CASE A- CASE A- THYROID THYROID

FUNCTION FUNCTION TESTSTESTS

MYLINH TRUONG. JEN CRAZE, KELLY STEWART, MYLINH TRUONG. JEN CRAZE, KELLY STEWART,

CASE ACASE A

Ms YWMs YW Age: early 20s Age: early 20s History of weight loss, heat intolerance, History of weight loss, heat intolerance,

nervousness, increased bowel frequency nervousness, increased bowel frequency and oligomenorrhoea.and oligomenorrhoea.

Current symptoms: tremor, sinus Current symptoms: tremor, sinus tachycardia, proximal myopathy, large tachycardia, proximal myopathy, large goitre (14cm), mild proptosis w/out goitre (14cm), mild proptosis w/out diplopia.diplopia.

What is What is THYROTOXICOSISTHYROTOXICOSIS??

Thyrotoxicosis Thyrotoxicosis refers to the refers to the hypermetabolism and increased hypermetabolism and increased sympathetic nervous activity associated sympathetic nervous activity associated with increased concentrations of free T4 with increased concentrations of free T4 and T3 hormones, irrespective of the and T3 hormones, irrespective of the source.source.

Symptoms can be vague and the clinical Symptoms can be vague and the clinical presentation can range from minimal presentation can range from minimal symptoms to life-threatening thyroid storm.symptoms to life-threatening thyroid storm.

Clinical ManifestationsClinical Manifestations

Amenorrhoea or Amenorrhoea or oligomenorrhoea.oligomenorrhoea.

Heat intoleranceHeat intolerance Excessive sweatingExcessive sweating Weight lossWeight loss Fatigue and appetite Fatigue and appetite

changeschanges PalpitationsPalpitations

Atrial fibrillationAtrial fibrillation CCFCCF Fine tremorFine tremor Exophthalmos Exophthalmos GoitreGoitre Muscle weaknessMuscle weakness DiarrhoeaDiarrhoea OsteoporosisOsteoporosis

GRAVE’S DISEASEGRAVE’S DISEASE

Most common cause of hyperthyroidism among Most common cause of hyperthyroidism among patients btw 20-50 yrs of agepatients btw 20-50 yrs of age..

More common among womenMore common among women.. Thyrotoxicosis associated with Grave’s disease Thyrotoxicosis associated with Grave’s disease

is due to stimulation of TSH receptors by TSH is due to stimulation of TSH receptors by TSH receptor antibodies ->excess hormone receptor antibodies ->excess hormone production and secretionproduction and secretion..

S&S: goitre, opthalmopathy, dermopathy.S&S: goitre, opthalmopathy, dermopathy.

TFT resultsTFT results

Initially:Initially: FT4 FT4 6565 (10-25) pmol/L(10-25) pmol/L FT3FT3 2020 (3-8) pmol/L(3-8) pmol/L TSH TSH suppressedsuppressed

CarbimazoleCarbimazole 15 mg tds for 1 month15 mg tds for 1 month FT4 reduced to 30 pmol/LFT4 reduced to 30 pmol/L

REDUCED dose to 10mg bd REDUCED dose to 10mg bd After 3 mths: FT4 is 9 pmol/L and TSH is suppressed After 3 mths: FT4 is 9 pmol/L and TSH is suppressed

Why has FT4 Why has FT4 decreased but decreased but symptoms of symptoms of

thyrotoxicosis still thyrotoxicosis still remain and TSH is remain and TSH is still suppressed?still suppressed?

??????????

After correction of hyperthyroidism, After correction of hyperthyroidism, TSH may fail to respond (months) to TSH may fail to respond (months) to a fall in FT4 ->if this time lag is a fall in FT4 ->if this time lag is overlooked, the patient may be over overlooked, the patient may be over treated, resulting in biochemical treated, resulting in biochemical hypothyroidism with clinical hypothyroidism with clinical thyrotoxicosis.thyrotoxicosis.

T4 and T3 may need to be measured.T4 and T3 may need to be measured.

What additional What additional TFTs are required in TFTs are required in

light of YW light of YW suppressed TSH?suppressed TSH?

Additional TFTsAdditional TFTs

FTI - Free thyroxine indexFTI - Free thyroxine index T4T4 T3T3

What TFTs should be What TFTs should be measured in patients measured in patients receiving antithyroid receiving antithyroid

treatment?treatment?

MonitoringMonitoring

Total T3Total T3 Total T4Total T4 Free T4Free T4 Thyroid scanThyroid scan TSAbTSAb

““Describe the analytical Describe the analytical principles behind the principles behind the

sensitive TSH assay and its sensitive TSH assay and its advantages and advantages and

disadvantages compared to disadvantages compared to the clinical utility of this the clinical utility of this

measurement.”measurement.”

Measurement of TSHMeasurement of TSH

Ivery, 2003 – lecture notes

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

The sensitive TSH assayThe sensitive TSH assay Also known as sTSHAlso known as sTSH All utilise antibodies for the All utilise antibodies for the β subunit of TSH. The α subunit is β subunit of TSH. The α subunit is

common for TSH, FSH, LH and CGcommon for TSH, FSH, LH and CG Mid-1980s, 2Mid-1980s, 2ndnd generation immunometric assays developed with generation immunometric assays developed with

lower detection rate than RIA methods – enabled differentiation lower detection rate than RIA methods – enabled differentiation between hyperthyroid patients with subnormal TSH and normal between hyperthyroid patients with subnormal TSH and normal subjectssubjects

Third generation assays, recently developed – assay functional Third generation assays, recently developed – assay functional sensitivities reported as 0.01-0.02 mU/lsensitivities reported as 0.01-0.02 mU/l

Sandwich assays with two antibodies. The use of the second Sandwich assays with two antibodies. The use of the second antibody gives better sensitivity.antibody gives better sensitivity.

Sensitive chemiluminescent enyzymeimmunoassay – analytical Sensitive chemiluminescent enyzymeimmunoassay – analytical sensitivity of 0.0016 mU/lsensitivity of 0.0016 mU/l

The clinical TSH assayThe clinical TSH assay

RIA methodRIA method Doesn’t have the sensitivity to detect Doesn’t have the sensitivity to detect

much below euthyroidmuch below euthyroid Currently being phased outCurrently being phased out

Advantages/disadvantagesAdvantages/disadvantages

22ndnd generation permits detection of generation permits detection of TSH levels below euthyroidTSH levels below euthyroid

33rdrd generation permits differentiation generation permits differentiation between complete suppression and between complete suppression and incomplete suppression of pituitary incomplete suppression of pituitary TSH outputTSH output

Clinical utility of TSH Clinical utility of TSH measurementmeasurement

TSH Thyroxine

Subclinical hypothyroidism

Elevated Normal

Subclinical hyperthyroidism

Undetectable Normal

Overt hypothyroidism

Elevated Low

Overt hyperthyroidism

Undetectable Elevated

Helfand et al, 1998

Subnormal TSH…Subnormal TSH…

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

Early detection and Early detection and monitoringmonitoring

The early detection of thyroid dysfunction if The early detection of thyroid dysfunction if important to.. important to.. ensure the necessary treatment is commenced as soon as ensure the necessary treatment is commenced as soon as

possiblepossible patients with subclinical thyroid dysfunction are monitored and patients with subclinical thyroid dysfunction are monitored and

that any changes to their status are detected and treated as that any changes to their status are detected and treated as early as possible.early as possible.

The clinical TSH assay does not have enough sensitivity to The clinical TSH assay does not have enough sensitivity to detect these small changes and cannot detect TSH levels below detect these small changes and cannot detect TSH levels below euthyroid.euthyroid.

It is important to detect subnormal levels of TSH as well as high It is important to detect subnormal levels of TSH as well as high levels.levels.

Kasagi et al, 1999Kasagi et al, 1999

ReferencesReferences Helfand, M. et al Helfand, M. et al Screening for thyroid Screening for thyroid

diseasedisease. Annals of internal medicine, 1998; . Annals of internal medicine, 1998; 129(2):141-143.129(2):141-143.

Ivery, M. Ivery, M. Thyroid function lecture notes. Thyroid function lecture notes. Clinical pathology B, 2003.Clinical pathology B, 2003.

Kasagi, K. et al Kasagi, K. et al Comparison of serum Comparison of serum thyrotrophin concentrations determined by thyrotrophin concentrations determined by a third generation assay in patients with a third generation assay in patients with various types of overt and subclinical various types of overt and subclinical thyrotoxicosis.thyrotoxicosis. Clinical Clinical EndocrinologyEndocrinology, 1999; , 1999; 50(2):185-189.50(2):185-189.