Thyroid Function Tests Case Study B

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Thyroid Function TestsCase Study B

• Presented by
• Owen Naidoo
• Abdullah Osman
• Christine Tanzil
• Ayse Togac

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• Ms MA (a middle-aged woman) presents to AE
  with
• History of abdominal pain
• Vomiting
• Features of sepsis.

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• Investigations resulted in the diagnosis of
• Ruptured appendix (surgically removed)
• Peritonitis

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• Her post-op recovery was complicated by
• Transient oliguric renal failure
• Pneumonia

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Her TFT results 6 days post-op were as follows
FT4 5pmol/L 10-25pmol/L
FT3 lt1pmol/L 3-8pmol/L
TSH 6 mU/L 0.4-4mU/L
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• She did not have clinical symptoms of thyroid
  dysfunction or a goitre and so throxine treatment
  was not commenced.

Thyroxine
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Two weeks post-op her TFT results were as follows
and still she displayed no clinical signs of
thyroid disorder
FT4 8pmol/L 10-25pmol/L
TSH 11mU/L 0.4-4mU/L
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After a further three weeks, her TFT results were
as follows
FT4 11pmol/L 10-25pmol/L
TSH 7mU/L 0.4-4mU/L
She also had a strongly positive peroxidase
antibody ? thyroxine treatment was commenced.
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Some definitions

• Thyroid Stimulating Hormone (TSH)
• The levels of TSH are controlled by the pituitary
  gland depending on the circulating levels of
  thyroxine
• Synthesises thyroid hormones from iodide and
  tyrosine residues
• Thyroid hormones
• These hormones are released into the peripheral
  circulation when required through a negative
  feedback system
• T4 is broken down in the peripheral circulation
  into T3 and r-T3
• T3 and r-T3 should be found in the same
  proportions

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What is hypothyroidism?

• Hypothyroidism occurs in patients where there are
  insufficient levels of thyroid hormones
• There are two types
• Congenital hypothyroidism
• Acquired hypothyroidism

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Congenital hypothyroidism

• Primary hypothyroidism
• This is the most common cause of congenital
  hypothyroidism
• Secondary hypothyroidism
• This occurs when the pituitary gland produces
  insufficient amounts of TSH (thyroid stimulating
  hormone)

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Acquired hypothyroidism

• Acquired hypothyroidism is caused by the thyroid
  gland being damaged (e.g. cancer therapy etc)
• Primary hypothyroidism
• The most common cause is Hashimotos disease
• Secondary hypothyroidism
• Is caused by a pituitary tumour
• Tertiary hypothyroidism
• Is caused by a hypothalmic tumour

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Signs Symptoms

• Weakness/ Lethargy/ Slowness
• Cold intolerance
• Memory loss
• Weight gain
• Dry skin
• Change in voice (deepening)
• Mild anaemia/pernicious anaemia
• Effusions pericardial, pleural, peritoneal
  joint spaces

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PART 2

• TASKS
• ANALYSE MAS RESULTS
• ARE THEY CONSISTENT WITH HYPOTHYROIDISM?

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MRS MAS TFT RESULTS
  At 35 days tested strongly positive peroxidase
antibody ? thyroxine commenced
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SUMMARY OF MAS TFTS POST OP

• DAY 6
• Decreased FT4, elevated TSH
• Day 14
• Decreased FT4, elevated TSH
• Day 35
• Normal FT4, elevated TSH

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GRAPH SHOWING RELATIONSHIP OF MAS TSH TO FT4
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DIAGNOSING MRS MA

• WHAT DO WE KNOW
• MA does have elevated TSH ?suggests
  hypothyroidism
• Most common cause of HT in the US is Hashimotos
  Disease.
• MA is middle aged female ? likely candidate for
  Hashimotos
• Strongly positive peroxidase antibody (an
  autoantibody)
• Positive autoantibodies in 95 of cases of
  Hashimotos
• Advanced Hashimotos low FT4, high TSH
• MA low FT4, elevated TSH BUT later normal FT4.

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GRAPH SHOWING RELATIONSHIP OF MAS TSH TO FT4
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POSSIBLITIES FOR MRS MA
 
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CONCLUSION

• ve antibody strongly suggests Hashimotos
• But why the drastic changes in TFTs?
• ?MA has a subclinical hypothyroidism disorder
  (typical of early Hashimotos disease)
• Unknown to patient since asymptomatic.
• During her illness she suffered from NTI which
  decreased her FSH and T4
• On recovering, levels return to her regular
  levels of subclinical hypothyroidism.

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TO TREAT OR NOT TO TREAT

• During stay at hospital (NTI) ? controversial
• Are patients TSH values decreasing and T4 values
  increasing?
• If yes ? no need to treat.
• If no ? controversial but guidelines recommend
• treat if TSHgt10mU/L or
• if TSH 5-10 mU/L and ve peroxidase Ab / goitre
  (AACE, 2002).

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WHY DO WE TREAT EVEN IF ASYMPTOMATIC

• Avoid progression to overt hypothyroidism (3-20,
  increased if ve Ab)
• Decrease
• CV effects,
• dyslipidemia,
• neuropsychiatric events

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The Results
6 days post-op 2 wks post-op 5 wks post-op Normal Range
T4 5 8 11 10-25 pmol/L
T3 lt 1 3 8 pmol/L
TSH 6 11 7 0.4 4 mU/L
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What are the likely explanations for this series
of TFT results?

• Hashimotos Thyroiditis
• Subclinical Hypothyroidism
• Euthyroid Sick Syndrome (aka NTI)

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1. Hashimotos Thyroiditis

• Refers to autoimmune disorders of the thyroid
  gland.
• Antibodies and WBCs damage the thyroid gland
• Due to excess WBCs and fluid in the thyroid
  gland a goitre is produced, leading to
  destruction of thyroid cells ? HYPOTHYROIDISM
• Destruction of thyroid gland decreases T4
  production and as a results TSH increases which
  makes the goiter even larger.
• In this condition thyroid antibodies and usually
  low however this is not the case for Ms MA
  (..strongly positive peroxidase antibody)

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2. Subclinical Hypothyroidism

• Scenario characterised by a normal serum T4 and
  moderately high TSH levels. (N.B T3 levels are
  usually normal and thus dont provide much extra
  in terms of diagnosis)
• Serum antithyroid antibodies against peroxidase
  are usually, but not always, positive (as
  witnessed by Ms MA)

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3. Euthyroid Sick Syndrome

• Situation whereby patients with other
  non-thyroidal illnesses may have abnormal TFTs,
  mainly because of decreased peripheral conversion
  of T4 to T3 and decreased binding to TBG.
• Clinical features of Euthyroid Sick Syndrome
  include low T3 normal or low T4 and variable TSH.

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Describe analytical principles behind free T4
measurement
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What is free T4?

• Free T4 or thyroxine is unbound and hence
  biologically active and responsible for the
  regulation of thyroid function through the
  pituitary feedback mechanism. Besides being a
  more specific indicator of thyroid function than
  total T4, free T4 is not subject to the
  spontaneous fluctuations or drug-induced changes
  that occur with total T4.

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Principles of free T4 measurement

• Principle methods for measuring free T4 is as
  follows
• Equilibrium Dialysis (ED)
• Equilibrium Dialysis-FT4 measured directly by a
  sensitive RIA in the dialysate
• Ultrafiltration
• Direct Immunoassays
• Free T4 index method

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Free T4 determination by Equilibrium Dialysis

• The serum is put inside the cylinder where bound
  is separated from free hormone.
• The gold standard for measuring free T4 is
  overnight equilibrium dialysis of serum
  containing 125I-T4. -The percentage of free T4 is
  calculated by determining the total counts in the
  dialysate divided by the total 125I-T4 added to
  the serum multiplied by the total T4 concentration

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Free T4 determination by Ultrafiltration

• Ultrafiltration has almost the same principle as
  ED.
• The serum has labelled T4 and this is filtered
  against a protein free buffer.
• Free T4 concentration is worked out as
  radiolabelled iodine is inversely proportional to
  free T4 concentration.

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Free T4 determination by Immunoassays

• There is a one step and two step method for
  calculating free T4 concentration by immunoassay
  (IAS).
• Step 1 method This method is based on the
  assumption that structurally modified and
  labelled analogues of T4 will not bind to serum
  thyroid hormone binding proteins but will compete
  with free T4 for binding to the T4 antibody
  introduced in the assay.

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Free T4 determination by Immunoassays (cont)

• Radio-labelled T4 analogue is added to anti-T4
  antibody.
• The serum is added to the anti-T4 antibody
  simultaneously.
• Competition occurs and both T4 is removed.
• Then you measure proportion of labelled T4 that
  became antibody bound.

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Step 2 method

• Free T4 in patient serum is removed by binding to
  T4 antibody, which is attached to a solid phase.
• The serum is then removed.
• Next, Radio-labelled 125I-T4 is incubated with
  the solid phase that has unbound sites available.
• Radio-labelled 125I-T4 is removed and activity is
  quantified.

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Free T4 determination by Index method

• The index method requires two independent tests.
• One measuring total serum T4 and the other
  measuring thyroid hormone-binding ratio or T3
  resin uptake.
• The free T4 index is then calculated using the
  total T4 and the TBG level, the thyroid binding
  ratio, or T3 resin uptake.
• The index is directly proportional to the free T4
  level.

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Advantages and Disadvantages

• Equilibrium Dialysis
• Advantages Gold standard, accurate
• Disadvantages Time consuming, expensive,
  technically demanding
• Immunoassay
• Advantages quick compared to ED, higher accuracy
  than ED, regularly available
• Disadvantages expensive, procedure has to be
  carried out precisely

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What factors can effect T4?

• Age
• Infection
• Stress
• Pregnancy

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What Drugs can effect T4?

• Amiodarone structurally resembles thyroxine
  molecule. Decreases serum T4 levels
• Phenytoin and Carbamazepine accelerate clearance
  of T4 and depress FT4
• Propranolol elevation of serum free T4 levels
• Lithium inhibits T4 release.
• Glucocorticoids suppress T4 levels