uk thyroid function tests guidelines
TRANSCRIPT
Can We Manage Thyroid Function TestsIn a Rational Way ?
Geoff BeckettEdinburgh
UK -10 Million Requests : £30 million
What Controls Our Workload?What Controls Our Workload?• ScreeningScreening• Expectations of the PatientExpectations of the Patient• Requesting StrategiesRequesting Strategies• Treatment of Sub-Clinical DiseaseTreatment of Sub-Clinical Disease• Treatment/follow-up regimens Treatment/follow-up regimens • Unnecessary testsUnnecessary tests
Managing Thyroid Function Tests
Guidelines !Guidelines !
Managing Thyroid Function Tests
1998200020022003
None tend to meet requirement ofpatients , physicians and laboratories
UK Guidelines For The Use of Thyroid Function Tests
Published on WebJuly 2006
Draft Consultation Document October 200533 responses
Group comprised of representatives from
•Association for Clinical Biochemistry
•British Thyroid Association •British Thyroid Foundation
Chaired by Dr Graham Beastall
Graham H Beastall BSc, PhD, FRCPath Secretary, Guidelines Development GroupConsultant Clinical Scientist, Glasgow Geoffrey J Beckett BSc, PhD, FRCPath Association for Clinical BiochemistryReader in Clinical Biochemistry, Edinburgh Jayne Franklyn MD, PhD, FRCP, FMedSci British Thyroid AssociationProfessor of Medicine, Birmingham William D Fraser MD, MRCP, FRCPath Association for Clinical BiochemistryProfessor of Clinical Biochemistry, Liverpool Janis Hickey British Thyroid FoundationFounder and Director Rhys John BSc, PhD, FRCPath Association for Clinical BiochemistryConsultant Clinical Scientist, Cardiff Pat Kendall-Taylor MD DCH FRCP British Thyroid AssociationProfessor of Endocrinology, Newcastle Upon Tyne Betty Nevens British Thyroid FoundationOffice Manager Mark Vanderpump MD, FRCP British Thyroid AssociationConsultant Physician, London
Introduction
Indications for thyroid function testing
Hypothyroidism
Hyperthyroidism
Thyroid function in pregnancy
Thyroid function testing in thyroid cancer
Laboratory aspects of thyroid function testing
UK Thyroid Guidelines - Chapters
Should Laboratories Make Local BiasAdjustments to the TSH Action Limits?
At several points in the text numerical results are represented (eg TSH > 10 mU/L)
WhickhamBias unknown Functional Sensitivity likely to be in the order of 1-2 mU/LIn-house RIA – Calibrated to 1st IRP
Colorado study London Diagnostics – Nichols Institute DiagnosticsBias ?
Rotterdam StudyBrahms LumitestBias?
Evidence Base
Introduction Chapter
At several points in the text numerical results are represented (eg TSH > 10 mU/L)These should be regarded as typical target figures rather than as absolute cut-offsThe historical nature of some of the evidence base together with uncertainty of the bias of the assays used in older studies means that absolute cut-offs cannot be presented.
Laboratories should use EQA and other data to determine if bias–related cut-offs are appropriate for the methods they use.
“In most cases it is unlikely that laboratories will have sufficient data to achieve an accurate adjustment of the TSH cut-offs quoted in these guidelines.”
Screening in the healthy population is not warranted
Screening
Women at the menopause or if visiting a GP with non-specific symptoms, may be justified to have TFTs in view of the high prevalence of thyroid failure
Hospitalised Patients
Routine testing of thyroid function in patientsadmitted acutely to hospital is not warranted
unless there are specific clinical indications exist.
Which Thyroid Function Test?
TSH alone as first line test ? Cascade to T4 / T3 if TSH abnormal
TSH with Free T4 as first-line tests ?Cascade with T3 if TSH is low
Digivote response from RCPath meeting in London• TSH alone
• TSH and T4 (free or total)
• TSH, T4, T3 (free or total)
• TSH and T3 (free or total)
• T4 (free or total) alone
Given no financial or other restrictions:- What would be your preferred TFT strategy?
72%
9 %
17%
2%
0%
TSH and FT4 needed in:-
•Symptomatic Patients being tested for the first time
•Screening/monitoring pregnancy
•Pituitary axis is not intact or unstable•Hyperthyroidism- Early months of anti-thyroid therapy•Hypothyroidism -Optimising T4 therapy (new patients) •Central hypothyroidism•TSHoma•End organ resistance
UK Guidelines
TSH alone
•Stable - on T4•Follow-up of “at risk” patients•AF •Dyslipidaemia•Osteoporosis•Subfertility
Cascade to FT4/FT3 if TSH is abnormal
Surveillance of “At Risk Patients”Using TSH
Diabetes
•Type 1 – Annual TFT check
•Type 2 – Check TFT at diagnosis – Routine annual testing is not recommended
Down and Turner’s syndromeAnnual check
Amiodarone Check before treatmentMonitor every 6 months; continue to 12 months after cessation
LithiumCheck before treatmentMonitor every 6 – 12 months
Post – neck irradiation Annual check
Radioiodine / Thyroid surgery
Needs T4 not TSH for first 6-12 months
4-8 weeks – post treatment3 monthly for first yearAnnually thereafter with TSH
It is the responsibility of the requesting physician to provide clinical information to guide the laboratory in the selection of the most appropriate TFT.
If labs are unable to identify those specimens that requireTSH and FT4, it may be prudent to measure TSH+FT4rather than embark on first-line TSH.
UK Guidelines
Sub-clinical HypothyroidismHigh TSH with normal FT4
Exclude transient and drug causes of elevated TSH,exclude recovery from NTI.
•Repeat to confirm at 3-6 months
No Change in recommendations:-
TSH > 10 mU/L – Treat with T4
Treating Sub-Clinical Hypothyroidism
S t a r t O n T 4W h e n T S H i s > 1 0 m U / L
A n n u a l T S HC h e c k E a r l i e r I f
S y m p t o m s D e v e l o p
T P O A bP o s i t i v e
M o n i t o r A p p r o xE v e r y 3 y e a r s
T P O A bN e g a t i v e
M e a s u r e T P O A b
T S H R a i s e d b u t < 1 0 m U / LD o N o t S t a r t O n T 4
Treating Sub-Clinical Hypothyroidism?
Many patients with raised TSH that is < 10 mU/L will normalise TSH with time
Spontaneous Normalization of Thyrotropin Concentrations in Patients with Subclinical Hypothyroidism Juan J. Díez, Pedro Iglesias and Kenneth D. Burman
40/107 patients normalised TSH on follow-up12 (18) 72 months
TSH raised but < 10 mU/L
•There is no clear evidence to support the benefit of routine early treatment with T4 in non-pregnantpatients.
A high percentage (~ 10%) of patients treated with T4will have a TSH < 0.1 mU/L (Harmful? to bone and heart)
Treating Sub-Clinical Hypothyroidism?
Physicians may wish to consider the suitability of a therapeutic trial of T4 on an individual patient basis eg goitre or seeking pregnancy
The primary target of T4 replacement therapy is:-
•Make the patient feel well
•Achieve a TSH that is within the reference range
(FT4 may have to be slightly above reference range to achieve this)
Thyroxine Replacement Therapy
There is no compelling evidence or need tolower the upper reference limit or treatment target to 2.5 mU/L in non-pregnant patients
NHANES study (USA)17,353 subjects 13,344 – Reference population
TPO Ab negativeReference Range was 0.45 – 4.2
Denmark1512 subjects 3 – Reference population
TPO Ab negative Reference Range 0.58 – 4.1
Studies Using Ultrasound Exclusion with TPOAb
SHIP study Germany1488 subjects (previous iodine deficiency)Ref range 0.25 – 2.12
Germany 453 blood donorsRef Range 0.4 – 3.77
Denmark3174 participantsRef Range 0.4 – 3.6
Published Reference Ranges
Monitoring T4 Therapy•TSH and T4 is required for initial optimisation of T4 therapy
•At least annual follow-up with TSH alone
•If T4 dose is changed allow 2-3 months before checking TFTs
•Be alert (inform patient) to concomitant drug treatment
Impaired Absorption of T4 PPIs / H2 antagonistsCalcium carbonateSoy proteinAluminium hydroxideFerrous sulphateCholestyramineCholestapolSucralfate
Increased metabolismPhenytoinCarbamazepineBarbituratesRifampicin
Altered TBGOestrogens, TamoxifenHeroin, MethadoneAndrogens, Anabolic steroidsGlucocorticoids
Sub-Clinical HyperthyroidismLow TSH normal T4 and T3
•Exclude NTI/drugs
•Repeat 1-2 months later
•Persistent sub-clinical hyperthyroidism should prompt a specialist referral.
•If treatment is not undertaken measure TSH every 6-12 months (with FT4 and FT3 if TSH is low)
Pregnancy
Use both TSH and FreeT4 (Free T3 if TSH is low) to asses thyroid status and monitor T4 therapy
Use Trimester-Related Ref Ranges For All Tests
0.1
5.0
TS
H m
U/L
Screening for Thyroid Disease in Pregnancy
•Type 1 diabetes•Previous history of thyroid disease•Current thyroid disease•Family history of thyroid disease•Goitre•Features of hypothyroidism
•Use TSH and Free T4 •Consider TPOAb as a predictor of post partum thyroiditisand foetal impairment
Hypothyroidism and Pregnancy
For patients with established hypothyroidism check TFTs•Before conception (if possible)•At diagnosis of pregnancy•At antenatal booking•At least one in each trimester and 2-4 weeks postpartum
Newly diagnosed patients •Should be checked ever 4-6 weeks until stabilised
T4 Therapy and Pregnancy
First trimester Adjust T4 dose such that Free T4 is at upper half of non-pregnant ref range and TSH is low normal 0.4 – 2.0 mU/L
Ideally monitor against trimester – related reference ranges
Patients who become pregnant usually need an extra 25-50 micrograms of T4. Reduce dose approx 4 weeks after delivery
TRAbs and Pregnancy
Patients with current or previous hyperthyroidism may benefit from a TRAbs at antenatal booking.
•If negative need not be measured again.•High titre can predict chance of intrauterine thyrotoxicosis
Post-partum Thyroiditis
Occurs in 5% of population within 2-6 months of delivery or miscarriage. (non-specific symptoms tiredness, anxiety, depression)
Post-partum patients should have TFTs at 6-8 weeks if they have:-•Goitre•Previous history of post-partum thyroiditis•Previous history of autoimmune thyroid disease•Positive TPOAb
•If thyrotoxic profile - differentiate from Graves’ disease (TRAbs)
•If hypothyroid and symptomatic start on T4 (for approx 6 months)
Thyroid CancerThyroglobulin and TgAb
TgAb are useful as :-
•A prognostic indicator •To validate the reliability of a Tg measurement
TgAb should be measured at diagnosis and simultaneously with Tg for follow-up
Thyroid CancerThyroglobulin and TgAb
Identify possible assay interference by
•RIA/IMA discordance •TgAb positive samples
•Recovery alone is not recommended
Discordant RIA / IMA Tg results at EdinburghRoyal Infirmary over a 17 month period.
14% of total results
RIA/IMA concordance in Tg Ab Negative Samples
IMA
Data from Edinburgh Royal Infirmary
RIA/IMA concordance in TgAb positive samples
Sanofi IRMA
Rad
ioim
mun
oassay
Data from Edinburgh Royal Infirmary
There is a UK NEQAS scheme for thyroglobulin.
Data from scheme illustrates the poor performance of Tg assays
How Should We Inform GPs ?
Guideline Group Plan to Produce a Version for GPs
ButPerhaps Labs should give GPs a brief version of the relevant points that are applicable to local practice. eg•When to request TSH and TSH + FT4•Screening in menopause•When to repeat tests in SC thyroid disease•When to refer SC hyperthyroidism•Target for T4 therapy•Drugs and T4 therapy•Pregnancy issuesAfter Consultation with the Local Endocrinologists And Obstetricians!