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.

Targeted thyroid function testing of only the high-risk group would miss about one third of pregnant women with overt/subclinical hypothyroidism.

No abstract

This large series suggests that the patients with classical pituitary apoplexy, who are without neuro-ophthalmic signs or exhibit mild and non-progressive signs, can be managed conservatively in the acute stage.

Thyroid hormone is essential for normal metabolism and development, and overt abnormalities in thyroid function lead to common endocrine disorders affecting approximately 10% of individuals over their life span. In addition, even mild alterations in thyroid function are associated with weight changes, atrial fibrillation, osteoporosis, and psychiatric disorders. To identify novel variants underlying thyroid function, we performed a large meta-analysis of genome-wide association studies for serum levels of the highly heritable thyroid function markers TSH and FT4, in up to 26,420 and 17,520 euthyroid subjects, respectively. Here we report 26 independent associations, including several novel loci for TSH (PDE10A, VEGFA, IGFBP5, NFIA, SOX9, PRDM11, FGF7, INSR, ABO, MIR1179, NRG1, MBIP, ITPK1, SASH1, GLIS3) and FT4 (LHX3, FOXE1, AADAT, NETO1/FBXO15, LPCAT2/CAPNS2). Notably, only limited overlap was detected between TSH and FT4 associated signals, in spite of the feedback regulation of their circulating levels by the hypothalamic-pituitary-thyroid axis. Five of the reported loci (PDE8B, PDE10A, MAF/LOC440389, NETO1/FBXO15, and LPCAT2/CAPNS2) show strong gender-specific differences, which offer clues for the known sexual dimorphism in thyroid function and related pathologies. Importantly, the TSH-associated loci contribute not only to variation within the normal range, but also to TSH values outside the reference range, suggesting that they may be involved in thyroid dysfunction. Overall, our findings explain, respectively, 5.64% and 2.30% of total TSH and FT4 trait variance, and they improve the current knowledge of the regulation of hypothalamic-pituitary-thyroid axis function and the consequences of genetic variation for hypo- or hyperthyroidism.

Our results require replication but suggest that commonly inherited variation in the DIO2 gene is associated both with impaired baseline psychological well-being on T(4) and enhanced response to combination T(4)/T(3) therapy, but did not affect serum thyroid hormone levels.

Marked associations among age at diagnosis, disease severity, goiter, ophthalmopathy, smoking, and FH provide evidence for interactions between genetic and environmental/endogenous factors; understanding these may allow preventive measures or better tailoring of therapies.

Autoimmune thyroid diseases (AITD) are common, affecting 2-5% of the general population. Individuals with positive thyroid peroxidase antibodies (TPOAbs) have an increased risk of autoimmune hypothyroidism (Hashimoto's thyroiditis), as well as autoimmune hyperthyroidism (Graves' disease). As the possible causative genes of TPOAbs and AITD remain largely unknown, we performed GWAS meta-analyses in 18,297 individuals for TPOAb-positivity (1769 TPOAb-positives and 16,528 TPOAb-negatives) and in 12,353 individuals for TPOAb serum levels, with replication in 8,990 individuals. Significant associations (P<5×10−8) were detected at TPO-rs11675434, ATXN2-rs653178, and BACH2-rs10944479 for TPOAb-positivity, and at TPO-rs11675434, MAGI3-rs1230666, and KALRN-rs2010099 for TPOAb levels. Individual and combined effects (genetic risk scores) of these variants on (subclinical) hypo- and hyperthyroidism, goiter and thyroid cancer were studied. Individuals with a high genetic risk score had, besides an increased risk of TPOAb-positivity (OR: 2.18, 95% CI 1.68–2.81, P = 8.1×10−8), a higher risk of increased thyroid-stimulating hormone levels (OR: 1.51, 95% CI 1.26–1.82, P = 2.9×10−6), as well as a decreased risk of goiter (OR: 0.77, 95% CI 0.66–0.89, P = 6.5×10−4). The MAGI3 and BACH2 variants were associated with an increased risk of hyperthyroidism, which was replicated in an independent cohort of patients with Graves' disease (OR: 1.37, 95% CI 1.22–1.54, P = 1.2×10−7 and OR: 1.25, 95% CI 1.12–1.39, P = 6.2×10−5). The MAGI3 variant was also associated with an increased risk of hypothyroidism (OR: 1.57, 95% CI 1.18–2.10, P = 1.9×10−3). This first GWAS meta-analysis for TPOAbs identified five newly associated loci, three of which were also associated with clinical thyroid disease. With these markers we identified a large subgroup in the general population with a substantially increased risk of TPOAbs. The results provide insight into why individuals with thyroid autoimmunity do or do not eventually develop thyroid disease, and these markers may therefore predict which TPOAb-positives are particularly at risk of developing clinical thyroid dysfunction.