Children with mild TSH resistance develop normally

Children who are carriers of thyroid-stimulating hormone receptor, or TSHR, variants resulting in mild hypothyroidism demonstrated normal neuropsychological development and physical growth, according to researchers in Italy.

“Changes in screening strategies for congenital hypothyroidism have led to an increased detection rate of mild forms of [congenital hypothyroidism],” Maria Cristina Vigone, MD, of the department of pediatrics at the IRCCS San Raffaele Scientific Institute at Vita-Salute San Raffaele University, Milan, and colleagues wrote. “To date, more than 60 [loss-of-function] mutations of the TSHR have been described with a variable prevalence depending on the population tested. There are only a few studies in literature that describe the long-term follow-up of subjects with TSHR mutations.”

The researchers performed an observational, retrospective study on 111 children aged 7 days to 11 years who were referred to San Raffaele Hospital for evaluation of elevated TSH and normal free thyroxine levels. Vigone and colleagues carried out TSHR gene sequencing, and measured patients’ thyroid ultrasounds, bone ages, bone mineral densities, IQ, and auxological and biochemical parameters during a follow-up ranging from 1 to 15 years.

Overall, 34 (30.6%) of the children demonstrated 17 different TSHR variants, eight of which were novel. Four patients (12%) were born preterm, five (15%) were born after multiple pregnancies and another four were small for gestational age at birth. Most patients (85%) were born to families with histories of thyroid diseases.

Twenty-seven of the 34 cases were familial, the researchers reported. Half of the children screened positive for congenital hypothyroidism. All patients showed normal growth, IQ, BMD and biochemical parameters, Vigone and colleagues wrote. Twenty patients, all of whom had compound mutations or single heterozygotes, underwent L-T4 replacement. The researchers reported that no adults in the study showed any clinical features indicative of impaired thyroid function.

“Pediatric patients carrying a TSHR mutation, regardless of L-T4 treatment, showed regular growth and neuropsychological development with no evident biochemical and [ultrasonography] alterations,” Vigone and colleagues wrote. “It seems that children with TSHR variants might not need treatment unless they are carriers of compound mutations or single heterozygotes with associated conditions at risk for thyroid impairment. In any case, a careful follow-up is necessary in all untreated cases. Our data should be confirmed by longitudinal studies.” – by Andy Polhamus

Disclosure: The researchers report no relevant financial disclosures.