Thyrotropin-Stimulating Hormone Receptor Gene Analysis in Pediatric Patients with Non-Autoimmune Subclinical Hypothyroidism

Nicoletti, Annalisa; Bal, Milva Orquidea; Marco, Giuseppina De; Baldazzi, Lilia; Agretti, Patrizia; Menabò, Soara; Ballarini, E; Cicognani, Alessandro; Tonacchera, Massimo; Cassio, Alessandra

doi:10.1210/jc.2009-0618

Cited by 64 publications

(48 citation statements)

References 27 publications

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“…Nicolleti et al (9) reported similar findings among children with nonautoimmune SCH in Italy, but in that study, all of individuals were heterozygous, whereas in the present cohort, 16 subjects had either homozygous or compound heterozygous mutations. Contrary to the Italian cohort, which enrolled only SCH subjects, both SCH and CH children with RTSH characteristics were included in the current study.…”

Section: Discussionsupporting

confidence: 49%

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Long-Term Outcome of Loss-of-Function Mutations in Thyrotropin Receptor Gene

Tenenbaum‐Rakover

Almashanu

Hess

et al. 2015

Thyroid

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Background: Loss-of-function mutations in the thyrotropin receptor (TSHR) gene lead to resistance to TSH (RTSH) presenting with either congenital hypothyroidism (CH) or subclinical hypothyroidism (SCH). Despite several reports of patients with TSHR mutations, data on the long-term outcome of this condition are limited, and no consensus exists on the need for hormone replacement therapy. The aim of the present study was to assess the long-term outcome in children and adolescents with RTSH due to TSHR mutations. Methods: The TSHR gene was sequenced in 94 subjects (aged 3 days-21 years) with either nonautoimmune SCH or CH with RTSH. Results: Twenty-seven subjects (29%) carried mutations in TSHR. Fifteen infants were identified by neonatal screening, and the other 79 patients were detected in the process of testing for various other conditions or because of family occurrence of thyroid test abnormalities. Six different mutations were identified: c. L653V), and c.1347C > T (p.R450C). Twelve subjects were homozygous, three were compound heterozygous, and 12 were heterozygous. Mean serum TSH levels at diagnosis and at last visit were significantly higher in patients with TSHR mutations than in those without mutations (29.04 vs. 14.15, p = 0.002; 31.73 vs. 6.19, p < 0.0001, respectively). Homozygous patients had a more severe phenotype (TSH 53.6 vs. 9.24, p < 0.0001). Mean serum free thyroxine (fT4) levels at the last visit were significantly lower than at the first visit in the homozygous individuals ( p = 0.05) for a follow-up period of as long as 11 years. Heterozygous subjects had only mild hyperthyrotropinemia with stable TSH levels. However, homozygous subjects showed a trend toward increased TSH and decreased fT4 with time. Conclusion: SCH in heterozygotes with TSHR mutations is a stable compensated condition with an appropriately adjusted set point for pituitary-thyroid feedback that does not require replacement therapy. However, homozygous subjects, with incompletely compensated SCH, show reduced fT4 levels over time and may require levothyroxine treatment. Replacement therapy should be considered on an individual basis, and longterm follow up is recommended.

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Section: Discussionsupporting

confidence: 49%

“…A prevalence of 4.3% biallelic TSHR mutations has been reported among Japanese infants with CH (8), whereas a high prevalence of 29% has been found among Italian children with nonautoimmune SCH (9).…”

mentioning

confidence: 97%

Long-Term Outcome of Loss-of-Function Mutations in Thyrotropin Receptor Gene

Tenenbaum‐Rakover

Almashanu

Hess

et al. 2015

Thyroid

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“…A prevalence of 4.3% biallelic TSHR mutations was found among 134 Japanese infants with CH (Narumi et al, 2009). Among 38 children with non-autoimmune subclinical hypothyroidism, 11 (29%) were carriers of TSHR mutations (Nicoletti et al, 2009). A prevalence of 12% TSHR mutations was shown in 42 subjects with non-autoimmune isolated hyperthyrotropinemia in Italy; all were with familial occurrence (Tonacchera et al, 2004).…”

Section: Prevalence Of Loss-of-function Mutationsmentioning

confidence: 95%

“…It was only in 1995 that the cause for RTSH syndrome in that case was shown to be a mutation in TSHR (Sunthornthepvarakul et al, 1995). Since the first report of CH caused by a TSHR mutation, several cases of loss-offunction mutations of TSHR have been reported: most are missense mutations, but deletions and insertions have been identified as well (see http: www.hgmd.cf.ac.uk/ac/ gene.php?gene=TSHR and OMIM#275200) (Abramowicz et al, 1997;Alberti et al, 2002;Biebermann et al, 1997Biebermann et al, , 2010Bretones et al, 2001;Camilot et al, 2005;Cangul et al, 2010;Clifton-Bligh et al, 1997;De Marco et al, 2009;de Roux et al, 1996;Fricke-Otto et al, 2005;Gagne et al, 1998;Grasberger et al, 2007;Jeziorowska et al, 2006;Jordan et al, 2003;Kanda et al, 2006;Nagashima et al, 2001;Narumi et al, 2009;Narumi et al, 2011;Park et al, 2004; …”

Section: Introductionmentioning

confidence: 99%

The Clinical Spectrum of Thyrotropin Receptor Gene (TSHR) Mutations

Tenenbaum‐Rakover¹

2012

Hypothyroidism - Influences and Treatments

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“…6 However, mutations in several proteins involved in TSH action including TSH receptor gene and mutations of dual oxidase 2 (DUOX2), phosphodiesterase 8B and thyroidperoxidase have also been demonstrated as causes of TSH elevation. [7][8][9][10] Although some clinicians consider SCH as a benign normal variation and thyroid hormone can be supplemented to lower the TSH levels and the exact cause of TSH elevation is unknown. But recent studies show higher mortality rates in young hypothyroid adults due to coronary heart disease and high TSH levels signify the importance of SCH and proving that SCH is not harmless.…”

Section: Introductionmentioning

confidence: 99%

Prevalence of subclinical hypothyroidism in children and adolescents of northern Andhra Pradesh population and its association with hyperlipidemia

2017

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Background: The thyroid dysfunction particularly, subclinical hypothyroidism (SCH) is quite a common clinical condition in paediatric population but there is limited data available regarding its prevalence in children and adolescents in our population. The present study was aimed to know the prevalence of thyroid dysfunction particularly SCH in children and adolescents of northern Andhra Pradesh population and its association with hyperlipidemia.Methods: A retrospective study of 600 subjects (Children=272, Adolescents=328) between 6-19 years of age were included and the following parameters were examined: age, sex, total triiodothyronine (tT3), total tetraiodothyronine (tT4), thyroid stimulating hormone (TSH), total cholesterol, triglycerides (TGL), LDL and HDL cholesterol. The subjects were divided into group I and group II on the basis of age (in years), subjects between 6- ≤12 years age were grouped as group I and 12-≤19 years were as group II.Results: Out of 272 children and 328 adolescents studied, the prevalence of thyroid dysfunction was found to be 9.9% and 10.4 % respectively. The prevalence of subclinical hypothyroidism in children was 7.7% where as 4.9% in adolescents. In both the groups, females were predominantly affected with thyroid dysfunction as compared to males. Significantly elevated serum levels of total cholesterol, TSH and TGL were observed in SCH subjects when compared to euthyroid subjects (p<0.05). Statistically significant lower levels of HDL cholesterol were found in SCH as compared to euthyroids (p<0.05). However, no difference was noticed in the levels of total T3, total T4 and LDL cholesterol between SCH and euthyroids.Conclusions: The prevalence of thyroid dysfunction was found to be 10.2% in study population. SCH was observed in 7.7 % and 4.9% respectively in children and adolescent groups. Subclinical hypothyroidism (SCH) was the most predominant thyroid dysfunction found in our studied population with a prevalence of 6.2% (both children and adolescents). Correction of thyroid dysfunction particularly SCH in early childhood is highly essential to prevent the impairment of psychomotor and cognitive development.

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Thyrotropin-Stimulating Hormone Receptor Gene Analysis in Pediatric Patients with Non-Autoimmune Subclinical Hypothyroidism

Cited by 64 publications

References 27 publications

Long-Term Outcome of Loss-of-Function Mutations in Thyrotropin Receptor Gene

Long-Term Outcome of Loss-of-Function Mutations in Thyrotropin Receptor Gene

The Clinical Spectrum of Thyrotropin Receptor Gene (TSHR) Mutations

Prevalence of subclinical hypothyroidism in children and adolescents of northern Andhra Pradesh population and its association with hyperlipidemia

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