The Clinical Spectrum of Thyrotropin Receptor Gene (TSHR) Mutations

Tenenbaum‐Rakover, Yardena

doi:10.5772/31153

Cited by 3 publications

(3 citation statements)

References 83 publications

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“…Loss-of-function mutations in the TSH receptor (TSHR) gene lead to RTSH characterized by either congenital hypothyroidism (CH) or subclinical hypothyroidism (SCH) (1)(2)(3)(4)(5)(6).…”

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confidence: 99%

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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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“…Loss-of-function mutations in the TSH receptor (TSHR) gene lead to RTSH characterized by either congenital hypothyroidism (CH) or subclinical hypothyroidism (SCH) (1)(2)(3)(4)(5)(6).…”

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confidence: 99%

“…To date, about 60 different loss-of-function mutations in the TSHR have been described (4)(5)(6). The degree of hyposensitivity to TSH depends on the type and location of the TSHR mutation and whether the patient is homozygous or heterozygous.…”

mentioning

confidence: 99%

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

Tenenbaum‐Rakover

Almashanu

Hess

et al. 2015

Thyroid

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“…Side effects of L-T 4 therapy on the heart with such as resting tachycardia and on individuals' behavior, such as restlessness and sleep disturbances, should be considered in the clinical decisions for initiation of therapy. In euthyroid hyperthyrotropinemia caused by heterozygous loss-of-function mutation of TSHR, TSH levels tend to be stable over the years and therefore no therapy is indicated (Tenenbaum- Rakover, 2012). In newborns, a different approach should be taken since delay in therapy may result in permanent intellectual damage.…”

Section: Treatmentmentioning

confidence: 99%

Current Topics in Hypothyroidism with Focus on Development

Potluková¹

2013

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Eliška Potluková graduated from the First Faculty of Medicine of the Charles University in Prague in 2001. During studies, she spent six months at the Yale School of Medicine (USA) working in a research lab. After graduation, she worked in the University Hospital Basel in Switzerland as a researcher in immunology and as a physician (internal medicine). She graduated from the Basel University in 2004. Since then, she has been working at the Third Department of Medicine of the General University Hospital in Prague as a physician (internal medicine, endocrinology), teacher and scientist. She is an author of a number of original articles published in well-regarded journals in the fields of endocrinology and immunology.

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Approach to Subclinical Hypothyroidism in Children

Tenenbaum‐Rakover¹

2013

Current Topics in Hypothyroidism With Focus on Development

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The Clinical Spectrum of Thyrotropin Receptor Gene (TSHR) Mutations

Cited by 3 publications

References 83 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

Current Topics in Hypothyroidism with Focus on Development

Approach to Subclinical Hypothyroidism in Children

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