Abnormal Thyroid Function tests

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Abnormal Thyroid Function tests
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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

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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
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TFTs
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TSH
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TFTs in the sick
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Hyperthyroidism

• High t4/t3, suppressed TSH
• Differential diagnosis
• Graves
• Autonomous nodules, toxic MNG
• Hyperemesis
• thyroiditis
• factitious/ectopic

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Causes of hyperthyroidism
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Clinical features of hyperthyroidism

• Multisystem
• Skin
• sweating
• onycholysis
• hyperpigmentation
• pruritis
• vitiligo / alopecia
• hair loss

• Eyes
• lid lag (100 - sympathetic activity
• opthalmopathy in Graves

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Dermopathy in Graves
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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)

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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

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Pathogenesis of Graves

• An autoimmune condition
• characterised by stimulating antibodies to the
  TSHR

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HLA and Graves
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TSH receptor
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TSHRab
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Antithyroid antibodies..
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Treatment options for Graves
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PTU vs Carbimazole
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Thionamide dosage..
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Predicting relapse .
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Radioiodine and TAO
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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)

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Subclinical hyperthyroidism

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Subclinical hyperthyroidism
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Subbclinical hyperthyroidism

• Associated with increased mortality
• 1200 subjects gt60y
• 65 mortality with suppressed TSH
• 55 mortality with normal TSH

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Thyroid storm
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Thyroiditis..
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Thyroiditis..
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Hypothyroidism
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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

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Hypothyroidism - clinical manifestations

• Generalised slowing of metabolic processes
• fatigue
• slow movement
• slow speech
• cold intolerance
• constipation
• weight gain
• bradycardia
• slow relaxation of reflexes

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Hypothyroidism - clinical manifestations

• Accumulation of matrix GAGs
• coarse hair
• coarse skin
• puffy facies
• macroglossia
• hoarse voice

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Hypothyroidism
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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

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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

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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

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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)

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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

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Interpretation of abnormal TFTS

• Usually straightforward...

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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

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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

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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

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TSH normal range
frequency
5.5
0.35
1.5
TSH (mIU/L)
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Probability of developing hypothyroidism over 20
years (BMJ 1997 314 1175)
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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)

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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
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Case 3 - Non-thyroidal illness (NTI)
T4
reference range
thyroid hormone level
T3
severity of illness
TSH
reference range
duration of illness
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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)

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So when are TFTs justified in ill patients?- A
summary of consensus/editorial statements
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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
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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?

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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
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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

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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)

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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
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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

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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?

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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?

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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)

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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?

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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?

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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

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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

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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

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