Thyroid Function Interpretation Flashcards
Possible tests for evaluation of thyroid function
- Thyroid function test - TSH, fT4
- Total T4 (tT4)
- Total T3 (tT3) and free T3 (fT3)
- Reverse T3 (RT3)
- Thyroid autoantibodies - anti-TPO, anti-TG, TRAb
- Thyroglobulin (TG)
- Calcitonin
- RAUI
- Thyroid scan
What are the significance of TSH
TSH is the primary regulator of thyroid hormone synthesis and secretion.
- Log-linear relationship between TSH and fT4 levels
- Small changes in T4 production results in large changes in TSH - Abnormal TSH appears way before T4 and T3 levels become deranged
- Diurnal pattern - highest TSH late afternoon to evening
- Low TSH -> hyperthyroidism
- High TSH -> hypothyroidism
TSH levels may not accurately reflect thyroid function in:
- Pituitary-hypothalamic disorders
- Non-thyroidal illness
- Glucocorticoid use
- Dopamine
- Mitotane
- Somatostatin analogues
How TSH is used to manage patients on thyroid hormone therapy?
Replacement goal - maintain TSH within reference range
Suppression goal - maintain TSH low-normal or slightly low; undetectable in metastatic thyroid cancer
What is the significance of measuring total T4 and T3 assays?
99.98% circulating T4 and 99.7% T3 are bound to proteins (thyroxine binding globulin TBG), pre-albumin (transthyretin) and albumin.
–> Altered by protein binding disorders
Total T4 and T3 assays measure total amounts of T4 and T3 (protein bound and free) in circulation
What is the function of free thyroid hormone assays?
How are free thyroid hormones tested?
What are the pitfalls of fT3 measurement?
fT4 and fT3 assays determine unbound, bioactive thyroid hormones in circulation.
Test categories
1. Equilibrium dialysis - not affected by thyroid hormone binding protein abnormalities
2. Analogue assays - variably affected by protein binding
fT3 measuremenet remains less accurate
–> Total T3 measurement preferred
Role of reverse T3 (RT3)
RT3 - inactive thyroid metabolite with 100-fold lower affinity for T3 receptor
Useful in distinguishing NTI vs central hypothyroidism
- RT3 may rise significantly in non-thyroidal illness due to reduced D1 activity
- RT3 may drop significantly with enhanced D1 activity in hypothyroidism
Thyroid hormone-binding protein disorders
- Pregnancy
- Estrogen use
- Congenital TBG excess
- Congenital TBG deficiency
- Familial dysalbuminaemic hyperthyroxinaemia (FDH) - enhanced albumin affinity for T4 resulting in high tT4 but not T3
T3 resin uptake (T3RU) may help distinguish protein binding disorders from true thyroid disease
- T3RU inversely proportional to protein-binding capacity
-> T3RU low when T4 binding increased
-> T3RU high when protein binding reduced
Thyroid autoantibodies
- Anti-TPO and anti-TG: Hashimoto’s thyroiditis
(anti-TPO moresensitive) - TSH receptor Ab (TRAb) and TSIg: Graves
When is thyroglobulin (TG) measurement useful?
TG - major iodoprotein constituent of thyroid follicles
- Diagnosis of diseases
- Mildy increased in thyroid diseases
- Marked increased in thyroid cancer and destructive thyroiditis (subacute, postpartum, silent) - Monitoring of thyroid cancer
- TG should be undetectable when thyroid cancer treated
- Normal or rising TG suggest residual or metastatic thyroid cancer - NOT USEFUL when anti-TG is positive
- interferes with TG measurement
When is calcitonin measurement useful?
Calcitonin secreted by thyroid parafollicular C cells
- Diagnosis of medullary carcinoma
- Elevated in medullary carcinoma of thyroid and C-cell hyperplasia
Radioactive iodine uptake (RAIU) test
Thyroid follicular cells have sodium iodine symporters that bring iodine into cells for thyroid hormone synthesis.
- RAIU measure activity of symporters
RAUI - uses I-131 or I-123 to assess quantitatively functional status of thyroid gland
- Oral radioisotope given, followed by measurement of radioactivity of thyroid in 4-24 hours (2 measurements: 4-6h and 24h)
Normal: 10-25% uptake - varies with country
Useful in diagnosis of thyrotoxicosis:
- High RAIU thyrotoxicosis (hyperthyroidism)
- Low RAIU thyrotoxicosis - low to absent uptake in destruction or extrathyroidal source
What is a thyroid scan?
When is thyroid scan indicated?
Thyroid scan - 2D image distribution of isotope trapping within thyroid gland
- Uniform distribution: Graves
- Patchy: TMNG
- Unifocal = nodule toxic adenoma
- Distinguish high-RAIU thyrotoxicosis with low TSH levels
- Graves - diffuse tracer uptake
- Toxic multinodular goitre - multiple discrete areas of increased uptake
- Solitary toxic adenoma - single area of intense intake - NOT useful in low RAIU thyrotoxicosis
Interference of thyroid function test
- Biotin - reagent used in many assays (TSH, fT4, TRAb) -> titrated at precise standard amount
- Biotic supplements, cosmetics and hair conditioners may contain high biotin -> high circulating biotin level -> falsely high assays and erroneous diagnosis
- Repeat TFT 2 days after cessation of biotin supplements - HAMAs - exposure to rodents (lab workers, farmers, homeless) - interferes with TSH and TG
