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 Table of Contents  
Year : 2023  |  Volume : 14  |  Issue : 1  |  Page : 11

The consensus on the diagnosis and management of congenital hypothyroidism in term neonates

1 Metabolic Liver Disease Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
2 Growth and Development Research Center, Tehran University of Medical Sciences, Tehran, Iran
3 Child Growth and Development Research Center, Research Institute for Primordial Prevention of Non-Communicable Disease, Isfahan University of Medical Sciences, Isfahan; Pediatric Diseases Research Center, Guilan University of Medical Sciences, Rasht, Iran
4 Pediatric Diseases Research Center, Guilan University of Medical Sciences, Rasht, Iran

Date of Submission24-Dec-2021
Date of Acceptance31-Jan-2022
Date of Web Publication25-Jan-2023

Correspondence Address:
Setila Dalili
Pediatric Diseases Research Center, Guilan University of Medical Sciences, Rasht
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijpvm.ijpvm_535_21

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Congenital hypothyroidism (CH) is one of the most treatable endocrine disorders in infants and children that can influence the function of many organs in the body. On-time diagnosis and treatment can prevent the adverse effects of thyroid hormone deficiency on the child's neurodevelopment. There are many challenges in screening, post-screening, diagnosis, and managing this disorder. Therefore, this article aimed to mention updated information on this issue. Although there are different approaches for the treatment of hypothyroidism, the authors decided to create a national approach based on the conditions of our country.

Keywords: Congenital hypothyroidism, infant, newborn

How to cite this article:
Hashemipour M, Rabbani A, Rad AH, Dalili S. The consensus on the diagnosis and management of congenital hypothyroidism in term neonates. Int J Prev Med 2023;14:11

How to cite this URL:
Hashemipour M, Rabbani A, Rad AH, Dalili S. The consensus on the diagnosis and management of congenital hypothyroidism in term neonates. Int J Prev Med [serial online] 2023 [cited 2023 Sep 28];14:11. Available from: https://www.ijpvmjournal.net/text.asp?2023/14/1/11/368551

  Introduction Top

Congenital hypothyroidism (CH) is one of the most common treatable disorders. If not treated appropriately, it could have many adverse effects on the child's neurodevelopment.[1],[2] Most neonates born with CH may be missed due to normal appearance and no detectable physical signs.[3] Despite the on-time diagnosis and proper treatment, deterioration in neurodevelopmental outcomes might occur due to missed diagnosis and interpretation of laboratory tests.[4]

  Screening of CH in Term Neonates Top

Despite the limited observations, screening newborns for congenital hypothyroidism seems logical because it is a cost-effective strategy that provides maximum health improvement, especially in countries with limited resources.[5] There are different screening strategies for CH worldwide.[3] Based on the diversity of screening programs in other countries, only thyroid stimulating hormone (TSH) or T4 plus TSH should be measured.[3],[6],[7]

The prevalence of primary congenital hypothyroidism and central hypothyroidism is 1 in 3000–4000 and 1 in 11000–100000 live births, respectively.[8] In Iran, the prevalence of primary congenital hypothyroidism is estimated to be 1 in 1100–1400 live births.[9],[10],[11]

Although T4 is a sensitive screening test, it has a high frequency of false-positive mainly in low birth weight and premature infants.

Therefore, due to the low incidence of central hypothyroidism, screening newborns with only TSH is the most sensitive screening test.[3] It is noteworthy that clinicians screen patients with free T4 (FT4) plus or followed by TSH in case of financial approval. By this protocol, central hypothyroidism and thyroid-binding globulin (TBG) disorders could not be missed.[3],[12]

In countries with economic difficulties, clinicians recommend screening of T4 and TSH in all neonates with the following conditions:

  • A familial history of central CH
  • Signs or symptoms of hypopituitarism such as micropenis with undescended testes, hypoglycemia, prolonged jaundice, or unexplained failure to thrive.
  • Dysmorphic and mid-facial abnormality and cleft lip and palate.

  Post-Screening Conditions Top

Who are the appropriate candidates for the second screening test?

The exact characteristics of the second screening for hypothyroidism in infants have been updated over time.[13],[14],[15]

Generally, a second screening is performed on the following neonates:

Preterm neonates, birth weight <2500 g, low and very low birth weight neonates, birth weight >4000 g, history of hospitalization due to non-thyroidal illness, history of blood transfusion, TSH of 5-9.9 in first screening test, insufficient sampling, history of taking corticosteroid and dopamine, iodine exposure in mother and neonate, same-sex twins, multiple births, gestational age >40 weeks, history of thyroid disease and diabetes in mothers, administration of steroid, amiodarone, and dopamine to the mothers, congenital heart disease in the neonate, DOWN syndrome, other malformations and syndromes, and hemangioma. It is better to have a monthly hypothyroidism screening in patients with hemangioma for a year. It is better to have a hypothyroidism screening at least for the first month and every 6 to 12 months until three years of age in patients with Down syndrome due to an extra chromosome 21[16],[17],[18] that causes thyroid damage.

  Second Screening Time Top

The second screening must be performed at 2, 6, and 10 weeks after birth. Recently, it has been recommended that in case of normal results at four to six weeks of age in preterm infants born at >33 weeks of gestation, no further screening is required. For infants born <33 weeks of pregnancy, it may be prudent to perform other screening tests until they reach term-corrected (37 weeks) gestation.[19] Although second screening at 2, 6, and 10 weeks is recommended in many countries, further investigation is needed to assess the necessity of the 10th-week of screening.[20]

  Normal Range of FT4 and TSH Top

The authors had previously published a guideline for premature neonates[21] to avoid clinicians' confusion due to differences in the normal range of FT4 based on different gestational ages. Fortunately, the guideline indicated a specific range of FT4 (between 0.8 and 2.6 ng/dl) in premature neonates. However, there is still confusion regarding hypothyroidism in term infants despite a certain age. Therefore, the same reference range of FT4 (0.8 and 2.6) of premature neonates is accepted in this guideline.[22]

  Guideline of Treatment Top

The treatment guideline is similar in preterm and term neonates, except when TSH is between 6- 10 mIU/L, and FT4 is low. In this case, FT4 and TSH should be repeated two weeks later in preterm and term neonates. In addition, in term neonates, the pituitary axis, especially the adrenal axis, should be checked and treatment started. Treatment based on various types of TSH is summarized in [Table 1] and [Figure 1].
Table 1: Guideline of treatment in term and premature neonates

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Figure 1: Guideline of treatment in term and premature neonates. *In premature neonates, tests should be rechecked at 2, 6, and 10 weeks despite normal laboratory tests. **The only difference between term and premature neonates

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  Evaluation of Central Hypothyroidism Top

As [Figure 2] shows, low-dose (LD) ACTH is usually given to diagnose central hypothyroidism. Clinicians have to measure cortisol, inject one microgram of ACTH intravenously, and measure cortisol again 30 and 60 min later.
Figure 2: Evaluation of central hypothyroidism by low dose ACTH results. CH: Congenital hypothyroidism. HC: Hydrocortisone

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It should be noted that cortisol is naturally low in infants. Still, increased cortisol to above 18 μg/dL is valuable because the interpretation of the LD ACTH test is challenging in neonates. Investigators believe that in central hypothyroidism, first clinicians should blindly give low-dose hydrocortisone for at least 48 hrs, then start levothyroxine and finally taper the drug dose over time. Others believe in performing a low dose ACTH test for the patient to check the adrenal axis.

To evaluate congenital hypothyroidism, clinicians should do a low dose of ACTH test if they had an abnormal test (cortisol level less than 18 μg/dL in stimulation with one microgram of ACTH). Hydrocortisone is recommended before starting treatment with levothyroxine. However, sometimes in moderate deficiency, only hydrocortisone is recommended under stress.

In case of combined pituitary deficiency (CPD), LH and FSH, GH, and ACTH should be assessed in these infants, and magnetic resonance imaging (MRI) for abnormal low dose ACTH test is recommended.

In patients with normal low-dose ACTH tests, first clinicians should evaluate isolated TSH deficiency with the genetic study. Although MRI is recommended in these cases, it should be delayed because the infants cannot tolerate MRI under anesthesia.[23]

  Dose of Levothyroxine Top

For congenital hypothyroidism, it is better to start treatment based on FT4 because general therapy of 10–15 μg/Kg sometimes causes hyperthyroidism.[17],[24],[25] Treatment based on FT4 is summarized in [Table 2].
Table 2: Dose of levothyroxine in primary and central hypothyroidism based on FT4

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  Permanent and Transient Hypothyroidism Top

At the age of three years, in patients who have no evidence of thyroid dysgenesis on ultrasound or thyroid scan and do not have any increase in TSH during treatment, we can discontinue levothyroxine for one month and retest of T4 or FT4 and TSH.

The patient would have transient hypothyroidism if the TSH was below 5 mIU/L with normal FT4 two or three times. After discontinuing levothyroxine, if TSH reaches above 20 mIU/L with one testing or above 10mIU/L after two testings, the patient would have permanent hypothyroidism, and we have to restart treatment.

If, after stopping treatment, TSH was between 5 and 9.9 mIU/L, the patient has permanent hyperthyrotropinemia and does not need treatment and needs follow-up.

Some physicians believe that treatment may be temporarily started as off-treatment in suspected cases. If the patient has euthyroidism taking levothyroxine at a dose of fewer than 3 μg/Kg, we can discontinue its treatment at six months of age and reevaluate it.[17],[18]

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

Mohebbi Moghaddam A, Norooziasl S. Comparison of intelligence quotient between permanent congenital hypothyroid children and healthy children. Int J Pediat 2021;9:14710-8.  Back to cited text no. 1
Dalili S, Rezvani SM, Dalili H, Amiri ZM, Mohammadi H, Kesh SA, et al. Congenital hypothyroidism: Etiology and growth-development outcome. Acta Med Iran 2014:752-6.  Back to cited text no. 2
Büyükgebiz A. Newborn screening for congenital hypothyroidism. J Clin Res Pediatr Endocrinol 2013;5(Suppl 1):8-12.  Back to cited text no. 3
Komur M, Ozen S, Okuyaz C, Makharoblıdze K, Erdogan S. Neurodevelopment evaluation in children with congenital hypothyroidism by Bayley-III. Brain Dev 2013;35:392-7.  Back to cited text no. 4
Karunarathna N, Hettiarachchi M. Cost-effective analysis of the congenital hypothyroidism screening program in Sri Lanka. Value Health Reg Issues 2021;24:181-6.  Back to cited text no. 5
Olivieri A, Fazzini C, Medda E, Italian Study Group for Congenital Hypothyroidism. Multiple factors influencing the incidence of congenital hypothyroidism detected by neonatal screening. Horm Res Paediatr 2015;83:86-93.  Back to cited text no. 6
Corbetta C, Weber G, Cortinovis F, Calebiro D, Passoni A, Vigone MC, et al. A 7-year experience with low blood TSH cutoff levels for neonatal screening reveals an unsuspected frequency of congenital hypothyroidism (CH). Clin Endocrinol 2009;71:739-45.  Back to cited text no. 7
Persani L, Cangiano B, Bonomi M. The diagnosis and management of central hypothyroidism in 2018. Endocr Connect 2019;8:R44-54.  Back to cited text no. 8
Hemati Z, Hashemipour M, Hovsepian S, Mansourian M, Zandieh M, Ahmadian M, et al. Congenital hypothyroidism in different cities of the Isfahan province: A descriptive retrospective study. J Educ Health Promot 2019;8:137.  Back to cited text no. 9
Hashemipour M, Hovsepian S, Kelishadi R. High prevalence of congenital hypothyroidism in Isfahan: Do familial components have a role? Adv Biomed Res 2012;1:37.  Back to cited text no. 10
[PUBMED]  [Full text]  
Hashemipour M, Hovsepian S, Kelishadi R, Iranpour R, Hadian R, Haghighi S, et al. Permanent and transient congenital hypothyroidism in Isfahan–Iran. J Med Screen 2009;16:11-6.  Back to cited text no. 11
Hashemipour M, Ghasemi M, Hovsepian S, Heiydari K, Sajadi A, Hadian R, et al. Prevalence of permanent congenital hypothyroidism in Isfahan-Iran. Int J Prev Med 2013;4:1365-70.  Back to cited text no. 12
Cortez AB, Lin B, May JA. Targeted secondary screening for congenital hypothyroidism in high-risk neonates: A 9 year review in a large california health care system. Int J Neonatal Screen 2021;7:81.  Back to cited text no. 13
Medda E, Vigone MC, Cassio A, Calaciura F, Costa P, Weber G, et al. Neonatal screening for congenital hypothyroidism: What can we learn from discordant twins? J Clin Endocrinol Metab 2019;104:5765-79.  Back to cited text no. 14
Dalili S, Rezvany SM, Dadashi A, Medghalchi A, Mohammadi H, Dalili H, et al. Congenital hypothyroidism: A review of the risk factors. Acta Med Iran 2012:735-9.  Back to cited text no. 15
Kariyawasam D, Rachdi L, Carré A, Martin M, Houlier M, Janel N, et al. DYRK1A BAC transgenic mouse: A new model of thyroid dysgenesis in Down syndrome. Endocrinology 2015;156:1171-80.  Back to cited text no. 16
van Trotsenburg P, Stoupa A, Léger J, Rohrer T, Peters C, Fugazzola L, et al. Congenital hypothyroidism: A 2020–2021 consensus guidelines update—An ENDO-European reference network initiative endorsed by the European society for pediatric endocrinology and the European society for endocrinology. Thyroid 2021;31:387-419.  Back to cited text no. 17
Cherella CE, Wassner AJ. Update on congenital hypothyroidism. Curr Opin Endocrinol Diabetes Obes 2020;27:63-9.  Back to cited text no. 18
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Hemmati F, Moghtaderi M, Hasanshahi P. Congenital hypothyroidism in preterm newborns: A retrospective study arising from a screening program in Fars Province, Southwestern Iran. Oman Med J 2019;34:262-5.  Back to cited text no. 20
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  [Full text]  
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Lauffer P, Zwaveling-Soonawala N, Naafs JC, Boelen A, Van Trotsenburg AP. Diagnosis and management of central congenital hypothyroidism. Front Endocrinol 2021;12:686317. doi: 10.3389/fendo. 2021.686317.  Back to cited text no. 23
Aleksander PE, Brückner-Spieler M, Stoehr A-M, Lankes E, Kühnen P, Schnabel D, et al. Mean high-dose l-thyroxine treatment is efficient and safe to achieve a normal IQ in young adult patients with congenital hypothyroidism. J Clin Endocrinol Metabol 2018;103:1459-69.  Back to cited text no. 24
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  [Figure 1], [Figure 2]

  [Table 1], [Table 2]


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