MANAGEMENT OF ENDOCRINE DISEASE: Isolated maternal hypothyroxinemia during pregnancy: knowns and unknowns

Abstract

Isolated maternal hypothyroxinemia (IMH) during pregnancy is defined as a low maternal T 4 in the absence of TSH elevation. As IMH is common, with a prevalence of 1-2% in iodine-sufficient populations, and early research has suggested adverse effects on fetal neurodevelopment, it has been the focus of many studies in the last decade. In the current review, we first discuss the significance of IMH based on data from animal models and recent discoveries regarding the role of thyroid hormone on neurodevelopment. We address issues surrounding the definition and prevalence of this entity and discuss new insights into the etiologies, clinical consequences and management of IMH. A number of large cohort studies have investigated the effects of IMH on the risk of various pregnancy complications and child neurodevelopment. We review these studies in detail and describe their limitations. We discuss the available research on management of IMH, including two recent randomized controlled trials (RCTs). Finally, we delineate the remaining uncertainties in this field and emphasize the need for a sufficiently powered, placebo-controlled RCT on the treatment of IMH early in the first trimester of pregnancy.

Effect of Thyroid Hormones on Neurons and Neurodevelopment

“…It has been mainly associated with iodine deficiency but novel studies are focusing on environmental disruptors, obesity, iron deficiency, and angiogenic factor impairment [54]. It is essential to recall that the TH metabolism remarkably changes in pregnant women, with up to a 50% raise in TH levels.…”

“…Recent studies investigating the effects of hypothyroxinemia on fetal neurodevelopment, in general terms, have reported a negative correlation, especially when it occurs during the first trimester [30]. However, data on the later phases of pregnancy are less concordant [54]. A recent metanalysis concluded that there is a 3-fold increased risk of child cognitive impairment when hypothyroxinemia is detected in mothers during gestation, although the big heterogeneity among the definitions of cognitive delay, the tests performed, and the assessment periods limits these findings [59].…”

Avaliação da suficiência de iodo e sua relação com a função tireoidiana materna em gestantes provenientes da cidade de São Paulo, SP

“…O mecanismo pelo qual a obesidade poderia cursar com hipotiroxinemia não está totalmente esclarecido. A principal hipótese é a de que a leptina, produzida pelos adipócitos, estimule a conversão periférica de T4 em T3 45,77 . Vários autores encontraram correlação negativa entre IMC e T4l [78][79][80] .…”

“…Da mesma forma que o HS, não há um consenso sobre a indicação de tratamento com levotiroxina para a hipotiroxinemia materna isolada 45 .…”

“…A hipotiroxinemia grave, observada no hipotireoidismo franco, acarreta em retardo no desenvolvimento psicomotor. Já a hipotiroxinemia leve, principalmente nas primeiras semanas pode estar associada a déficit de atenção e hiperatividade, clinicamente evidentes somente na idade escolar 7,[44][45][46][47][48][49][50][51][52][53] . No entanto, um estudo realizado por Craig et al 54 não encontrou correlação entre hipotiroxinemia materna e alteração no desenvolvimento neurológico das crianças avaliadas aos dois anos de idade.…”