Dichotomous Responses to Thyroid Hormone Treatment in a Patient with Primary Hypothyroidism and Thyroid Hormone Resistance

Sabet, Amin; Pallotta, Johanna A.

doi:10.1089/thy.2010.0450

Cited by 3 publications

(2 citation statements)

References 23 publications

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“…As shown in Figure 4, treatment with roxadustat significantly induced the transcriptional activity of wild-type THRβ in Gal-4 driven reporter assays, to a lesser extent than that of T3. As expected, the native ligand T3 abolished or substantially diminished the transcriptional activity of four THRβ mutants associated with thyroid hormone resistance, V264D, H435L, R438H, and R438W, respectively (Wakasaki et al., 2016, Nomura et al., 1996, Sabet and Pallotta, 2011, Narumi et al., 2010). Surprisingly, the treatment of roxadustat either enhanced or retained the transcriptional activity of these THRβ mutants, all leading to higher induced transcriptional activity than those of T3 (Figure 4).…”

Section: Resultssupporting

confidence: 78%

Revealing a Mutant-Induced Receptor Allosteric Mechanism for the Thyroid Hormone Resistance

et al. 2019

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SummaryResistance to thyroid hormone (RTH) is a clinical disorder without specific and effective therapeutic strategy, partly due to the lack of structural mechanisms for the defective ligand binding by mutated thyroid hormone receptors (THRs). We herein uncovered the prescription drug roxadustat as a novel THRβ-selective ligand with therapeutic potentials in treating RTH, thereby providing a small molecule tool enabling the first probe into the structural mechanisms of RTH. Despite a wide distribution of the receptor mutation sites, different THRβ mutants induce allosteric conformational modulation on the same His435 residue, which disrupts a critical hydrogen bond required for the binding of thyroid hormones. Interestingly, roxadustat retains hydrophobic interactions with THRβ via its unique phenyl extension, enabling the rescue of the activity of the THRβ mutants. Our study thus reveals a critical receptor allosterism mechanism for RTH by mutant THRβ, providing a new and viable therapeutic strategy for the treatment of RTH.

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Section: Resultssupporting

confidence: 78%

Revealing a Mutant-Induced Receptor Allosteric Mechanism for the Thyroid Hormone Resistance

et al. 2019

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“…For example, many studies have illustrated that individuals with subclinical hypothyroidism (increased TSH and T4 levels) have an increased risk of MDD [50][51][52][53]. Patients with subclinical hypothyroidism are more likely to have psychotic symptoms, including hallucinations and delusions [54][55][56]. Further, evidence supports that the hypothalamic-pituitary adrenal (HPA) axis disorder may be related to psychotic symptoms [41].…”

Section: Discussionmentioning

confidence: 99%

Thyroid dysfunction in first-episode drug-naïve major depressive disorder patients with or without psychotic symptoms

Yang,

Zhao,

Kang

et al. 2023

Preprint

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Background It is a common of comorbid psychotic symptoms in patients with major depressive disorder (MDD). However, there are few studies on the thyroid function of psychotic depression (PD) in first-episode drug naïve (FEDN) MDD patients. This study was to examine the difference in thyroid function between PD and NPD of first-episode drug-naïve (FEDN) major depression (MDD) and explore the related risk factors for PD in a large sample size of patients in a Chinese population. Methods We recruited 1718 outpatients diagnosed with FEDN MDD. The thyroid function-related parameters, including thyroid-stimulating hormone (TSH), free thyroxin (FT4, FT3)7, thyroid peroxidase antibodies (TPOAb), and anti-thyroglobulin (TGAb), socio-demographic and clinical data were collected. The Hamilton Anxiety Rating Scale (HAMA), Hamilton Depression Rating Scale (HAMD), and the positive subscale of the Positive and Negative Syndrome Scale (PANSS) were administered to score patients’ anxiety, depression, and psychotic symptoms. Results The elevated TSH, TPOAb, and TGAb serum accounted for 79.5%, 28.7%, and 35.9% of PD patients, respectively. Compared to NPD patients, PD patients had higher serum levels of TSH, TGAb, and TPOAb (all P < 0.001). Furthermore, logistic regression analysis demonstrated a strong association between the serum level of TSH and PD, with an odds ratio of 1.189. Conclusions Our findings suggest that elevated TSH levels may increase the risk of PD and highlight the importance of thyroid screening tests for the accurate diagnosis and effective treatment of PD.

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Thyroid Profiles in a Patient with Resistance to Thyroid Hormone and Episodes of Thyrotoxicosis, Including Repeated Painless Thyroiditis

Taniyama

Otsuka

Tozaki

et al. 2013

Thyroid

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Dichotomous Responses to Thyroid Hormone Treatment in a Patient with Primary Hypothyroidism and Thyroid Hormone Resistance

Abstract: Patients with RTH may develop significant hypothyroidism with normal TH levels in the setting of Hashimoto's thyroiditis. RTH presents a unique challenge in both the diagnosis and management of autoimmune hypothyroidism.

Cited by 3 publications

References 23 publications

Revealing a Mutant-Induced Receptor Allosteric Mechanism for the Thyroid Hormone Resistance

Revealing a Mutant-Induced Receptor Allosteric Mechanism for the Thyroid Hormone Resistance

Thyroid dysfunction in first-episode drug-naïve major depressive disorder patients with or without psychotic symptoms

Thyroid Profiles in a Patient with Resistance to Thyroid Hormone and Episodes of Thyrotoxicosis, Including Repeated Painless Thyroiditis

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