Association of Mild-to-Moderate Iodine Deficiency With Thyroid Function-A Systematic Review and Meta-analysis

Abstract

The only known function of iodine in the human body is as a component of thyroid hormones. Thus, all consequences of iodine deficiency should be mediated through altered thyroid hormone production. Although it is well established that severe iodine deficiency affects thyroid hormone production, the association between mild-to-moderate iodine deficiency and thyroid function remains unclear. This review aimed to review and summarize observational studies that examine the association between mild-to-moderate iodine deficiency and thyroid hormone function in the general population, including infants, children, adolescents, adults, pregnant and lactating women. Systematic searches of the literature were performed in November 2022 and repeated in February 2024 using the Medline Ovid, Embase Ovid, and Cochrane Central databases. Mild-to-moderate iodine deficiency was defined as a median urinary iodine concentration (UIC) of 20-100 μg/L in children, adolescents, and general adults, and 50-150 μg/L in pregnant women. Thyroid function outcomes included thyroid-stimulating hormone (TSH), free thyroxine (fT3), and free triiodothyronine (fT4) and clinical thyroid dysfunction entities. A total of 72 studies were included: 59 cross-sectional, 12 repeated cross-sectional (longitudinal), and 1 cohort study. Populations studied included infants, children, and adolescents (n = 7); women of reproductive age, including lactating women (n = 5); general adults (n = 20); and pregnant women (n = 43). For all population groups, most studies found no clear association between iodine status and thyroid function. Meta-analyses for 8 studies in pregnant women showed no difference in TSH, fT4, or fT3 for those with mild-to-moderate iodine deficiency compared with adequate status [mean difference (95% CI): TSH, 0.03 (-0.05, 0.12) mIU/L; fT4, -0.20 (-0.94, 0.53) pmol/L; fT3, 0.05 (-0.14, 0.03) pmol/L]. In conclusion, no clear association between mild-to-moderate iodine deficiency and thyroid function in the different population groups was found. This trial was registered at www.crd.york.ac.uk/PROSPERO as CRD42022360447.

Keywords: iodine; mild-to-moderate iodine deficiency; systematic review; thyroid dysfunction; thyroid function; urinary iodine concentration.

FIGURE 1

PRISMA diagram showing the flow of information through the different phases of the systematic review. UIC, urinary iodine concentration; UIC:Cr, urinary iodine:creatinine ratio.

FIGURE 2

Forest plot of the mean difference in TSH (mIU/L) in pregnant women with mild-to-moderate iodine deficiency (defined as UIC = 50–150 μg/L) compared with adequate iodine status (defined as UIC = 150–249 μg/L). Data were analyzed using random-effect meta-analysis with the restricted maximum likelihood technique. ID, iodine deficiency; TSH, thyroid-stimulating hormone; UIC, urinary iodine concentration.

FIGURE 3

Forest plot of the mean difference in fT3 (pmol/L) in pregnant women with mild-to-moderate iodine deficiency (defined as UIC = 50–150 μg/L) compared with adequate iodine status (defined as UIC = 150–249 μg/L). Data were analyzed using random-effects meta-analysis with the restricted maximum likelihood technique. ID, iodine deficiency; fT3, free triiodothyronine; UIC, urinary iodine concentration.

FIGURE 4

Forest plot of the mean difference in fT4 (pmol/L) in pregnant women with mild-to-moderate iodine deficiency (defined as UIC = 50–150 μg/L) compared with adequate iodine status (defined as UIC = 150–249 μg/L). Data were analyzed using random-effects meta-analysis with the restricted maximum likelihood technique. ID, iodine deficiency; fT4, free thyroxine; UIC, urinary iodine concentration.