Non-autoimmune subclinical hypothyroidism due to a mutation in TSH receptor: report on two brothers

Cerbone, Manuela; Agretti, Patrizia; Marco, Giuseppina De; Improda, Nicola; Pignata, Claudio; Santamaria, Francesca; Tonacchera, Massimo; Salerno, Mariacarolina

doi:10.1186/1824-7288-39-5

Cited by 7 publications

(5 citation statements)

References 34 publications

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“…Understanding the clinical relevance of SH and L-T4 therapy on CV morbidity in SH children may help in driving the management of these subjects and in defining recommendations for their treatment. Indeed, current recommendations suggest L-T4 treatment only in children with TSH levels >10 mU/L, whereas the management of mild idiopathic SH is still a matter of debate (1,3,20,21,22).…”

Section: Introductionmentioning

confidence: 99%

Effects of L-thyroxine treatment on early markers of atherosclerotic disease in children with subclinical hypothyroidism

Cerbone¹,

Capalbo²,

Waśniewska

et al. 2016

European Journal of Endocrinology

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Objective: To investigate the effect of levothyroxine (L-T4) treatment on early markers of atherosclerotic disease in children with mild idiopathic subclinical hypothyroidism (SH). Design: Two-year, open, case-control prospective study. Methods: A total of 39 children, aged 9.18 ± 3.56 years, with SH and 39 healthy controls were enrolled in the study. Waist-to-height ratio (WHtR), blood pressure, triglycerides, total cholesterol (total-C), HDL-C, LDL-C, non-HDL-C, triglycerides/HDL-C, atherogenic index (AI), homocysteine (Hcy), asymmetric dimethylarginine (ADMA), flow-mediated dilation (FMD) and intima-media thickness (IMT) were evaluated at baseline and after 2 years of L-T4 treatment in SH children and after 2 years of follow-up in controls. Results: At study entry WHtR was higher in SH subjects compared with controls (0.56 ± 0.08 vs 0.49 ± 0.07, P = 0.04) and significantly decreased after 2 years of treatment (0.50 ± 0.06, P < 0.0001). Mean HDL-C levels (50.47 ± 11.43 vs 61.06 ± 13.83 mg/dL, P = 0.002) were lower, while triglycerides/HDL-C (1.63 ± 1.07 vs 1.19 ± 0.69, P = 0.05), AI (3.32 ± 0.90 vs 2.78 ± 0.68, P = 0.005), and Hcy (9.35 ± 2.61 vs 7.71 ± 1.94 μmol/L, P = 0.01) were higher in SH subjects compared with controls and improved after 2 years of treatment (HDL-C 56.26 ± 13.76 mg/dL, P < 0.0001; triglycerides/HDL-C 1.23 ± 0.78, P = 0.006; AI 2.82 ± 0.68, P < 0.0001; and Hcy 8.25 ± 2.09 μmol/L, P = 0.06). ADMA concentrations at baseline were higher in SH subjects compared with controls (0.77 ± 0.21 vs 0.60 ± 0.16 μmol/L, P = 0.001) and decreased after therapy (0.58 ± 0.13 μmol/L, P < 0.0001). FMD, IMT and other metabolic parameters were not different among SH subjects and controls at baseline and after 2 years. Conclusions: Children with SH may have subtle pro-atherogenic abnormalities. Although L-T4 treatment exerts some beneficial effects, the long-term impact of therapy on metabolic outcomes in SH children still remains unclear.

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Section: Introductionmentioning

confidence: 99%

Effects of L-thyroxine treatment on early markers of atherosclerotic disease in children with subclinical hypothyroidism

Cerbone¹,

Capalbo²,

Waśniewska

et al. 2016

European Journal of Endocrinology

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“…The second one has a neonatal persistent moderate TSH levels increase associated with a thyroid gland hypoplasia and was treated with L-T4 since the first months of life although had an IQ of 80 at age 16, possibly due to initial low dosage/delay in starting treatment which its known to be associated with such outcomes. 97 The mutation R109Q in the extracellular domain of TSH-Xr, found in these 2 brothers was described by Clifton-Bligh et al in a child with compound heterozygous for another missense mutation in the fourth transmembrane segment of receptor. 98 In the 2 siblings reported by Nicoletti et al 95 having the same R109Q mutation, milder phenotype was found, characterized by slight increase in serum TSH, normal thyroid gland at ultrasound and no clinical features of thyroid dysfunction.…”

Section: Subclinical Hypothyroidism (Sh)mentioning

confidence: 87%

“…TSHR is a member of the G protein-coupled receptor family, which also includes calcitonin or PTH receptors. Cerbone et al 97 reported non autoimmune SH in 2 brothers carrying the same mutation in the extracellular domain of TSH-R but presenting with different clinical, biochemical and morphological features. The first one had only a slight persistent elevation of TSH, abnormal thyroid on ultrasound and did never require l-thyroxine (L-T4) replacement treatment and had a normal IQ of 108 at age 16.…”

Section: Subclinical Hypothyroidism (Sh)mentioning

confidence: 99%

Male Hypothyroidism-Clinical Relevance Including Role in Reproduction

Kaur¹

2015

JDMDC

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Purpose: Overt Hypothyroidism is defined as arise of S.TSH>10mIU/L. Since its incidence is more common in females one generally tends to ignore this diagnosis in males and usually the diagnosis is made in an emergency situation when the patient presents either with coma or with a severe form of Hashimoto's thyroiditis (HT) like IgG4 related thyroiditis. Methods: A systemic literature search was performed using PubMed for all English articles till Sept 2014 regarding male hypothyroidism using MeSH terms like congenital hypothyroidism, male hypothyroidism and reproduction; subclinical hypothyroidism; Hoffmann's syndrome; myxedemic coma. Results: To eradicate congenital hypothyroidism all over the world many countries have incorporated in their neonatal screening programme (NNSP), yet occasional cases of cretinism still get diagnosed .Important causes being genes encoding Transcription factor TTX1, TTX2 presenting as Bamforth syndrome, Thyroglobulin gene, Thyroid peroxidase (TPO), TSHR gene abnormalities, Pendreds syndrome coexisting with thyroid developmental abnormalities etc. Context Ig superfamily1deficiency (IGSF1), Fryns Anophthalmia Plus syndrome (APS), TSHβ gene deletion, frame shift mutation in first exon of Fibroblast growth factor8 (FGF8) can present as Central hypothyroidism. The first presentation maybe a neurological emergency like myxedemic coma either secondary to neurofibromatosis, lithium toxicity which responds to L-thyroxin or occasionally may not, responding only to steroids. Some patients may present as different forms of Hoffmann's syndrome or stiff leg syndromes. Subclinical hypothyroidis, (SH) and its aetiology along with TSH R mutations R109 Qreported as causation in 2 brothers and importance of treatment is highlighted. Importance of treatment of SH in children and adults is discussed. Mechanism of reversible kidney dysfunction in hypothyroidism is highlighted along with discussing its relationship with treatment. Changes in serum testosterone and gonadotropins are discussed in a patient of male hypothyroidism and the way it may affect reproduction. Conclusion: Hypothyroidism may be the primary cause of a male presenting with Hypogonadotropic hypogonadism (HH) and should be suspected in a man presenting with delayed puberty. Untreated hypothyroidism should be suspected as the cause of presentation of myopathies like Hoffmann Syndrome or other myopathies or myxedema coma. SH may warrant treatment in young males with known adverse affects on cardiovascular system although its affect on cognitive function has not been found especially in elderly.

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“…The current study has been discussed whether or not the association of TSHR rs2268458 with thyroid function tests (FT3, FT4, and TSH) as well as other physio-biochemical parameters in Iraqi hypothyroidism women in Babylon province. Many studies have investigated the role of mutations and the polymorphism in TSHR gene in the development of different thyroid diseases [12], [13], [8], [14].…”

Section: Discussionmentioning

confidence: 99%

The Association of TSHR Gene rs2268458 Polymorphism with Hypothyroidism in Females of Babylon Province-Iraq

Hussain

Hadi

Al-Harbi

2018

JUBPAS

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The Aim: To evaluate the association of TSHR gene polymorphism rs2268458 with some Physio-biochemical parameters among hypothyroidism women. Methods: This study included 51 hypothyroidism women and 43 healthy women as a control group. Some Physio-biochemical (body mass index (BMI), cytochrome 450 1A1 (CYP1A1), calcium, and phosphorus) and hormonal assay (Osteopontin (OPN), thyroid stimulating hormone (TSH), fT3, fT4 and Calcitonin (CT)) assay were performed. Genotyping of rs-2268458 of TSHR gene was carried out using the polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) technique. Results: TSHR rs2268458 was associated with hypothyroidism in Iraqi women and allele C can be a risk factor for disease by OR= 4.393, CI=1.42-13.53 where TC and CC genotypes were associated with high BMI, while TC genotype was associated with high calcitonin and CYP1A1 levels. Conclusion: The TSHR rs2268458 polymorphism was associated with hypothyroidism in Iraqi women and allele C can be a risk factor for some Physio-biochemical and hormonal disorder in hypothyroidism women.

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Non-autoimmune subclinical hypothyroidism due to a mutation in TSH receptor: report on two brothers

Cited by 7 publications

References 34 publications

Effects of L-thyroxine treatment on early markers of atherosclerotic disease in children with subclinical hypothyroidism

Effects of L-thyroxine treatment on early markers of atherosclerotic disease in children with subclinical hypothyroidism

Male Hypothyroidism-Clinical Relevance Including Role in Reproduction

The Association of TSHR Gene rs2268458 Polymorphism with Hypothyroidism in Females of Babylon Province-Iraq

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