Thyroid function tests

Thyroid function tests
Intervention
MeSH	D013960

Thyroid function tests (TFTs) is a collective term for blood tests used to check the function of the thyroid.^[1]

TFTs may be requested if a patient is thought to suffer from hyperthyroidism (overactive thyroid) or hypothyroidism (underactive thyroid), or to monitor the effectiveness of either thyroid-suppression or hormone replacement therapy. It is also requested routinely in conditions linked to thyroid disease, such as atrial fibrillation and anxiety disorder.

A TFT panel typically includes thyroid hormones such as thyroid-stimulating hormone (TSH, thyrotropin) and thyroxine (T4), and triiodothyronine (T3) depending on local laboratory policy.

Thyroid hormones

Thyroid-stimulating hormone

Thyroid-stimulating hormone (TSH, thyrotropin) is generally elevated in hypothyroidism and decreased in hyperthyroidism.^[2]

Reference ranges:

Patient type	Lower limit	Upper limit	Unit
Adults - standard range	0.3^[3], 0.4^[4], 0.5^[5], 0.6^[6]	3.0 , 4.0^[3], 4.5^[4], 6.0^[5]	mIU/L or μIU/mL
Adults - optimal range	0.3^[7] , 0.5^[8]	2.0^[8] , 3.0^[7]	mIU/L or μIU/mL
Infants	1.3^[9]	19^[9]	mIU/L or μIU/mL

Total thyroxine

Total thyroxine (Total T₄) is generally elevated in hyperthyroidism and decreased in hypothyroidism.^[2] It is usually slightly elevated in pregnancy secondary to increased levels of thyroid binding globulin (TBG).^[2]

Reference ranges:

Lower limit	Upper limit	Unit
4^[10], 5.5^[4]	11^[10], 12.3^[4]	μg/dL
60^[10]^[11]	140^[10], 160^[11]	nmol/L

Free thyroxine

Free thyroxine (Free T₄) is generally elevated in hyperthyroidism and decreased in hypothyroidism.^[2]

Patient type	Lower limit	Upper limit	Unit
Normal adult	0.7^[12] ,0.8^[4]	1.4^[12], 1.5^[4], 1.8^[13]	ng/dL
Normal adult	9^[14]^[3], 10^[10], 12 ^[11]	18^[3]^[14] , 23^[11]	pmol/L
Infant 0–3 d	2.0^[12]	5.0^[12]	ng/dL
Infant 0–3 d	26^[14]	65^[14]	pmol/L
Infant 3–30 d	0.9^[12]	2.2^[12]	ng/dL
Infant 3–30 d	12^[14]	30^[14]	pmol/L
Child/Adolescent 31 d – 18 y	0.8^[12]	2.0^[12]	ng/dL
Child/Adolescent 31 d – 18 y	10^[14]	26^[14]	pmol/L
Pregnant	0.5^[12]	1.0^[12]	ng/dL
Pregnant	6.5^[14]	13^[14]	pmol/L

Total triiodothyronnine

Total triiodothyronine (Total T₃) is generally elevated in hyperthyroidism and decreased in hypothyroidism.^[2]

Reference ranges:

Test	Lower limit	Upper limit	Unit
Total triiodothyronine	60^[4], 75^[10]	175^[10], 181^[4]	ng/dL
Total triiodothyronine	0.9^[3] , 1.1^[10]	2.5^[3] , 2.7^[10]	nmol/L

Free triiodothyronnine

Free triiodothyronine (Free T₃) is generally elevated in hyperthyroidism and decreased in hypothyroidism.^[2]

Reference ranges:

Patient type	Lower limit	Upper limit	Unit
Normal adult	0.2^[10]	0.5^[10]	ng/dL
Normal adult	3.1^[15]	7.7^[15]	pmol/L
Children 2–16 y	0.1^[16]	0.6^[16]	ng/dL
Children 2–16 y	1.5^[15]	9.2^[15]	pmol/L

Calculated indices of free hormones

Free T4 index
Free T3 index

Carrier proteins

Thyroxine-binding globulin

An increased thyroxine-binding globulin results in an increased total thyroxine and total triiodothyronine without an actual increase in hormonal activity of thyroid hormones.

Reference ranges:

Lower limit	Upper limit	Unit
12^[4]	30^[4]	mg/L

Thyroglobulin

Reference ranges:

Lower limit	Upper limit	Unit
1.5^[10]	30^[10]	pmol/L
1^[10]	20 ^[10]	μg/L

Other binding hormones

Transthyretin (prealbumin)
Albumin

Protein binding function

Thyroid hormone uptake

Thyroid hormone uptake (T_uptake or T_{3 uptake}) is a measure of the unbound thyroxine binding globulins in the blood, that is, the TBG that is unsaturated with thyroid hormone.^[2] Unsaturated TBG increases with decreased levels of thyroid hormones. It is not directly related to triiodothyronine, despite the name T_{3 uptake}.^[2]

Reference ranges:

Patient type	Lower limit	Upper limit	Unit
Females	25^[2]	35^[2]	%
In pregnancy	15^[2]	25^[2]	%
Males	25^[2]	35^[2]	%

Other protein binding tests

Thyroid hormone binding ratio (THBR)
Thyroxine-binding index (TBI)

Mixed parameters

Free thyroxine index

The Free Thyroxine Index (FTI or T7) is obtained by multiplying the total T₄ with T_uptake.^[2] FTI is considered to be a more reliable indicator of thyroid status in the presence of abnormalities in plasma protein binding.^[2]

FTI is elevated in hyperthyroidism and decreased in hypothyroidism.^[2]

Patient type	Lower limit	Upper limit	Unit
Females	1.8^[2]	5.0^[2]
Males	1.3^[2]	4.2^[2]

Structure parameters

For special purposes, e.g. in diagnosis of nonthyroidal illness syndrome or central hypothyroidism, derived structure parameters that describe constant properties of the overall feedback control system, may add useful information.^[17]^[18]

Secretory capacity (GT)

Thyroid's secretory capacity (GT) is the maximum stimulated amount of thyroxine the thyroid can produce in one second.^[19] GT is elevated in hyperthyroidism and reduced in hypothyroidism.^[20]

GT is calculated with

$\hat G_T = {{\beta _T (D_T %2B [TSH])(1 %2B K_{41} [TBG] %2B K_{42} [TBPA])[FT_4 ]} \over {\alpha _T [TSH]}}$

$\hat G_T = {{\beta _T (D_T %2B [TSH])[TT_4 ]} \over {\alpha _T [TSH]}}$

$\alpha _T$ : Dilution factor for T4 (reciprocal of apparent volume of distribution, 0.1 l^-1)
$\beta _T$ : Clearance exponent for T4 (1.1e-6 sec^-1)
K₄₁: Dissociation constant T4-TBG (2e10 l/mol)
K₄₂: Dissociation constant T4-TBPA (2e8 l/mol)
D_T: EC₅₀ for TSH (2.75 mU/l)^[19]

Lower limit	Upper limit	Unit
1.41^[19]	8.67^[19]	pmol/s

Web Link

SPINA Thyr: Open source software for calculating GT and GD

Sum activity of peripheral deiodinases (GD)

The sum activity of peripheral deiodinases (GD) is reduced in nonthyroidal illness with hypodeiodination.^[18]

GD is obtained with

$\hat G_D = {{\beta _{31} (K_{M1} %2B [FT_4 ])(1 %2B K_{30} [TBG])[FT_3 ]} \over {\alpha _{31} [FT_4 ]}}$

$\hat G_D = {{\beta _{31} (K_{M1} %2B [FT_4 ])[TT_3 ]} \over {\alpha _{31} [FT_4 ]}}$

$\alpha _{31}$ : Dilution factor for T3 (reciprocal of apparent volume of distribution, 0.026 l^-1)
$\beta _{31}$ : Clearance exponent for T3 (8e-6 sec^-1)
K_M1: Dissociation constant of type-1-deiodinase (5e-7 mol/l)
K₃₀: Dissociation constant T3-TBG (2e9 l/mol)^[19]

Lower limit	Upper limit	Unit
20^[19]	40^[19]	nmol/s

Web Link

SPINA Thyr: Open source software for calculating GT and GD

TSH index

TSH index (TSHI) helps to determine thyrotropic function of anterior pituitary on a quantitative level.^[21]

It is calculated with

$TSHI = LN(TSH) %2B 0.1345 * FT4$ .

Additionally, a standardized form of TSH index may be calculated with

$sTSHI = (TSHI - 2.7)/0.676$ .^[21]

Parameter	Lower limit	Upper limit	Unit
TSHI	1.3^[21]	4.1^[21]
sTSHI	-2^[21]	2^[21]

References

^ Dayan CM (February 2001). "Interpretation of thyroid function tests". Lancet 357 (9256): 619–24. doi:10.1016/S0140-6736(00)04060-5. PMID 11558500. http://linkinghub.elsevier.com/retrieve/pii/S0140-6736(00)04060-5.
^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j ^k ^l ^m ⁿ ^o ^p ^q ^r ^s ^t ^u Military Obstetrics & Gynecology > Thyroid Function Tests In turn citing: Operational Medicine 2001, Health Care in Military Settings, NAVMED P-5139, May 1, 2001, Bureau of Medicine and Surgery, Department of the Navy, 2300 E Street NW, Washington, D.C., 20372-5300
^ ^a ^b ^c ^d ^e ^f Reference range list from Uppsala University Hospital ("Laborationslista"). Artnr 40284 Sj74a. Issued on April 22, 2008
^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j Normal Reference Range Table from The University of Texas Southwestern Medical Center at Dallas. Used in Interactive Case Study Companion to Pathologic basis of disease.
^ ^a ^b Blood Test Results - Normal Ranges Bloodbook.Com
^ The TSH Reference Range Wars: What's "Normal?", Who is Wrong, Who is Right... By Mary Shomon, About.com. Updated: June 19, 2006. About.com Health's Disease and Condition
^ ^a ^b 2006 Press releases: Thyroid Imbalance? Target Your Numbers Contacts: Bryan Campbell American] Association of Clinical Endocrinologists
^ ^a ^b The TSH Reference Range Wars: What's "Normal?", Who is Wrong, Who is Right... By Mary Shomon, About.com. Updated: June 19, 2006
^ ^a ^b Demers, Laurence M.; Carole A. Spencer (2002). "LMPG: Laboratory Support for the Diagnosis and Monitoring of Thyroid Disease". National Academy of Clinical Biochemistry (USA). http://www.nacb.org/lmpg/thyroid_LMPG_PDF.stm. Retrieved 2007-04-13. — see Section 2. Pre-analytic factors
^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j ^k ^l ^m ⁿ ^o Table 4: Typical reference ranges for serum assays - Thyroid Disease Manager
^ ^a ^b ^c ^d van der Watt G, Haarburger D, Berman P (July 2008). "Euthyroid patient with elevated serum free thyroxine". Clin. Chem. 54 (7): 1239–41. doi:10.1373/clinchem.2007.101428. PMID 18593963. http://www.clinchem.org/cgi/content/full/54/7/1239.
^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j Free T4; Thyroxine, Free; T4, Free UNC Health Care System
^ Derived from molar values using molar mass of 776.87 g/mol
^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j Derived from mass values using molar mass of 776.87 g/mol
^ ^a ^b ^c ^d Derived from mass values using molar mass of 650.98 g/mol
^ ^a ^b Cioffi M, Gazzerro P, Vietri MT, et al. (2001). "Serum concentration of free T3, free T4 and TSH in healthy children". J. Pediatr. Endocrinol. Metab. 14 (9): 1635–9. PMID 11795654.
^ Dietrich, J. W., A. Stachon, B. Antic, H. H. Klein, and S. Hering (2008). "The AQUA-FONTIS Study: Protocol of a multidisciplinary, cross-sectional and prospective longitudinal study for developing standardized diagnostics and classification of non-thyroidal illness syndrome." BMC Endocrine Disorders 8 (13). PMID 18851740.
^ ^a ^b Rosolowska-Huszcz D, Kozlowska L, Rydzewski A (2005). Influence of low protein diet on nonthyroidal illness syndrome in chronic renal failure. Endocrine. 27(3):283-8. PMID 16230785
^ ^a ^b ^c ^d ^e ^f ^g Dietrich, J. W. (2002), Der Hypophysen-Schilddrüsen-Regelkreis, Berlin, Germany: Logos-Verlag Berlin, ISBN 978-3-89722-850-4, OCLC 50451543, 3897228505, http://openlibrary.org/books/OL24586469M/Der_Hypophysen-Schilddrüsen-Regelkreis
^ Dietrich, J., M. Fischer, J. Jauch, E. Pantke, R. Gärtner und C. R. Pickardt (1999). "SPINA-THYR: A Novel Systems Theoretic Approach to Determine the Secretion Capacity of the Thyroid Gland." European Journal of Internal Medicine 10, Suppl. 1 (5/1999): S34.
^ ^a ^b ^c ^d ^e ^f Jostel A, Ryder WD, Shalet SM. The use of thyroid function tests in the diagnosis of hypopituitarism: definition and evaluation of the TSH Index. Clin Endocrinol (Oxf). 2009 Oct;71(4):529-34. PMID 19226261.