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

MC Vigone, Marianna Di Frenna, F Guizzardi, G Gelmini, T de Filippis, S Mora, S Caiulo, Micol Sonnino, M Bonomi, L Persani, G Weber

Research output: Contribution to journalArticlepeer-review


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: 34 children (age 7d-11yr) 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 yr). RESULTS: Seventeen different TSHR variants (8 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, 6 patients resumed L-T4 therapy: they were compound heterozygous, or single heterozygous and with associated conditions at-risk for 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. This article is protected by copyright. All rights reserved.
Original languageEnglish
Pages (from-to)587-596
Number of pages10
JournalClinical Endocrinology
Issue number5
Publication statusPublished - 2017


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