1. Thyroid Function tests
Dr Danielle B Freedman
please see January 2015 PULSE p
April 2018

3. Incidence of Thyroid disease
Hypothyroidism
Spontaneous 2%, 10 Females : 1 Male
Another 1% due to destructive treatment for Hyperthyroidism
Congenital Hypothyroidism 1/4000 births
Hyperthyroidism
0.5 – 2%, 10 Females :1 Male
So what is Lab Tests Online UK and what can it offer you?
It’s a free resource in the form of a website and free mobile app which provides:
Detailed descriptions of laboratory tests Descriptions of conditions and diseases, cross- referenced to the relevant tests News on advances in laboratory testing
Links to other relevant and useful websites that can help answer any further questions

4. Important Clinical Manifestations
Hyperthyroidism
5-10% of patients with thyrotoxicosis have Atrial Fibrillation
Correctable cause of osteoporosis
Associated with menstrual irregularity, subfertility and foetal loss
Hypothyroidism
Well recognised secondary cause of hyperlipidaemia
So what is Lab Tests Online UK and what can it offer you?
It’s a free resource in the form of a website and free mobile app which provides:
Detailed descriptions of laboratory tests Descriptions of conditions and diseases, cross- referenced to the relevant tests News on advances in laboratory testing
Links to other relevant and useful websites that can help answer any further questions

5. Causes of Hyperthyroidism
Grave’s disease
Toxic Mutinodular goitre
Solitary toxic adenoma
Thyroiditis
Exogenous iodine and iodine-containing drugs eg amiodarone
Excessive T4 or T3 ingestion
Ectopic thyroid tissue, eg struma ovarii, functioning metastatic thryoid cancer
hCG dependent: choriocarcinoma
TSH dependent: pituitary tumour
Account for >90% cases

6. Causes of hypothyroidism
Atrophic hypothyroidism (may represent the end-stage of Hashimoto’s disease)
Automimmune hypothyroidism (Hashimoto’s thyroiditis)
Post-surgery, radioactive iodine, anti-thyroid drugs (eg carbimazole) and other agents (eg lithium)
Congenital
Dyshormonogenic
Secondary (pituitary or hypothalamic disease)
Iodine deficiency
Account for >90% cases

7. Drugs and thyroid disease
Amiodarone
Hyperthyroidism (iodine deficient) 10%
Hypothyroidism (iodine replete) 20%
Lithium
Hypothyroidism: Mild 34% Overt 15%
Monitoring for patients taking either drug
6 monthly TFT’s
12 monthly review
So what is Lab Tests Online UK and what can it offer you?
It’s a free resource in the form of a website and free mobile app which provides:
Detailed descriptions of laboratory tests Descriptions of conditions and diseases, cross- referenced to the relevant tests News on advances in laboratory testing
Links to other relevant and useful websites that can help answer any further questions

8. Patients on Levothyroxine
Annual measurement TSH (+FT4)
Starting dose 50 mcg
Check TFT’s 6-8 weeks after commencing treatment and following change of dose
Dose increment 25 mcg
Average dose 1.6 mcg/kg
Caution with elderly patients –
In pregnancy
Increase dose by 50 mcg
Measure TFT’s each trimester
TSH should be mU/L
So what is Lab Tests Online UK and what can it offer you?
It’s a free resource in the form of a website and free mobile app which provides:
Detailed descriptions of laboratory tests Descriptions of conditions and diseases, cross- referenced to the relevant tests News on advances in laboratory testing
Links to other relevant and useful websites that can help answer any further questions

9. Patients on Carbimazole
If patient toxic refer to Endocrine clinic /start
Cz 20mg bd, ? Beta blockers
TFTs checked every 4 – 6 weeks
Once stable ,every 2 – 3 months
Other investigations, anti-TPO abs and US
Duration, 18 months – 2 years

10. Thyroid disorders in pregnancy and the post partum period

11. Introduction
4% of pregnant women:
Have a history of thyroid disease
Develop thyroid disease during pregnancy
1st time develop thyroid disease within 5 years following pregnancy
Beware ‘Gestational transient thyrotoxicosis’- hCG induced hyperthryoidism – TSH receptor sensitivity to (appropriately) high hCG concentrations
Remember the reference range for Free T4 and Free T3 decreases approx 20% in the 2nd and 3rd trimesters
During pregnancy TSH can be up to 50% lower in the 1st trimester and within the non-pregnant reference range in the 2nd and 3rd trimesters, while Free T4 can be up to 20% lower in the 2nd and 3rd trimesters and within the non-pregnant reference range in the 1st trimester based on current scientific evidence.
ATA & AACE do NOT recommend universal screening for thyroid function in pregnancy

12. Hypothyroidism in pregnancy
2-3% of iodine-sufficient pregnant women will have undiagnosed hypothyroidism – mostly subclinical
Main cause in iodine sufficient is chronic autoimmune thyroiditis
10-20% of women of child bearing age have positive anti-TPO antibodies
Untreated overt hypothyroidism is associated with:
Increased risk of miscarriage
Preterm delivery
PET
Neonatal mortality
Low birth weight
Decreased IQ

13. Treatment and monitoring in pregnancy
ATA recommend diagnosis of hypothryoidism in all pregnant women with; - a TSH > reference interval and a low FT4
- All with TSH > 10mU/L irrespective of FT4
In women with subclinical hypothryoidism who are not initially treated; ATA recommends monitoring FT4 and TSH every 4 weeks until 16-20/40 and once between 26/ /40 weeks gestation
Dosage of levothyroxine will go up during pregnancy ( 30-50%)
Aim for TSH 1.0 – 2.5 mU/L, monitor TSH as above
Post partum revert back to original dosage and check TFT’s 6 weeks post partum

14. Thyrotoxicosis in pregnancy
Grave’s disease occurs in 0.1-1% of all pregnancies
Transient gestational hyperthyroidism can occur in the 1st trimester (prevalence 2-3 %)
In patients with Grave’s:
Monitor TFT’s every 4-6 weeks
TRAb at 24 weeks – can cross the placenta and cause foetal and neontal hyperthryoidism (<1%)
Uncontrolled Grave’s:
Foetal loss
PET
Miscarriage
Premature labour
CCF
Thyroid storm

15. Treatment of thyrotoxicosis in pregnancy
1st trimester PTU
2nd and 3rd trimester PTU/CBZ
Block replacement and I131: CONTRAINDICATED
Aim to keep: FT4 in within or slightly above reference range TSH within the reference range
30-40% of women are able to remain euthyroid without treatment in the last few weeks of pregnancy
Can relapse post partum
Breast-feeding is ok if the dose of PTU < 300mg/day CBZ < 30 mg/day

16. Post partum thyroiditis
May be difficult to distinguish from Grave’s
4-9% of women develop post partum thyroiditis
Positive Anti-TPO antibodies (which rise in titre 6 weeks PP)
Can be transiently hyperthyroid (unless Grave’s) – do not treat with antithyroid drugs
Can become transiently hypothryoid or permanent ( %)
If ‘transient’ check TFT’s annually – can recur with subsequent pregnancy

17. Development of thyroid dysfunction in the postpartum period

18. Adapted from the ACB/RCPath ‘Minimum Retesting Intervals’
2016

19. Clinical situation
Recommendation
Hyperthyroid-monitoring CBZ/PTU treatment
TFTs should be performed every 4–6 weeks after commencing thioamides. Testing at 3 month intervals is recommended once maintenance dose achieved.
Hyperthyroidmonitoring ‘block and replace’
Assess TSH and fT4 at 4–6 week intervals, then after a further 3 months once maintenance dose achieved, and then 6 monthly thereafter

20. Clinical situation
Recommendation
Hyperthyroid - monitoring of treatment in Graves’ disease
Follow-up in first 1–2 months after radioactive iodine treatment for Graves’ should include fT4 and TSH. If patient remains thyrotoxic then biochemical monitoring to continue at 4–6 week intervals
Following thyroidectomy for Graves’ disease (and commencement of levothyroxine), serum TSH to be measured 6–8 weeks post-op
Hyperthyroid - monitoring of treatment in toxic multinodular goitre and toxic adenoma
Follow-up in first 1–2 months after radioactive iodine treatment for toxic multinodular goitre and toxic adenoma should include fT4 and TSH. Should be repeated at 1–2 month intervals until stable results, and then annually thereafter. Following surgery for toxic multinodular goitre and start of thyroxine therapy, TSH should be measured 1–2 monthly until stable and annually thereafter. Following surgery for toxic adenoma TSH and fT4 concentrations should be measured 4–6 weeks post-op.

21. Hypothyroidism - monitoring treatment
Clinical situation
Recommendation
Hypothyroidism - monitoring treatment
The minimum period to achieve stable concentrations after a change of dose of thyroxine is 2 months and TFTs should not normally be assessed before this period has elapsed.
Patients stabilised on long-term thyroxine therapy should have serum TSH checked annually.
An annual fT4 should be performed in all patients with secondary hypothyroidism stabilised on thyroxine therapy.

22. Clinical situation
Recommendation
Monitoring adult sub-clinical hypothyroidism
Patients with subclinical hypothyroidism should have the pattern confirmed within 3–6 months to exclude transient causes of elevated TSH. Subjects with subclinical hypothyroidism who are Anti-TPO-Ab positive should have TSH and fT4 checked annually. Subjects with subclinical hypothyroidism who are Anti-TPO-Ab negative should have TSH and fT4 checked every 3 years.
Monitoring Adult sub-clinical hyperthyroidism
If a serum TSH below ref range but >0.1 mU/L is found, then the measurement should be repeated 1–2 months later along with fT4 and fT3 after excluding non-thyroidal illness and drug interferences.

23. Clinical situation
Recommendation
Secondary Care
Follow up of patients who have had differentiated (papillary and follicular) thyroid carcinoma and a total thyroidectomy and 131I ablation
TSH and fT4 should be measured as dose of levothyroxine increased (every 6 weeks) until the serum TSH is <0.1 mIU/L. Thereafter annually unless clinically indicated/pregnant.
Samples for thyroglobulin (Tg) should not be collected sooner than 6 weeks post-thyroidectomy or 131I ablation/therapy. TSH, fT4/fT3 (whichever is being supplemented) and Tg autoantibodies (TgAb) should be requested when Tg is measured. If TgAb are detectable, measurement should be repeated every 6 months.

24. 1 58 year old male with strong FHx of CHD. Non-smoker with BMI = 26.5.
Fasting glu = 4.6 mmol/L
Chol = 8.4 mmol/L
HDL = 1.1 mmol/L
Trig = 2.1 mmol/L
1/52 – complaining of malaise
CK = 850 U/L [<170]

25. What test(s) are required to investigate the raised CK. a. Magnesium b
What test(s) are required to investigate the raised CK ? a. Magnesium b. FBC c. TFT’s d. HbA1c e. U+E

26. a. TFT

27. 2.
Which one of the following findings in a patient with primary hypothyroidism could not be explained by this condition ?
a). Hyponatraemia
b). Increased mean red cell volume
c). Plasma cholesterol of 7.2 mmol/L
d). Plasma ALP 2x the ULN
e). Plasma CK 2x the ULN

28. d). Plasma ALP 2x the ULN

29. 3. 25-year-old female with menorrhagia FT4 = 11.5 pmol/L [10 – 20]
TSH = 8.3 mu/L [0.4 – 4.5]
What do you do next?
Repeat in 3 months
Measure serum anti-TPo abs
Treat with levothyroxine
Measure 9 am Cortisol

30. Answer
Repeat in 3 months
Anti TPO abs

31. 4. Mr DW Home visit dob 20/8/41 LVF A fibrillation PMH CABG 1989
Angioplasty 2004
MI – 1998
Hypertension
Hypercholesterolaemia
Type 2 DM

32. DH Frusemide
Clopidogrel
Nicorandil
Amiodarone
Simvastatin
Ezetimibe
Warfarin
Ramipril
Bisoprolol
Allergies None
SH Ex smoker
Occasional alcohol
Lives with wife
FH none

33. O/E p = 130 AF
bp = 143/76
chest basal crackles
JVP  5 cm
No ankle oedema
HS I and II and 0

34. U = 10.7 mmol/l [2.5 – 6.5]
Cr = 124 mmol/l [60 – 120]
Na = 131 mmol/l
K = 3.6 mmol/l
FT4 = pmol/l [12 – 23]
TSH = <0.06 mu/l [0.35 – 5.5]

35. Start Propylthiouracil Treat with radioactive iodine
Question In addition to treating his AF and LVF, how do you think the patient’s deranged thyroid function should be treated? interactive
Do nothing
Stop Amiodarone
Start Propylthiouracil
Treat with radioactive iodine

36. Answer
Stop Amiodarone
PTU

37. 5.
81 yr old female just discharged from hospital with diagnosis of pneumonia.
FT4 = 9 pmol/l (10-20)
TSH = 0.10 mu/l ( )
FT3 = 1.8 pmol/l ( )

38. What would you do next ? a) Nothing b) Treat with carbimazole
c) Treat with levothyroxine
d) repeat TFTs in 4 weeks

39. 6. 45 yr old female on 125mcg levothyroxine c/o TAT
FT4 = 13pmol/l ( 12-23)
TSH = 4.3 mu/l ( 0.35 – 5.5 )

40. What would you do?
a) Nothing
b) reduce T4 to 100mcg
c) Increase T4 to 150mcg
d) rpt TFTs in 2 months

41. 7. 65-year old man c/o TATT, muscle aches, loss of libido DH nil
Sodium 137 mmol/L
Potassium mmol/L
Creatinine 76 umol/L
eGFR >60 ml/min/1.73m2
TSH mU/L
Testosterone nmol/L
Creatine Kinase 223 U/L
Hb g/L

42. Diagnosis? Free T4 5.5 pmol/L Duty Biochemist added:
Cortisol 52 nmol/L
LH 1.2 U/L
FSH 0.8 U/L
Diagnosis?

44. What most determines a clinician’s test ordering. 1
What most determines a clinician’s test ordering? 1. Fear of litigation 2. Cost of test 3. Evidence based guidelines 4. Patient went to Lab Tests Online 5. Watched an episode of ‘House’ last night

45. ACB SPOTLIGHT MEETING

46. Analysis of malpractice claims – US Ann Intern Med 2006; 145: 488-496
Faulty process leading to missed diagnosis:
Failure to order appropriate dx /lab test %
Inappropriate/inadequate follow-up %
Failure to obtain adequate history/exam %
Incorrect interpretation of diag. test %
Failure to refer %
Provider did not receive test results %
Tests ordered but not done %
Tests performed incorrectly %
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47. Patient Safety and Laboratory Medicine
Pre Analytical right test
right patient
right label
‘request form’
right sample
Analytical right lab
EQA right conditions -
Accreditation (CPA) temperature
Post Analytical right result
right clinician
right communication
right interpretation
right Mx and further investigations

48. How much is spent in the US on unnecessary testing and procedures a
How much is spent in the US on unnecessary testing and procedures a. $ 1.5 billion b. $ 3.0 billion c. $ 6.8 billion d. $ 18.0 billion
17.4 % of US GDP was spent on health care in 2009
$65 billion per annum on > 4.3 billion laboratory tests

50. g:\hod\icb\slides\key pathology drivers - reading may 06

51. Some Causes of Overutilization
Patient pressure
Duplicate requesting
Lack of understanding of the diagnostic value of a test
“just in case”
Ordering ‘wrong’ test
Failure to understand the consequences of overutiliz’n
Defensive testing
Perverse financial incentives (more tests = more £ )
“Availability creates demand “

52. Laboratory investigations £2.5 billion / year
Approximately 4% of total NHS expenditure
Annual increase in workload 8-10%
25% of pathology tests unnecessary
Department of Health Independent Review of Pathology Services 2009
BUT same amount of under requesting?
30% “Consensus” estimate AACC Webinar 26th Oct 2010 ”

54. Which points in the process have the highest incidence of errors?
Test selection by clinicians?
Interpretation of test results by clinicians?
Yes
Laposata,2008

55. Types and frequency of errors in the different
phases of the TTP
Phase of the TTP Relative Frequency (%)
Pre-pre-analytic – 68.2
Wrong test choice accounts for up to 50 – 60% of missed / delayed diagnoses
Approx 30% of total laboratory medicine errors have direct impact on patient care, and 2.7%-12% cause an adverse event.
Plebani Ann Clin Biochem 2010,47:

56. UK junior hospital doctors: “How confident are you in requesting laboratory tests?”
(Khromova & Gray, 2008)
g:\hod\icb\slides\key pathology drivers - reading may 06

57. How confident are you in interpreting laboratory tests?

58. Both a low serum iron and low transferrin
Questions
Oxford ,2010
Answer Options
Correct Answer
% Correct
1. Which of the following blood groups would it be unsafe to transfer to a man of blood group O Rhesus positive?
O Rh positive
O Rh negative
A Rh positive 77
2. In a patient on Warfarin in whom there is no, or only minor bleeding, at what INR would you consider administering Vitamin K? 3 5 7 8 10 36
3. The following test result would confirm a diagnosis of iron deficiency:
A low serum iron
Both a low serum iron and low transferrin
A low serum ferritin 61

59. Strategies for Changing Physician Behaviour in Ordering Lab Tests
Bandolier Review of 49 articles between 1966 and 1998
Strategies that don’t work by themselves
Physician consensus building
Test guideline dissemination
Traditional education
Utilisation audits
Inform physicians of lab test charges

60. Published:
J Clin Path
B M JMJ

61. National Minimum Re-testing Interval Project 2013:
A final report detailing consensus recommendations for
minimum re-testing intervals for use in Clinical Biochemistry
Box 1 Minimum Re-testing Interval Work Streams
Renal
Liver and Bone
Endocrine
Lipids and Diabetes
Specific Proteins
Cardiac
Tumour Markers
Gastro-Intestinal
Occupational/Toxicology
Therapeutic Drug Monitoring
Pregnancy and Paediatrics
The Association for Clinical Biochemistry

62. Unnecessary testing 73,000 requests pa to 3.5million requests pa
Australia – Vit D requests increased by 4,600 % from 2002/3 to 2011/12 !!
73,000 requests pa to 3.5million requests pa
Vasikaran,Ann Clin Biochem 2013: 50: 283-4

64. Ordering by clinical condition with defined options for primary care reduce inappropriate tests and reduce variation in practice.

65. Tests linked to diagnostic algorithms at time of order promote appropriate investigations, ensure adequate investigation and improve compliance with care pathways.

67. Need to minimize variation in test ordering
Guidelines, education and audit
Use of Formularies
Electronic order systems (CPOE)
Diagnostic algorithms
Minimum retesting intervals
Request vetting and restrictions
Feedback to users – activity data and costs
Multiple interventions
MUST stay in place otherwise behaviour will drift back to the unwanted condition

68. ‘Better do a few lab tests…’
‘I could give you a copy of your lab report but…
…I doubt you’d understand it.’
Language confusing
FBC
LFT
TFT
IgE
If patient is interested may not get the information they require

70. Why do I need this blood test?
What does this laboratory result mean?
“Laboratory medicine empowering patients”

71. - Practicing laboratory doctors and scientists
Peer-reviewed
- Practicing laboratory doctors and scientists
Non- commercial
Who are we and what do we do?
Lab tests online-UK is not for profit organisation set up in 2004 following an agreement between the by American Association of Clinical Chemistry and the association of clinical biochemistry in the UK to initiate a UK version of the existing american website.
Initial funding was provided by the Health foundation (one of UK’s largest charitable independent healthcare charitable foundations) and the royal college of pathologists, the association of clinical biochemistry and the institute of biomedical scientists continue to support the website.
The information on the site is peer-reviewed by practising laboratory doctors and scientists to ensure it is accurate and up to date.
And is designed for patients using language that’s easy to understand and allowing access for all
Patient centered
- Language that’s easy to understand - Access for all

72. Lab Tests Online-UK provides:
Detailed descriptions of 302 laboratory tests
Descriptions of 114 conditions and diseases, cross-referenced to the relevant tests
News on advances in laboratory testing
Links to other relevant and useful websites that can help answer any further questions
So what is Lab Tests Online UK and what can it offer you?
It’s a free resource in the form of a website and free mobile app which provides:
Detailed descriptions of laboratory tests Descriptions of conditions and diseases, cross- referenced to the relevant tests News on advances in laboratory testing
Links to other relevant and useful websites that can help answer any further questions

73. Thyroid function tests
Top ten tests
Platelet
Count UE
ESR
LFT
CRP
Calprotectin
RBC
Thyroid function tests
D-dimer
GGT

74. Lab Tests Online-UK monthly stats Annual visitors > three million
240,050 UK website hits per
month 2017
In August 2014 we had 146,000 hits on the website and reach 9492 app downloads
App downloads reached 23,294
by Dec 2017
Annual visitors > three million

75. Links to Lab Tests Online-UK (existing or working towards)
NHS Choices
Microtest
DrDoctor
Welsh specialist virology unit
Choosing Wisely UK
Websites:
UCLH OCS project
Many More!!
InPS
i-Patient
OMNI lab
Manage your health
TPP(System One)
HealthFabric
iSOFT
GP systems:

76. Some comments from users 2016/17
Nicely presented and well written. A good educational resource for a retired GP
As a nurse just starting to learn how to interpret blood tests ..the site is amazing…love it. Thank you.
Very helpful to be able to see differences between one test and another. I am noting INR kidney filtration rate potassium and blood sugar levels. Thanks for info.
Excellent and easy to understand
Loved the sumple explanations of what the test means, what it measures and what it can be used to indicate eg high ESR and inflammation
Brilliant & reliable. The mobile app is excellent, too.

78. Volume: 53 issue: 6, page(s): 669-679
Article first published online: March 24, 2016;Issue published: November 1, 2016
DOI: 

79. Who uses the Lab Tests Online-UK website?
Patients, their carers and health care professionals
In our 2014 survey (661 responders):
40% of respondents were healthcare professionals
60% were patients or carers
We did a survey in 2014 which showed that the majority of people using the website were patients or carers and the rest were healthcare professionals

80. 2014 Survey results Patients and carers
71% found what they were looking for when visiting the website
71% found the information was written at the right level for them
93% found the information very easy or fairly easy to understand
87% understood their test/diagnosis/condition better after visiting our website
These are the results from patients and carers who responded to the survey

81. Q3. Which of these best describes your reason for visiting Lab Tests Online-UK?
From talking to healthcare professionals who have used the website they have Leaflets in waiting areas which introduces the patients to lab tests online uk and provides a way for them to record what blood tests they’re having done
They will then suggest the use of lab tests online when they tell them what blood tests they’re having and may give them a leaflet at this point.
This allows them to go away and look up their blood tests online when they get home, or download the free app

82. Q 13. Which of these best describes what you are looking for today on this website?
I have been told my white blood count is low
Doctors lack of time/complacency etc
Trying to understand what raised white blood cells means
My wife desires to know what poisoned her. Current doctors are monitoring her recovery but are not finding the source

83. Please could you state what was missing on the site
Q16. You stated that you did not find what you were looking for on the website (11%)
Please could you state what was missing on the site
I’m suffering from joint pain in my hands and feet and was wondering if this would be a consequence of taking statins over a period of years
Wanted to find test results online
Why I have high plate count
What is a normal cholesterol
I am suffering from a sewage leak over a year and want to test for ammonia inhalation if possible (local water board not repairing) and possibly other V.O.C.s Also any precautions or cures I need to take.
Home testing for mercury
Was looking to find out if HRT for menopause safe to take after radioiodine
Testosterone cream for women

86. Please may we ask why you do not want to view your laboratory results
Q23. Only 4% would NOT like to see their laboratory test results, at the same time as their doctor/nurse
Please may we ask why you do not want to view your laboratory results
They know how to interpret them, I’d just worry
I wouldn’t know what I’m looking at and it would probably make patient feel they know better than their GPs who are the experts
Doctor can interpret the results, I can’t
Would not understand them. The consultant provides me with a copy of his letter to my GP. I therefore have info for discussion with GP

87. it's v good
Excellent, doesn't need improvement
Very good and informative web site
love it
it is better If you are able to add drugs information relevant to the specific conditions if drugs are involved with the condition.

88. Summary / Key Findings
661 users responded but not all surveys were completed
Liked / Loved website – right level of information / very useful
Patients WANT to see their lab results and want to know what they mean
Professionals like the information – right level
Large number of users from outside the UK [Asia and America]
Editorial comments: cluttered front page / font size
Users unaware LTOL - UK Team are working voluntarily
App rated 4.35/5

91. William Osler
(adapted)
Laboratories are … to the GP as the knife and scalpel are to the surgeon.