ISSN: 1308-5727 | E-ISSN: 1308-5735
Volume : 5 Issue : 1 Year : 2024
Forms

Abstracting & Indexing
Turkish Society for Pediatric Endocrinology and Diabetes
Current Loss-of-Function Mutations in the Thyrotropin Receptor Gene: When to Investigate, Clinical Effects, and Treatment [J Clin Res Pediatr Endocrinol]
J Clin Res Pediatr Endocrinol. 2013; 5(1): 29-39 | DOI: 10.4274/Jcrpe.864

Current Loss-of-Function Mutations in the Thyrotropin Receptor Gene: When to Investigate, Clinical Effects, and Treatment

Alessandra Cassio1, Annalisa Nicoletti1, Angela Rizzello1, Emanuela Zazzetta1, Milva Bal1, Lilia Baldazzi1
Department of Gynaecologic, Obstetric and Paediatric Sciences, S.Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy

Thyroid-stimulating hormone receptor (TSHR) loss-of-function (LOF) mutations lead to a wide spectrum of phenotypes, ranging from severe congenital hypothyroidism (CH) to mild euthyroid hyperthyrotropinemia. The degree of TSH resistance depends on the severity of the impairment of the receptor function caused by the mutation and on the number of mutated alleles In this review data about genotype-phenotype correlation and criteria for clinical work-up will be presented and discussed. Complete TSH resistance due to biallelic LOF TSHR mutations must be suspected in all patients with severe not syndromic CH and severe thyroid hypoplasia diagnosed at birth by neonatal screening. Partial forms of TSH resistance show a more heterogeneous hormonal and clinical pattern . In these cases TSH serum levels are above the upper limit of normal range for the age but with a very variable pattern, free thyroxine (T4) concentrations are within the normal range and thyroid size can be normal or hypoplastic at ultrasound scan. An early substitutive treatment with L-T4 must be mandatory in all patients with severe CH due to complete uncompensated TSH resistance diagnosed at birth by neonatal screening. The usefulness of substitutive treatment appears much more controversial in patients with subclinical hypothyroidism due to partial TSH resistance in whom the increased TSH concentration should be able to compensate the mild functional impairment of the mutant receptor. Together with standard criteria we recommend also an accurate clinical work-up to select patients who are candidates for a LOF TSHR mutation.

Keywords: Thyrotropin receptor gene mutations, congenital hypothyroidism, neonatal screening, subclinical hypothyroidism

Alessandra Cassio, Annalisa Nicoletti, Angela Rizzello, Emanuela Zazzetta, Milva Bal, Lilia Baldazzi. Current Loss-of-Function Mutations in the Thyrotropin Receptor Gene: When to Investigate, Clinical Effects, and Treatment. J Clin Res Pediatr Endocrinol. 2013; 5(1): 29-39
Manuscript Language: English
LookUs & Online Makale