Congenital hypothyroidism in Scotland, guidelines for the management of

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Objectives

  • To guide the management of infants referred with an elevated TSH concentration on Guthrie blood spot screening.
  • To give guidance on the initial investigations for infants diagnosed with congenital hypothyroidism.
  • To give guidance for ongoing management and monitoring of infants and children with congenital hypothyroidism.

Scope

Patients to whom this document applies:

  •  Infants in Scotland with an elevated TSH on Guthrie blood spot screening.

Audience

Who should use this document?

  • General paediatricians
  • Neonatologists
  • Paediatricians with an interest in paediatric endocrinology
  • Paediatric endocrinologists.
Summary

Diagnosis:

  • A screening test is performed on a newborn blood spot sample for the measurement of thyroid stimulating hormone (TSH). A high TSH suggests hypothyroidism.
  • Confirmatory tests:
    • pre-treatment thyroid function tests (TSH and free thyroxine – fT4)
    • quantitative thyroglobulin (Tg).
  • Optional confirmatory tests may include:
    • thyroid imaging (ultrasound and/or radio-isotope scans of the neck, sub-lingual and upper chest area)
    • thyroid autoantibodies (thyroid peroxidase and TSH receptor antibodies) in the infant (and if indicated, mother)
    • maternal TFTs
  • Genetic testing 

Treatment:

Replacement therapy with levothyroxine (thyroxine, L-thyroxine, LT4).

Clinical aims
  • To bring thyroid function into the normal range as rapidly as possible while avoiding adverse effects.
  • To maintain fT4 in the upper quartile of the normal reference range and concurrent TSH in the normal range.
  • To diagnose the cause of congenital hypothyroidism following positive screening.
Screening laboratory notification protocol

 

Laboratory notification list

Referral procedure by laboratory:

Laboratory staff notifying abnormal result must speak directly to a Consultant Paediatrician – either one of the two named paediatricians shown in the table below or the on-call paediatrician for the maternity unit.

NB all results are notified simultaneously to the person managing the Scottish CHT Register at RHC Glasgow.

Table 1 – Named paediatricians for Notification of Raised TSH

Centre

1st named paediatrician

2nd named paediatrician

Default

Ayrshire

Scott Williamson

Jon Staines

On-call paediatrician in maternity/ neonatal unit

Borders

Graeme Eunson

Andy Duncan

Dumfries

Rajendran Shyam

On Call consultant

Fife

Anthony Tasker

Jo Watt

Forth Valley

John Schulga

Michael Colvin

Glasgow

Guftar Shaikh

Avril Mason

Grampian

Amalia Mayo

Craig Oxley

Highland

Stuart Henderson

Alan Webb

Lanarkshire

Iain Hunter

Shubhangi Shewale

Lothian

Via Paed endo secretary

Endocrine Cons. of week

Paisley

Graham Stewart

Hilary Conetta

Tayside

Nicky Conway

Clare Webster

 

Table 2 - Telephone numbers

Centre

Hospital

Switchboard

Ayrshire

Crosshouse, Ayr

01563 521133

Borders

Borders General

01896 826000

Clyde

Royal Alexander, Paisley

0141 887 9111

Dumfries

Dumfries General

01387 246246

Fife

Victoria Hospital

01592 643355

Forth Valley

Forth Valley Royal, Larbert

01324 566000

Glasgow

Royal Hospital for Children, Glasgow

0141 201 0000

Glasgow

Princess Royal Maternity Hospital

0141 211 5400

Grampian

Children’s Hospital, Aberdeen

0845 456 6000

Highland

Raigmore, Inverness

01463 704000

Lanarkshire

Wishaw General, Wishaw

01698 361100

Lothian

Royal Hospital for Sick Children, Edinburgh

0131 536 0611

Lothian

Royal Infirmary, Edinburgh

0130 536 1000

Tayside

Ninewells, Dundee

01382 660111

Procedure by clinician following notification

Clinical evaluation

HISTORY – to include:

  • Whether a sibling is affected.

  • A family history of thyroid illness/problems.

  • A history of thyroid disease or anti-thyroid therapy in the mother.

  • Any symptoms of hypothyroidism (e.g. poor feeding, sleepiness, jaundice, constipation, cold peripheries, hoarse cry).

EXAMINATION – to include:

  •  Measurement of weight, head circumference and length.

  • Measurement of (c.f. reported) parental heights.

  • Presence or absence of goitre.

  • Signs of hypothyroidism (e.g. coarse facies, hoarse cry, umbilical hernia).

INITIAL INVESTIGATION:

  • A minimum of 1 mL of blood for TFTs in heparinised bottle or paediatric heparin tube (be prepared to make several attempts in order to get sufficient blood). (It is vital that sufficient blood is taken)

  • 1 mL clotted blood for quantitative thyroglobulin.

  • Blood for genetics if sufficient blood is available (sample can be stored for use later).

 

Clinician treatment decision tree

This decision tree is based on referenced evidence (1,2)

Dosage

Preparations of Levothyroxine

Written instructions on how to give thyroxine should be available and supplied to the parents.

LevoThyroxine Tablets

  • Available as 12.5 microgram, 25 microgram, 50 microgram, 75 microgram or 100 microgram strength.
  •  The tablets should be crushed and mixed with a small volume (less than 5ml) of liquid (formula, expressed breast milk or boiled and cooled water).
  •  If necessary, a tablet cutter for halving tablets should be supplied to the family.
  • The first dose should be given by parents under the supervision of a nurse or pharmacist.

SPEG does not recommend using any of the liquid forms of thyroxine which are available including syrups, solutions and suspensionsTablets have been used extensively and successfully in the management of congenital hypothyroidism and therefore SPEG recommends the use of tablets, in accordance with European Society for Paediatric Endocrinology guidelines (ESPE) [1]. Tablets are also much cheaper to use than other preparations.

Initial counselling and management

ESSENTIAL INFORMATION TO GIVE AT THE INITIAL VISIT:

  •  Thyroid hormone is vital for normal brain development and somatic growth
  •  The thyroid gland is either absent, too small or not producing thyroid hormone properly
  • It is likely to be permanent, or there is insufficient evidence to determine whether or not it is permanent
  • With treatment, it has a good prognosis.
  • Adherence to treatment is crucial, especially from birth to 3 years of age when the brain is developing most rapidly
  • The treatment is easy to administer, but should be given with care.
  • Verbal and written instructions should be given on how to give medicines.

It is important to give the family written information about congenital hypothyroidism.

There are several excellent leaflets and booklets available (National Newborn screening, British Society for Paediatric Endocrinology and Diabetes (BSPED)):

Congenital hypothyroidism (CHT) suspected: description in brief (Public Health England, last updated April 2018)

Congenital hypothyroidism (CHT) confirmed: description in brief (Public Health England, last updated April 2018)

Hypothyroidism (underactive thyroid gland) in childhood (BSPED)

How to give thyroxine to babies and children (SPEG, last updated August 2017)

Thyroid imaging

ESPE consensus statement (1) on Congenital Hypothyroidism recommends thyroid imaging for all babies with suspected congenital hypothyroidism because:

  • It is more informative than blood tests alone
  • It will aid in guiding options for genetic counselling
  • With the results, it is possible to determine the likelihood of lifelong treatment if permanent Congenital Hypothyroidism is proven
  • It provides a useful additional guide as to thyroxine dose (agenesis is likely to require larger doses). 

Isotope scans should be performed by day 5 of the start of treatment[5] to ensure the avoidance of false negatives, due to TSH suppression (it is advisable to check thyroid function on the day of scans to confirm the reliability of results).

Currently, if imaging is to be performed, the Hospital for Children, Glasgow is currently the only site that is able to perform these scans. If scanning is to be considered, there should be early discussion with a paediatric endocrinologist.

  • Imaging should never be allowed to delay the initiation of treatment. 
Mutation analysis in suspected cases of dyshormonogenesis

If thyroid imaging suggests that the cause of the hypothyroidism might be due to an enzyme defect in the function of the thyroid gland, there is a mutation analysis service available in Scotland. This is based in the genetics laboratories at the Queen Elizabeth University Hospital.

The service offers analysis for the three most common mutations responsible for dyshormonogenesis in Scotland, namely mutations in thyroperoxidase (TPO), thyroglobulin (Tg) and the TSH receptor (TSHR) genes. 

For genetic testing, a sample of blood in an EDTA bottled is required. The lab requires at least 1 ml volume.

Samples should be obtained from the infant, and also from both parents. This can be performed at a subsequent follow-up visit as it may be difficult to obtain sufficient blood samples at the initial diagnostic visit.

The service is managed by Dr Therese Bradley who can be contacted on: therese.bradley@ggc.scot.nhs.uk or by telephone on 0141 354 9330

If unavailable the duty scientist can be contacted on: geneticlabs@ggc.scot.nhs.uk

Subsequent monitoring and follow up

N .B We would also suggest additional clinic visits following dosage alteration or when there are problems with poor adherence.  

At puberty/rapid growth or weight gain, more frequent monitoring is recommended

What to do at each visit
  1. Calculate the optimal dose and adjust dosage pre-emptively, using Thyroid Function Tests to confirm adherence.

  2. Assess Growth:

    • weight measurement
    • supine length measurement until 2 years, then height measurement
    • head circumference measurement until 3 years
  3. Developmental assessment:

    1. Consider pre-school formal audiology (for subtle hearing impairment due to Congenital Hypothyroidism [1])
      • if aged <4-5 years, developmental progress
      • aged over 4-5 years, school progress
    2. Consider neurodevelopmental assessment.
  1. Education:

    • from secondary school onwards ensure that patient has reasonable knowledge of CH.
  2. Adult transfer:

    • Boys – to GP.
    • Girls – to GP, give pre-pregnancy counselling.
      Transfer to Primary care for 6 to 12 monthly monitoring of TFT’s

Aim for: fT4 in the upper quartile of reference range and TSH <5.0 mU/l (but avoid undetectable TSH)

Re-evaluation of Thyroid Axis

This may be required if no cause has been identified for the hypothyroidism in the neonatal period and should be considered after the age of 3 years.

Re-evaluation should be considered in patients with a normally sited thyroid gland and/or those who have had no increase in thyroxine requirement since infancy.

This can consist of either:

  • An initial reduction in thyroxine dose followed by monitoring of thyroid function and further reductions in thyroxine dose and monitoring of thyroid function if results remain normal, until thyroxine is discontinued.
  • Discontinuation of thyroxine with thyroid function assessment in 4-6 weeks.

If the TSH is elevated, hypothyroidism is confirmed and treatment should be recommenced as soon as possible.

Re- evaluation is not indicated if there has been a rise in the TSH in the first year, if there is a genetic cause or if there is an abnormal gland on imaging.

References
  1. Leger J, Olivieri A, Donaldson M, Torresani T, Krude H, van VG, Polak M, Butler G: European Society for Paediatric Endocrinology consensus guidelines on screening, diagnosis, and management of congenital hypothyroidism. Horm Res Paediatr 2014;81:80-103.
  2. Pokrovska T, Jones J, Shaikh MG, Smith S, Donaldson MD: How well does the capillary thyroid-stimulating hormone test for newborn thyroid screening predict the venous free thyroxine level? Arch Dis Child 2016;101:539-545.
  3. Jones JH, Gellen B, Paterson WF, Beaton S and Donaldson MDC. Effect of high versus low initial doses of L-thyroxine for congenital hypothyroidism on thyroid function and somatic growth. Arch Dis Child (2008); 93: 940-44.
  4. Selva KA, Harper A, Downs A, Blasco PA and LaFranchi SH. Neurodevelopmental outcomes in congenital hypothyroidism: comparison of initial T4 dose and time to reach target T4 and TSH. J Pediatr 2005; 147: 775-780.
  5. Perry RJ, Maroo S, Maclennan AC, Jones JH and Donaldson MDC. Combined ultrasound and isotope scanning is more informative in the diagnosis of congenital hypothyroidism than single scanning. Arch Dis Child 2006; 91: 972-976.

 

Editorial Information

Last reviewed: 10 June 2018

Next review: 10 June 2021

Author(s): Jeremy Jones; M Guftar Shaikh; John Schulga

Version: 1.1

Co-Author(s): Group Committee: SPEG NMCN Steering Group; SPEG Guidelines sub-group

Approved By: SPEG Guidelines Group and West of Scotland Neonatal MCN Guideline Group