Hypothyroidism

1. Screening and Management of
Congenital Hypothyroidism –
Guidelines by American Academy
of Pediatrics, 2023
Presented by
Dr Anjali MK

2. •Sushree Smita Behura, Gannavarapu Phanisri Nikhila,
Santosh Kumar Panda Department of Paediatrics,
Kalinga Institute of Medical Sciences, KIIT DU,
Bhubaneswar, Odisha
•. Correspondence to: Dr Santosh Kumar Panda,
Professor, Department of Pediatrics,Kalinga Institute
of Medical Sciences, KIIT DU, Bhubaneswar, Odisha.
Doc.sant@yahoo.co.in

3. • Guidelines for screening and management of congenital
hypothyroidism in neonates have been recently updated
by the American Academy of Pediatrics (AAP).
• This article compares new AAP guideline with the Indian
Society for Pediatric and Adolescent Endocrinology
(ISPAE) Guidelines, 2018 and lists the changes in
screening, diagnosis, and management of congenital
hypothyroidism suggested in the new guidelines, along
with clinical utilization in the Indian scenario.

4. • Early detection of congenital hypothyroidism (CH)
through newborn screening (NBS) and prompt
treatment can prevent morbidities
• Preterm or VLBW infants Indian infants are at higher
risk of CH (approximately 1 in 1000) because of
ethnicity, increased survival of VLBW neonates, and
endemic iodine deficiency belts.

9. • The new guideline suggests CH-NBS by measuring primary
TSH in DBS, preferably at 48-72 hours of age in all neonates.
• In the Indian setup, considering earlier hospital discharge of
term healthy neonates and simultaneous screening of other
metabolic disorders, DBS may be preferred over cord
sample and sampling timing may be preferred at 48-72 hour
rather than after 72 hour of age.
• However, in the clinical setup with hospital discharge before
48 h or high chance of failure of recall, cord blood TSH may
be considered

10. • Preterm (GA < 32 w) or VLBW infants are at risk of
transient hypothyroxinemia of prematurity or delayed
TSH rise, so second NBS is recommended at 2-4 week;
and GA-specific TSH references should be followed .
• As the peak period of delayed TSH elevation is around 8
weeks of age, further retesting after 4 weeks or at 36
weeks post menstrual age (PMA) (whichever is earlier) is
recommended, if second NBS is done at <36 weeks PMA.

11. • When NBS is collected beyond the first week of age, an age-
adjusted TSH cutoff is recommended as opposed to the fixed
TSH cutoff of >20 mIU/L recommended by ISPAE .
• However, by reducing the TSH cutoff with age advancement
there will be a demand for confirmatory testing in a large
number of neonates to identify a few mild CH case.
• Hence, age-specific TSH cutoff may be used in individual
institutional protocols (targeting not to miss mild CH cases);
and the TSH cutoff > 20 mIU/L may be adopted in national
programs.

14. • New guideline suggests measuring free thyroxine
(FT4) in place of thyroxine (T4) in confirmatory
testing to eliminate the false positivity in cases of
thyroid binding globulin (TBG) deficiency.

15. • To avoid delay in initiation of treatment of
severe CH cases, levothyroxine (L-T4)
supplementation should be initiated upon NBS -
TSH values above 40 mIU/L (vs NBS-TSH > 80
mIU/L recommended by ISPAE), after taking the
confirmatory serum sample and for any
abnormal TSH 40 mIU/L, a confirmatory
testing is preferred earliest within 24 hours.

16. • When the clinical symptoms favor CH, such as a
large posterior fontanelle, macroglossia,
umbilical hernia, prolonged jaundice,
constipation, lethargy, or hypothermia
measurement of TSH and FT4 in a venous sample
is advised, even if NBS is normal.

17. EVALUATION FOR ETIOLOGY
• The new guideline emphasizes on genetic testing in
primary CH cases associated with syndromic infants
or clinical features suggestive of a genetic condition
or central CH infants or when genetic diagnosis may
influence clinical management.
• As monogenic mutations are associated with thyroid
dysgenesis, dyshormonogenesis or hypothalamic
pituitary development, genetic testing may help to
identify the etiology of CH .

18. • Presence of thyroid agenesis or ectopia in
ultrasonography, high TSH more than 10 mIU/L
after one year of treatment, or the requirement of
a higher dose of L-T4 during the first year of life are
predictors of permanent CH as per AAP guidelines.
• If the patient is adequately treated with a low dose
of L-T4 (<2 mcg/kg/day), a trial-off L-T4
supplementation should be considered at 3 years
of age.
Assessment for permanence of hypothyroidism

19. MANAGEMENT AND FOLLOW- UP
• Presence of low FT4 irrespective of TSH level (low FT4 and raised TSH, or
low FT4 and normal or low TSH-central hypothyroidism) on confirmatory
test, suggest for L-T4 supplementation.
• Need for L-T4 supplementation in mild CH is explained by physiological
deficit of thyroxine hormone as per hypothalamic-pituitary axis.
• In absence of strong evidence for treatment of mild CH cases, the TSH
threshold for L-T4 initiation is based on expert opinion, and either ISPAE or
AAP guidelines can be followed

20. • L-T4 tablet should be given in a consistent time
and manner; and preferred from a particular
brand or generic tablet of same manufacturer.
• Alternatively, intravenous LT4 may be used
when enteral administration is not feasible .
• In CH resistance to L-T4, the addition of
liothyronine (L-T3) has been suggested .

21. • AAP gives more priority to close monitoring of
serum TSH and FT4 during the first year of life
because of the relatively rapid growth during
infancy, increased metabolic clearance of thyroid
hormone, and risk of overtreatment of L-T4.
• The initial downward adjustment of L-T4 may be
attempted after 2 weeks of starting treatment to
avoid overtreatment as compared to suggestion
of no downward adjustment of L-T4 with a single
higher level of FT4 in ISPAE.

22. • These AAP guidelines in a developed country
scenario aimed to eliminate the morbidities from
CH inspite of universal NBS practice and establish
the etiology in diagnosed cases of CH.
• Whereas, we herein re-emphasize the need to
implement universal NBS, and ensuring optimal
treatment in diagnosed cases of CH in developing
country like India.

23. REFERENCE
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