This guideline has been produced as the official statement of the European Thyroid Association guideline committee. Subclinical hypothyroidism (SCH) in pregnancy is defined as a thyroid-stimulating hormone (TSH) level above the pregnancy-related reference range with a normal serum thyroxine concentration. Isolated hypothyroxinaemia (defined as a thyroxine level below the 2.5th centile of the pregnancy-related reference range with a normal TSH level) is also recognized in pregnancy. In the majority of SCH the cause is autoimmune thyroiditis but may also be due to iodine deficiency. The cause of isolated hypothyroxinaemia is usually not apparent, but iodine deficiency may be a factor. SCH and isolated hypothyroxinaemia are both associated with adverse obstetric outcomes. Levothyroxine therapy may ameliorate some of these with SCH but not in isolated hypothyroxinaemia. SCH and isolated hypothyroxinaemia are both associated with neuro-intellectual impairment of the child, but there is no evidence that maternal levothyroxine therapy improves this outcome. Targeted antenatal screening for thyroid function will miss a substantial percentage of women with thyroid dysfunction. In children SCH (serum TSH concentration >5.5-10 mU/l) normalizes in >70% and persists in the majority of the remaining patients over the subsequent 5 years, but rarely worsens. There is a lack of studies examining the impact of SCH on the neuropsychological development of children under the age of 3 years. In older children, the evidence for an association between SCH and impaired neuropsychological development is inconsistent. Good quality studies examining the effect of treatment of SCH in children are lacking.

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2014 European Thyroid Association Guidelines for the Management of Subclinical Hypothyroidism in Pregnancy and in Children

Context: The WHO Technical Consultation recommends urinary iodine concentrations (UIC) from 250 to 499 μg/L as more-than-adequate iodine intake and UIC ≥500 μg/L as excessive iodine for pregnant and lactating women, but scientific evidence for this is weak. Objective: We investigated optimal and safe ranges of iodine intake during early pregnancy in an iodine-sufficient region of China. Method: Seven thousand one hundred ninety pregnant women at 4–8 weeks gestation were investigated and their UIC, serum thyroid stimulating hormone (TSH), free thyroxine (FT4), thyroid-peroxidase antibody (TPOAb), thyroglobulin antibody (TgAb), and thyroglobulin (Tg) were measured. Results: The prevalence of overt hypothyroidism was lowest in the group with UIC 150–249 μg/L, which corresponded to the lowest serum Tg concentration (10.18 μg/L). Prevalences of subclinical hypothyroidism (2.4%) and isolated hypothyroxinemia (1.7%) were lower in the group with UIC 150–249 μg/L. Multivariate logistic regression indicated that mo...

Optimal and Safe Upper Limits of Iodine Intake for Early Pregnancy in Iodine-Sufficient Regions: A Cross-Sectional Study of 7190 Pregnant Women in China

Objectives: Obesity can alter the thyroid hormone status as a result of a dysregulated endocrine loop between the hypothalamo-pituitary unit and adipose tissue. The adipocytokine leptin has been shown to promote autoimmunity; hence, we aimed to clarify whether leptin excess of obesity could increase the susceptibility to develop autoimmune thyroid disease (AITD). Study design: This cross-sectional study was performed in a tertiary care center. Methods: Free thyroid hormones, TSH, thyroglobulin, and antithyroid antibodies levels were tested in 165 obese and 118 lean subjects. Results were plotted against variables related to body composition, leptin levels, glucose homeostasis, energy expenditure, and pattern of weight accrual. Results: Compared with controls, obese patients had lower free T3 levels and free T4 levels (P < 0.01), greater prevalence of hypothyroidism (P < 0.05), and higher commonness of antithyroid antibodies (P < 0.05). As a marker of AITD, thyroid peroxidase antibodies were more frequent ...

/pdf/investigations-of-thyroid-hormones-and-antibodies-in-obesity-11ae7nshwl.pdf

Investigations of thyroid hormones and antibodies in obesity: leptin levels are associated with thyroid autoimmunity independent of bioanthropometric, hormonal, and weight-related determinants.

Urine iodine has been measured in the U.S. population by the National Health and Nutrition Examination Survey (NHANES) since 1971. A downward trend was noted between NHANES I (320 ± 6 µg/L in 1971–...

/pdf/urinary-iodine-concentration-united-states-national-health-176kpeheiz.pdf

Urinary iodine concentration : United States National Health and Nutrition Examination Survey 2001-2002

Objective: With the introduction of iodized salt worldwide, more and more people are exposed to more than adequate iodine intake levels with median urinary iodine excretion (MUI 200–300 mg/l) or excessive iodine intake levels (MUI O300 mg/l). The objective of this study was to explore the associations between more than adequate iodine intake levels and the development of thyroid diseases (e.g. thyroid dysfunction, thyroid autoimmunity, and thyroid structure) in two Chinese populations. Design: A population-based cross-sectional study was conducted in two areas in which people are exposed to different levels of iodine intake (Rongxing, MUI 261 mg/l; Chengshan, MUI 145 mg/l). A total of 3813 individuals were recruited by random sampling. Thyroid hormones, thyroid autoantibodies in serum, and iodine levels in urine were measured. B-mode ultrasonography of the thyroid was also performed for each participant. Results: The prevalence of subclinical hypothyroidism was significantly higher for subjects who live in Rongxing than those who live in Chengshan (5.03 vs 1.99%, P!0.001). The prevalence of positive anti-thyroid peroxidase antibody (TPOAb) and positive anti-thyroglobulin antibody (TgAb) was significantly higher for subjects in Rongxing than those in Chengshan (TPOAb: 10.64 vs 8.4%, PZ0.02; TgAb: 10.27 vs 7.93%, PZ0.01). The increase in thyroid antibodies was most pronounced in the high concentrations of TPOAb (TPOAb: R500 IU/ml) and low concentrations of TgAb (TgAb: 40–99 IU/ml) in Rongxing. Conclusions: More than adequate iodine intake could be a public health concern in terms of thyroid function and thyroid autoimmunity in the Chinese populations.

/pdf/more-than-adequate-iodine-intake-may-increase-subclinical-1end863h9h.pdf

More than adequate iodine intake may increase subclinical hypothyroidism and autoimmune thyroiditis: a cross-sectional study based on two Chinese communities with different iodine intake levels.

Iodine is essential for thyroid function. Thyroid disorders related to iodine deficiency decreased progressively with the continuous iodine prophylaxis and the increased iodine intake. An adverse effect resulting from iodine prophylaxis may be the induction of thyroid autoimmunity. Although experiments performed in animal models suggest that iodine could initiate or exacerbate thyroid autoimmunity, the role of iodine in humans remains controversial. Several observational studies in areas with adequate or high iodine intake suggest that there is an increase in the incidence of thyroid autoimmune disease. Moreover, intervention studies suggest that increased iodine intake may enhance thyroid autoimmunity too. However, not all studies generated the same findings, probably because of genetic, racial, and environmental differences. It seems that autoimmune exacerbation is a transient phenomenon. Studies have shown that in persons presenting thyroid antibodies, the levels of these antibodies progressively decrease when the majority of them react against a nonspecific pattern of thyroglobulin (Tg) epitopes. However, in a small number of these persons, the anti-Tg antibodies are similar to those in patients with patent thyroid autoimmune disease, reacting against specific immunodominant Tg epitopes, and their levels persist. One possible attractive explanation is that enhanced iodine intake increases the antigenicity of Tg through the incorporation of iodine into its molecule and the formation of iodinated Tg epitopes or even the generation of noniodinated pathogenetic Tg epitopes that are normally cryptic.

Thyroid autoimmunity in the current iodine environment.

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in the developed world and its pathogenesis is complex and multifactorial. It is considered the hepatic manifestation of the metabolic syndrome and is the leading cause of hepatic cirrhosis. This review aims to present current knowledge on the involvement of the adrenal glands in the development of NAFLD. Clinical and animal studies have shown that excess glucocorticoids (GC) have been implicated in the pathogenesis of NAFLD. Patients with NAFLD seem to have a subtle chronic activation of the hypothalamic pituitary adrenal axis leading to a state of subclinical hypercortisolism. Regulators of GC such as 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), an enzyme that regenerates cortisol from inactive cortisone, and 5α/5β-reductases, enzymes that increase cortisol clearance, are implicated in the development of NAFLD by amplifying local GC action. Adrenal androgen (dehydroepiandrosterone) abnormalities and increased aldosterone levels may also have a role in the development of NAFLD whereas the contribution of adrenergic signaling in NAFLD pathogenesis remains unclear.

Adrenal disorders and non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in the developed world and its pathogenesis is complex and multifactorial. It is considered the hepatic manifestation of the metabolic syndrome and is the leading cause of hepatic cirrhosis. This review aims to present current knowledge on the involvement of the adrenal glands in the development of NAFLD. Clinical and animal studies have shown that excess glucocorticoids (GC) have been implicated in the pathogenesis of NAFLD. Patients with NAFLD seem to have a subtle chronic activation of the hypothalamic pituitary adrenal axis leading to a state of subclinical hypercortisolism. Regulators of GC such as 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), an enzyme that regenerates cortisol from inactive cortisone, and 5alpha /5beta-reductases, enzymes that increase cortisol clearance, are implicated in the development of NAFLD by amplifying local GC action. Adrenal androgen (dehydroepiandrosterone) abnormalities and increased aldosterone levels may also have a role in the development of NAFLD whereas the contribution of adrenergic signaling in NAFLD pathogenesis remains unclear.

Ioannis-Anastasios Vatalas

Papers

Thyroid autoimmunity in the current iodine environment.

Adrenal disorders and non-alcoholic fatty liver disease.

Adrenal disorders and nonalcoholic fatty liver disease.