by authorities in the literature. There is a compelling need for further research on the nonsurgical treatment of this subgroup. Many dissatisfied patients have psychosomatic symptoms because of the burden of having a chronic disease, the need to take regular medication, and other psychosocial concerns. They have medically not yet explained symptoms (MNYES) and require support, counselling, and sometimes cognitive behaviour therapy. True thyroxine allergy and\/or sensitivity does occur but is extremely rare. These four subgroups could be designated as \u2013 (1) T3-hypothyroidism; (2) Anti-TPO-toxic hypothyroidism; (3) Hypothyroidism-in-denial; and (4) Thyroxine- sensitivity. Recognition of these individual categories is necessary to achieve agreement among physicians and to promote further targeted research.<\/jats:p>","DOI":"10.3389\/fendo.2025.1640663","type":"journal-article","created":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T06:05:59Z","timestamp":1758607559000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Addressing the hypothyroidism impasse - seeking a consensus for the treatment of dissatisfied hypothyroid patients"],"prefix":"10.3389","volume":"16","author":[{"given":"Tim","family":"Welborn","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,9,23]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgad224","article-title":"Critical approach to hypothyroid patients with persistent symptoms","volume":"108","author":"Biondi","year":"2023","journal-title":"J Clin Endocrinol Metab"},{"key":"B2","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1038\/s41574-024-01055-y","article-title":"Limiting the use and misuse of liothyronine in hypothyroidism","volume":"21","author":"Hegedus","year":"2025","journal-title":"Nat Rev Endocrinol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1111\/cen.15228","article-title":"Shared decision making in the treatment of hypothyroidism","volume":"103","author":"Bianco","year":"2025","journal-title":"Clin Endocrinol (Oxf)"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2020.0720","article-title":"Evidence-based use of levothyroxine\/liothyronine combinations in treating hypothyroidism: A consensus document","volume":"31","author":"Jonklaas","year":"2021","journal-title":"Thyroid"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2023.0580","article-title":"Patients\u2019 persistent symptoms, clinician demographics, and geo-economic factors are associated with choice of therapy for hypothyroidism by European Specialists: The \u201cTHESIS\u201d collaboration (*Treatment of Hypothyroidism in Europe by Specialists, an International Survey)","volume":"34","author":"Attanasio","year":"2024","journal-title":"Thyroid"},{"key":"B6","doi-asserted-by":"publisher","first-page":"887","DOI":"10.1210\/clinem\/daea651","article-title":"Treatment preferences in patients with hypothyroidism: An analysis of 11 randomised controlled trials","volume":"110","author":"de Lima Beltrao","year":"2024","journal-title":"J Clin Endocrinol Metab"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.37871\/jbres2000","article-title":"Hypothyroidism revisited: Defining the subgroups on optimal thyroxine replacement who have persisting symptoms","volume":"5","author":"Welborn","year":"2024","journal-title":"J BioMed Res Environ Sci"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2022.04.010","article-title":"More trials for the unhappy hypothyroid patient on thyroxine: A clinician\u2019s perspective","volume":"3","author":"Welborn","year":"2022","journal-title":"Trends Endocrinol Metab"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMicm1713796","article-title":"Woltman\u2019s sign of hypothyroidism","volume":"379","author":"Iwasaki","year":"2018","journal-title":"N Engl J Med"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1111\/j.1445-5994.1990.tb01286.x","article-title":"A comparison of two methods of eliciting the ankle jerk","volume":"20","author":"Schwartz","year":"1990","journal-title":"Aust N Z J Med"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.4158\/endp.19.6.266x613757j22j36","article-title":"Practice guidelines for hypothyroidism in adults: Clinical issues and the controversy about combination therapy","volume":"19","author":"Welborn","year":"2013","journal-title":"Endocrin Pract"},{"key":"B12","first-page":"49","article-title":"Hypothyroidism: A small clinical trial will quickly resolve the combination therapy controversy","volume":"8","author":"Welborn","year":"2022","journal-title":"Int J Clin Biostat Biom"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2017.01.029","article-title":"The ups and downs of the thyroxine pro-hormone hypothesis","volume":"458","author":"Galton","year":"2017","journal-title":"Mol Cell Endocrinol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2010.0191","article-title":"Hashimoto\u2019s thyroiditis affects symptom load and quality of life unrelated to hypothyroidism: A prospective case-control study in women undergoing thyroidectomy for benign goitre","volume":"21","author":"Ott","year":"2011","journal-title":"Thyroid"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.7326\/M18-0284","article-title":"Thyroidectomy versus medical management for euthyroid patients with Hashimoto disease and persisting symptoms. 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