Impact of Lower Screening TSH Cutoff Level on the Increasing Prevalence of Congenital Hypothyroidism

Abstract

Lower cutoff levels in screening programs have led to an increase in the proportion of detected cases of transient hypothyroidism, leading to an increase in the overall prevalence of primary congenital hypothyroidism (CH) in several countries. We have performed a retrospective evaluation on the data from 251,008 (96.72%) neonates screened for thyroid-stimulating hormone (TSH) level in dried blood spot specimens taken 48 h after birth, between 2002 and 2015, using the DELFIA method. A TSH value of 15 mIU/L whole blood was used as the cutoff point until 2010 and 10 mIU/L thereafter. Primary CH was detected in 127 newborns (1/1976) of which 81.1% had permanent and 18.9% had transient CH. The prevalence of primary CH increased from 1/2489 before 2010 to 1/1585 thereafter (p = 0.131). However, the prevalence of permanent CH increased only slightly (p = 0.922), while the transient CH prevalence showed an 8-fold increase after lowering the TSH cutoff level (p < 0.001). In cases of permanent CH, we observed a lower prevalence of thyroid dysgenesis (82.7% vs. 66.7%) and a higher prevalence of a normal in situ thyroid gland (17.3% vs. 33.3%), for the period with a lower TSH cutoff value. Our findings support the impact of a lower TSH cutoff on the increasing prevalence of congenital hypothyroidism.

Genetics of Gland-in-situ or Hypoplastic Congenital Hypothyroidism in Macedonia

“…It is located in the paired domain; although the p.K135A substitution has been shown to impair wild-type transactivation function, substitution of lysine (K) for arginine (R), which is also positively charged, may be better tolerated. There is also one homozygote for PAX8 p.K135R in the ExAC database, suggesting its functional consequences are likely to be mild despite its association with CH in a previous study (8,30).…”

“…Whole-blood TSH was measured from filter paper blood spots (Whatman 903), sampled 48 to 72 h after birth. The TSH cutoff level was 15 mU/L in the period 2002-2010, and 10 mU/L thereafter, which resulted in an increased prevalence of primary CH in Macedonia, from 1/2,489 live births before 2010 to 1/1,585 from 2011 onward (an increment of 36.3%) (8). A total of 153 patients were diagnosed with primary CH over this 15-year period (8)(9)(10).…”

“…The TSH cutoff level was 15 mU/L in the period 2002-2010, and 10 mU/L thereafter, which resulted in an increased prevalence of primary CH in Macedonia, from 1/2,489 live births before 2010 to 1/1,585 from 2011 onward (an increment of 36.3%) (8). A total of 153 patients were diagnosed with primary CH over this 15-year period (8)(9)(10). At reevaluation, 48.4% had permanent hypothyroidism, 30% transient CH, and 21.6% isolated hyperthyrotropinemia.…”

Diagnostic re-evaluation of congenital hypothyroidism in Macedonia: predictors for transient or permanent hypothyroidism

“…The TSH cut-off was lowered in our national thyroid screening program from 15 to 10 IU/L after 2010. The overall incidence of CH significantly increased from 1/2489 up to 2010 to 1/1585 thereafter, with increasing the prevalence of transient CH cases ( 10 ). However, the optimal cut-off in this study was 30.5 IU/L.…”

“…A total of 251,008 newborns were screened with a mean coverage of the 96.7%. The overall incidence of primary CH was 1/1967 and female-to-male ratio was 1.35:1 ( 9 , 10 ). Children with CH detected by neonatal screening program were followed at a single center of the University Children’s Hospital.…”