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Abnormal Thyroid Function tests

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Abnormal Thyroid Function tests Thyroid hormone release Thyroid hormone metabolism TFTs TSH TFTs in the sick Hyperthyroidism High t4/t3, suppressed TSH Differential ... – PowerPoint PPT presentation

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Title: Abnormal Thyroid Function tests


1
Abnormal Thyroid Function tests
2
Thyroid hormone release
hypothalamus
-ve
TRH ve, Somatostatin -ve
-ve
pituitary
TSH
thyroid
T4 - 90 T3 - 10
  • thyroid hormones
  • directly inhibit TSH release
  • inhibit the effects of TRH on pituitary
  • promote somatostatin release

3
Thyroid hormone metabolism
5deiodinase type 1 liver, kidney, decreased in
illness/starvation
T4
5 deiodinase
5deiodinase type 2 pituitary, brain
T3
rT3
thyroid hormone receptor binding
DNA transcription
4
TFTs
5
TSH
6
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7
TFTs in the sick
8
Hyperthyroidism
  • High t4/t3, suppressed TSH
  • Differential diagnosis
  • Graves
  • Autonomous nodules, toxic MNG
  • Hyperemesis
  • thyroiditis
  • factitious/ectopic

9
Causes of hyperthyroidism
10
Clinical features of hyperthyroidism
  • Multisystem
  • Skin
  • sweating
  • onycholysis
  • hyperpigmentation
  • pruritis
  • vitiligo / alopecia
  • hair loss
  • Eyes
  • lid lag (100 - sympathetic activity
  • opthalmopathy in Graves

11
Dermopathy in Graves
12
Clinical features of hyperthyroidism
  • Multisystem
  • GI
  • weight loss (inc calorigenesis, gut motility
  • hyperphagia
  • dysphagia (goitre)
  • vomiting
  • LFTs
  • GU system
  • urinary frequency
  • polydipsia
  • oligomanorrhoea (inc SHBG)
  • gynaecomastia, erectile dysfunction, loss of
    libido (T-E conversion)

13
Clinical features of hyperthyroidism
  • Multisystem
  • Skeleton
  • loss in cortical bone density
  • increase in bone resorption
  • increased calcium
  • Neuromuscular
  • tremor
  • hyperactive reflexes
  • emotional lability
  • anxiety
  • prox muscle weakness
  • hypokalemic periodic paralysis
  • myaesthenia

14
Pathogenesis of Graves
  • An autoimmune condition
  • characterised by stimulating antibodies to the
    TSHR

15
HLA and Graves
16
TSH receptor
17
TSHRab
18
Antithyroid antibodies..
19
Treatment options for Graves
20
PTU vs Carbimazole
21
Thionamide dosage..
22
Predicting relapse .
23
Radioiodine and TAO
24
Subclinical hyperthyroidism
  • Low TSH normal fT4 (and fT3)
  • common and controversial
  • 1210 subjects gt60y - 6.3 men and 5.5 women had
    TSH lt0.5
  • Persistent in 88 of subjects with TSHlt0.05 (20
    TSH 0.05-0.5)

25
Subclinical hyperthyroidism

26
Subclinical hyperthyroidism
27
Subbclinical hyperthyroidism
  • Associated with increased mortality
  • 1200 subjects gt60y
  • 65 mortality with suppressed TSH
  • 55 mortality with normal TSH

28
Thyroid storm
29
Thyroiditis..
30
Thyroiditis..
31
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32
Hypothyroidism
33
Hypothyroidism - the cause
  • Important to determine the cause
  • usually primary autoimmune.but..
  • May be transient
  • subacute lymphocytic or postpartum thyroiditis
  • drug induced (eg lithium or iodine containing)
  • OR
  • maybe manifestation of pituitary/hypothalamic
    disease

34
Hypothyroidism - clinical manifestations
  • Generalised slowing of metabolic processes
  • fatigue
  • slow movement
  • slow speech
  • cold intolerance
  • constipation
  • weight gain
  • bradycardia
  • slow relaxation of reflexes

35
Hypothyroidism - clinical manifestations
  • Accumulation of matrix GAGs
  • coarse hair
  • coarse skin
  • puffy facies
  • macroglossia
  • hoarse voice

36
Hypothyroidism
37
Hypothyroidism - problems
  • My TFTs are normal but I still feel awful
  • temptation is to increase T4 but low TSH is bad
    for you
  • check other causes of fatigue and consider CFS
  • rarely can try combination T4T3
  • not really proven in RCT
  • difficult to monitor

38
Subclinical hypothyroidism
  • Normal fT4, high (5-25) TSH
  • Vague and non specific symptoms
  • Prevalence 7-8 women, 3-4 men
  • More common in patients with other AI
  • High TSH and high anti TPO abs develop overt
    hypothyroidism at 4.5 per year

39
Subclinical hypothyroidism
  • Do we need to treat with T4
  • 4 RCTs suggest benefit
  • improvement in symptom scores and psychometric
    test results
  • improvement in lipid profile
  • improvement in myocardial function

40
Subclinical hypothyroidism
  • Do we need to treat with T4
  • risk factor for impaired development in pregnancy
    - lower IQ at age 7 (103 vs 107, plt0.006)

41
Subclinical hypothyroidism
  • Do we need to treat with T4
  • concensus view 1998 (ACP) - not enough data!!
  • General view - because of theoretical reduction
    in CVS risk factors, prevention of goitre growth
    and improvement in wellbeing - TREAT - but care
    in the elderly and avoid suppressing TSH

42
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43
Interpretation of abnormal TFTS
  • Usually straightforward...

44
Case 1 30 year old woman who felt anxious and
shaky and had a pulse of 94/min
Reference ranges fT4 9.1-23.8 pmol/L fT3 2.5-5.3
pmol/L TSH 0.49-4.67 mIU/L
  • fT4 37.0, fT3 12.6, TSH lt0.05 interpret these
    results
  • treated with I131 and carbimazole 2/12 later
    fT4 21.0, fT3 4.6, TSH lt0.05 comment on these
    results
  • 2/12 later fT4 7.2, fT3 2.2, TSH lt0.05 comment
    on these results
  • 2/12 later fT4 6.9, fT3 2.2, TSH 1.90

45
Case 1 - use of TFTs in treatment of
hyperthyroidism
  • Thyrotroph cells may remain suppressed for
    several months after thyrotoxicosis
  • TSH is not a useful marker for monitoring the
    initial efficacy of treatment for hyperthyroidism

46
Case 2 - 49 year old woman c/o tiredness
weakness
Reference ranges fT4 9.1-23.8 pmol/L fT3 2.5-5.3
pmol/L TSH 0.49-4.67 mIU/L
  • fT4 14.5 pmol/L
  • TSH 6.5 mIU/L
  • no medication
  • interpret these results

47
TSH normal range
frequency
5.5
0.35
1.5
TSH (mIU/L)
48
Probability of developing hypothyroidism over 20
years (BMJ 1997 314 1175)
49
Compensated (subclinical) hypothyroidism
  • Low normal fT4 maintained by increased pituitary
    drive
  • Gradual deterioration in thyroid function
  • Recent recommendations state such patients should
    receive T4 if microsomal (thyroid peroxidase) Ab
    ve
  • If Ab -ve and TSH lt10 mIU/L then watch and wait
  • Benefits of treatment symptomatic improvement,
    slight reduction in cholesterol, reduced
    progression of atherosclerotic disease
  • (DTB January 1998, BMJ 1996 313 539)

50
Case 3 - 80 year old woman with breast cancer and
liver secondaries
  • TFT requested as a screening test fT4 16.9
    pmol/L fT3 1.1 pmol/L TSH 2.3 mIU/L
  • Interpret these results

Reference ranges fT4 9.1-23.8 pmol/L fT3 2.5-5.3
pmol/L TSH 0.49-4.67 mIU/L
51
Case 3 - Non-thyroidal illness (NTI)
T4
reference range
thyroid hormone level
T3
severity of illness
TSH
reference range
duration of illness
52
Case 3 - Non-thyroidal illness (NTI)
  • In a hospital population a) suppressed TSH
    3x more likely to be due to NTI than
    hyperthyroidism b) elevated TSH as likely to
    be due to NTI as hypothyroidism
  • TFTs should be requested conservatively in ill
    patients and the results interpreted with caution
  • (BMJ 1993 307 177 - Thyroid status in the
    elderly)

53
So when are TFTs justified in ill patients? - A
summary of consensus/editorial statements
54
Case 4 - 72 year old woman went to GP c/o
tiredness
  • PMH - AF 10 years - on digoxin diverticular
    disease
  • fT4 11.8 pmol/L TSH lt0.05 mU/L
  • What further test would you do?

Reference ranges fT4 9.1-23.8 pmol/L TSH
0.49-4.67 mIU/L
55
Case 4 - 72 year old woman went to GP c/o
tiredness
Reference ranges fT4 9.1-23.8 pmol/L fT3 2.5-5.3
pmol/L TSH 0.49-4.67 mIU/L
  • fT4 11.8 pmol/L fT3 7.8 pmol/L TSH lt0.05
    mU/L
  • What is the diagnosis?
  • What would you do?

56
Case 4 - 72 year old woman went to GP c/o
tiredness
  • Three years later - GP still concerned
  • fT4 13.6 pmol/L fT3 6.2 pmol/L TSH lt0.05
    mU/L Thyroid Abs -ve
  • Patient referred to Nuclear Medicine

Reference ranges (note - these have
changed) fT4 11.5-23.2 pmol/L fT3 3.5-6.5
pmol/L TSH 0.35-5.5 mIU/L
57
Case 4 - ? T3 toxicosis/subclinical thyrotoxicosis
  • Appeared jumpy and on edge Pulse
    96/min Palpable multi-nodular
    gland Thyroid scan - areas of irregular
    increased uptake TFTs - essentially as
    before
  • Diagnosis - subclinical thyrotoxicosis

58
Subclinical thyrotoxicosis
  • .must be confirmed to be persistent before any
    action taken
  • .is more likely to convert to clinical when TSH
    suppressed
  • . may be associated with cardiac abnormalities
    (esp. AF)
  • . probably warrants treatment in elderly
    patients with AF
  • (BMJ 1999 319 894-898. Controversies in thyroid
    management)

59
Case 5- started amiodarone for cardiac
arrhythmia's
  • TFTs requested 2 weeks after starting amiodarone
  • fT4 28.5 pmol/L
  • fT3 2.7 pmol/L
  • TSH 6.5 mIU/L
  • Comment on these results

Reference ranges fT4 9.1-23.8 pmol/L fT3 2.5-5.3
pmol/L TSH 0.49-4.67 mIU/L
60
Amiodarone and the thyroid
  • Amiodarone inhibits T4 T3 conversion Reduced
    intrapituitary T3 TSH release TSH release
    increased T4
  • TSH may rise to approx 3x pre-treatment level in
    first two weeks but may later (4 weeks) return to
    normal - patients are EUTHYROID
  • Amiodarone may also cause iodine-induced
    hypothyroidism and iodine-induced thyrotoxicosis
  • Request TFT BEFORE starting treatment

61
Case 6 - 76 year old woman
  • clinically hypothyroid
  • absent body hair
  • pallor
  • postural hypotension
  • TSH 2.0 mIU/L
  • What further investigations would you request?

62
Case 6 - 76 year old woman
  • fT4 5 pmol/L (9.1-23.8 pmol/L)
  • Na 128 mmol/L
  • Cortisol (9 am) 141 nmol/L
  • Prolactin 162 mU/L
  • FSH 0.6 U/L
  • LH 1.2 U/L
  • What is the diagnosis?

63
Case 6 - secondary hypothyroidism
  • Dynamic pituitary function testing showed
    anterior pituitary insufficiency
  • Skull X-ray normal
  • T4 and hydrocortisone replacement produced marked
    improvement
  • Hypopituitarism can be missed by protocols
    employing TSH as front-line test
  • (Belchetz BMJ 1985 291 247)

64
Case 7 - 30 year old male
  • Presenting features
  • nausea, giddiness, wheezing, sweating, tremor,
    weight stable, BP normal
  • Soft, diffuse goitre noted
  • What investigations would you request?

65
Case 7 - 30 year old clinically hyperthyroid male
  • Free T4 47.5 pmol/L (9-24)
  • Total T4 245 nmol/L (80-150)
  • Total T3 5.0 nmol/L (0.8-2.7)
  • TSH 4.2 mIU/L (0.5-4.5)
  • SHBG 101 nmol/L (18-50)
  • Interpret these results and give a differential
    diagnosis
  • What is the significance of the SHBG?

66
Case 7 - 30 year old clinically hyperthyroid male
  • Differential diagnosis
  • 1) generalised thyroid hormone resistance
    (euthyroid or hypothyroid)
  • 2) pituitary thyroid hormone resistance
    (thyrotoxic)
  • 3) TSHoma (thyrotoxic)
  • Further investigations? TRH
    test pituitary MRI scan alpha-subunit

67
Case 7 - 30 year old clinically hyperthyroid male
  • TRH test
  • 0 FT4 39.4 TSH 2.1
  • 30 38.8 2.8
  • 60 38.8 2.7
  • Flat response commoner in TSHoma than resistance
    syndromes (gt90 respond in resistance syndromes,
    lt40 in TSHoma)
  • alpha-subunit 1.4 ug/L (normal lt0.73 ug/L)
  • MRI large, non-invasive pituitary tumour

68
Case 7 - TSHomas
  • 1 of pituitary tumours1
  • Monoclonal in origin
  • Diagnostic tests
  • TRH test, alpha subunit and alpha subunit/ TSH
    ratio
  • MRI pituitary
  • Criteria for cure3_Euthyroidism, normalized TRH
    test and absence of tumour on follow up MRI.
  • Cure rate

69
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