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

Maria Cristina Vigone, Marianna Di Frenna, Fabiana Guizzardi, Giulia Gelmini, Tiziana de Filippis, Stefano Mora, Silvana Caiulo, Micol Sonnino, Marco Bonomi, Luca Persani, Giovanna 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: 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.

Original languageEnglish
Pages (from-to)587-596
Number of pages10
JournalClinical Endocrinology
Issue number5
Publication statusPublished - Nov 1 2017


  • congenital hypothyroidism (CH)
  • L-thyroxine therapy (L-T4)
  • subclinical hypothyroidism (SCH)
  • thyroid-stimulating hormone receptor (TSHR) mutation
  • TSH resistance (RTSH)

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism


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