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Thyrotropin N-glycosylation and Glycan Composition in Severe Primary Hypothyroidism
Open accessAbstract
Context: In severe primary hypothyroidism (sPH), the serum thyrotropin (TSH) levels are elevated with an increased degree of sialylation. The circulating TSH comprises 2 different TSH glycoforms: TSHdi with 2 and TSHtri with 3 N-glycans and methods have developed to determine their contents of anionic monosaccharides (AMS), that is, sialic acid (SA) and sulfonated N-acetylglactosamine (SU) residues. Objective: Characterize N-glycosylation and glycan composition of circulating TSH molecules and determine the effects during levothyroxine treatment in patients with sPH. Methods: Serum samples were obtained from 25 patients with sPH, from 159 euthyroid individuals, and from 12 women during treatment with levothyroxine for sPH. Degrees of N-glycosylation and concentrations of TSHdi and TSHtri as well as their contents of AMS, SA, and SU residues were determined. Results: The circulating TSH molecules in sPH patients had lower degrees of N-glycosylation, higher degrees of sialylation, and lower degrees of sulfonation than in euthyroid individuals. Levothyroxin restored sialylation and sulfonation of the glycans already at low free thyroxine (FT4) levels, while degree of N-glycosylation was not restored until the FT4 levels were normal. Conclusions: The majority of TSH molecules in severe primary hypothyroidism were less N- glycosylated, more sialylated, and less sulfonated compared with euthyroid individuals. This glycan pattern favors a prolonged half-life in the circulation combined with lower in vitro biopotency at the target cells. During levothyroxine treatment of sPH patients, the sialylation and sulfonation of glycans were restored already at low FT4 levels, while N-glycosylation of TSH was not restored until the FT4 levels were normal.
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The immunoreactivity of TSH may be affected by changes in glycosylation state such that immunoreactive TSH concentration may not reflect bioactivity at the thyroidal TSH receptor.
“As well as these analytical issues, as previously discussed, the immunoreactivity of TSH may be affected by changes in glycosylation state such that the immunoreactive TSH concentration may not reflect bioactivity at the thyroidal TSH receptor.122–124”
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Metadata
- Authors
- Wide, L., & Eriksson, K.
- Affiliations
- Uppsala University (SE)
- Corresponding author
- Wide, Leif
- ORCID
- Wide, Leif
- Venue
- Journal of the Endocrine Society
- Publisher
- The Endocrine Society
- Published
- 2021-02-04
- Volume
- 5
- Issue
- 4
- Pages
- bvab006-bvab006
- ISSN
- 2472-1972 (ISSN-L)
- PMC
- PMC7896355
- OpenAlex
- W3127098572
- Cited by
- 9
- References
- 30
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 1 · 2023: 3 · 2022: 1 · 2021: 1
- FWCI
- 0.47
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Journal of the Endocrine Society (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- KTH Publication Database DiVA (KTH Royal Institute of Technology) (submittedVersion, other-oa)
- Funders
- Uppsala University (467320301)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Glycosylation and Glycoproteins Research
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Health Sciences › Medicine › Physiology (medical) › Salivary Gland Disorders and Functions
- Keywords
- thyroid-stimulating hormone, glycan composition, sialylation, sulfonation, sialic acid, levothyroxine therapy, free thyroxine
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