Guidance

Congenital hypothyroidism: initial clinical referral guidelines

Published 27 March 2020

This document provides guidelines for the referral and management of babies with congenital hypothyroidism (CHT).

For more detail on the laboratory protocol, please see the CHT laboratory handbook.

1. Categorisation of initial screening result

1.1 CHT not suspected

Babies with a thyroid-stimulating hormone (TSH) concentration in whole blood (WB) of <8.0 mU/L on the initial screening sample (or on a second sample for preterm babies <32 weeks gestation) have a negative screening result for congenital hypothyroidism (CHT).

Report these babies as ‘CHT not suspected’.

1.2 CHT suspected

Babies with a TSH concentration of ≥20.0 mU/L in whole blood on the initial screening sample (or on a second sample for preterm babies <32 weeks gestation) have a positive screening result for CHT.

Report and refer these babies as ‘CHT suspected’.

1.3 Borderline CHT screening result

Babies with a TSH concentration of between ≥8.0 and <20.0 mU/L in WB on the initial screening sample (or on a second sample for preterm babies <32 weeks gestation) have a borderline screening result for CHT.

On detecting a borderline screening result, take a second sample (or a third sample for preterm babies <32 weeks gestation) 7 to 10 calendar days after the initial sample.

If the TSH concentration is <8.0 mU/L in WB on this second sample (or on the third sample for a preterm baby <32 weeks gestation), the baby has a negative screening result for CHT. Report the baby as ‘CHT not suspected’.

If the TSH concentration is ≥8.0 mU/L in whole blood on this second sample (or on the third sample for a preterm baby <32 weeks gestation), report and refer the baby as ‘CHT suspected’.

2. Referral of babies with positive screening results

The laboratory refers babies with positive screening results for CHT on the same or next working day to an expert paediatrician.

An ‘expert paediatrician’ in this context is defined as an individual who regularly manages babies with CHT and is therefore aware of the objectives of management and the potential complexities. This individual will usually be a member of a regional specialist endocrine team. In some regions, the baby may be managed at a local centre with support from the expert paediatrician. The expert paediatrician helps to arrange access to diagnostic investigations and provides access to the agreed regional protocol.

Appropriate failsafe mechanisms must be in place to make sure CHT suspected babies have entered into the diagnostic and management pathway.

The first clinical appointment with the expert paediatrician must take place on the same day or the next day after parents are informed of their baby’s positive screening result.

3. Communication flows

3.1 Communication with the healthcare team

Laboratories will notify a positive screening test (blood spot results expressed to one decimal place) verbally and electronically or in writing, to the expert paediatrician or deputy.

The laboratory or expert paediatrician or a deputy (depending upon the agreed regional protocol) will notify the informed health professional responsible for communicating results to the family. This initiates the clinical referral of screen positive cases.

3.2 Communication with the family

An informed health professional should communicate the screening result to the family. The health professional making initial contact should give the family:

• the suspected congenital hypothyroidism patient information leaflet
• details of the time and date of the appointment with the paediatrician and appropriate contact telephone numbers

The expert paediatrician or team managing the baby should report the outcome of the first appointment to the newborn screening laboratory within 48 hours. The laboratory will then know that the child has entered the management pathway.

The regional endocrine centre should also be informed about the diagnostic outcome to support regional and national audit.

If the baby is diagnosed with CHT, the expert paediatrician or deputy should give the family a copy of the confirmed congenital hypothyroidism patient information leaflet (available online, and can be downloaded and printed).

4. Clinical evaluation and confirmatory diagnostic tests

The expert paediatrician or team member responsible for assessing the baby with a positive screening result will take a clinical history and perform a clinical exam.

Babies with CHT are more likely to have associated anomalies, particularly congenital heart defects and hearing loss, and require careful neonatal examination and follow up. A complete history, including maternal thyroid status (previous history of thyroid dysfunction, maternal anti-thyroid medications), maternal diet (for example a vegan or other low iodine diet) and family history should be obtained.

4.1 Diagnostic tests

Essential diagnostic tests are:

• free T4 (plasma or serum)
• (TSH) (plasma or serum)

Perform diagnosis using free T4 and TSH on a plasma or serum sample using the appropriate age-related reference range as defined by the laboratory in relation to the equipment used.

4.2 Imaging

Appropriate imaging techniques (ultrasound and or radioisotope scan) performed by appropriately skilled and experienced professionals helps to establish whether the thyroid gland is:

• absent
• ectopic
• normally situated but abnormal in size and shape
• normally situated and normal in size and shape

The advantages of investigating and establishing the likely cause of the underlying CHT should be discussed with families.

An ultrasound examination and or a radioisotope scan may establish the cause of the baby’s CHT and indicate whether the condition is likely to be permanent. Initiation of treatment should not be delayed while waiting for an isotope scan, which can be performed up to 5 days after starting therapy. An ultrasound scan can be performed at any stage and investigation need not be confined to the neonatal period. These investigations may increase awareness of potential related problems such as deafness and can provide information about recurrence risk. Recurrence is unusual in the case of thyroid dysgenesis, but there is likely to be autosomal recessive inheritance with a 1 in 4 recurrence risk for families of babies with thyroid dyshormonogenesis. Both isotope scanning and thyroid ultrasound in neonates require specialist skills to be interpreted correctly.

5. Advisable tests for the mother

Diagnostic tests considered advisable for the mother to exclude interference in the baby’s TSH measurement and to exclude thyroid dysfunction in the mother include:

• free T4 (plasma or serum)
• TSH (plasma or serum)

Extend these investigations to include an assessment of TSH receptor antibody status in mothers with a current or previous history of autoimmune thyroid disease.

6. Treatment

Babies diagnosed with CHT should start treatment with oral levothyroxine within the following timeframes.

6.1 CHT suspected on initial screening sample

Acceptable standard: by 14 days of age (100% of babies)

6.2 CHT suspected on a second sample that follows a borderline TSH

Acceptable standard: by 21 days of age (100% of babies)

The starting dose of oral levothyroxine should be 10 to 15 mcg/kg/day, with a maximum dose of 50 mcg/day. Only licensed solutions and tablets of levothyroxine should be used. Suspensions may be unreliable.

The aim of treatment is to increase free T4 close to the upper age appropriate reference range within the first 2 weeks of treatment and to normalise the TSH within the first month.

Free T4 concentrations may exceed the normal reference range at the time of TSH normalisation but significant elevation should be avoided.

The thyroxine dose may need to be reduced at an early stage if TSH is suppressed or if the baby is showing signs of overtreatment.

Regular dose adjustments may be required.

Babies with significant endogenous thyroid hormone production and associated modest TSH elevation may need smaller initial doses of thyroxine than babies with thyroid agenesis.

Experienced staff should show parents how to administer preparations, and also provide written instructions. Staff should explain to families the potential for confusion and incorrect dosing (due to the different preparations available).

7. Monitoring treatment

Once levothyroxine treatment has been started, check TSH and thyroid hormone concentrations at an appointment with the expert paediatrician or team member at approximately 2 weeks, 4 weeks, 8 weeks, 3 months, 4 months, 6 months, 8 months 10 months and 12 months after treatment is started, and thereafter as indicated.

More intensive biochemical monitoring is frequently required, particularly in babies with no endogenous thyroid hormone production or following dose adjustment.

8. Assessment of permanence of hypothyroidism

In cases where the cause or persistence and or permanence of hypothyroidism has not been confirmed, undertake confirmatory testing by stopping thyroxine at 2 to 3 years of age and carrying out thyroid function tests 2 to 4 weeks later (see criteria for retesting below).

Feed back the assessment outcome to the regional endocrine centre to support regional and national audit.

9. Criteria for retesting

Babies with CHT should undergo a trial of thyroxine at 2 to 3 years of age to establish whether or not they have permanent CHT unless 1 or more of the following conditions are true:

• an isotope or ultrasound scan has demonstrated an absent or ectopic thyroid gland
• there is additional information pointing to a diagnosis of permanent CHT; this might (for example) include the identification of a specific genetic cause of permanent CHT (such as a defect in the gene for thyroid peroxidase or thyroglobulin)
• there is biochemical evidence of a persistent abnormality of thyroid function that is reflected by a rising TSH above 10mU/L beyond 12 months of age and an associated thyroxine requirement of ≥50mcg

If in any doubt, please discuss retesting with the regional tertiary endocrine team.