Mexico shows a high birth prevalence of congenital hypothyroidism (CH) due to thyroid dysgenesis (TD). PAX8 defects underlie only 1% of these cases and NKX2-1 does not seem to be involved. Here, we analyzed other TD-related genes in 128 non-related Mexican patients (females 77.3%; 6 months to 16.6 years) with non-syndromic CH-TD diagnosis established by clinical evaluation, thyroid hormone serum profiling, and scintigraphy (74%) or ultrasonography (26%). We performed Sanger sequencing of FOXE1, NKX2-5, and TSHR and evaluated copy number variations (CNVs) in TSHR, FOXE1, PAX8, and NKX2-1 by multiplex ligation-dependent probe amplification. Odds ratios for TD risk were explored for FOXE1 polyalanine stretches [polyAla-rs71369530] in cases and controls (N = 116). Five rare missense changes cataloged as benign (NKX2-5:p.(Ala119Ser)-rs137852684), of unknown significance (FOXE1:p.(Ala335Gly)-rs543372757; TSHR:p.(Asp118Asn)-rs1414102266), and likely pathogenic (FOXE1:p.(Gly124Arg)-rs774035532; TSHR:p.(Trp422Arg)-rs746029360) accounted for 1.5% (N = 2/128) of clinically relevant genotypes (supported in part by protein modeling) in CH-TD. No CNVs were identified, nor did polyAla > 14 alanines in FOXE1 significantly protect against TD. The present and previously published data collectively show that small clinically relevant germline variants in PAX8, FOXE1, and TSHR are found in only a very small proportion (2.5%) of isolated CH-TD Mexican patients.

According to the Iodine Global Network, Mexico is considered a country with adequate national iodine intake (297 mg/L), but some regions have not been studied. We aimed to evaluate urinary iodine concentration (UIC) and its association with thyroid stimulating hormone (TSH) levels and the nutritional status in 307 children (aged 5 to 11 years) from three elementary schools of Monterrey, northern Mexico. UIC in spot urine samples and capillary TSH levels were measured to assess thyroid function, in addition to weight, height, body mass index (BMI), and waist circumference (WC). We found a median UIC of 442 mg/L and a significant association between UIC and TSH levels by logistic regression when data were adjusted for (1) age and sex; (2) age, sex, and WC; and (3) age, sex, and weight status. UIC values were higher in 7-year-old children compared to 11-year-old children. High prevalences of overweight/obesity (41%) and WC >90 pctl (22%) were observed. This study identified higher UIC levels in children than those previously reported in the country. The UIC showed a positive and significant correlation between TSH levels in the three models evaluated. More studies are needed to assess the causes and possible outcomes of high UIC levels.