ESPE Abstracts (2014) 82 P-D-2-1-587

Mutation of the TSH Receptor Gene: a Longitudinal Study in Children with Non-Autoimmune Subclinical Hypothyroidism

Maria Cristina Vigonea, Micol Sonninoa, Fabiana Guizzardic, Marianna Di Frennaa, Silvana Caiuloa, Giulia Gelminic, Luca Persanib,c & Giovanna Webera


aDepartment of Pediatrics, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy; bDepartment of Clinical Sciences and Communitye Health, University of Milan, Milan, Italy; cLaboratory of Endocrine and Metabolic Diseases, IRCCS Istituto Auxologico Italiano, Milan, Italy


Background: Neonatal screening strategies revealed an increase in hypothyroidism associated with an in-situ thyroid gland due to TSH receptor (TSHR) mutations. While there are many genetic and functional studies regarding TSHR mutations, few are found concerning the clinical course and long-term outcome of TSH resistance involving the pediatric population.

Objective and hypotheses: To determine the impact of TSHR mutations on clinical course, biochemical parameters and therapeutic approach in children carrying this mutation.

Method: Data regarding diagnosis, etiological reevaluation, family history, thyroid function, thyroid ultrasound, clinical and auxological parameters, were collected and evaluated in a group of 33 children with non-autoimmune subclinical hypothyroidism (SH) due to a TSHR mutation. DEXA scan, bone age, biochemical parameters, and questionnaire on QOL were also administered. Fifty-four children, negative for a TSHR mutation, were enrolled as our controls.

Results: Fourteen different mutations (five new) of the TSHR gene were identified. Only 45% of TSHR+ patients were identified at screening while the remaining 55% were diagnosed in early childhood. All patients at diagnosis demonstrated FT4 values within range with the exception of one patient. 60% of our TSHR+ patients began treatment, however only 35% within one month of age. Diagnostic re-evaluation, carried out in 15 patients, demonstrated that TSHR+ patients had a greater tendency of discontinuing treatment compared to TSHR− patients (60 vs 43%). The six patients who resumed treatment were either compound heterozygous for the mutation, SGA or both. During follow up, we analyzed different aspects of thyroid hormone competence and no significant alterations were found.

Conclusions: We found different arguments in favor of avoiding substitute hormonal treatment in patients carrying a single heterozygous TSHR mutation.

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