Subclinical hypothyroidism in pregnancy Purpose of review Subclinical hypothyroidism (SCH) is a common diagnosis among women of reproductive age. The importance of sufficient maternal thyroid supply during pregnancy is well known. Nevertheless, the effects of SCH during pregnancy and the efficacy of its treatment on maternofetal outcomes are not well established. This review discusses the recent evidence on SCH in pregnancy and how this evidence is reflected in current clinical care. Recent findings Recent observational studies have found a positive association between SCH during pregnancy and adverse maternal, neonatal and offspring outcomes, mainly in thyroid peroxidase autoantibody positive women. Although interventional studies have shown a benefit of levothyroxine (LT4) treatment on selected pregnancy outcomes, there was no effect on offspring neurodevelopment. Summary Current evidence strengthens the association between SCH with both maternofetal and offspring adverse outcomes. An earlier and more individualized diagnostic assessment taking into consideration predictors of thyroid dysfunction and major risk factors for complications could result in better management of SCH during pregnancy. The effectiveness of LT4 on improving maternofetal and long-term offspring outcomes is still not fully elucidated.

Graves’ hyperthyroidism in pregnancy Purpose of review Graves’ hyperthyroidism is associated with significant obstetric, maternal, fetal, and neonatal complications. Early diagnosis and an understanding of the management of Graves’ hyperthyroidism in pregnancy can help to prevent these complications. Antithyroid drugs (ATD) should be avoided in early pregnancy, given their association with congenital malformations. Recent findings TSH-receptor antibodies (TRAb) are integral in the management of Graves’ hyperthyroidism in pregnancy and in the preconception period. TRAb are indicative of the current activity of Graves’ hyperthyroidism and the likelihood of relapse. Furthermore, TRAb predicts the risk of fetal and neonatal hyperthyroidism. The incidence of congenital malformations is roughly the same for propylthiouracil (PTU) and methimazole (MMZ). Exposure to both ATDs in early pregnancy has been associated with increased incidence of congenital malformations compared with exposure to either ATD alone. Summary The goal of the physician is maintaining euthyroidism throughout pregnancy and delivery of a healthy, euthyroid baby. An understanding of the natural progression of Graves’ hyperthyroidism in pregnancy and the proper utilization of TRAb enables the physician to minimize the risks associated with Graves’ hyperthyroidism and side effects of ATDs unique to pregnancy. The physician should prioritize preconception counseling in women with Graves’ hyperthyroidism in order to avoid hyperthyroidism and having to use ATDs in pregnancy.

Nonthyroidal illness in critically ill children Purpose of review This review summarizes recent literature on nonthyroidal illness syndrome (NTI) and outcome of pediatric critical illness, to provide insight in pathophysiology and therapeutic implications. Recent findings NTI is typically characterized by lowered triiodothyronine levels without compensatory TSH rise. Although NTI severity is associated with poor outcome of pediatric critical illness, it remains unclear whether this association reflects an adaptive protective response or contributes to poor outcome. Recently, two metabolic interventions that improved outcome also altered NTI in critically ill children. These studies shed new light on the topic, as the results suggested that the peripheral NTI component, with inactivation of thyroid hormone, may represent a beneficial adaptation, whereas the central component, with suppressed TSH-driven thyroid hormone secretion, may be maladaptive. There is currently insufficient evidence for treatment of NTI in children. However, the recent findings raised the hypothesis that reactivation of the central NTI component could offer benefit, which should be tested in RCTs. Summary NTI in critically ill children can be modified by metabolic interventions. The peripheral, but not the central, component of NTI may be a beneficial adaptive response. These findings open perspectives for the development of novel strategies to improve outcome of critical illness in children.

Immunotherapies for thyroid eye disease Purpose of review Thyroid eye disease is a complex autoimmune disorder which causes substantial morbidity. It can result in orbital disfigurement, double vision, and visual loss. Consequently, it has a substantial negative effect on quality of life, mental health, and socioeconomic status. Most signs and symptoms of thyroid eye disease (TED) can be explained by the expansion of the orbital contents. Steroids are the mainstay of treatment in TED. However, recurrence may occur once steroids are withdrawn. Furthermore, in most cases, normal orbital anatomy is not restored, and skilled rehabilitative surgery is required to reduce disfigurement, double vision, and to preserve vision. Therefore, novel, causal, and more efficacious treatment strategies are warranted. Recent findings In the last decade, the pathophysiology of TED has also been revised with the identification of new potential therapeutic targets. Recent clinical trials have shown that considerable benefit may be derived from the addition of antiproliferative agents (e.g., mycophenolate sodium) in preventing deterioration after steroid cessation. In addition, targeted biologic therapies have shown promise, including teprotumumab (anti-IGFR) which appears to substantially reduce proptosis, rituximab (anti-CD20) which reduces inflammation and tocilizumab (anti-IL-6) which potentially benefits both of these parameters. Summary This short review summarizes the recent research developments in this area.

Thyroid disease and the metabolic syndrome Purpose of review To summarize recent developments in the association of thyroid function with metabolic syndrome (MetS). Recent findings Although thyroid hormones even within low normal range are associated with various metabolic abnormalities, the risk of MetS remains a controversial issue. Hyperthyroid state might be associated only with insulin resistance and dysglycemia. Autoimmune thyroid diseases may be a potential risk factor for metabolic abnormalities even in those with low normal thyroid function. Summary The interrelation between thyroid stimulating hormone, free T3, freeT4 and metabolic parameters is complex and might be affected by age, sex, BMI, insulin resistance, smoking, iodine intake and inflammatory markers.

Thyroid nodules in children and adolescents Purpose of review Compared with adults, there is a two-fold to three-fold increased risk of malignancy for a pediatric patient undergoing evaluation of a thyroid nodule. In 2015, the American Thyroid Association published guidelines on the evaluation and management of pediatric patients with thyroid nodules and differentiated thyroid cancer. The goal of this clinical update is to review recent additions to the literature and propose opportunities how to best incorporate these findings into clinical practice. Recent findings Recent additions to the literature include assessment of ultrasound-based scoring systems to improve selection of patients for fine needle aspiration, defining the pediatric-specific risk of malignancy within The Bethesda System for Reporting Thyroid Cytopathology, and broadening our knowledge of the oncogene landscape that supports incorporation of adjunct oncogene testing to rule-in malignancy of nodules with indeterminate cytology. Summary There have been significant additions to the literature on the evaluation and management of children and adolescents with thyroid nodules since publication of the 2015 American Thyroid Association guidelines. Incorporating these changes into clinical care, within the setting of multidisciplinary, pediatric-specific, regional centers, will maximize ongoing efforts to improve the care of children and adolescents with thyroid nodules.

Long noncoding RNAs in thyroid cancer Purpose of review Our understanding of the molecular pathology events involved in thyroid cancer initiation and progression and its subtypes has markedly improved as a result of multiomic studies. Recently, long noncoding RNA (lncRNA) have been shown to have a role in cancer initiation and progression and have also been studied in thyroid cancer. Recent findings lncRNA are dysregulated in thyroid cancer. lncRNA have tumor suppressive and oncogenic function in thyroid cancer cells and play a role in some of the established genetic drivers of thyroid cancer initiation and progression. Lastly, some lncRNA are associated with clinicopathologic features of thyroid cancer and circulating blood lncRNA could potentially detect the presence of thyroid cancer. Summary We highlight the possible clinical utility of analyzing lncRNAs as biomarkers for thyroid cancer diagnosis and prognosis and their association with common genetic changes associated with thyroid cancer.