Close
New

Medscape is available in 5 Language Editions – Choose your Edition here.

 

Congenital Hypothyroidism

  • Author: Maala S Daniel, MBBS; Chief Editor: Stephen Kemp, MD, PhD  more...
 
Updated: Dec 16, 2015
 

Practice Essentials

Congenital hypothyroidism is inadequate thyroid hormone production in newborn infants. It can occur because of an anatomic defect in the gland, an inborn error of thyroid metabolism, or iodine deficiency. See the image below.

An infant with cretinism. Note the hypotonic postu An infant with cretinism. Note the hypotonic posture, coarse facial features, and umbilical hernia.

Signs and symptoms

Infants with congenital hypothyroidism are usually born at term or after term. Symptoms and signs include the following:

  • Decreased activity
  • Large anterior fontanelle
  • Poor feeding and weight gain
  • Small stature or poor growth
  • Jaundice
  • Decreased stooling or constipation
  • Hypotonia
  • Hoarse cry

Often, affected infants are described as "good babies" because they rarely cry and they sleep most of the time.

The physical findings of hypothyroidism may or may not be present at birth. Signs include the following:

  • Coarse facial features
  • Macroglossia
  • Large fontanelles
  • Umbilical hernia
  • Mottled, cool, and dry skin
  • Developmental delay
  • Pallor
  • Myxedema
  • Goiter

Anemia may occur, due to decreased oxygen carrying requirement. A small but significant number (3-7%) of infants with congenital hypothyroidism have other birth defects, mainly atrial and ventricular septal defects.[1]

See Clinical Presentation for more detail.

Diagnosis

Diagnosis of primary hypothyroidism is confirmed by demonstrating decreased levels of serum thyroid hormone (total or free T4) and elevated levels of thyroid-stimulating hormone (TSH). If maternal antibody–mediated hypothyroidism is suspected, maternal and neonatal antithyroid antibodies may confirm the diagnosis.[2] Such antibodies are an uncommon cause of congenital hypothyroidism.[3, 4]

The combination of low or low-normal serum total T4 levels and a serum TSH within the reference range suggests thyroid-binding globulin (TBG) deficiency. This congenital disorder causes no pathologic consequence, but should be recognized to avoid unnecessary thyroid hormone administration.

Thyroid scanning

Thyroid scanning is not required to make or confirm the diagnosis of congenital hypothyroidism, but can provide important information about the etiology.

On thyroid scanning (using technetium-99m or iodine-123), the absence of radionuclide uptake suggests sporadic athyreotic hypothyroidism but can also occur when uptake is blocked by excess iodide or thyroid receptor blocking antibodies. If no uptake is found on isotope scanning, thyroid ultrasonography may demonstrate thyroid tissue.[5]

Thyroid scans can also demonstrate the presence of an ectopic thyroid, such as a lingual or sublingual gland, which is also sporadic. The presence of a bilobed thyroid in the appropriate position or a goiter would suggest either an inborn error of thyroid hormone production or transient hypothyroidism or hyperthyrotropinemia

Other imaging studies

Ultrasonography may be a reasonable alternative or addition to scintigraphy but may fail to reveal some ectopic glands.[6]

A lateral radiograph of the knee may be obtained to look for the distal femoral epiphysis; this ossification center appears at about 36 weeks' gestation, and its absence in a term or postterm infant indicates prenatal effects of hypothyroidism.[7]

See Workup for more detail.

Management

The mainstay in the treatment of congenital hypothyroidism is early diagnosis and thyroid hormone replacement. Optimal care may include diagnosis before age 10-13 days and normalization of thyroid hormone blood levels by age 3 weeks.[8, 9]

Only levothyroxine is recommended for treatment.[10] Parents should be provided the hormone in pill form and taught proper administration, as follows:

  • The pills can be crushed in a spoon; dissolved with a small amount of breast milk, water, or other liquid immediately before administration; and administered to the child with a syringe or dropper
  • The pills should not be mixed in a full bottle of formula

Toddlers typically chew the tablets without problems or complaints.

Initial dosages of 10-15 mcg/kg/d, equivalent to a starting dose of 50 mcg in many newborns, have been recommended.[11] Equally good developmental results, but with higher thyroid-stimulating hormone (TSH) levels, have been reported with half this starting dose (25 mcg/d).[12]

See Treatment and Medication for more detail.

Next

Background

Congenital hypothyroidism is inadequate thyroid hormone production in newborn infants. This can occur because of an anatomic defect in the gland, an inborn error of thyroid metabolism, or iodine deficiency.

The term endemic cretinism is used to describe clusters of infants with goiter and hypothyroidism in a defined geographic area. Such areas were discovered to be low in iodine, and the cause of endemic cretinism was determined to be iodine deficiency. In the 1920s, adequate dietary intake of iodine was found to prevent endemic goiter and cretinism.[13] Endemic goiter and cretinism are still observed in some areas, such as regions of Bangladesh, Chad, China, Indonesia, Nepal, Peru, and Zaire.

The term sporadic cretinism was initially used to describe the random occurrence of cretinism in nonendemic areas. The cause of these abnormalities was identified as nonfunctioning or absent thyroid glands. This led to replacement of the descriptive term sporadic cretinism with the etiologic term congenital hypothyroidism. Treatment with thyroid replacement therapy was found to elicit some improvement in these infants (see the images below), although many remained impaired.

An infant shown a few months after starting thyroi An infant shown a few months after starting thyroid hormone replacement.
Infant a few months after starting thyroid hormone Infant a few months after starting thyroid hormone replacement.

The morbidity from congenital hypothyroidism can be reduced to a minimum by early diagnosis and treatment.[14] Although initial preliminary studies were performed using thyroid-stimulating hormone (TSH) levels in cord blood,[15, 16] mass screening was made feasible by the development of radioimmunoassay for TSH and thyroxine (T4) from blood spots on filter paper, obtained for neonatal screening tests.[17, 18]

Previous
Next

Pathophysiology

The thyroid gland develops from the buccopharyngeal cavity between 4 and 10 weeks' gestation. The thyroid arises from the fourth branchial pouches and ultimately ends up as a bilobed organ in the neck. Errors in the formation or migration of thyroid tissue can result in thyroid aplasia, dysplasia, or ectopy. By 10-11 weeks' gestation, the fetal thyroid is capable of producing thyroid hormone. By 18-20 weeks' gestation, blood levels of T4 have reached term levels. The fetal pituitary-thyroid axis is believed to function independently of the maternal pituitary-thyroid axis.

The thyroid gland uses tyrosine and iodine to manufacture T4 and triiodothyronine (T3). Iodide is taken into the thyroid follicular cells by an active transport system and then oxidized to iodine by thyroid peroxidase. Organification occurs when iodine is attached to tyrosine molecules attached to thyroglobulin, forming monoiodotyrosine (MIT) and diiodotyrosine (DIT). The coupling of 2 molecules of DIT forms tetraiodothyronine (ie, T4). The coupling of one molecule of MIT and one molecule of DIT forms T3. Thyroglobulin, with T4 and T3 attached, is stored in the follicular lumen. TSH activates the enzymes needed to cleave T4 and T3 from thyroglobulin. In most situations, T4 is the primary hormone produced by and released from the thyroid gland.

Inborn errors of thyroid metabolism can result in congenital hypothyroidism in children with anatomically normal thyroid glands.

T4 is the primary thyronine produced by the thyroid gland. Only 10-40% of circulating T3 is released from the thyroid gland. The remainder is produced by monodeiodination of T4 in peripheral tissues. T3 is the primary mediator of the biologic effects of thyroid hormone and does so by interacting with a specific nuclear receptor. Receptor abnormalities can result in thyroid hormone resistance.

The major carrier proteins for circulating thyroid hormones are thyroid-binding globulin (TBG), thyroid-binding prealbumin (TBPA), and albumin. Unbound, or free, T4 accounts for only about 0.03% of circulating T4 and is the portion that is metabolically active. Infants born with low levels of TBG, as in congenital TBG deficiency, have low total T4 levels but are physiologically normal. Familial congenital TBG deficiency can occur as an X-linked recessive or autosomal recessive condition.

The contributions of maternal thyroid hormone levels to the fetus are thought to be minimal, but maternal thyroid disease can have a substantial influence on fetal and neonatal thyroid function. Immunoglobulin G (IgG) autoantibodies, as observed in autoimmune thyroiditis, can cross the placenta and inhibit thyroid function. Thioamides used to treat maternal hyperthyroidism can also block fetal thyroid hormone synthesis. Most of these effects are transient. Radioactive iodine administered to a pregnant woman can ablate the fetus's thyroid gland permanently.

The importance of thyroid hormone to brain growth and development is demonstrated by comparing treated and untreated children with congenital hypothyroidism. Thyroid hormone is necessary for normal brain growth and myelination and for normal neuronal connections. The most critical period for the effect of thyroid hormone on brain development is the first few months of life.[14]

Previous
Next

Frequency

United States

The incidence of congenital hypothyroidism, as detected through newborn screening, is approximately 1 per 4000 births.[19] An increase in the diagnosis of primary congenital hypothyroidism has been reported in New York.[20] This trend has also been observed in some other states,[21] although not all. Possible explanations include changing demographics of the birth population, including changes in race, ethnicity, and the incidence of low birth weight.[21] Changes in laboratory and screening methodology may also play a role in this reported rise in incidence.[22] Some infants identified as having primary congenital hypothyroidism may have transient disease and not permanent congenital hypothyroidism.[5]

Twins

An increased incidence of congenital hypothyroidism is observed in twins.[23, 24, 25] Twin births are approximately 12 times as likely to have congenital hypothyroidism as singletons.[26] Usually, only one twin is hypothyroid, but a common in-utero exposure can cause hypothyroidism in both.[27]

International

In central Africa, where iodine deficiency occurs along with excess dietary cyanate from cassava (Manihot esculenta),[28] as many as 10% of newborns may have both low cord blood T4 concentration and TSH concentrations over 100 mU/L.[29]

Data from most countries with well-established newborn screening programs indicate an incidence of congenital hypothyroidism of about 1 per 3000-4000.[30, 31] Some of the highest incidences (1 in 1400 to 1 in 2000) have been reported from various locations in the Middle East.[32]

Although percentages of specific etiologies vary from country to country, ranges are as follows:

  • Ectopic thyroid - 25-50%
  • Thyroid agenesis - 20-50%
  • Dyshormonogenesis - 4-15%
  • Hypothalamic-pituitary dysfunction - 10-15%
Previous
Next

Mortality/Morbidity

Congenital hypothyroidism does not affect the all-cause standardized mortality ratio in treated patients.[33]

Profound mental retardation is the most serious effect of untreated congenital hypothyroidism. Severe impairment of linear growth and bone maturation also occurs. Affected infants whose treatment is delayed can have neurologic problems such as spasticity and gait abnormalities, dysarthria or mutism, and autistic behavior.

Race

Congenital hypothyroidism is observed in all populations. The prevalence at birth is increased in Hispanics, particularly in Hispanic females, who have a birth prevalence of 1 in 1886 births.[34] Black infants have about one third the prevalence rate of white infants.

Sex

Most studies of congenital hypothyroidism suggest a female-to-male ratio of a 2:1. Devos et al showed that much of the discrepancy is accounted for by infants with thyroid ectopy.[35] The sex ratio for Hispanics is more striking, with a 3:1 female-to-male ratio. The ratio is lower among Black infants.

Age

By definition, congenital hypothyroidism is present at, or before, birth. Children who develop primary hypothyroidism when aged 2 years or older have poor growth and slow mentation but generally do not exhibit the profound and incompletely reversible neurologic abnormalities observed in untreated congenital hypothyroidism.

Previous
 
 
Contributor Information and Disclosures
Author

Maala S Daniel, MBBS Attending Physician, Division of Pediatric Endocrinology, Helen DeVos Children's Hospital

Maala S Daniel, MBBS is a member of the following medical societies: American Academy of Pediatrics, American Medical Student Association/Foundation, Endocrine Society

Disclosure: Nothing to disclose.

Coauthor(s)

Daniel C Postellon, MD Associate Professor or Pediatrics and Human Development, Michigan State University College of Human Medicine; Consulting Staff, Pediatric Endocrine Clinic, Helen DeVos Children's Hospital

Daniel C Postellon, MD is a member of the following medical societies: American Academy of Pediatrics, Endocrine Society, Pediatric Endocrine Society, American Diabetes Association

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Barry B Bercu, MD Professor, Departments of Pediatrics, Molecular Pharmacology and Physiology, University of South Florida College of Medicine, All Children's Hospital

Barry B Bercu, MD is a member of the following medical societies: American Academy of Pediatrics, American Association of Clinical Endocrinologists, American Medical Association, American Pediatric Society, Association of Clinical Scientists, Endocrine Society, Florida Medical Association, Pediatric Endocrine Society, Society for Pediatric Research, Southern Society for Pediatric Research, Society for the Study of Reproduction, American Federation for Clinical Research, Pituitary Society

Disclosure: Nothing to disclose.

Chief Editor

Stephen Kemp, MD, PhD Former Professor, Department of Pediatrics, Section of Pediatric Endocrinology, University of Arkansas for Medical Sciences College of Medicine, Arkansas Children's Hospital

Stephen Kemp, MD, PhD is a member of the following medical societies: American Academy of Pediatrics, American Association of Clinical Endocrinologists, American Pediatric Society, Endocrine Society, Phi Beta Kappa, Southern Medical Association, Southern Society for Pediatric Research

Disclosure: Nothing to disclose.

Additional Contributors

Arlan L Rosenbloom, MD Adjunct Distinguished Service Professor Emeritus of Pediatrics, University of Florida College of Medicine; Fellow of the American Academy of Pediatrics; Fellow of the American College of Epidemiology

Arlan L Rosenbloom, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Epidemiology, American Pediatric Society, Endocrine Society, Pediatric Endocrine Society, Society for Pediatric Research, Florida Chapter of The American Academy of Pediatrics, Florida Pediatric Society, International Society for Pediatric and Adolescent Diabetes

Disclosure: Nothing to disclose.

Acknowledgements

The author wishes to thank Thomas P Foley Jr, for his instruction and for his efforts in diagnosing and managing this disease.

References
  1. Stoll C, Dott B, Alembik Y, Koehl C. Congenital anomalies associated with congenital hypothyroidism. Ann Genet. 1999. 42(1):17-20. [Medline].

  2. Zakarija M, McKenzie JM, Eidson MS. Transient neonatal hypothyroidism: characterization of maternal antibodies to the thyrotropin receptor. J Clin Endocrinol Metab. 1990 May. 70(5):1239-46. [Medline].

  3. Brown RS, Bellisario RL, Botero D, Fournier L, Abrams CA, Cowger ML. Incidence of transient congenital hypothyroidism due to maternal thyrotropin receptor-blocking antibodies in over one million babies. J Clin Endocrinol Metab. 1996 Mar. 81(3):1147-51. [Medline].

  4. Cortinhas Alves EA, Andrade RC, de Melo Amaral CE, Fernandes Caldato MC, Rocha Bastos AM, da Silva LC. Evaluation of the tshr gene reveals polymorphisms associated with typical symptoms in primary congenital hypothyroidism. J Pediatr Endocrinol Metab. 2015 Sep 10. [Medline].

  5. Parks JS, Lin M, Grosse SD, Hinton CF, Drummond-Borg M, Borgfeld L. The impact of transient hypothyroidism on the increasing rate of congenital hypothyroidism in the United States. Pediatrics. 2010 May. 125 Suppl 2:S54-63. [Medline].

  6. Perry RJ, Maroo S, Maclennan AC, Jones JH, Donaldson MD. Combined ultrasound and isotope scanning is more informative in the diagnosis of congenital hypothyroidism than single scanning. Arch Dis Child. 2006 Dec. 91(12):972-6. [Medline].

  7. Lowery GH, Aster RH, Carr EA, Ramon G, Beierwates WH, Spafford NR. Early Diagnostic Criteria of Congenital Hypothyroidism: A Comprehensive Study of Forty-Nine Cretins. Am J Dis Child. 1958. 96(2):131-143.

  8. Bongers-Schokking JJ, Koot HM, Wiersma D, et al. Influence of timing and dose of thyroid hormone replacement on development in infants with congenital hypothyroidism. J Pediatr. 2000 Mar. 136(3):292-7. [Medline].

  9. [Guideline] Donaldson M, Jones J. Optimising outcome in congenital hypothyroidism; current opinions on best practice in initial assessment and subsequent management. J Clin Res Pediatr Endocrinol. 2013 Mar 4. 5 Suppl 1:13-22. [Medline].

  10. LaFranchi SH, Austin J. How should we be treating children with congenital hypothyroidism?. J Pediatr Endocrinol Metab. 2007 May. 20(5):559-78. [Medline].

  11. Selva KA, Harper A, Downs A, Blasco PA, Lafranchi SH. Neurodevelopmental outcomes in congenital hypothyroidism: comparison of initial T4 dose and time to reach target T4 and TSH. J Pediatr. 2005 Dec. 147(6):775-80. [Medline].

  12. Campos SP, Sandberg DE, Barrick C, Voorhess ML, MacGillivray MH. Outcome of lower L-thyroxine dose for treatment of congenital hypothyroidism. Clin Pediatr (Phila). 1995 Oct. 34(10):514-20. [Medline].

  13. McClure RD. Goiter prophylaxis with iodized salt. Science. 1935 Oct 18. 82(2129):370-371. [Medline].

  14. Klein AH, Meltzer S, Kenny FM. Improved prognosis in congenital hypothyroidism treated before age three months. J Pediatr. 1972 Nov. 81(5):912-5. [Medline].

  15. Klein AH, Agustin AV, Foley TP Jr. Successful laboratory screening for congenital hypothyroidism. Lancet. 1974 Jul 13. 2(7872):77-9. [Medline].

  16. Buist NR, Murphey WF, Brandon GR, Foley TP Jr, Penn RL. Letter: Neonatal screening for hypothyroidism. Lancet. 1975 Nov 1. 2(7940):872-3. [Medline].

  17. Dussault JH, Parlow A, Letarte J, Guyda H, Laberge C. TSH measurements from blood spots on filter paper: a confirmatory screening test for neonatal hypothyroidism. J Pediatr. 1976 Oct. 89(4):550-2. [Medline].

  18. Larsen PR, Merker A, Parlow AF. Immunoassay of human TSH using dried blood samples. J Clin Endocrinol Metab. 1976 May. 42(5):987-90. [Medline].

  19. Delange F. Screening for congenital hypothyroidism used as an indicator of the degree of iodine deficiency and of its control. Thyroid. 1998 Dec. 8(12):1185-92. [Medline].

  20. Harris KB, Pass KA. Increase in congenital hypothyroidism in New York State and in the United States. Mol Genet Metab. 2007 Jul. 91(3):268-77. [Medline].

  21. Hinton CF, Harris KB, Borgfeld L, Drummond-Borg M, Eaton R, Lorey F. Trends in incidence rates of congenital hypothyroidism related to select demographic factors: data from the United States, California, Massachusetts, New York, and Texas. Pediatrics. 2010 May. 125 Suppl 2:S37-47. [Medline].

  22. Hertzberg V, Mei J, Therrell BL. Effect of laboratory practices on the incidence rate of congenital hypothyroidism. Pediatrics. 2010 May. 125 Suppl 2:S48-53. [Medline].

  23. Medda E, Olivieri A, Stazi MA, et al. Risk factors for congenital hypothyroidism: results of a population case-control study (1997-2003). Eur J Endocrinol. 2005 Dec. 153(6):765-73. [Medline].

  24. Kurinczuk JJ, Bower C, Lewis B, Byrne G. Congenital hypothyroidism in Western Australia 1981-1998. J Paediatr Child Health. 2002 Apr. 38(2):187-91. [Medline].

  25. Medda E, Olivieri A, Stazi MA, Grandolfo ME, Fazzini C, Baserga M. Risk factors for congenital hypothyroidism: results of a population case-control study (1997-2003). Eur J Endocrinol. 2005 Dec. 153(6):765-73. [Medline].

  26. Olivieri A, Medda E, De Angelis S, Valensise H, De Felice M, Fazzini C, et al. High risk of congenital hypothyroidism in multiple pregnancies. J Clin Endocrinol Metab. 2007 Aug. 92(8):3141-7. [Medline].

  27. Kurtoglu S, Keskin M, Koklu E, Akcakus M, Atabek ME, Hatipoglu N. Congenital goiter in premature twins due to propylthiouracil treatment. J Pediatr Endocrinol Metab. 2007 Jul. 20(7):771. [Medline].

  28. Akindahunsi AA, Grissom FE, Adewusi SR, Afolabi OA, Torimiro SE, Oke OL. Parameters of thyroid function in the endemic goitre of Akungba and Oke-Agbe villages of Akoko area of southwestern Nigeria. Afr J Med Med Sci. 1998 Sep-Dec. 27(3-4):239-42. [Medline].

  29. Delange F. Neonatal thyroid screening as a monitoring tool for the control of iodine deficiency. Acta Paediatr Suppl. 1999 Dec. 88(432):21-4. [Medline].

  30. de Vijlder JJ, Ris-Stalpers C, Vulsma T. Inborn errors of thyroid hormone biosynthesis. Exp Clin Endocrinol Diabetes. 1997. 105 Suppl 4:32-7. [Medline].

  31. Klett M. Epidemiology of congenital hypothyroidism. Exp Clin Endocrinol Diabetes. 1997. 105 Suppl 4:19-23. [Medline].

  32. Sack J, Feldman I, Kaiserman I. Congenital hypothyroidism screening in the West Bank: a test case for screening in developing regions. Horm Res. 1998 Sep. 50(3):151-4. [Medline].

  33. Azar-Kolakez A, Ecosse E, Dos Santos S, Léger J. All-Cause and Disease-specific Mortality and Morbidity in Patients With Congenital Hypothyroidism Treated Since the Neonatal Period: A National Population-based Study. J Clin Endocrinol Metab. 2013 Feb. 98(2):785-93. [Medline].

  34. Lorey FW, Cunningham GC. Birth prevalence of primary congenital hypothyroidism by sex and ethnicity. Hum Biol. 1992 Aug. 64(4):531-8. [Medline].

  35. Devos H, Rodd C, Gagne N, Laframboise R, Van Vliet G. A search for the possible molecular mechanisms of thyroid dysgenesis: sex ratios and associated malformations. J Clin Endocrinol Metab. 1999 Jul. 84(7):2502-6. [Medline].

  36. Waller DK, Anderson JL, Lorey F, Cunningham GC. Risk factors for congenital hypothyroidism: an investigation of infant's birth weight, ethnicity, and gender in California, 1990-1998. Teratology. 2000 Jul. 62(1):36-41. [Medline].

  37. Cao XY, Jiang XM, Dou ZH, Rakeman MA, Zhang ML, O'Donnell K. Timing of vulnerability of the brain to iodine deficiency in endemic cretinism. N Engl J Med. 1994 Dec 29. 331(26):1739-44. [Medline].

  38. Luca P, Davide C, Daniela C, et al. Genetics and phenomics of hypothyroidism due to TSH resistance. Mol Cell Endocrinol. 2010 Jan 18. [Medline].

  39. Evans C, Jordan NJ, Owens G, Bradley D, Ludgate M, John R. Potent thyrotrophin receptor-blocking antibodies: a cause of transient congenital hypothyroidism and delayed thyroid development. Eur J Endocrinol. 2004 Mar. 150(3):265-8. [Medline].

  40. l'Allemand D, Grüters A, Beyer P, Weber B. Iodine in contrast agents and skin disinfectants is the major cause for hypothyroidism in premature infants during intensive care. Horm Res. 1987. 28(1):42-9. [Medline].

  41. Ares S, Escobar-Morreale HF, Quero J, Durán S, Presas MJ, Herruzo R, et al. Neonatal hypothyroxinemia: effects of iodine intake and premature birth. J Clin Endocrinol Metab. 1997 Jun. 82(6):1704-12. [Medline].

  42. Kugelman A, Riskin A, Bader D, Koren I. Pitfalls in screening programs for congenital hypothyroidism in premature newborns. Am J Perinatol. 2009 May. 26(5):383-5. [Medline].

  43. Osborn DA. Thyroid hormones for preventing neurodevelopmental impairment in preterm infants. Cochrane Database Syst Rev. 2001. CD001070. [Medline].

  44. Thomas Jde V, Collett-Solberg PF. Perinatal goiter with increased iodine uptake and hypothyroidism due to excess maternal iodine ingestion. Horm Res. 2009. 72(6):344-7. [Medline].

  45. Frassetto F, Tourneur Martel F, Barjhoux CE, Villier C, Bot BL, Vincent F. Goiter in a newborn exposed to lithium in utero. Ann Pharmacother. 2002 Nov. 36(11):1745-8. [Medline].

  46. Gallagher MP, Schachner HC, Levine LS, Fisher DA, Berdon WE, Oberfield SE. Neonatal thyroid enlargement associated with propylthiouracil therapy of Graves' disease during pregnancy: a problem revisited. J Pediatr. 2001 Dec. 139(6):896-900. [Medline].

  47. Pavan-Senn CC, Nesi-França S, Pelaez J, Pereira RM, Boguszewski MC, Sandrini Neto R, et al. [Transient neonatal hypothyroidism due to amiodarone administration during pregnancy--two cases report and review of literature]. Arq Bras Endocrinol Metabol. 2008 Feb. 52(1):126-30. [Medline].

  48. Lomenick JP, Jackson WA, Backeljauw PF. Amiodarone-induced neonatal hypothyroidism: a unique form of transient early-onset hypothyroidism. J Perinatol. 2004 Jun. 24(6):397-9. [Medline].

  49. Ordookhani A, Pearce EN, Mirmiran P, Azizi F, Braverman LE. Transient congenital hypothyroidism in an iodine-replete area is not related to parental consanguinity, mode of delivery, goitrogens, iodine exposure, or thyrotropin receptor autoantibodies. J Endocrinol Invest. 2008 Jan. 31(1):29-34. [Medline].

  50. Korzeniewski SJ, Grigorescu V, Kleyn M, Young WI, Birbeck G, Todem D. Transient hypothyroidism at 3-year follow-up among cases of congenital hypothyroidism detected by newborn screening. J Pediatr. 2013 Jan. 162(1):177-82. [Medline].

  51. Srinivasan R, Harigopal S, Turner S, Cheetham T. Permanent and transient congenital hypothyroidism in preterm infants. Acta Paediatr. 2012 Apr. 101(4):e179-82. [Medline].

  52. Finnegan JT, Slosberg EJ, Postellon DC, Primack WA. Congenital nephrotic syndrome detected by hypothyroid screening. Acta Paediatr Scand. 1980 Sep. 69(5):705-6. [Medline].

  53. Trimarchi F, Gemelli M, Benvenga S, Genova R, De Luca F. Transient congenital hypothyroidism in an infant with congenital nephrosis of Finnish type. Acta Paediatr Scand. 1983 Jan. 72(1):145-7. [Medline].

  54. Zung A, Tenenbaum-Rakover Y, Barkan S, Hanukoglu A, Hershkovitz E, Pinhas-Hamiel O. Neonatal hyperthyrotropinemia: population characteristics, diagnosis, management and outcome after cessation of therapy. Clin Endocrinol (Oxf). 2009 May 18. [Medline].

  55. Perry RJ, Maroo S, Maclennan AC, Jones JH, Donaldson MD. Combined ultrasound and isotope scanning is more informative in the diagnosis of congenital hypothyroidism than single scanning. Arch Dis Child. 2006 Dec. 91(12):972-6. [Medline].

  56. Schoen EJ, Clapp W, To TT, Fireman BH. The key role of newborn thyroid scintigraphy with isotopic iodide (123I) in defining and managing congenital hypothyroidism. Pediatrics. 2004 Dec. 114(6):e683-8. [Medline].

  57. Sedassari Ade A, de Souza LR, Sedassari Nde A, Borges Mde F, Palhares HM, de Andrade Neto GB. Sonographic evaluation of children with congenital hypothyroidism. Radiol Bras. 2015 Jul-Aug. 48 (4):220-4. [Medline].

  58. Rovet J, Ehrlich R, Sorbara D. Intellectual outcome in children with fetal hypothyroidism. J Pediatr. 1987 May. 110(5):700-4. [Medline].

  59. Rovet JF. Children with congenital hypothyroidism and their siblings: do they really differ?. Pediatrics. 2005 Jan. 115(1):e52-7. [Medline].

  60. Simoneau-Roy J, Marti S, Deal C, Huot C, Robaey P, Van Vliet G. Cognition and behavior at school entry in children with congenital hypothyroidism treated early with high-dose levothyroxine. J Pediatr. 2004 Jun. 144(6):747-52. [Medline].

  61. Wassner AJ, Brown RS. Congenital hypothyroidism: recent advances. Curr Opin Endocrinol Diabetes Obes. 2015 Oct. 22 (5):407-12. [Medline].

  62. Chen ZP, Hetzel BS. Cretinism revisited. Best Pract Res Clin Endocrinol Metab. 2010 Feb. 24(1):39-50. [Medline].

  63. Chorazy PA, Himelhoch S, Hopwood NJ, Greger NG, Postellon DC. Persistent hypothyroidism in an infant receiving a soy formula: case report and review of the literature. Pediatrics. 1995 Jul. 96(1 Pt 1):148-50. [Medline].

  64. Conrad SC, Chiu H, Silverman BL. Soy formula complicates management of congenital hypothyroidism. Arch Dis Child. 2004 Jan. 89(1):37-40. [Medline].

  65. Lomenick JP, Wang L, Ampah SB, Saville BR, Greenwald FI. Generic levothyroxine compared with synthroid in young children with congenital hypothyroidism. J Clin Endocrinol Metab. 2013 Feb. 98(2):653-8. [Medline].

  66. Carswell JM, Gordon JH, Popovsky E, Hale A, Brown RS. Generic and brand-name L-thyroxine are not bioequivalent for children with severe congenital hypothyroidism. J Clin Endocrinol Metab. 2013 Feb. 98(2):610-7. [Medline]. [Full Text].

  67. [Guideline] Jones JH, Donaldson MD. Audit of initial management of congenital hypothyroidism in the United Kingdom--comparison of UK practice with European and UK guidelines. J Pediatr Endocrinol Metab. 2009 Nov. 22(11):1017-25. [Medline].

  68. Hindmarsh PC. Optimisation of thyroxine dose in congenital hypothyroidism. Arch Dis Child. 2002 Feb. 86(2):73-5. [Medline].

  69. Raymond J, LaFranchi SH. Fetal and neonatal thyroid function: review and summary of significant new findings. Curr Opin Endocrinol Diabetes Obes. 2010 Feb. 17(1):1-7. [Medline].

  70. Rovet JF. In search of the optimal therapy for congenital hypothyroidism. J Pediatr. 2004 Jun. 144(6):698-700. [Medline].

  71. Penny R, Frasier SD. Elevated serum concentrations of triiodothyronine in hypothyroid patients. Values for patients receiving USP thyroid. Am J Dis Child. 1980 Jan. 134(1):16-8. [Medline].

  72. Bargagna S, Dinetti D, Pinchera A, et al. School attainments in children with congenital hypothyroidism detected by neonatal screening and treated early in life. Eur J Endocrinol. 1999 May. 140(5):407-13. [Medline].

  73. Eugster EA, LeMay D, Zerin JM, Pescovitz OH. Definitive diagnosis in children with congenital hypothyroidism. J Pediatr. 2004 May. 144(5):643-7. [Medline].

  74. Benmiloud M, Chaouki ML, Gutekunst R, Teichert HM, Wood WG, Dunn JT. Oral iodized oil for correcting iodine deficiency: optimal dosing and outcome indicator selection. J Clin Endocrinol Metab. 1994 Jul. 79(1):20-4. [Medline].

  75. Tonglet R, Bourdoux P, Minga T, Ermans AM. Efficacy of low oral doses of iodized oil in the control of iodine deficiency in Zaire. N Engl J Med. 1992 Jan 23. 326(4):236-41. [Medline].

  76. Grosse SD, Van Vliet G. Prevention of intellectual disability through screening for congenital hypothyroidism: how much and at what level?. Arch Dis Child. 2011 Jan 31. [Medline].

  77. Leger J, Ecosse E, Roussey M, Lanoe JL, Larroque B,. Subtle Health Impairment and Socioeducational Attainment in Young Adult Patients with Congenital Hypothyroidism Diagnosed by Neonatal Screening: A Longitudinal Population-Based Cohort Study. J Clin Endocrinol Metab. 2011 Mar 9. [Medline].

  78. Dallas JS, Foley TP. Hypothyroidism. Sperling MA, ed. Pediatric Endocrinology. 3rd ed. Philadelphia, Pa: WB Saunders Co; 1996. 391-9.

  79. Delange F. Iodine deficiency as a cause of brain damage. Postgrad Med J. 2001 Apr. 77(906):217-20. [Medline].

  80. Delange FM. Endemic cretinism. Werner & Ingbar's The Thyroid: A Fundamental and Clinical Text. 7th ed. Philadelphia, Pa: Lippincott Williams & Wilkins; 1996. 756-68.

  81. DeLong GR. The neuromuscular system and brain in hypothyroidism. In: Werner & Ingbar's The Thyroid: A Fundamental and Clinical Text. 7th ed. Philadelphia, Pa:. Lippincott Williams & Wilkins. 1996:826-36.

  82. Desai MP. Disorders of thyroid gland in India. Indian J Pediatr. 1997 Jan-Feb. 64(1):11-20. [Medline].

  83. Elbualy M, Bold A, De Silva V, Gibbons U. Congenital hypothyroid screening: the Oman experience. J Trop Pediatr. 1998 Apr. 44(2):81-3. [Medline].

  84. Fagman H, Nilsson M. Morphogenesis of the thyroid gland. Mol Cell Endocrinol. 2009 Dec 21. [Medline].

  85. Foley T, Malvaux P, Blizzard RM. Thyroid disorders. Kappy MS, Blizzard RM, Migeon CJ, eds. The Diagnosis and Treatment of Endocrine Disorders in Childhood and Adolescence. 4th ed. Baltimore, Md: Williams & Wilkins; 1994. 457-534.

  86. Foley TP Jr, Klein AH, Foley B, Agustin AV, MacDonald HM, Hopwood N. [TSH-screening program for congenital hypothyroidism. Experiences with early thyrotropin (TSH) screening]. Fortschr Med. 1979 Feb 8. 97(6):221-4. [Medline].

  87. Gruters A, Krude H. Update on the management of congenital hypothyroidism. Horm Res. 2007. 68 Suppl 5:107-11. [Medline].

  88. Hsiao PH, Chiu YN, Tsai WY, et al. Intellectual outcomes of patients with congenital hypothyroidism not detected by neonatal screening. J Formos Med Assoc. 1999 Jul. 98(7):512-5. [Medline].

  89. Jalil MQ, Mia MJ, Ali SM. Epidemiological study of endemic cretinism in a hyperendemic area. Bangladesh Med Res Counc Bull. 1997 Apr. 23(1):34-7. [Medline].

  90. Korzeniewski SJ, Kleyn M, Young WI, Chaiworapongsa T, Schwartz AG, Romero R. Screening for congenital hypothyroidism in newborns transferred to neonatal intensive care. Arch Dis Child Fetal Neonatal Ed. 2013 Jul. 98(4):F310-5. [Medline].

  91. Kouame P, Bellis G, Tebbi A, et al. The prevalence of goitre and cretinism in a population of the west Ivory Coast. Coll Antropol. 1998 Jun. 22(1):31-41. [Medline].

  92. LaFranchi S. Congenital hypothyroidism: etiologies, diagnosis, and management. Thyroid. 1999 Jul. 9(7):735-40. [Medline].

  93. LaFranchi SH, Buist NR, Murphey WH, Larsen PR, Foley TP Jr. Transient neonatal hypothyroidism detected by newborn screening program. Pediatrics. 1977 Oct. 60(4):539-41. [Medline].

  94. Mikelsaar RV, Zordania R, Viikmaa M, Kudrjavtseva G. Neonatal screening for congenital hypothyroidism in Estonia. J Med Screen. 1998. 5(1):20-1. [Medline].

  95. Mirabella G, Feig D, Astzalos E, et al. The effect of abnormal intrauterine thyroid hormone economies on infant cognitive abilities. J Pediatr Endocrinol Metab. 2000 Feb. 13(2):191-4. [Medline].

  96. Moltz KC, Postellon DC. Congenital hypothyroidism and mental development. Compr Ther. 1994. 20(6):342-6. [Medline].

  97. Moreno-Reyes R, Suetens C, Mathieu F, et al. Kashin-Beck osteoarthropathy in rural Tibet in relation to selenium and iodine status. N Engl J Med. 1998 Oct 15. 339(16):1112-20. [Medline].

  98. Murdoch DR, Harding EG, Dunn JT. Persistence of iodine deficiency 25 years after initial correction efforts in the Khumbu region of Nepal. N Z Med J. 1999 Jul 23. 112(1092):266-8. [Medline].

  99. Postellon DC. Diagnosis and treatment of congenital hypothyroidism. Compr Ther. 1983 Feb. 9(2):41-4. [Medline].

  100. Postellon DC, Abdallah A. Congenital hypothyroidism: diagnosis, treatment, and prognosis. Compr Ther. 1986 Jan. 12(1):67-71. [Medline].

  101. Postellon DC, Hale PM. Diagnosis and treatment of thyroid disease in infants. Compr Ther. 1991 Jul. 17(7):57-61. [Medline].

  102. Rajatanavin R, Chailurkit L, Winichakoon P, et al. Endemic cretinism in Thailand: a multidisciplinary survey. Eur J Endocrinol. 1997 Oct. 137(4):349-55. [Medline].

  103. Rovet JF. Congenital hypothyroidism: long-term outcome. Thyroid. 1999 Jul. 9(7):741-8. [Medline].

  104. Rovet JF. Long-term neuropsychological sequelae of early-treated congenital hypothyroidism: effects in adolescence. Acta Paediatr Suppl. 1999 Dec. 88(432):88-95. [Medline].

  105. Rovet JF, Ehrlich R. Psychoeducational outcome in children with early-treated congenital hypothyroidism. Pediatrics. 2000 Mar. 105(3 Pt 1):515-22. [Medline].

  106. Salerno M, Militerni R, Di Maio S, et al. Intellectual outcome at 12 years of age in congenital hypothyroidism. Eur J Endocrinol. 1999 Aug. 141(2):105-10. [Medline].

  107. Schoen EJ, Clapp W, To TT, Fireman BH. The key role of newborn thyroid scintigraphy with isotopic iodide (123I) in defining and managing congenital hypothyroidism. Pediatrics. 2004 Dec. 114(6):e683-8. [Medline]. [Full Text].

  108. Sfakianakis GN, Ezuddin SH, Sanchez JE, et al. Pertechnetate scintigraphy in primary congenital hypothyroidism. J Nucl Med. 1999 May. 40(5):799-804. [Medline].

  109. Taketomo CK, Hodding JH, Kraus DM. Pediatric Dosage Handbook. 7th ed. Hudson, Ohio: Lexi-Comp; 2000.

  110. Vela M, Gamboa S, Loera-Luna A, et al. Neonatal screening for congenital hypothyroidism in Mexico: experience, obstacles, and strategies. J Med Screen. 1999. 6(2):77-9. [Medline].

 
Previous
Next
 
An infant with cretinism. Note the hypotonic posture, coarse facial features, and umbilical hernia.
Note the macroglossia.
An infant shown a few months after starting thyroid hormone replacement.
Infant a few months after starting thyroid hormone replacement.
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2016 by WebMD LLC. This website also contains material copyrighted by 3rd parties.