The incidence of congenital hypothyroidism (CH) in Guangxi, China and the predictors of permanent and transient CH

Abstract

BackgroundThe incidence of congenital hypothyroidism (CH) differs significantly among different ethnicities and regions, and early differentiation of transient CH is important to avoid unnecessary prolonged treatment with L-T4.ObjectiveTo investigate the incidence of CH based on the newborn screening program in Guangxi Zhuang Autonomous Region, China, and to analyze the predictors that might allow for an early differentiation between permanent (P) and transient (T) CH.Design and methodsData from newborn screening program over a seven-year period (January 2009 to January 2016) at Guangxi Maternal and Child Health Hospital are analyzed. Blood samples were collected on filter paper between 3 and 7 days after birth, and TSH level was measured by time-resolved fluorescence assay. Individuals with increased TSH (TSH ≥ 8 IU/L) levels detected by newborn screening were recalled for further evaluation. Serum TSH, FT3 and FT4 were determined by electrochemiluminescence assay using venous blood samples. Diagnosis of CH is based on elevated TSH levels (>10 IU/L) and decreased FT4 levels (<12 pmol/L). Patients with elevated TSH levels and normal FT4 levels were diagnosed as hyperthyrotropinemia. Permanent or transient CH was determined by using the results of thyroid function tests after temporary withdrawal of L-T4 therapy at approximately 2–3 years of age.ResultsAmong 1,238,340 infants in the newborn screening program, 14,443 individuals were recalled for reevaluation (re-call rate 1.18%), 911 and 731 individuals were subsequently determined to have hyperthyrotropinemia and CH respectively; thus, a prevalence of 1:1359 and 1:1694 for hyperthyrotropinemia and CH. Of the 731 patients with CH, 161 patients were diagnosed with permanent CH (PCH), and 159 patients were diagnosed with transient CH (TCH), the other 411 patients are too young to determine their subtypes. Patients with PCH required an increasing dose of L-T4 during the first few years, whereas patients with TCH required a decreased dose of L-T4. The TSH levels at diagnosis and the dose of L-T4 used were significantly higher in PCH cases than in transient cases. The FT4 levels at diagnosis were significantly lower in PCH cases than in TCH cases. The TSH levels at diagnosis, FT4 levels at diagnosis and L-T4 doses at 90 days were evaluated as predictors for differentiating PCH and TCH, and their accuracy at their respective optimal cutoffs were determined to be 60.6%, 66.7% and 93.9%, respectively.ConclusionsThe CH incidence in Guangxi Zhuang Autonomous Region is slightly higher (1:1694) compared to the worldwide levels (1/2000–1/4000). The PCH and TCH ratio is close to 1; thus, the estimated PCH incidence is 1/3388, which is similar to reported worldwide average incidence (1/3000). The L-T4 dose required at 90 days (>30 μg/day) has the highest predictive value for PCH. Earlier differentiation of PCH and TCH helps to determine appropriate treatment course.

Levothyroxine dosages less than 2.4 μg/kg/day at 1 year and 1.3 μg/kg/day at 3 years of age may predict transient congenital hypothyroidism

“…At present, using TSH levels to differentiate between P-CH and T-CH, is controversial. As reported in five previous studies, they were higher in thyroid agenesis and dysgenesis patients, than in those with eutopic thyroid glands (5, 9,10,11,12). Contrarily, in four previous studies, no significant difference in P-CH and T-CH TSH levels were reported, despite the inclusion of thyroid agenesis and dysgenesis patients in the P-CH group (1,2,3, 7).…”

“…Thyroid ultrasonography is an important diagnostic tool used to differentiate between P-CH and T-CH. Although in this study, there were no significant differences in the thyroid gland size and position between P-CH and T-CH patients, abnormal thyroid gland morphology was found to be associated with P-CH, as reported in previous studies (1, 2, 9, 10). There might have been no significant difference due to the small number of cases.…”

“…Congenital hypothyroidism (CH) can be permanent (P-CH) or transient (T-CH), and based on factors such as sex, birth wt, and levels of TSH, T 4 , free T 4 (fT 4 ), and Tg (1,2,3,4,5,6,7,8,9,10,11,12) at the time of neonatal screening tests, these two CH types are difficult to differentiate prior to treatment initiation. However, previous studies have reported significant differences in the levothyroxine (LT4) dosages for 3-yr-old children with P-CH vs. T-CH (1, 3, 5, 7,8,9,10,11,12), and six studies have also identified LT4 dosage cutoff values for differentiating between P-CH and T-CH in 3-yr-old children (7,8,9,10,11,12). The aim of this study was to determine the presently unknown LT4 dosage cutoff values for Japanese children of ages 1 and 3 yr.…”

The genetic characteristics of congenital hypothyroidism in China by comprehensive screening of 21 candidate genes

“…Then, mappings were converted to Binary Alignment/Map file format using SAMtools (0.1.18). Initial mappings were post-processed using GATK, and the variants were considered credible if they met the following criteria: ( 1 ) quality scores for variant base pair ≥30; ( 2 ) mapping quality scores ≥50; ( 3 ) sequencing depth for variant base pair ≥20; ( 4 ) variant allele frequency ≥20%; ( 5 ) variant read depth ≥5 and ( 6 ) variant present on both strands. To exclude common single-nucleotide polymorphisms (SNP), we searched the dbSNP 135, and ESP6500 v2 databases, filtering out variants with frequencies >1% in these databases.…”

“…Thus, most developed countries conduct newborn screening for CH, and all patients are diagnosed in early infancy. Newborn screening for CH have been conducted in China from 2006, the data showed that the incidence of CH was approximately 1 in 2000–2500 live births in China ( 2 , 3 , 4 ),which was higher compared to the worldwide levels (1/3000–1/4000). Data obtained from newborn screening have enabled us to investigate the pathogenesis of this disorder.…”