Current Loss-of-Function Mutations in the Thyrotropin Receptor Gene: When to Investigate, Clinical Effects, and Treatment
| Autor: | Emanuela Zazzetta, Angela Rizzello, Alessandra Cassio, Annalisa Nicoletti, Lilia Baldazzi, Milva Orquidea Bal |
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| Přispěvatelé: | Cassio, A, Nicoletti, A, Rizzello, A, Zazzetta, E, Bal, M, Baldazzi, L |
| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
medicine.medical_specialty
endocrine system Thyrotropin Receptor Gene TSHR LOF mutations TSH resistance endocrine system diseases Endocrinology Diabetes and Metabolism Review medicine.disease_cause Thyrotropin receptor Endocrinology Subclinical hypothyroidism Internal medicine medicine Congenital Hypothyroidism Humans Euthyroid Subclinical infection Mutation business.industry Thyroid Receptors Thyrotropin medicine.disease Congenital hypothyroidism Thyrotropin receptor gene mutations medicine.anatomical_structure Hormone receptor Pediatrics Perinatology and Child Health business Neonatal screening hormones hormone substitutes and hormone antagonists Hormone |
| Zdroj: | Journal of Clinical Research in Pediatric Endocrinology |
| ISSN: | 1308-5735 1308-5727 |
| Popis: | 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. Conflict of interest:None declared. |
| Databáze: | OpenAIRE |
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