CASE A- THYROID FUNCTION TESTS

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CASE A- THYROID FUNCTION TESTS

• MYLINH TRUONG. JEN CRAZE, KELLY STEWART,

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CASE A

• Ms YW
• Age early 20s
• History of weight loss, heat intolerance,
  nervousness, increased bowel frequency and
  oligomenorrhoea.
• Current symptoms tremor, sinus tachycardia,
  proximal myopathy, large goitre (14cm), mild
  proptosis w/out diplopia.

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What is THYROTOXICOSIS?

• Thyrotoxicosis refers to the hypermetabolism and
  increased sympathetic nervous activity associated
  with increased concentrations of free T4 and T3
  hormones, irrespective of the source.
• Symptoms can be vague and the clinical
  presentation can range from minimal symptoms to
  life-threatening thyroid storm.

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Clinical Manifestations

• Amenorrhoea or oligomenorrhoea.
• Heat intolerance
• Excessive sweating
• Weight loss
• Fatigue and appetite changes
• Palpitations

• Atrial fibrillation
• CCF
• Fine tremor
• Exophthalmos
• Goitre
• Muscle weakness
• Diarrhoea
• Osteoporosis

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GRAVES DISEASE

• Most common cause of hyperthyroidism among
  patients btw 20-50 yrs of age.
• More common among women.
• Thyrotoxicosis associated with Graves disease is
  due to stimulation of TSH receptors by TSH
  receptor antibodies -gtexcess hormone production
  and secretion.
• SS goitre, opthalmopathy, dermopathy.

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TFT results

• Initially
• FT4 65 (10-25) pmol/L
• FT3 20 (3-8) pmol/L
• TSH suppressed
• Carbimazole 15 mg tds for 1 month
• FT4 reduced to 30 pmol/L
• REDUCED dose to 10mg bd
• After 3 mths FT4 is 9 pmol/L and TSH is
  suppressed

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Why has FT4 decreased but symptoms of
thyrotoxicosis still remain and TSH is still
suppressed?
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?????

• After correction of hyperthyroidism, TSH may fail
  to respond (months) to a fall in FT4 -gtif this
  time lag is overlooked, the patient may be over
  treated, resulting in biochemical hypothyroidism
  with clinical thyrotoxicosis.
• T4 and T3 may need to be measured.

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What additional TFTs are required in light of YW
suppressed TSH?
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Additional TFTs

• FTI - Free thyroxine index
• T4
• T3

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What TFTs should be measured in patients
receiving antithyroid treatment?
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Monitoring

• Total T3
• Total T4
• Free T4
• Thyroid scan
• TSAb

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Describe the analytical principles behind the
sensitive TSH assay and its advantages and
disadvantages compared to the clinical utility of
this measurement.
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Measurement of TSH
Methods Principle Comments
RIA Competetive binding of radiolabled TSH and non-labeled TSH to limited binding sites on the antibody Being phased out
Immunoradiometric assay Binding of TSH to radiolabeled antibody Utilises 2 antibodies sandwhich method
Ivery, 2003 lecture notes
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The sensitive TSH assay

• Also known as sTSH
• All utilise antibodies for the ß subunit of TSH.
  The a subunit is common for TSH, FSH, LH and CG
• Mid-1980s, 2nd generation immunometric assays
  developed with lower detection rate than RIA
  methods enabled differentiation between
  hyperthyroid patients with subnormal TSH and
  normal subjects
• Third generation assays, recently developed
  assay functional sensitivities reported as
  0.01-0.02 mU/l
• Sandwich assays with two antibodies. The use of
  the second antibody gives better sensitivity.
• Sensitive chemiluminescent enyzymeimmunoassay
  analytical sensitivity of 0.0016 mU/l

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The clinical TSH assay

• RIA method
• Doesnt have the sensitivity to detect much below
  euthyroid
• Currently being phased out

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Advantages/disadvantages

• 2nd generation permits detection of TSH levels
  below euthyroid
• 3rd generation permits differentiation between
  complete suppression and incomplete suppression
  of pituitary TSH output

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Clinical utility of TSH measurement
TSH Thyroxine
Subclinical hypothyroidism Elevated Normal
Subclinical hyperthyroidism Undetectable Normal
Overt hypothyroidism Elevated Low
Overt hyperthyroidism Undetectable Elevated
Helfand et al, 1998
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Subnormal TSH

• Subnormal TSH levels are apparent in patients
  with
• overt thyrotoxicosis
• T4 therapy
• treated hyperthyroidism
• subclinical Graves disease
• autonomously functioning thyroid nodule
• central hypothyroidism
• psychiatric illness
• nonthyroidal illness
• Kasagi et al, 1999

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Early detection and monitoring

• The early detection of thyroid dysfunction if
  important to..
• ensure the necessary treatment is commenced as
  soon as possible
• patients with subclinical thyroid dysfunction are
  monitored and that any changes to their status
  are detected and treated as early as possible.
• The clinical TSH assay does not have enough
  sensitivity to detect these small changes and
  cannot detect TSH levels below euthyroid.
• It is important to detect subnormal levels of TSH
  as well as high levels.
• Kasagi et al, 1999

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References

• Helfand, M. et al Screening for thyroid disease.
  Annals of internal medicine, 1998
  129(2)141-143.
• Ivery, M. Thyroid function lecture notes.
  Clinical pathology B, 2003.
• Kasagi, K. et al Comparison of serum thyrotrophin
  concentrations determined by a third generation
  assay in patients with various types of overt and
  subclinical thyrotoxicosis. Clinical
  Endocrinology, 1999 50(2)185-189.