Novel presentation of the c.1856A > G (p.Asp619Gly) TSHR gene-activating variant: relapsing hyperthyroidism in three subsequent generations manifesting in early childhood and an in vitro functional study

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11120%2F21%3A43921728" target="_blank" >RIV/00216208:11120/21:43921728 - isvavai.cz</a>

Alternative codes found

RIV/00216208:11110/21:10428604 RIV/00064203:_____/21:10428604 RIV/00064165:_____/21:10428604 RIV/00216208:11130/21:10428604 RIV/00064173:_____/21:N0000243

Result on the web

<a href="https://doi.org/10.1007/s42000-021-00299-x" target="_blank" >https://doi.org/10.1007/s42000-021-00299-x</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1007/s42000-021-00299-x" target="_blank" >10.1007/s42000-021-00299-x</a>

Result language

angličtina

Original language name

Novel presentation of the c.1856A > G (p.Asp619Gly) TSHR gene-activating variant: relapsing hyperthyroidism in three subsequent generations manifesting in early childhood and an in vitro functional study

Original language description

BACKGROUND: Familial non-autoimmune hyperthyroidism is a rare disease caused by germline activating variants in the thyroid-stimulating hormone receptor (TSHR) gene. The c.1856A &gt; G (p.Asp619Gly) pathogenic variant has been described in cases of toxic adenoma but never before, to our knowledge, in a case of familial non-autoimmune hyperthyroidism. PATIENT FINDINGS: A 3-year-old boy was admitted for acute gastroenteritis presenting with goiter and tall stature. Laboratory findings revealed peripheral hyperthyroidism and negativity for thyroid autoantibodies. Antithyroid drug treatment was effective, but relapses occurred shortly after attempts to decrease the drug dose. As the boy&apos;s father and paternal grandmother also experienced relapsing hyperthyroidism manifesting in early childhood, genetic testing of TSHR was indicated. The c.1856A &gt; G (p.Asp619Gly) pathogenic variant was found in all three affected family members. Functional in vitro characterization of the variant verified that it enhances constitutional activation of the receptor, leading to increased production of cyclic adenosine monophosphate. Total thyroidectomy was indicated in the boy due to an unsatisfactory prognosis. Due to persistent positive thyroglobulin serum concentration, a diagnostic radioiodine scan was performed approximately 2 years later. Residual thyroid tissue was revealed; therefore, radioiodine ablative therapy was performed. Despite adequate thyroxine substitution over a long period of follow-up, TSH remained suppressed. CONCLUSIONS: Unlike Graves&apos; disease, familial non-autoimmune hyperthyroidism cases present with antithyroid drug-dependence. Not ultrasound but positive thyroglobulin serum concentration indicated residual thyroid tissue. Early detection of residual thyroid tissue and radioiodine ablation prevented the subject from experiencing relapsing hyperthyroidism and undergoing unnecessary repeated surgery. Life-long hormone substitution should be adjusted to free thyroxine rather than TSH serum concentrations.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30202 - Endocrinology and metabolism (including diabetes, hormones)

Project

<a href="/en/project/NU20-03-00285" target="_blank" >NU20-03-00285: BIOINFORMATICS AND FUNCTIONAL ANALYSES OF SUSCEPTIBILITY VARIANTS SUPPORTING THE NGS-BASED TESTING OF HEREDITARY CANCERS IN THE CZECH REPUBLIC (II)</a><br>

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2021

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Hormones

ISSN

1109-3099

e-ISSN

—

Volume of the periodical

20

Issue of the periodical within the volume

4

Country of publishing house

CH - SWITZERLAND

Number of pages

10

Pages from-to

803-812

UT code for WoS article

000662799800001

EID of the result in the Scopus database

2-s2.0-85108210944