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  • Title: The key role of newborn thyroid scintigraphy with isotopic iodide (123I) in defining and managing congenital hypothyroidism.
    Author: Schoen EJ, Clapp W, To TT, Fireman BH.
    Journal: Pediatrics; 2004 Dec; 114(6):e683-8. PubMed ID: 15574601.
    Abstract:
    BACKGROUND: Thyroid imaging with isotopic iodide (123I) or technetium Tc 99m pertechnetate has been available for decades but is not routinely used in newborn infants diagnosed with congenital hypothyroidism (CH). Among clinicians who believe that presence, absence, or abnormal location of a thyroid does not alter management of CH, imaging is not advocated for anatomic diagnosis of CH. OBJECTIVE: To define the role of thyroid scintigraphy in diagnosing and managing newborn CH. METHODS: Retrospective review of 249 confirmed cases of CH seen at a large, group-model managed care organization during the 24-year period extending from September 1978 through December 2002. Neonatal thyroid scintigraphy was performed in 210 cases (86%): 123I was used in 143 cases (68%), and technetium Tc 99m pertechnetate was used in 67 cases (32%). To perform scintigraphy with 123I, 30 to 50 microCi ([1.11-1.85] x 10(6) Bq) of 123I was administered orally; an uptake image was taken in 3 to 6 hours; and, if necessary, another image was taken in 24 hours. For technetium, 0.5 to 1 mCi ([1.85-3.7] x 10(7) Bq) of technetium Tc 99m pertechnetate was administered intravenously with imaging 20 minutes later. Thyroid dysplasia was defined as an absent or ectopic gland requiring lifetime therapy and eutopic thyroid as a normal-appearing thyroid gland in the proper location but possibly malfunctioning and requiring therapy. RESULTS: Of the 210 infants with CH receiving scintigraphy, 90 (43%) had eutopic (normal-appearing) thyroid diagnosed, and 120 (57%) had ectopic or absent gland (25% ectopic, 32% absent) diagnosed. Of these 210 infants, ethnicity was known in 198; of these, 76 (38%) were Latino/Hispanic, and 122 (62%) of the infants were non-Latino/non-Hispanic. Prevalence of CH differed between ethnic groups in our population of >700,000 newborn infants; total prevalence of CH was 1 per 3139. Prevalence of CH in Latino/Hispanic infants was highest at 1 per 1750 infants (1:1357 females, 1:2463 males). Prevalence of CH in non-Latino/non-Hispanic infants was 1 per 4648 infants (1:3500 females, 1:6914 males). Given that the total Kaiser Permanente infant population was approximately 19% Latino/Hispanic, the percentage of Latino/Hispanic infants with CH was significantly higher than expected. Dysplastic thyroid was more common in Latino/Hispanic females (69%) than in non-Latino/non-Hispanic females (52%). The female-to-male ratio of patients with CH was 1.9:1. Among the 210 infants with CH, normal thyroid was diagnosed more by 123I scintigraphy (49% of cases) than by scintigraphy using technetium Tc 99m pertechnetate (31% of cases). Use of technetium Tc 99m pertechnetate could have diagnosed dysplastic thyroid in some cases that would be considered eutopic had 123I been used. Eight familial cases of CH were identified. COMMENTS: CH, a heterogeneous disorder with prevalence influenced by familial, ethnic, and gender factors, is more common in Latino/Hispanic females. When present, a eutopic thyroid is more likely to be detected by 123I scintigraphy; this method is therefore preferred over scintigraphy using technetium Tc 99m pertechnetate for optimal management of CH. Parents can then be counseled on either the certainty of lifetime therapy (for dysplastic thyroid) or the possibility of later discontinuing therapy (for eutopic thyroid, because CH may be transient in these children). If the dysplastic thyroid gland is absent or ectopic (usually a small sublingual gland), parents can be told that the infant will need lifetime thyroid therapy. If the thyroid gland is present in the normal position (eutopic) and the condition is transient (as shown by controlled withdrawal of thyroid in older children), lifelong treatment may not be needed. Parents rightly expect this maximal clinical and laboratory information in the immediate newborn period. Some clinicians hesitate to recommend neonatal scintigraphy for children with CH because of concern about delaying L-thyroxine therapy, concern about radiation exposure, or both. We believe that neither concern is warranted. 123I thyroid imaging has been used for many decades without evidence of risk for thyroid cancer. Treatment need not be delayed until scintigraphy is done. We did not use ultrasonography for thyroid imaging because this technique was not available in the early years of our study and may still not have sufficient sensitivity. Sources of discrepancy in our study could include scintigraphy interpreter bias due to lack of objective standards. We cannot estimate the true prevalence of transient CH because not all physicians give children with CH a trial off therapy at 2 to 3 years old, even if a eutopic thyroid is shown by 123I scintigraphy. Because therapy with L-thyroxine is simple and inexpensive and the outcome of untreated CH can be devastating, some parents and physicians are reluctant to discontinue treatment in children with CH, even when scans show a eutopic thyroid. Additionally, the clinical information contained in our database was not detailed enough to enable us to discover all cases of CH in which thyroxine therapy was discontinued. Because the study began in 1978 (>25 years ago), some patients were unavailable for long-term follow-up. In addition to allowing a more rational clinical approach to CH, 123I thyroid scintigraphy may help define underlying genetic factors and mechanisms of thyroid development and differentiation. This study's findings, that prevalence of CH and of thyroid dysplasia differed between genders and among racial/ethnic groups, seem to support a genetic basis for CH. Our results confirm previously published reports from the State of California Department of Health Services, Genetic Disease Branch and other studies describing multiple genetic abnormalities associated with CH. CONCLUSIONS: Despite data limitations, we believe that neonatal diagnosis of CH represents perhaps the greatest success of newborn screening programs. Initial laboratory diagnosis is simple and sufficiently accurate; treatment is simple, inexpensive, and effective. Severe mental retardation and growth failure can be prevented. Considering today's rapid advances in understanding the basic mechanisms of thyroid embryogenesis and gene abnormalities, thyroid scintigraphy may provide insight into clinical and genetic correlates in CH.
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