- Email: [email protected]
Congenital Hypothyroidism: Delayed Detection after Birth and Monitoring Treatment in the First Year of Life
Congenital Hypothyroidism: Delayed Detection after Birth and Monitoring Treatment in the First Year of Life
T
he addition of tests to detect infants with congenital hylayed TSH rise, with an overall incidence of 1:67 226.2 Quespothyroidism to newborn screening programs in the tions that naturally arise include the following: (1) Do cases mid-1970s has resulted in early detection and treatof delayed TSH rise occur in all newborn populations, but ment of these infants. This is a great success story, as congendo they go undetected in programs that perform only one ital hypothyroidism is one of the most common preventable newborn screening test?; (2) Does the incidence of delayed causes of mental retardation. Programs TSH rise vary with gestational age and/or See related articles, p 532 screen infants for congenital hypothyroidbirth weight?; (3) What is known about and p 538 ism with one of three strategies: (1) an inithe etiology of delayed TSH rise?; (4) What tial thyroxine measurement with a ‘‘reflex’’ thyroidis the natural history of thyroid function in babies with destimulating hormone (TSH) determination on infants with layed TSH rise?; (5) Should infants with delayed TSH rise a thyroxine below a specified cutoff (typically <10th percenbe treated with thyroid hormone or observed with serial testtile); (2) an initial TSH measurement; or (3) a combined thying to see if thyroid function normalizes?; (6) What is the roxine and TSH determination.1 Once identified by an neurocognitive outcome in babies with delayed TSH rise?; abnormal screening test, infants then have confirmation of and (7) Should newborn screening programs modify their diagnosis by measurement of serum thyroid function tests, testing protocol to detect infants with delayed TSH rise? typically a free thyroxine and TSH. Infants with primary conThe report by Woo et al3 from the Newborn Screening Program in Rhode Island in this issue of The Journal provides angenital hypothyroidism have a low free thyroxine and eleswers to some of these questions. The Rhode Island Newborn vated TSH level. With confirmation of diagnosis, thyroid Screening program measures both thyroxine and TSH simulhormone treatment is then started. The developing brain is taneously. Specimens are collected at approximately 48 hours critically dependent on thyroid hormone during the first 2 of age; repeat specimens are collected in infants <1500 g birth to 3 years of life. The treating physician must therefore monweight at 2, 6, and 10 weeks of age or until they reach 1500 g. In itor thyroid function at intervals frequent enough to ensure addition, it appears that some infants >1500 g birth weight that thyroid hormone dosing is adjusted in a timely manner. with acute illnesses or other medical conditions also undergo Two articles published in this issue of The Journal address derepeat testing. In an analysis of 92 800 babies over a 6-year petection of congenital hypothyroidism in babies with delayed riod, these investigators found an increasing incidence of conTSH elevation after birth and the recommended frequency of genital hypothyroidism with delayed TSH rise in lower birth monitoring of thyroid function tests in the first year of life. weight babies: extremely low birth weight (ELBW) (<1000 g) As has been the experience with essentially all new disor= 1:58; very low birth weight (VLBW) (1000-1499 g) = 1:295, ders added to screening programs, when a large population and in babies >1500 g = 1:30 329 (the actual incidence in of infants undergo comprehensive testing, new and previbabies >1500 g may be higher, because most did not undergo ously undescribed patterns of dysfunction are discovered. a second test). These findings are similar to those from the In screening infants for congenital hypothyroidism, one Massachusetts Newborn Screening Program,4 which reported such pattern is ‘‘delayed TSH rise.’’ Infants with delayed the incidence of delayed TSH rise in VLBW (<1500 g) = 1:324, TSH rise typically have a low thyroxine level but a normal in low birth weight (1501-2499) = 1:4225, and in normal birth TSH value on the first newborn screening test (collected at weight (>2500 g) = 1:77 820. The overall incidence of delayed 2 to 5 days of age), whereas subsequent testing (collected at TSH rise was 1:18 412. Reports of congenital hypothyroidism 2 to 6 weeks of age) shows a persistently low thyroxine but with delayed TSH rise are not limited to programs that use now elevated TSH level. Such cases only will be detected by a primary thyroxine reflex TSH or simultaneous thyroxine newborn screening programs that either undertake a routine and TSH test approach. The Newborn Screening Program second newborn screening test or perform a ‘‘discretionary’’ in Sydney, Australia, which uses a primary TSH test and colsecond test in targeted populations. The Northwest Regional lects a second test in babies <1500 g, reported an incidence of Newborn Screening Program, which has performed a routine congenital hypothyroidism with delayed TSH rise in VLBW second screening test since inception, reported detection of (<1500 g) = 1:111.5 infants with congenital hypothyroidism associated with deThus congenital hypothyroidism with delayed TSH rise is clearly associated with low birth weight, and, because birth weight correlates with gestational age, by inference with AAP American Academy of Pediatrics ELBW TSH VLBW
Extremely low birth weight Thyroid-stimulating hormone Very low birth weight
0022-3476/$ - see front matter. Copyright ª 2011 Mosby Inc. All rights reserved. 10.1016/j.jpeds.2010.11.030
525
THE JOURNAL OF PEDIATRICS
www.jpeds.com
lower gestational age. Most investigators ascribe the cause of delayed TSH rise to immaturity of the hypothalamicpituitary-thyroid axis. This is based on the fact that fetal serum thyroxine and TSH levels are low in mid-gestation, gradually rising in the second half of pregnancy to reach levels we are familiar with at term.6 In addition, there is evidence that pituitary-thyroid feedback relationships are not mature until term or even until a few months of age. However, ‘‘immaturity’’ of the hypothalamic-pituitary-thyroid axis is disputed by the fact that most cases of permanent, primary congenital hypothyroidism in premature infants are detected by results from the initial newborn screening test. In a report from Quebec, all four cases of congenital hypothyroidism in VLBW infants (<1500 g) were detected by an elevated TSH level on the initial newborn screening test.7 Two cases had thyroid dysgenesis and the other two had dyshormonogenesis. Does the fact that these four cases manifested a TSH elevation mean that all cases of permanent, primary congenital hypothyroidism will have an elevated TSH on initial testing? The answer is unknown. It should be pointed out that two of the Quebec cases had an initial newborn screening test at 34 and 64 days of age, respectively. The findings from Quebec suggest that cases of congenital hypothyroidism with delayed TSH rise may represent transient hypothyroidism, rather than a permanent form of congenital hypothyroidism. Of the 19 cases of congenital hypothyroidism with delayed TSH rise in ELBW or VLBW babies reported by Woo et al,3 16 had serial monitoring of thyroid function without thyroid hormone treatment. Serum TSH elevation was first noted at a mean age of 22 days (range 8 to 58 days of age). Serum T4 and TSH normalized at a mean of 51 days of age (range 22 to 121 days of age).3 This is the first study (to my knowledge) to confirm that most cases of congenital hypothyroidism with delayed TSH rise have transient hypothyroidism. Does this ‘‘transient hypothyroidism’’ reflect maturation of the hypothalamic-pituitary-thyroid axis? Or could other factors play a role in delayed TSH rise? It is possible that some drugs used to treat comorbidities in preterm infants might contribute to this picture. Steroids8 and dopamine9 are two such drugs known to suppress TSH secretion. One half of the infants from the Rhode Island study were exposed to dopamine3 (the investigators were unable to tell us the percentage of ELBW or VLBW infants who did not have development of delayed TSH rise who were exposed to dopamine). Excess iodine ingestion, usually from iodinecontaining skin antiseptics, is another potential cause of transient hypothyroidism in preterm infants. A study from the New England Screening Program examining risk factors associated with delayed TSH elevation in VLBW infants reported that 23% of such cases were exposed to iodine.10 Is the hypothyroidism associated with delayed TSH rise harmful? The Rhode Island investigators tried to address this question, but their data is limited. Of their 19 cases, three died, and another six were lost to follow-up. They were able to carry out neurodevelopmental testing on the remaining 10 cases at age 18 months (2 of the 10 received thyroid hormone treatment). No differences were found in mental or 526
Vol. 158, No. 4 psychomotor developmental indexes compared with matched controls.3 Length, weight, and head circumference also were not different from those in control subjects. The only hint of a problem was their finding that three infants with congenital hypothyroidism and delayed TSH rise had a head circumference <10th percentile versus none in the controls (P = .014). I believe the evidence supports the concept that congenital hypothyroidism with delayed TSH rise occurs in all newborn populations. On the basis of the Rhode Island study, it appears that most cases represent transient hypothyroidism. Until further studies of neurocognitive outcome are available, I believe it is prudent to treat this hypothyroidism until it resolves. As such, I also believe those newborn screening programs that do not currently detect congenital hypothyroidism with delayed TSH rise should consider a modification of their screening protocol to detect these cases. For most, this would entail adding a ‘‘discretionary’’ second newborn screening test in targeted newborn populations, which would include low birth weight or preterm babies, acutely ill term babies, babies with significant congenital anomalies (ie, with congenital heart disease), same-sex twins, and those with specific drug exposure (steroids, dopamine, or iodine). Similar conclusions were reached in guidelines published by the Clinical Laboratory and Standards Institute.11 In a related report in this issue of The Journal, Balhara et al12 from Boston reported a retrospective study of 70 infants detected with congenital hypothyroidism to evaluate current recommendations for monitoring thyroid function in these infants. At the crux of their study are the most recent guidelines from the American Academy of Pediatrics (AAP) that recommend thyroxine (or free thyroxine) and TSH measurements ‘‘every 1 to 2 months in the first 6 months of life’’ and ‘‘every 3 to 4 months’’ between 6 months and 3 years of life.’’13 Balhara et al12 focused on monitoring in the first year of life. It is their practice to monitor thyroid function test results monthly for the first 6 months of life and at least every other month between 6 and 12 months of age (ie, at more frequent intervals than recommended by the AAP guidelines). Balhara et al12 developed thyroid test monitoring criteria by which most physicians would deem a thyroid hormone dose adjustment indicated. These included (1) any TSH elevation >10 mU/L; (2) a TSH elevation in the 5- to 10-mU/L range accompanied by a thyroxine or free thyroxine in the lower half of the normal range for age; (3) a thyroxine (or free thyroxine) level not in the upper half of the normal range within a month of the previous visit, and (4) any TSH <0.10 mU/L. Using these criteria, they were able to determine the percentage of babies who benefited or would have benefited from monthly testing. Monthly testing was justified in 75% in the first 6 months of life and 36% in the second 6 months of life. On the basis of the findings, most physicians would choose to monitor thyroid function test results every 1 to 2 months for the first 12 months of life (interestingly, this was the recommendation of the previous AAP guidelines, published in 199314). The investigators do not have any data to show that this increased frequency of monitoring leads to improved neurocognitive outcome. It would seem prudent, however, that until such
EDITORIALS
April 2011 evidence is available, monitoring in infants with congenital hypothyroidism should be frequent enough to ensure timely dose adjustments to keep thyroxine (or free thyroxine) and TSH test results in the recommended target ranges. n Stephen H. LaFranchi, MD Department of Pediatrics Oregon Health & Science University Portland, Oregon Reprint requests: Stephen H. LaFranchi, MD, Department of Pediatrics [CDRCP], Oregon Health & Science University, 707 SW Gaines St, Portland, OR 97239-3098. E-mail: [email protected]
References 1. LaFranchi SH. Newborn screening strategies for congenital hypothyroidism: an update. J Inherit Metab Dis 2010;33(Suppl 2):S225-33. 2. Hunter MK, Mandel SH, Sesser DE, Miyahira RS, Rien L, Skeels MR, LaFranchi SH. Follow-up of newborns with low thyroxine and nonelevated thyroid-stimulating hormone-screening concentrations: results of the 20-year experience in the Northwest Regional Newborn Screening Program. J Pediatr 1998;132:70-4. 3. Woo CH, Lizarda A, Tucker R, Mitchell ML, Vohr G, Oh W, Phornphutkul C. Congenital hypothyroidism with a delayed thyroid-stimulating hormone (TSH) elevation in very premature infants: Incidence and growth and developmental outcomes. J Pediatr 2011;158:538-42. 4. Mandel SJ, Hermos RJ, Larson CA, Prigozhin AB, Rojas DA, Mitchell ML. Atypical hypothyroidism and the very low birth weight infant. Thyroid 2000;10:693-5.
5. Wiley V, Bijarnia S, Wikcken B. Screening for hypothyroidism in very low birth weight babies. Rev Invest Clin 2009;61(Supp 1): 31. 6. Fisher DA. Thyroid function and dysfunction in premature infants. Pediatr Endocrinol Rev 2007;4:317-28. 7. Vincent MA, Rodd C, Dussault JH, Van Vliet G. Very low birth weight newborns do not need repeat screening for congenital hypothyroidism. J Pediatr 2002;140:311-4. 8. Re RN, Kourides IA, Ridgway EC. The effect of glucocorticoid administration on human pituitary secretion of thyrotropin and prolactin. J Clin Endocrinol Metab 1976;43:338-46. 9. Filippi L, Pezzati M, Pogi C, Rossi S, Cecchi A, Santoro C. Dopamine versus dobutamine in very low birthweight infants: endocrine effects. Arch Dis Child Fetal Neonatal Ed 2007;92:F367-71. 10. Larson C, Hermos R, Delaney A, Daley D, Mitchell M. Risk factors associated with delayed thyrotropin elevations in congenital hypothyroidism. J Pediatr 2003;143:587-91. 11. Miller J, Tureck J, Awad K, Chase DH, Copeland S, Rasmussen SA, Rien L, Valentine CJ, Webster DR, Wilcken B, Clinical Laboratory Standards Institute (CLSI). Newborn screening for preterm, low birth weight, and sick newborns: approved guidelines. CLSI document 1/ LA31-A 2009;29:1-69. 12. Balhara B, Misra M, Levitsky LL. Clinical monitoring guidelines for congenital hypothyroidism: Laboratory outcome data in the first year of life. J Pediatr 2011;158:532-7. 13. Rose SR, Brown RS, Foley T, et al. Update of newborn screening and therapy for congenital hypothyroidism. Pediatrics 2006;117: 2290-303. 14. American Academy of Pediatrics, Section on Endocrinology and Committee on Genetics; American Thyroid Association, Committee on Public Health. Newborn screening for congenital hypothyroidism: recommended guidelines. Pediatrics 1993;91:1203-9.
The Challenge of Communicating Cardiovascular Risk Information to Our Patients
P
ediatricians have become increasingly aware that the and socioeconomic status/education. The incidence of carinitial insults leading to cardiovascular disease begin diovascular events is tightly linked to age, with a geometric in childhood. Each of the major cardiovascular risk increase from decade to decade of life until the eighth decade. factors presents unique challenges to the clinician caring For the pediatrician, the challenge is recognizing those chilfor children. Dyslipidemia and hypertension do not cause dren whose risk level suggests likelihood of a premature overt symptoms and require measurement; event, potentially in young adulthood or See related article, p 594 management challenges include classificamiddle age. A second challenge is communition and then communicating strategies for treatment, with cating health information traditionally geared toward adults attendant cost, in the absence of perceptible disease morbidto the pediatric population, which is often contrary to curity. Obesity and physical inactivity require change in lifestyle rent lifestyle preferences. Socioeconomic status and educafor successful management; the challenge is to convince the tion level are not strictly medical variables, but the patient to make that change. Diabetes mellitus requires comcontribution of these to the prevalence of both risk and subplex self-management strategies for glycemic control; the sequent disease is extraordinarily high, perhaps greater than challenge is to add cardiovascular risk reduction strategies any other single risk factor.1,2 The challenge to the clinician is to overcome the economic and communication barriers to the difficulties of regular diabetes treatment. Tobacco created by poverty and lack of education. Not meeting this use is an addiction; the challenge is the lack of useful prevenlast challenge is perhaps one of the great failures of tion or treatment strategies available in the pediatric office contemporary medicine. setting. There are two additional risk factors, not often discussed, but at least as important as dyslipidemia, hypertension, obesity, physical inactivity, diabetes mellitus, and tobacco use in the prediction of future cardiovascular disease. These are age 0022-3476/$ - see front matter. Copyright ª 2011 Mosby Inc. All rights reserved. 10.1016/j.jpeds.2010.11.031
527
T
he addition of tests to detect infants with congenital hylayed TSH rise, with an overall incidence of 1:67 226.2 Quespothyroidism to newborn screening programs in the tions that naturally arise include the following: (1) Do cases mid-1970s has resulted in early detection and treatof delayed TSH rise occur in all newborn populations, but ment of these infants. This is a great success story, as congendo they go undetected in programs that perform only one ital hypothyroidism is one of the most common preventable newborn screening test?; (2) Does the incidence of delayed causes of mental retardation. Programs TSH rise vary with gestational age and/or See related articles, p 532 screen infants for congenital hypothyroidbirth weight?; (3) What is known about and p 538 ism with one of three strategies: (1) an inithe etiology of delayed TSH rise?; (4) What tial thyroxine measurement with a ‘‘reflex’’ thyroidis the natural history of thyroid function in babies with destimulating hormone (TSH) determination on infants with layed TSH rise?; (5) Should infants with delayed TSH rise a thyroxine below a specified cutoff (typically <10th percenbe treated with thyroid hormone or observed with serial testtile); (2) an initial TSH measurement; or (3) a combined thying to see if thyroid function normalizes?; (6) What is the roxine and TSH determination.1 Once identified by an neurocognitive outcome in babies with delayed TSH rise?; abnormal screening test, infants then have confirmation of and (7) Should newborn screening programs modify their diagnosis by measurement of serum thyroid function tests, testing protocol to detect infants with delayed TSH rise? typically a free thyroxine and TSH. Infants with primary conThe report by Woo et al3 from the Newborn Screening Program in Rhode Island in this issue of The Journal provides angenital hypothyroidism have a low free thyroxine and eleswers to some of these questions. The Rhode Island Newborn vated TSH level. With confirmation of diagnosis, thyroid Screening program measures both thyroxine and TSH simulhormone treatment is then started. The developing brain is taneously. Specimens are collected at approximately 48 hours critically dependent on thyroid hormone during the first 2 of age; repeat specimens are collected in infants <1500 g birth to 3 years of life. The treating physician must therefore monweight at 2, 6, and 10 weeks of age or until they reach 1500 g. In itor thyroid function at intervals frequent enough to ensure addition, it appears that some infants >1500 g birth weight that thyroid hormone dosing is adjusted in a timely manner. with acute illnesses or other medical conditions also undergo Two articles published in this issue of The Journal address derepeat testing. In an analysis of 92 800 babies over a 6-year petection of congenital hypothyroidism in babies with delayed riod, these investigators found an increasing incidence of conTSH elevation after birth and the recommended frequency of genital hypothyroidism with delayed TSH rise in lower birth monitoring of thyroid function tests in the first year of life. weight babies: extremely low birth weight (ELBW) (<1000 g) As has been the experience with essentially all new disor= 1:58; very low birth weight (VLBW) (1000-1499 g) = 1:295, ders added to screening programs, when a large population and in babies >1500 g = 1:30 329 (the actual incidence in of infants undergo comprehensive testing, new and previbabies >1500 g may be higher, because most did not undergo ously undescribed patterns of dysfunction are discovered. a second test). These findings are similar to those from the In screening infants for congenital hypothyroidism, one Massachusetts Newborn Screening Program,4 which reported such pattern is ‘‘delayed TSH rise.’’ Infants with delayed the incidence of delayed TSH rise in VLBW (<1500 g) = 1:324, TSH rise typically have a low thyroxine level but a normal in low birth weight (1501-2499) = 1:4225, and in normal birth TSH value on the first newborn screening test (collected at weight (>2500 g) = 1:77 820. The overall incidence of delayed 2 to 5 days of age), whereas subsequent testing (collected at TSH rise was 1:18 412. Reports of congenital hypothyroidism 2 to 6 weeks of age) shows a persistently low thyroxine but with delayed TSH rise are not limited to programs that use now elevated TSH level. Such cases only will be detected by a primary thyroxine reflex TSH or simultaneous thyroxine newborn screening programs that either undertake a routine and TSH test approach. The Newborn Screening Program second newborn screening test or perform a ‘‘discretionary’’ in Sydney, Australia, which uses a primary TSH test and colsecond test in targeted populations. The Northwest Regional lects a second test in babies <1500 g, reported an incidence of Newborn Screening Program, which has performed a routine congenital hypothyroidism with delayed TSH rise in VLBW second screening test since inception, reported detection of (<1500 g) = 1:111.5 infants with congenital hypothyroidism associated with deThus congenital hypothyroidism with delayed TSH rise is clearly associated with low birth weight, and, because birth weight correlates with gestational age, by inference with AAP American Academy of Pediatrics ELBW TSH VLBW
Extremely low birth weight Thyroid-stimulating hormone Very low birth weight
0022-3476/$ - see front matter. Copyright ª 2011 Mosby Inc. All rights reserved. 10.1016/j.jpeds.2010.11.030
525
THE JOURNAL OF PEDIATRICS
www.jpeds.com
lower gestational age. Most investigators ascribe the cause of delayed TSH rise to immaturity of the hypothalamicpituitary-thyroid axis. This is based on the fact that fetal serum thyroxine and TSH levels are low in mid-gestation, gradually rising in the second half of pregnancy to reach levels we are familiar with at term.6 In addition, there is evidence that pituitary-thyroid feedback relationships are not mature until term or even until a few months of age. However, ‘‘immaturity’’ of the hypothalamic-pituitary-thyroid axis is disputed by the fact that most cases of permanent, primary congenital hypothyroidism in premature infants are detected by results from the initial newborn screening test. In a report from Quebec, all four cases of congenital hypothyroidism in VLBW infants (<1500 g) were detected by an elevated TSH level on the initial newborn screening test.7 Two cases had thyroid dysgenesis and the other two had dyshormonogenesis. Does the fact that these four cases manifested a TSH elevation mean that all cases of permanent, primary congenital hypothyroidism will have an elevated TSH on initial testing? The answer is unknown. It should be pointed out that two of the Quebec cases had an initial newborn screening test at 34 and 64 days of age, respectively. The findings from Quebec suggest that cases of congenital hypothyroidism with delayed TSH rise may represent transient hypothyroidism, rather than a permanent form of congenital hypothyroidism. Of the 19 cases of congenital hypothyroidism with delayed TSH rise in ELBW or VLBW babies reported by Woo et al,3 16 had serial monitoring of thyroid function without thyroid hormone treatment. Serum TSH elevation was first noted at a mean age of 22 days (range 8 to 58 days of age). Serum T4 and TSH normalized at a mean of 51 days of age (range 22 to 121 days of age).3 This is the first study (to my knowledge) to confirm that most cases of congenital hypothyroidism with delayed TSH rise have transient hypothyroidism. Does this ‘‘transient hypothyroidism’’ reflect maturation of the hypothalamic-pituitary-thyroid axis? Or could other factors play a role in delayed TSH rise? It is possible that some drugs used to treat comorbidities in preterm infants might contribute to this picture. Steroids8 and dopamine9 are two such drugs known to suppress TSH secretion. One half of the infants from the Rhode Island study were exposed to dopamine3 (the investigators were unable to tell us the percentage of ELBW or VLBW infants who did not have development of delayed TSH rise who were exposed to dopamine). Excess iodine ingestion, usually from iodinecontaining skin antiseptics, is another potential cause of transient hypothyroidism in preterm infants. A study from the New England Screening Program examining risk factors associated with delayed TSH elevation in VLBW infants reported that 23% of such cases were exposed to iodine.10 Is the hypothyroidism associated with delayed TSH rise harmful? The Rhode Island investigators tried to address this question, but their data is limited. Of their 19 cases, three died, and another six were lost to follow-up. They were able to carry out neurodevelopmental testing on the remaining 10 cases at age 18 months (2 of the 10 received thyroid hormone treatment). No differences were found in mental or 526
Vol. 158, No. 4 psychomotor developmental indexes compared with matched controls.3 Length, weight, and head circumference also were not different from those in control subjects. The only hint of a problem was their finding that three infants with congenital hypothyroidism and delayed TSH rise had a head circumference <10th percentile versus none in the controls (P = .014). I believe the evidence supports the concept that congenital hypothyroidism with delayed TSH rise occurs in all newborn populations. On the basis of the Rhode Island study, it appears that most cases represent transient hypothyroidism. Until further studies of neurocognitive outcome are available, I believe it is prudent to treat this hypothyroidism until it resolves. As such, I also believe those newborn screening programs that do not currently detect congenital hypothyroidism with delayed TSH rise should consider a modification of their screening protocol to detect these cases. For most, this would entail adding a ‘‘discretionary’’ second newborn screening test in targeted newborn populations, which would include low birth weight or preterm babies, acutely ill term babies, babies with significant congenital anomalies (ie, with congenital heart disease), same-sex twins, and those with specific drug exposure (steroids, dopamine, or iodine). Similar conclusions were reached in guidelines published by the Clinical Laboratory and Standards Institute.11 In a related report in this issue of The Journal, Balhara et al12 from Boston reported a retrospective study of 70 infants detected with congenital hypothyroidism to evaluate current recommendations for monitoring thyroid function in these infants. At the crux of their study are the most recent guidelines from the American Academy of Pediatrics (AAP) that recommend thyroxine (or free thyroxine) and TSH measurements ‘‘every 1 to 2 months in the first 6 months of life’’ and ‘‘every 3 to 4 months’’ between 6 months and 3 years of life.’’13 Balhara et al12 focused on monitoring in the first year of life. It is their practice to monitor thyroid function test results monthly for the first 6 months of life and at least every other month between 6 and 12 months of age (ie, at more frequent intervals than recommended by the AAP guidelines). Balhara et al12 developed thyroid test monitoring criteria by which most physicians would deem a thyroid hormone dose adjustment indicated. These included (1) any TSH elevation >10 mU/L; (2) a TSH elevation in the 5- to 10-mU/L range accompanied by a thyroxine or free thyroxine in the lower half of the normal range for age; (3) a thyroxine (or free thyroxine) level not in the upper half of the normal range within a month of the previous visit, and (4) any TSH <0.10 mU/L. Using these criteria, they were able to determine the percentage of babies who benefited or would have benefited from monthly testing. Monthly testing was justified in 75% in the first 6 months of life and 36% in the second 6 months of life. On the basis of the findings, most physicians would choose to monitor thyroid function test results every 1 to 2 months for the first 12 months of life (interestingly, this was the recommendation of the previous AAP guidelines, published in 199314). The investigators do not have any data to show that this increased frequency of monitoring leads to improved neurocognitive outcome. It would seem prudent, however, that until such
EDITORIALS
April 2011 evidence is available, monitoring in infants with congenital hypothyroidism should be frequent enough to ensure timely dose adjustments to keep thyroxine (or free thyroxine) and TSH test results in the recommended target ranges. n Stephen H. LaFranchi, MD Department of Pediatrics Oregon Health & Science University Portland, Oregon Reprint requests: Stephen H. LaFranchi, MD, Department of Pediatrics [CDRCP], Oregon Health & Science University, 707 SW Gaines St, Portland, OR 97239-3098. E-mail: [email protected]
References 1. LaFranchi SH. Newborn screening strategies for congenital hypothyroidism: an update. J Inherit Metab Dis 2010;33(Suppl 2):S225-33. 2. Hunter MK, Mandel SH, Sesser DE, Miyahira RS, Rien L, Skeels MR, LaFranchi SH. Follow-up of newborns with low thyroxine and nonelevated thyroid-stimulating hormone-screening concentrations: results of the 20-year experience in the Northwest Regional Newborn Screening Program. J Pediatr 1998;132:70-4. 3. Woo CH, Lizarda A, Tucker R, Mitchell ML, Vohr G, Oh W, Phornphutkul C. Congenital hypothyroidism with a delayed thyroid-stimulating hormone (TSH) elevation in very premature infants: Incidence and growth and developmental outcomes. J Pediatr 2011;158:538-42. 4. Mandel SJ, Hermos RJ, Larson CA, Prigozhin AB, Rojas DA, Mitchell ML. Atypical hypothyroidism and the very low birth weight infant. Thyroid 2000;10:693-5.
5. Wiley V, Bijarnia S, Wikcken B. Screening for hypothyroidism in very low birth weight babies. Rev Invest Clin 2009;61(Supp 1): 31. 6. Fisher DA. Thyroid function and dysfunction in premature infants. Pediatr Endocrinol Rev 2007;4:317-28. 7. Vincent MA, Rodd C, Dussault JH, Van Vliet G. Very low birth weight newborns do not need repeat screening for congenital hypothyroidism. J Pediatr 2002;140:311-4. 8. Re RN, Kourides IA, Ridgway EC. The effect of glucocorticoid administration on human pituitary secretion of thyrotropin and prolactin. J Clin Endocrinol Metab 1976;43:338-46. 9. Filippi L, Pezzati M, Pogi C, Rossi S, Cecchi A, Santoro C. Dopamine versus dobutamine in very low birthweight infants: endocrine effects. Arch Dis Child Fetal Neonatal Ed 2007;92:F367-71. 10. Larson C, Hermos R, Delaney A, Daley D, Mitchell M. Risk factors associated with delayed thyrotropin elevations in congenital hypothyroidism. J Pediatr 2003;143:587-91. 11. Miller J, Tureck J, Awad K, Chase DH, Copeland S, Rasmussen SA, Rien L, Valentine CJ, Webster DR, Wilcken B, Clinical Laboratory Standards Institute (CLSI). Newborn screening for preterm, low birth weight, and sick newborns: approved guidelines. CLSI document 1/ LA31-A 2009;29:1-69. 12. Balhara B, Misra M, Levitsky LL. Clinical monitoring guidelines for congenital hypothyroidism: Laboratory outcome data in the first year of life. J Pediatr 2011;158:532-7. 13. Rose SR, Brown RS, Foley T, et al. Update of newborn screening and therapy for congenital hypothyroidism. Pediatrics 2006;117: 2290-303. 14. American Academy of Pediatrics, Section on Endocrinology and Committee on Genetics; American Thyroid Association, Committee on Public Health. Newborn screening for congenital hypothyroidism: recommended guidelines. Pediatrics 1993;91:1203-9.
The Challenge of Communicating Cardiovascular Risk Information to Our Patients
P
ediatricians have become increasingly aware that the and socioeconomic status/education. The incidence of carinitial insults leading to cardiovascular disease begin diovascular events is tightly linked to age, with a geometric in childhood. Each of the major cardiovascular risk increase from decade to decade of life until the eighth decade. factors presents unique challenges to the clinician caring For the pediatrician, the challenge is recognizing those chilfor children. Dyslipidemia and hypertension do not cause dren whose risk level suggests likelihood of a premature overt symptoms and require measurement; event, potentially in young adulthood or See related article, p 594 management challenges include classificamiddle age. A second challenge is communition and then communicating strategies for treatment, with cating health information traditionally geared toward adults attendant cost, in the absence of perceptible disease morbidto the pediatric population, which is often contrary to curity. Obesity and physical inactivity require change in lifestyle rent lifestyle preferences. Socioeconomic status and educafor successful management; the challenge is to convince the tion level are not strictly medical variables, but the patient to make that change. Diabetes mellitus requires comcontribution of these to the prevalence of both risk and subplex self-management strategies for glycemic control; the sequent disease is extraordinarily high, perhaps greater than challenge is to add cardiovascular risk reduction strategies any other single risk factor.1,2 The challenge to the clinician is to overcome the economic and communication barriers to the difficulties of regular diabetes treatment. Tobacco created by poverty and lack of education. Not meeting this use is an addiction; the challenge is the lack of useful prevenlast challenge is perhaps one of the great failures of tion or treatment strategies available in the pediatric office contemporary medicine. setting. There are two additional risk factors, not often discussed, but at least as important as dyslipidemia, hypertension, obesity, physical inactivity, diabetes mellitus, and tobacco use in the prediction of future cardiovascular disease. These are age 0022-3476/$ - see front matter. Copyright ª 2011 Mosby Inc. All rights reserved. 10.1016/j.jpeds.2010.11.031
527