40 Questions
What should be considered first when interpreting confusing thyroid function test results?
Revisiting the clinical context and considering potential confounding factors
What could cause confusion in thyroid function test results despite the clinical picture?
Raised thyroid hormones (TH) with non-suppressed thyrotropin (TSH)
What should be screened for to avoid unnecessary further investigation and/or treatment in cases of assay interference?
Laboratory artefacts in commonly used TSH or TH immunoassays
What is the first step once potential confounding factors have been excluded in cases of confusing thyroid function test results?
Screening for rare genetic and acquired disorders of the HPT axis
What is the primary concern when interpreting thyroid function test results?
Assay interference
What are the most commonly requested laboratory investigations in both primary and secondary care?
Thyroid function tests (TFTs)
What is the focus of the article 'Pitfalls in the measurement and interpretation of thyroid function tests'?
Measurement and interpretation of thyroid function tests
Where is the Metabolic Research Laboratories located?
Wellcome Trust – MRC Institute of Metabolic Science, University of Cambridge
What should be screened for to avoid unnecessary further investigation and/or treatment in cases of confusing thyroid function test results?
Assay interference
What is the role of thyroid function tests (TFTs) in healthcare?
To help in diagnosing and managing thyroid disorders
What can cause a falsely high TSH in an immunoradiometric assay?
Presence of a human anti-animal antibody capable of cross-linking capture and detection antibodies
What effect does a human anti-animal antibody have if it blocks TSH binding to either capture or detection antibodies?
Causes a falsely low TSH readout
How does the use of several different detection antibodies improve assay sensitivity?
By further improving assay sensitivity
What is the purpose of immobilizing TSH to the solid phase in an immunoradiometric assay?
To ensure good separation between bound and unbound label
What can a human anti-animal antibody capable of cross-linking capture and detection antibodies cause in an immunoradiometric assay?
Positive interference, leading to a falsely high TSH
What impact does the presence of human anti-animal antibodies have on TSH measurement?
Can cause both positive and negative interference
Which of the following can cause transient disturbance of thyroid function?
Inorganic iodide
What can lead to persistent FT4 elevation?
Amiodarone inhibiting T4 / T3 conversion
Which medication can lead to hypothyroidism but self-limiting thyroiditis in a small number of patients?
Lithium
What can suppress pituitary TSH secretion?
Octreotide and lanreotide
Which of the following can reduce risk of artifactual hyperthyroxinaemia?
Delayed blood sampling after heparin injection
Which type of assay are most commercially available TSH assays based on?
Immunometric two-site format
What is the primary reason for the challenges in interpreting thyroid function tests (TFTs)?
Confounding factors such as pregnancy, illness, or medication usage
What is the percentage of T3 secretion by the thyroid gland in the euthyroid state?
10-15%
What is crucial for establishing the correct diagnosis in patients presenting with anomalous TFTs?
Sound knowledge of HPT axis physiology and TH action
What should be systematically screened for to avoid unnecessary investigation or treatment due to assay interference?
Laboratory artefacts in TSH or TH immunoassays
What remains relatively constant throughout life and reflects the 'set-point' of the HPT axis in an individual?
T4 and T3 concentrations
In cases where anomalies persist, what should be considered as potential causes?
Resistance to thyroid hormone (RTH) or thyrotropinoma (TSHoma)
Which deiodinase mediates peripheral $T4$ to $T3$ conversion?
DIO2
Which thyroid hormone receptor isoform is highly expressed in the liver and kidney?
TRb1
What is the principal bioactive hormone among thyroid hormones?
$T3$
Which type of deiodinase converts $T4$ to reverse $T3$ and $T3$ to $T2$?
DIO3
Which thyroid hormone receptor gene exists on chromosome 17?
THRA
What is recommended as a frontline screening test for thyroid dysfunction?
TSH measurement
Which enzyme converts T4 to T3?
Type 1 deiodinase
What is the principal bioactive hormone mediated by thyroid receptors in the nucleus of target cells?
T3
What are the alternate splicing products of the thyroid hormone receptor genes THRA and THRB?
TRa1, TRa2, TRb1, and TRb2
What do thyroid receptors bind to in target genes?
Thyroid hormone response elements (TREs)
Which hormone is recommended as a frontline screening test for thyroid dysfunction?
TSH
What can confound interpretation of thyroid hormone concentrations?
Changes in circulating binding proteins
Study Notes
Interpreting Thyroid Function Tests
- Thyroid function tests (TFTs) can present challenges in interpretation, especially in cases where results seem discordant with the clinical picture.
- It is important to consider potential confounding factors such as pregnancy, illness, or medication usage before further investigation.
- Laboratory artefacts in TSH or TH immunoassays should be screened for to avoid unnecessary investigation or treatment due to assay interference.
- Rare genetic and acquired disorders of the hypothalamic–pituitary–thyroid (HPT) axis, such as resistance to thyroid hormone (RTH) or thyrotropinoma (TSHoma), should be considered in cases where anomalies persist.
- Minor perturbations of thyroid status can be challenging to diagnose clinically and require accurate measurement and interpretation of TH and TSH concentrations.
- In most cases, TFT results are straightforward and consistent with the clinical impression of thyroid status.
- A structured approach to further investigation is required for cases where the interpretation of TFTs is more challenging.
- Clinical reassessment of thyroid status and consideration of possible confounding factors can often identify the cause of anomalous TFTs.
- Interference in TH or TSH assays should be systematically screened for, and specialist laboratory workup may be necessary.
- A sound knowledge of HPT axis physiology and TH action is crucial for establishing the correct diagnosis in patients presenting with anomalous TFTs.
- TH production is tightly regulated by hypothalamic thyrotropin releasing hormone (TRH) and pituitary TSH. T4 and T3 concentrations remain relatively constant throughout life and reflect the 'set-point' of the HPT axis in an individual.
- In the euthyroid state, the thyroid gland secretes 85-90% T4 and 10-15% T3, both heavily protein bound to thyroxine binding globulin (TBG), albumin, and transthyretin.
Thyroid Hormone Action and Regulation
- Transporters govern thyroid hormone (TH) efflux from the thyroid gland, balancing secreted T4 and T3
- Intracellular deiodinases (DIOs) regulate TH action: Type 1 DIO converts T4 to T3, DIO2 mediates negative feedback regulation, and DIO3 limits TH action
- T3 is the principal bioactive hormone, mediated by thyroid receptors (TR) in the nucleus of target cells
- Two thyroid hormone receptor genes (THRA, THRB) undergo alternate splicing to generate TRa1, TRa2, TRb1, and TRb2 isoforms with differing tissue distributions
- TRs bind to thyroid hormone response elements (TREs) in target genes, exerting opposing effects depending on T3 binding
- Changes in thyroid status are associated with concordant changes in TH and TSH concentrations
- Population reference ranges for TH are broad, but individual variations are narrow
- TSH is recommended as a frontline screening test for thyroid dysfunction, but screening exclusively with TSH may lead to misdiagnosis
- Laboratories now routinely offer combination screening with both T4 and TSH measurement
- Changes in circulating binding proteins can confound interpretation of TH concentrations
- Patients receiving exogenous thyroid hormone replacement therapy may report ongoing symptoms despite optimal thyroid function tests
- Heparin therapy can lead to FT4 (and FT3) elevation, affecting TH measurement
Test your knowledge of thyroid function tests (TFTs) with this quiz. Explore the interpretation of results for euthyroidism, hypothyroidism, and hyperthyroidism, as well as the complexities of discordant test results in certain patient subgroups.
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