Congenital hypothyroidism: management of infants with positive and borderline screening results

The purpose of this guideline is to provide guidance about the management of infants with positive and borderline screening results for congenital hypothyroidism at Great Ormond Street Hospital.

Background

Newborn screening for congenital hypothyroidism was first introduced in the mid 1970s in the United States, after the discovery that children with symptoms of congenital hypothyroidism had a better developmental outcome the earlier treatment was started (Klein, Meltzer & Kenny 1972; Virtanen et al 1983). 

Prospective studies of the intellectual development of infants diagnosed with congenital hypothyroidism as a result of screening, also confirmed this finding (New England Congenital Hypothyroidism Collaborative 1981). Screening for congenital hypothyroidism was first introduced in the UK in 1981.

Congenital hypothyroidism is associated with neuro-developmental delay and although this may in part be related to low levels of thyroxine in utero during the latter part of the pregnancy, in severe hypothyroidism (Hindmarsh 2002), further delay in diagnosis and commencing treatment may potentially compound the problem. 

Thus confirming the diagnosis and initiating treatment should be regarded as a medical emergency and treated as such (Hopwood 2002).

The screening process for congenital hypothyroidism in the UK involves the detection of raised concentrations of thyroid stimulating hormone (TSH) in filter paper samples collected ideally on day five after birth (UK Newborn Screening Programme Centre 2005).

Secondary or tertiary hypothyroidism will not be detected by the screening programme as it uses a primary TSH method, and infants may only present with other signs of congenital hypothyroidism such as prolonged jaundice. 

Similarly, infants with a delayed TSH rise, thyroid binding globulin deficiency and hyperthyroxinaemia (Brown 2001) will not be detected by the screening programme.

Presenting problem(s)

Positive or borderline screening result for congenital hypothyroidism

For Great Ormond Street Hospital Newborn Screening laboratory:

• A positive screening result applies with TSH ≥ 20 mU/l. 
  

• A borderline screening result applies with TSH between 6-19.9 mU/l.

Diagnostic criteria

For congenital hypothyroidism to be confirmed, the Free T4 concentration should be below the laboratory's normal reference range and the TSH raised (Toublanc et al 1999).

Permanent congenital hypothyroidism is usually seen when the presenting venous TSH is > 50 mU/l (Brown 2001; Toublanc 1999).

Investigations

In infant:

• Weight, head circumference and length recorded.

• Blood for Free T4, TSH and anti-thyroid antibodies taken.

• Liver function tests with split bilirubin if infant jaundiced.

• Thyroid technetium scan (to obtain prognostic information and establish if levothyroxine requirement is for life). TSH must be elevated (ideally > 15 mU/l) for the scan to be undertaken. In Pendred's syndrome a  perchlorate discharge scan is indicated. Occasionally a thyroid ultrasound will also be necessary to confirm the thyroid technetium scan results if the thyroid technetium scan results suggest thyroid agenesis (Brown 2001).

• Audiology review (at six weeks of age - must be corrected in premature infants).

In mother:

• Blood for Free T4, TSH and anti-thyroid antibodies taken.

Management

Once treatment with Levothyroxine sodium oral solution has commenced the aim is to keep Free T4 in the upper part of the normal range, with a normal TSH. 

In some infants however, the TSH can remain persistently raised for many months despite high-normal concentrations of Free T4 (Hindmarsh 2002) and such infants may need their Free T4 concentrations slightly above the top of the normal reference range in order to sustain a normal TSH concentration. 

With the higher doses of levothyroxine sodium (10-15 micrograms/kg/day) there is a risk to the infant of hyperthyroxinaemia, craniosynostosis or behavioural problems (Rovet & Daneman 2003; Hopwood 2002).

Monitoring

• Initial visit as above (Rovet & Daneman 2003; Hindmarsh 2002).

• After two weeks on treatment for repeat Free T4 and TSH.

• After six weeks on treatment for repeat Free T4, TSH and clinic review.

• Eight weeks later for repeat Free T4, TSH and clinic review.

• Every eight to 12 weeks for repeat Free T4, TSH and clinic review until one year of age.

• Thereafter three- to six-monthly as appropriate.

• Refer to local paediatrician with endocrine experience by three years of age.

Rationale

Rationale 1: To ensure a consistent approach in the management of infants with abnormal screening results for congenital hypothyroidism.
Rationale 2: To start levothyroxine treatment as soon as is possible after a positive screening result for congenital hypothyroidism has been recorded.

References

Reference 1:
Brown RS (2001) The thyroid gland Brook, CGD & Hindmarsh PC in Clinical Pediatric Endocrinology. London, Blackwell Science.

Reference 2:
Hindmarsh PC (2002) Optimisation of thyroxine dose in congenital hypothyroidism. Arch Dis Child 86 (2): 73-5.

Reference 3:
Hopwood NJ (2002) Treatment of the infant with congenital hypothyroidism. J. Pediatr 141: 752-754.

Reference 4:
Klein AH, Meltzer S, Kenny FM (1972) Improved prognosis in congenital hypothyroidism treated before age three months. The Journal of Pediatrics 81 (5): 912-915.

Reference 5:
New England congenital hypothyroidism collaborative (1981) Effects of neonatal screening for hypothyroidism: prevention of mental retardation by treatment before clinical manifestations. New England congenital hypothyroidism collaborative. Lancet 2 (8255): 1095-8.

Reference 6:
Rovet J, Daneman D (2003) Congenital hypothyroidism: a review of current diagnostic and treatment practices in relation to neuropsychologic outcome. Paediatr Drugs 5 (3): 141-9.

Reference 7:
Toublanc JE et al (1999) Revised Guidelines for Neonatal Screening Programmes for Primary Congenital Hypothyroidism: Working Group on Neonatal Screening of the European Society for Paediatric Endocrinology. Horm Res 52: 49-52.

Reference 8:
UK Newborn Screening Programme Centre (2005) Newborn bloodspot screening in the UK: Policies and standards. Viewed on: 21/10/2007

Reference 9:
Virtanen M, Maenpaa J, Santavouri E, Hirvonen E, Perheentupa J (1983) Congenital hypothyroidism: age at start of treatment versus outcome. Acta Paediatr Scand 72: 197-201.

Document control information

Shirley Langham, Clinical Nurse Specialist, Endocrine

Document owner
Shirley Langham, Clinical Nurse Specialist, Endocrine

Approved by
Professor Peter Hindmarsh, Consultant, Endocrinology

First introduced: 25 February 2008 
Date approved: 26 October 2011
Review schedule: Two years
Next review: 28 October 2013
Document version: 1.1
Replaces version: 1.0