congenital hypothyroidism kuwait
TRANSCRIPT
Methods: though analyzing our results of screening newborns in two years from
October 2014 to October 2016 as first year using unique cutoff and second year using
age depending cutoff. Confirmed congenital hypothyroidism cases were based on
confirmatory thyroid profile, thyroid imaging and local endocrinologist’s opinion.
Introduction: Congenital hypothyroidism is a disorder which results in inadequate
thyroid hormone production by the thyroid gland. The thyroid gland produces
thyroxine (T4), a hormone essential for normal growth and development and is
regulated by thyroid-stimulating hormone (TSH – also known as thyrotropin)
produced by the pituitary gland. At approximately 20 week’s gestation, the foetus’
thyroid gland should commence producing thyroxine as the mother’s thyroxine
supply fails to meet demands. The current TSH-based screening test may not detect
all those preterm infants (especially those born between 23 and 27 weeks gestation)
whose TSH levels may not be increased at 5-8 days of age, mainly due to the
immaturity of the hypothalamic-pituitary axis.
Thyroid hormone is essential for normal central nervous system development
especially in early life of newborns although untreated congenital hypothyroidism
lead to permanent, irreversible congenital delay, impaired motor function and
growth. The newborn screening aiming in prevention of these complication by early
detection and treatment.
Thyroid dysgenesis occurs mostly as a sporadic disease, but a genetic cause has been
identified in about 2% of cases. Transient hypothyroidism occurs when babies are
biochemically hypothyroid, then later revert to normal thyroxine levels naturally. The
majority of these babies are sick, preterm (<37 weeks gestation) neonates and the
process is not well understood. This is very rare in full term babies (37-41 weeks
gestation) and congenital hypothyroidism detected via newborn blood spot screening
in full term babies is likely to be permanent. Preterm infants are potentially
susceptible to transient hypothyroidism due to immaturity of thyroid function and
other acute illness . The screening for congenital hypothyroidism in neonatal period
started in the early 1970’s and adopted in many countries throughout the world. In
Kuwait the screening for congenital hypothyroidism start since 2005 with screening
for phenylketonuria but the program at this time not adapted to include all newborns
in Kuwait, the protocol and strategies in predicting positive cases through determine
cutoff for the positive cases (high risk baby) after that developing of two cutoff which
were 15 uU/ml for borderline and 25 uU/ml for positive “high risk”
>15 uU/ml Normal “low risk”
15 – 25 uU/ml Borderline
<25 uU/ml Positive “high risk”
These cutoffs continuous used until the screening program official startup with
expanding of the program panel to include 22. Disorders after bringing of tandem
mass spectrophotometry and program start to include all newborn inside Kuwait in
governmental and private hospitals.
Methods: Subjects were identified from all newborns screened in Kuwait between
October 2014 and October 2016. Confirmatory thyroid function profile was collected
by newborn screening offices and analyzed in Sabah biochemistry lab. We collecting
all data from the newborn screening offices monthly statistic and these data is
madePublically available in our annual statistic report but the record level data not
publically available. Screening blood samples were collected by heel stick blood spot
on filter paper and analyzed using manual Perkin-Elmer DELFIA immunoassay system
measuring TSH in uU/L blood volume and no changes to the assay occurred during
the study period. The protocol of sample collection for newborn screening is
collection of sample after 48 hours and before 72 hours after birth and sample
collected early another sample collected for re-screen it. Also premature baby
screened with three sample first collected after 48 -72 hours, second after two weeks
and last sample after one month. We did not exclude any sample with mother history
of taking anti-thyroid drugs or other medical consideration. All samples with initial
screening TSH level ≥15 repeated in duplicate from the same samples and inform
report made if the average still high the sent to newborn screening office to evaluate
the baby clinically and collect confirmatory sample for thyroid profile test and for any
positive sign they refer the baby to the endocrinologist for thyroid imaging and start
management. At October 2015 we found that the results of TSH show high false
positive rate and positive predictive of the test was 11 %. We make statistic study for
our results and we found that most of false positive results for sample collected early
before 48 hours so, we separate our samples to three groups according to the age,
Due to the neonatal TSH surge in the first few hours of life (less than 24 hours – 24-48
hours and more than 48 hours) for each group we calculate the mean and standard
deviation using normal values excluding extremis.
Less than 24 hrs.
24-48hrs More than 48 hrs.
mean 10.7 5.1 2.9
SD 9.5 6.5 4
We calculate new cutoff as mean+3SD
The new cutoff which started from October 2015
> 40 uU/ml if 0-23 hrs. / > 25 uU/ml if 24-48 hrs. / < 15 uU/ml if > 48 hrs.
Results: Subjects included 112,163 samples for newborns between October 2014 to
October 2016. From October 2014 to October 2015 we inform 270 as positive screen
in rate of 1:195 screened with rate of 1 true positive :30 false positive and from
October 2015 to October 2016 we inform 81 as positive screen in rate of rate of 1:733
screened
Discussion: This cohort of 112,163 samples represent large analysis in newborns
inside Kuwait (Kuwaiti and non-Kuwaiti newborns). Diagnosed newborns include
those with both permanent and transient forms of congenital hypothyroidism and
they will be under treatment until reassess to determine if they have transient or
permanent congenital hypothyroidism. The incidence about 1: 800 in these two year
included in this study. there is a wide range of screening TSH cutoffs used in neonatal
screening programs all over the world .Much of this discrepancy has to do with the of
the sample collection as TSH falls over the first few days of life . Basically the testing
of babies who are <24 h old is not recommended and should only be performed if no
other specimen is available. As high TSH in babies <24 h old is unreliable for screening
newborns for hypothyroidism. But we must deal with it as many times the second
samples not available for many issues. Cautiously we increase the cutoffs for the early
collected sample as well as to never decrease the sensitivity of the test. And this is
the important of maintaining a low screening cutoffs level. Also the lower cutoff
important in discover the mild permanent thyroid dysfunction.
The positive predictive value was 11.4% with the old non age dependence cutoff and
become 75% with the new age depending cutoffs which is expected. Also when we
calculate the PPV% in samples collected after 48 hours higher than the PPV% in early
collected samples. TSH – based screening programs could potentially use age of
sample collection data, in addition to absolute screening TSH level as a better tool for
capturing true positive cases and predicting the risk of true congenital
hypothyroidism.
The limitation of this study that is discover of false negative cases must done clinically
which may not accurate and delay in discover these cases if present . Recently we
have two false positive confirmed cases with congenital hypothyroidism with positive
family history and test become positive in the repeat after one week. So the diagnosis
of false negative based on inform from the endocrinologist
Conclusion: This study show that age depending cutoffs improve the positive
predictive value of the TSH test in screening of newborn and decrease the false
positive rate.
Background: using of thyroid stimulating
hormone (TSH) as unique in screening for
congenital hypothyroidism in newborns
mean that TSH cutoff level is critical to
ensure that true cases of congenital
hypothyroidism are not missed. The
purpose of our study is to evaluate the
predictive value of TSH as marker used in
newborn screening and evaluate the
recently used age depending cutoff after
one year of suggestion.
Designed by :Dr.Amir Abdelazim - Biochemistry registrar at KMGC