ENDOCRINE DISORDERS IN CHILDHOOD AND ADOLESCENCE: Natural history of subclinical hypothyroidism in children and adolescents and potential effects of replacement therapy: a review

Monzani, Alice; Prodam, Flavia; Rapa, Anna; Moia, Stefania; Agarla, Valentina; Bellone, Simonetta; Bona, Gianni

doi:10.1530/eje-12-0656

Cited by 90 publications

(82 citation statements)

References 59 publications

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“…Only few studies have evaluated the effect of shortterm trials with L-T4 in heterogeneous populations of children with mild to severe SH (5,20,23), and none of them have focused on the relationship between SH and metabolic aspects.…”

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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“…In childhood, this is an even more controversial issue (6,7,8,9,10) and the only available study comparing the effects of L-T 4 treatment vs no therapy in idiopathic SH suggests that therapy is unable to modify post-therapy outcome of hyperthyrotropinemia and to prevent the risks of a subsequent TSH increase after treatment withdrawal (11). In the children with HT-related mild SH, it has been just recently reported that the evolution of thyroid function tests seems to be frequently characterized by a deterioration over time, whereas such risk is very low in the children with idiopathic SH (12).…”

Section: Introductionmentioning

confidence: 99%

Five-year prospective evaluation of thyroid function in girls with subclinical mild hypothyroidism of different etiology

Waśniewska

Aversa

Salerno

et al. 2015

European Journal of Endocrinology

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Aim: To follow-up for 5 years thyroid status evolution in 127 girls with mild (TSH 5-10 mU/l) subclinical hypothyroidism (SH) of different etiologies. Patients: The population was divided into two age-matched groups of 42 and 85 girls with either idiopathic (group A) or Hashimoto's thyroiditis (HT)-related SH (group B). Group B was in turn divided into three subgroups, according to whether SH was either isolated or associated with Turner syndrome (TS) or Down syndrome (DS). Results: At the end of follow-up the rate of girls who became euthyroid was higher in group A (61.9% vs 10.6%), whereas the rates of patients who remained SH (55.3% vs 26.2%), became overtly hypothyroid (30.6% vs 11.9%) or required levothyroxine (L-T 4 ) therapy (63.5% vs 23.8%) were higher in group B. Among the girls of group B, the risk of remaining SH or developing overt hypothyroidism was higher in the subgroups with TS or DS than in those with isolated HT. Conclusions: Long-term prognosis of mild and idiopathic SH is frequently benign, even though a L-T 4 treatment may be needed throughout follow-up in almost a quarter of cases; long-term prognosis is different in the girls with either idiopathic or HT-related SH; and the association with either TS or DS impairs the outcome of HT-related SH.

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“…For subclinical hypothyroidism, there are only a few studies in children/adolescents, and it appears that thyroxine treatment leads to increased growth (29). Our finding of a relation between rs4704397 SNP and body height is therefore plausible.…”

Section: Jorde Et Almentioning

confidence: 58%

The Phosphodiesterase 8B Gene rs4704397 is Associated with Thyroid Function, Risk of Myocardial Infarction, and Body Height: The Tromsø Study

Jorde

Schirmer

Wilsgaard

et al. 2014

Thyroid

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Objective: High serum thyrotropin (TSH) levels predict cardiovascular disease (CVD). Recently several single nucleotide polymorphisms (SNPs) associated with TSH levels have been identified, one of them being the rs4704397 SNP in the phosphodiesterase 8B (PDE8B) gene. If the relation between thyroid function and CVD is causal, one could also expect rs4704397 genotypes to predict CVD and possibly health in general. Methods: DNA was prepared and genotyping performed for rs4704397 in subjects who participated in the fourth survey of the Tromsø Study in 1994-1995 and who were registered with the endpoints myocardial infarction (MI), type 2 diabetes (T2DM), cancer, or death, as well as a randomly selected control group. Similarly, genotyping was performed in subjects who had participated in clinical trials where serum TSH, free T4 (fT4), and free T3 (fT3) were measured. Results: From the Tromsø Study, 8938 subjects without thyroid disease or thyroid medication were successfully genotyped for rs4704397. Among these, 2098 were registered with MI, 1025 with T2DM, 2748 with cancer, and 3592 had died. The minor homozygote genotype (A:A) had a median serum TSH level that was 0.29 mIU/L higher than in the major homozygote genotype (G:G). The A:A genotype had a significantly increased risk of MI as compared to the G:G genotype (1.14 [1.00-1.29], hazard ratio [confidence interval], Cox regression with adjustment for age, sex, and body mass index). No significant associations were seen with the other endpoints or CVD risk factors. Furthermore, subjects with the G:G genotype were significantly taller than subjects with the A:A genotype (mean difference 1.5 cm). In 584 subjects with serum TSH, fT4, and fT3 measurements, the subjects with the A:A genotype had significantly higher serum TSH and nonsignificantly lower serum fT3 (mean difference 0.15 pmol/L) levels than subjects with the G:G genotype. Conclusion: rs4704397 is associated with thyroid function, risk of MI, and body height. However, confirmation in other cohorts is needed before firm conclusions can be drawn.

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ENDOCRINE DISORDERS IN CHILDHOOD AND ADOLESCENCE: Natural history of subclinical hypothyroidism in children and adolescents and potential effects of replacement therapy: a review

Cited by 90 publications

References 59 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

Five-year prospective evaluation of thyroid function in girls with subclinical mild hypothyroidism of different etiology

The Phosphodiesterase 8B Gene rs4704397 is Associated with Thyroid Function, Risk of Myocardial Infarction, and Body Height: The Tromsø Study

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