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

Kód výsledku v 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>

Nalezeny alternativní kódy

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

Výsledek na webu

<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>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30202 - Endocrinology and metabolism (including diabetes, hormones)

Projekt

<a href="/cs/project/NU20-03-00285" target="_blank" >NU20-03-00285: BIOINFORMATICKÉ ZPRACOVÁNI NGS DAT A FUNKČNÍ ANALÝZY KANDIDÁTNÍCH VARIANT PRO TESTOVÁNÍ HEREDITÁRNÍCH NÁDOROVÝCH SYNDROMŮ V ČR (II)</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2021

Kód důvěrnosti údajů

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

Název periodika

Hormones

ISSN

1109-3099

e-ISSN

—

Svazek periodika

20

Číslo periodika v rámci svazku

4

Stát vydavatele periodika

CH - Švýcarská konfederace

Počet stran výsledku

10

Strana od-do

803-812

Kód UT WoS článku

000662799800001

EID výsledku v databázi Scopus

2-s2.0-85108210944