Objective: Mutations in TSH receptor (TSHR) are associated with TSH resistance, a genetic defect characterized by a heterogeneous phenotype ranging from severe hypothyroidism to subclinical hypothyroidism (SCH). We assessed the clinical and hormonal pattern of TSHR variants in a series of pediatric patients, and the long-term outcome of growth, biochemical measurements of metabolism, and neuropsychological functions in TSHR mutations carriers. Design: Observational, retrospective study. Patients: Thirty four children (age 7 days to 11 years) and 18 adult carriers of TSHR variants. Measurements: The TSHR gene was sequenced by PCR-amplified direct sequencing in 111 pediatric patients with slight to moderate elevation of TSH and normal FT4 levels. The study focused on the: auxological and biochemical parameters, thyroid ultrasound, bone age, bone mineral density (BMD), and intellectual outcome (IQ) were collected during the long follow-up (1-15 years). Results: Seventeen different TSHR variants (eight novel) were identified in 34 of the 111 pediatric patients, with a high prevalence of familial cases (27/34). Neonatal screening for congenital hypothyroidism was positive in half of the TSHR carriers. Growth, IQ, BMD, and biochemical parameters were normal in all subjects. Twenty patients received L-T4 replacement therapy, in all cases before genetic analysis. After re-evaluation, six patients resumed L-T4 therapy: they were compound heterozygous, or single heterozygous and with associated conditions at risk of thyroid impairment (SGA). No adults presented clinical features consistent with impaired thyroid function. Conclusions: Children carriers of TSHR variants, regardless of L-T4 treatment, show regular growth and neuropsychological development, with no evident biochemical and US alterations.

Mild TSH resistance : Clinical and hormonal features in childhood and adulthood / M.C. Vigone, M. Di Frenna, F. Guizzardi, G. Gelmini, T. de Filippis, S. Mora, S. Caiulo, M. Sonnino, M. Bonomi, L. Persani, G. Weber. - In: CLINICAL ENDOCRINOLOGY. - ISSN 0300-0664. - 87:5(2017 Nov), pp. 587-596. [10.1111/cen.13387]

Mild TSH resistance : Clinical and hormonal features in childhood and adulthood

M. Bonomi;L. Persani;WEBER, GIOVANNA
2017-11

Abstract

Objective: Mutations in TSH receptor (TSHR) are associated with TSH resistance, a genetic defect characterized by a heterogeneous phenotype ranging from severe hypothyroidism to subclinical hypothyroidism (SCH). We assessed the clinical and hormonal pattern of TSHR variants in a series of pediatric patients, and the long-term outcome of growth, biochemical measurements of metabolism, and neuropsychological functions in TSHR mutations carriers. Design: Observational, retrospective study. Patients: Thirty four children (age 7 days to 11 years) and 18 adult carriers of TSHR variants. Measurements: The TSHR gene was sequenced by PCR-amplified direct sequencing in 111 pediatric patients with slight to moderate elevation of TSH and normal FT4 levels. The study focused on the: auxological and biochemical parameters, thyroid ultrasound, bone age, bone mineral density (BMD), and intellectual outcome (IQ) were collected during the long follow-up (1-15 years). Results: Seventeen different TSHR variants (eight novel) were identified in 34 of the 111 pediatric patients, with a high prevalence of familial cases (27/34). Neonatal screening for congenital hypothyroidism was positive in half of the TSHR carriers. Growth, IQ, BMD, and biochemical parameters were normal in all subjects. Twenty patients received L-T4 replacement therapy, in all cases before genetic analysis. After re-evaluation, six patients resumed L-T4 therapy: they were compound heterozygous, or single heterozygous and with associated conditions at risk of thyroid impairment (SGA). No adults presented clinical features consistent with impaired thyroid function. Conclusions: Children carriers of TSHR variants, regardless of L-T4 treatment, show regular growth and neuropsychological development, with no evident biochemical and US alterations.
congenital hypothyroidism (CH); L-thyroxine therapy (L-T4); subclinical hypothyroidism (SCH); thyroid-stimulating hormone receptor (TSHR) mutation; TSH resistance (RTSH); Endocrinology, Diabetes and Metabolism
Settore MED/13 - Endocrinologia
Settore MED/38 - Pediatria Generale e Specialistica
CLINICAL ENDOCRINOLOGY
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/551256
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