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Thyroid Disorders


severe CH cases were transient in the older cohort and only 4 % of the severe cases were transient in the younger cohort; 43 % of the mild CH cases were transient in the older cohort and 36 % of the mild cases were transient in the younger cohort. Unfortunately, there are no criteria to discriminate between children who will have transient and those who will have persistent hypothyroidism. Because there are no long-term follow-up studies on outcomes with and without treatment, it is unclear whether patients benefit from treatment. In the absence of essential long-term follow-up data, patients with mild CH and delayed TSH rise are managed similarly to those with severe CH, with the same treatment and monitoring plan.


Monitoring Thyroid Function in Newborns at Risk of Developing Delayed Thyroid Stimulating Hormone Rise


Delayed TSH rise is defined as a normal TSH level with low T4 level on a newborn’s initial screening, with detection of elevated TSH and persistent low T4 on subsequent screening. Since newborn screening programmes differ in their screening methods and indications for repeat screening, some programmes will miss this pattern. Screening programmes using a primary TSH test that do not routinely obtain a second sample will miss this pattern of abnormal TFTs.


The current American Academy of Pediatrics (AAP) guidelines include measurement of TFTs at two weeks if the initial screening has shown low T4 and normal TSH in pre-term infants, low birth weight infants and sick full-term newborns.2


There are no recommendations


regarding the initial method and timing of screening to ensure that those ‘delayed TSH rise’ babies will be identified. Data from the Massachusetts Newborn Screening Program in 2000 suggested that delayed TSH rise is more common in low birth weight babies.7


A few


possible aetiologies have been suggested to explain delayed TSH rise in sick premature infants. One possible explanation is an attenuated response of the hypothalamic–pituitary–thyroid axis secondary to its immaturity. Another possible cause is an increased incidence of sick euthyroid syndrome. Some premature and sick babies are exposed to iodine and receive dopamine, both known to suppress TSH secretion. There are insufficient data to distinguish between the different possible aetiologies.


Recent reports from screening programmes in New South Wales in Australia8


and Rhode Island in the US9 more common in low birth weight babies.


In 2006–2008, the newborn screening programme in Australia monitored TSH levels in 2,117 very low birth weight (VLBW) babies (weight ≤1,500 g) during the first days of life and at one month of age. A spot TSH level was considered positive if ≥20 mIU/l during week one or ≥7 mIU/l at one month. Forty-three babies had transient hypothyroidism, with TFTs normalising before two months of age, usually without treatment. Eighteen babies required treatment beyond two months of age (1:128 of surviving babies). Sixteen had normal TSH results on initial testing, and 12 had TSH levels <6 mIU/l, a finding supporting the delayed TSH rise phenomenon as well as indicating the need for secondary screening at one month of age.8


The Rhode Island study looked at the incidence of CH with a delayed TSH rise in VLBW and extremely low birth weight (ELBW) infants as well as at their developmental, growth and endocrine outcomes at a corrected age of 18 months. It included a retrospective analysis of the


54 confirm that delayed TSH rise is


TFTs of 92,800 newborns. CH with a delayed TSH rise occurred in 1 in 58 ELBW infants, 1 in 95 VLBW infants, and 1 in 30,329 infants weighing >1,500 g. The incidence found in the >1,500 g group in this study was probably an underestimation, because, in that group, repeat TFTs were not systematically carried out but only undertaken if medically indicated. The outcomes of VLBW and ELBW infants with CH and delayed TSH rise were comparable with matched controls without CH or delayed TSH rise in terms of mean head circumference, weight, length and developmental score. A higher incidence of head circumference measurements below the 10th percentile was found in the VLBW infants with delayed TSH elevation.9


The long-term outcomes of subclinical hypothyroidism with mildly elevated TSH and normal T4 remains unclear. The finding that, in patients with delayed TSH rise, TFTs may normalise without treatment raises the question of whether or not treatment is indicated.


With increasing numbers of premature infants surviving, larger numbers of children with delayed TSH rise can be expected. Additional studies are required to determine the need for treatment and establish appropriate guidelines for the monitoring of TFTs in at-risk newborns.


Monitoring Thyroid Function in Newborns Diagnosed with Congenital Hypothyroidism During the First Three Years of Life The current AAP guidelines include measurement of T4 and TSH two to four weeks after starting treatment, every one to two months during the first six months of life, every three to four months between six months and three years of age, and every six to 12 months until growth is complete. More frequent testing is suggested when non-adherence to treatment is suspected or when TFTs are abnormal. Furthermore, TFTs should be repeated four weeks after any change in levothyroxine (L-T4) dose.2


Endocrinology (ESPE) recommends monitoring TFTs every one to two weeks after initiation of treatment until T4 and TSH have normalised, but does not give guidelines for long-term monitoring.10


While the AAP recommends repeat TFTs to be carried out two to four weeks after initiation of therapy, the UK guidelines recommend that the first follow-up should be within 14 days, and the ESPE guidelines recommend follow-up within 7–14 days of treatment initiation. The shorter interval in the ESPE guidelines is based on a study showing that 7.4 % of infants started on a dose of 25 µg of L-T4 had subnormal free T4 (fT4) seven days after treatment initiation. The percentage was lower with higher initial doses (5.1 % with a 37.5 µg dose and 0 % with a 50 µg dose).11


The shorter interval is important for monitoring adherence to treatment and verifying the adequacy of the dose and delivery method, but it is less important if the AAP recommendation of a high initial dose of 10–15 µg/kg of body weight is followed.


A recent paper published by our group suggests monthly monitoring during the first year of life is needed to maintain fT4 levels in the upper half of the normal range and TSH in the normal range.12


This


retrospective study evaluated 70 children with CH for initial TSH levels, frequency of follow-up, changes in dose and TFTs during the first year of life. Age-appropriate normal ranges for TFT levels were used until three months of age, after which adult normal ranges were used. TFTs were regarded as abnormal if total T4 (tT4) or fT4 were not in the upper half of the normal range, or if TSH was not in the normal range.


EUROPEAN ENDOCRINOLOGY


The European Society for Paediatric


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