Thyroid function

tests(TFTs)
Yutapong Raruenrom

Introductions

TFTs: a daily necessity in virtually every

field of medical practice
- Screening a neonate for congenital
hypothyroidism
- Evaluating a patient with nonspecific
complaints
- Evaluating a woman with infertility
- Assessing a thyroid nodule

Iodine balance
- Synthesis of thyroid hormones require
iodine
- Iodide is actively concentrated in the
thyroid gland, salivary glands, gastric
glands, lacrimal glands, mammary glands,
and choroid plexus
- The total iodide content of the thyroid
gland averages 7500 g, virtually all of
which is in the form of iodothyronines
-In the steady state, 70 to 80 g of iodide, or
about 1% of the total, is released from the
gland daily

Iodine balance

An average of 400 g of iodide/person

ingested daily in the US.

n the steady state, virtually

he same amount, 400 g,
excreted in urine.

70-80 g of Iodine is uptaken

y the thyroid and the same
mount is excreted daily.

Thyroid hormone
synthesis

Thyroid hormones
- T4 and T3 in the bloodstream almost entirely
bind to proteins
- Protein binding of circulating T4 and T3:
70%
bound to thyroxine-binding
globulin(TBG)
10%-15% bound to transthyretin (TTR)
15%-20% bound to albumin
3%
bound to lipoproteins
- TBG is synthesized in the liver and binds one
molecule of T4 or T3

Thyroid hormones
Free hormone
- 0.03% of total plasma T4
- 0.3% of total plasma T3
Free T3 is biologically active and
mediates the effects of thyroid hormone
on peripheral tissues
: 3-4 times more potent than T4

Difference between T3
and T4

TFTs: Which test to order?

- Choose Free hormone over Total

hormone since its results are less int
erfered by protein binding

Clinical uses of TFTs

Screening for thyroid disease
- May use TSH as an initial test
It is both sensitive and specific for both
hyperthyroidism and hypothyroidism
- If abnormal continue to test FT3 or FT4

Conditions when TSH alone can be

misleading
Common
- Recent treatment of thyrotoxicosis
- Pituitary disease
- Non-thyroidal illness
Rare
- TSH-secreting pituitary tumor
- Thyroid hormone resistance

Clinical uses of TFTs

Suspected hyperthyroidism
Strategy 1
FT4 then TSH
Will miss Graves disease and toxic
adenoma (which are usually T3
toxicosis)
Strategy 2
TSH then FT3 or FT4

Clinical uses of TFTs

Suspected hypothyroidism
- In patients with hypothyroid symptoms who
lack a history of known thyroid or pituitary
disease: use TSH as the initial screening with
confirmation of diagnosis provided by
subsequent determination of the FT4 level
- In settings that are likely to encounter
complicated cases : testing TSH, FT3 and
FT4 all together is not unreasonable

Interpretation of TFTs

Low TSH Raised FT3 or Raised

FT4
Common
FT3 or FT4
Primary hyperthyroidism:
Graves disease
Multinodular goitre
Toxic nodule

TSH

Low TSH Raised FT3 or Raised

FT4
Relatively common
FT3 or FT4
with low radioiodine uptake
Transient thyroiditis:
Postpartum
Postviral infection
(granulomatous, subacute, De Quervains)

TSH

Rarewith a low radioiodine uptake

Thyroxine ingestion
Ectopic thyroid tissue or struma ovarii
Amiodarone therapy

Low TSH Raised FT3 or Raised

FT4
Rarewith a positive
FT3 or FT4
pregnancy test
Gestational thyrotoxicosis with
hyperemesis gravidarum
Hydatidiform mole
Familial gestational hyperthyroidism

TSH

Low TSH Normal FT3 or

Normal FT4
Common
Subclinical hyperthyroidism
Thyroxine ingestion

FT3 or
FT4

TSH

Rare
Steroid therapy
Dopamine and dobutamine infusion
Non-thyroidal illness

Low or Normal TSH Low FT3 or

Low FT4
Common
Non-thyroidal illness
Recent treatment for
hyperthyroidism
(TSH remains suppressed)

TSH

Rare
Pituitary disease
(secondary hypothyroidism)
Congenital TSH or TRH deficiency

TSH FT3 or
FT4

Raised TSH Low FT3 or Low FT4

Primary hypothyroidism

TSH

Common
Chronic autoimmune thyroiditis
Post radioiodine
Post thyroidectomy
FT3 or FT4
Hypothyroid phase of transient thyroiditis

Raised TSH Low FT3 or Low FT4

Primary hypothyroidism
Rare (anti-TPO negative,
no RAI or surgery)

TSH

Post EBRT to the neck

Drugs: amiodarone, lithium,
interferons, interleukin-2
FT3 or FT4
Iodine deficiency
Goitrogens
Amyloid goitre (large, firm goitre with
systemic amyloidosis)

Raised TSH Low FT3 or Low FT4

Primary hypothyroidism
Congenital
thyroid tissue absent
Thyroid dysgenesis

TSH

Congenitalthyroid tissue present

FT3 or FT4
Iodine transport defects
low radioiodine uptake or saliva iodine
Iodine organification defect

Raised TSH Normal FT3 or

Normal FT4
Common
Subclinical autoimmune
hypothyroidism

TSH

FT3
or FT4

Rare
Heterophile (interfering) antibody
Intermittent T4 therapy for hypothyroidism
Drugs: amiodarone, sertraline,
cholestyramine
Recovery phase after non-thyroidal illness

Raised TSH Normal FT3 or

Normal FT4
Congenital
TSH-receptor defects
Resistance to TSH associated with
other (unspecified) defects

TSH

FT3
or FT4

Normal or Raised TSH Raised

TSH
FT3 or Raised FT4

FT3
or FT4

Rare
TSH
Intermittent T4 therapy
T4 overdose
Resistance to thyroid hormone
TSH secreting pituitary tumour
(hyperthyroid)
Acute psychiatric illness (first 13 weeks)

References
Colin M Dayan. Interpretation of thyroid
function tests. Lancet 2001; 357: 61924
Cooper, David S.Medical Management of
Thyroid Disease. 2nd. New York: Informa Hea
lthcare USA, 2008. 1-27. Print
Kronenberg, Henry, and Robert
Hardin.Williams textbook of endocrinology.
W.B. Saunders Company, 2008. eBook