ReviewCurrent opinion in endocrinology, diabetes, and obesity2018
Pathophysiological relevance of deiodinase polymorphism.
Review in Current opinion in endocrinology, diabetes, and obesity, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
36 citing papers in PubMed, 2 syntheses or guidelines pooled it, 58 citations in OpenAlex.
- LT4/LT3 Combination Therapy vs. Monotherapy with LT4 for Persistent Symptoms of Hypothyroidism: A Systematic Review.International journal of molecular sciences · 2024Pooled it
- The Type 2 Deiodinase Thr92Ala Polymorphism Is Associated with Higher Body Mass Index and Fasting Glucose Levels: A Systematic Review and Meta-Analysis.BioMed research international · 2021Pooled it
- Thyroid hormones and metabolic flexibility: tissue-specific control of energy homeostasis.Frontiers in physiology · 2026Review
- Thyroid-Microbiome Allostasis and Mitochondrial Performance: An Integrative Perspective in Exercise Physiology.Nutrients · 2025Review
- A Combination of L-Triiodothyronine and Levothyroxine in the Treatment of Tyrosine Kinase Inhibitor-Induced Hypothyroidism in Renal Cell Carcinoma: A Case Report.Clinical case reports · 2025Article
- Iodothyronine deiodinases in patients with stable chronic obstructive pulmonary disease - preliminary results.Pharmacological reports : PR · 2025Observational
- Thyroid Hormone Dynamics and DIO2 Variants in Schizophrenia: Exploring Genetic Links to Neuroendocrine Imbalance.Journal of cellular and molecular medicine · 2025Article
- Psychological factors and obesity, not thyroid biomarkers, predict thyroid-dependent quality of life in treated hypothyroidism: a cross-sectional study.BMC endocrine disorders · 2025Article
- Correlation of Residual Symptoms With Triiodothyronine (T3) in Patients Treated for Hypothyroidism.Cureus · 2025Article
- Association between sensitivity to thyroid hormone indices and type 2 diabetic microvascular complications in euthyroid patients.Scientific reports · 2024Article
- Beyond Calories: Individual Metabolic and Hormonal Adaptations Driving Variability in Weight Management-A State-of-the-Art Narrative Review.International journal of molecular sciences · 2024Review
- Gene polymorphisms and thyroid hormone signaling: implication for the treatment of hypothyroidism.Endocrine · 2024Review
- Emerging Therapies in Hypothyroidism.Annual review of medicine · 2024Review
- Are We Restoring Thyroid Hormone Signaling in Levothyroxine-Treated Patients With Residual Symptoms of Hypothyroidism?Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists · 2023Review
- The Physiological Functions and Polymorphisms of Type II Deiodinase.Endocrinology and metabolism (Seoul, Korea) · 2023Review
- Weight Gain and Asthenia Following Thyroidectomy: Current Knowledge from Literature Review.Journal of clinical medicine · 2022Review
- Brain Fog in Hypothyroidism: What Is It, How Is It Measured, and What Can Be Done About It.Thyroid : official journal of the American Thyroid Association · 2022Review
- Type 2 deiodinase p.Thr92Ala polymorphism does not affect the severity of obesity and weight loss after bariatric surgery.Scientific reports · 2022Article
- The relevance of TThe lancet. Diabetes & endocrinology · 2022Review
- Primary hypothyroidism and quality of life.Nature reviews. Endocrinology · 2022Review
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
Abstract
purpose of reviewTo assess new findings and clinical implications of deiodinase gene polymorphism. Deiodinases are enzymes that can activate or inactivate thyroid hormone molecules. Whereas the types 1 and 2 deiodinase (D1 and D2) activate thyroxine (T4) to 3,5,3'-triiodothyronine (T3) via deiodination of T4's outer ring, D1 and D3 inactivate both T4 and T3 and terminate thyroid hormone action via deiodination of T4's inner molecular ring. A number of polymorphisms have been identified in the three deiodinase genes; the most investigated and likely to have clinical relevance is the Thr92 substitution for Ala substitution in DIO2 (Thr92Ala-DIO2). There are a number of reports describing the association between the Thr92Ala-DIO2 polymorphism and clinical syndromes that include hypertension, type 2 diabetes, mental disorders, lung injury, bone turnover, and autoimmune thyroid disease; but these associations have not been reproduced in all population studies. RECENT
findingsA new report indicates that carriers of the Thr92Ala-DIO2 polymorphism exhibit lower D2 catalytic activity and localized/systemic hypothyroidism. This could explain why certain groups of levothyroxine-treated hypothyroid patients have improved quality of life when also treated with liothyronine (LT3). Furthermore, Ala92-D2 was abnormally found in the Golgi apparatus, what could constitute a disease mechanism independent of T3 signaling. Indeed, brain samples of Thr92Ala-DIO2 carriers exhibit gene profiles suggestive of brain degenerative disease. In addition, African American carriers of Thr92Ala-DIO2 exhibit an about 30% higher risk of developing Alzheimer's disease. SUMMARY: The finding of deiodinase polymorphisms that can diminish thyroid hormone signaling and/or disrupt normal cellular function opens the door to customized treatment of hypothyroidism. Future studies should explore how the racial background modulates the clinical relevance of the Thr92Ala-DIO2 gene polymorphism.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.