Thyroid function tests

Thyroid function tests
Intervention
MeSH	D013960
MedlinePlus	003444

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 increased in hypothyroidism and decreased in hyperthyroidism.^[2]

Its measurement is the most sensitive test for thyroid hormone function. TSH is produced in the pituitary gland. The production of TSH is controlled by thyrotropin-releasing hormone (TRH), which is produced in the hypothalamus. TSH levels may be suppressed by excess free T3 (fT3) or free T4 (fT4) in the blood.

Total thyroxine

Total thyroxine is rarely measured, having been largely superseded by free thyroxine tests. 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]

Total T4 is measured to see the bound and unbound levels of T4. The total T4 is less useful in cases where there could be protein abnormalities. The total T4 is less accurate due to the large amount of T4 that is bound. The total T3 is measured in clinical practice since the T3 has decreased amount that is bound as compared to T4.

Reference ranges depend on the method of analysis. Results should always be interpreted using the range from the laboratory that performed the test. Example values are:

Lower limit	Upper limit	Unit
4,[3] 5.5[4]	11,[3] 12.3[4]	μg/dL
60[3][5]	140,[3] 160[5]	nmol/L

Free thyroxine

Free thyroxine (fT₄) is generally elevated in hyperthyroidism and decreased in hypothyroidism.^[2]

Reference ranges depend on the method of analysis. Results should always be interpreted using the range from the laboratory that performed the test. Example values are:

Patient type	Lower limit	Upper limit	Unit
Normal adult	0.7,[6] 0.8[4]	1.4,[6] 1.5,[4] 1.8[7]	ng/dL
	9,[8][9] 10,[3] 12 [5]	18,[8][9] 23[5]	pmol/L
Infant 0–3 d	2.0[6]	5.0[6]	ng/dL
	26[9]	65[9]	pmol/L
Infant 3–30 d	0.9[6]	2.2[6]	ng/dL
	12[9]	30[9]	pmol/L
Child/Adolescent 31 d – 18 y	0.8[6]	2.0[6]	ng/dL
	10[9]	26[9]	pmol/L
Pregnant	0.5[6]	1.0[6]	ng/dL
	6.5[9]	13[9]	pmol/L

Total triiodothyronine

Total triiodothyronine (Total T₃) is rarely measured, having been largely superseded by free T3 tests. Total T3 is generally elevated in hyperthyroidism and decreased in hypothyroidism.^[2]

Reference ranges depend on the method of analysis. Results should always be interpreted using the range from the laboratory that performed the test. Example values are:

Test	Lower limit	Upper limit	Unit
Total triiodothyronine	60,[4] 75[3]	175,[3] 181[4]	ng/dL
	0.9,[8] 1.1[3]	2.5,[8] 2.7[3]	nmol/L

Free triiodothyronine

Free triiodothyronine (fT₃) is generally elevated in hyperthyroidism and decreased in hypothyroidism.^[2]

Reference ranges depend on the method of analysis. Results should always be interpreted using the range from the laboratory that performed the test. Example values are:

Patient type	Lower limit	Upper limit	Unit
Normal adult	3.0[3]	7.0[3]	pg/mL
	3.1[10]	7.7[10]	pmol/L
Children 2–16 y	3.0[11]	7.0[11]	pg/mL
	1.5[10]	15.2[10]	pmol/L

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[3]	30[3]	pmol/L
1[3]	20 [3]	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] This test is rarely used now that reliable free thyroxine and free triiodothyronine assays are routinely available.

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

Derived structure parameters that describe constant properties of the overall feedback control system may add useful information for special purposes, e.g. in diagnosis of nonthyroidal illness syndrome or central hypothyroidism.^{[12][13][14][15]}

Secretory capacity (GT)

Thyroid's secretory capacity (GT, also referred to as SPINA-GT) is the maximum stimulated amount of thyroxine the thyroid can produce in one second.^[16] GT is elevated in hyperthyroidism and reduced in hypothyroidism.^[17]

GT is calculated with

${\hat G}_{T}={{\beta _{T}(D_{T}+[TSH])(1+K_{{41}}[TBG]+K_{{42}}[TBPA])[FT_{4}]} \over {\alpha _{T}[TSH]}}$

or

${\hat G}_{T}={{\beta _{T}(D_{T}+[TSH])[TT_{4}]} \over {\alpha _{T}[TSH]}}$

$\alpha _{T}$: 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)^[16]

Lower limit	Upper limit	Unit
1.41[16]	8.67[16]	pmol/s

Sum activity of peripheral deiodinases (GD)

The sum activity of peripheral deiodinases (GD, also referred to as SPINA-GD) is reduced in nonthyroidal illness with hypodeiodination.^[13][14][18]

GD is obtained with

${\hat G}_{D}={{\beta _{{31}}(K_{{M1}}+[FT_{4}])(1+K_{{30}}[TBG])[FT_{3}]} \over {\alpha _{{31}}[FT_{4}]}}$

or

${\hat G}_{D}={{\beta _{{31}}(K_{{M1}}+[FT_{4}])[TT_{3}]} \over {\alpha _{{31}}[FT_{4}]}}$

$\alpha _{{31}}$: 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)^[16]

Lower limit	Upper limit	Unit
20[16]	40[16]	nmol/s

TSH index

Jostel's TSH index (TSHI) helps to determine thyrotropic function of anterior pituitary on a quantitative level.^[19] It is reduced in thyrotropic insufficiency^[19] and in certain cases of non-thyroidal illness syndrome.^[18]

It is calculated with

$TSHI=LN(TSH)+0.1345*FT4$.

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

$sTSHI=(TSHI-2.7)/0.676$.^[19]

Parameter	Lower limit	Upper limit	Unit
TSHI	1.3[19]	4.1[19]
sTSHI	-2[19]	2[19]

Effect of drugs

Listed below are some of the effects of drugs on thyroid function.

Effects of some drugs on Tests of Thyroid function^[20]

Cause	Drug	Effect
Inhibit TSH secretion	Dopamine, L-dopa, Glucocorticoids, Somatostatin	↓T4; ↓T3; ↓TSH
Inhibit thyroid hormone synthesis or release	Iodine, Lithium	↓T4; ↓T3; ↑TSH
Inhibit conversion of T4 to T3	Amiodarone, Glucocorticoids, Propranolol, Propylthiouracil, Radiographic contrast agents	↓T3; ↑rT3; ↓, ↔, ↑T4 and fT4; ↔, ↑TSH
Inhibit binding of T4/T3 to serum proteins	Salicylates, Phenytoin, Carbamazepine, Furosemide, Nonsteroidal anti-inflammatory agents, Heparin (in vitro effect)	↓T4; ↓T3; ↓fT4E, ↔, ↑fT4; ↔TSH
Stimulate metabolism of iodothyronines	Phenobarbital, Phenytoin, Carbamazepine, Rifampicin	↓T4; ↓fT4; ↔TSH
Inhibit absorption of ingested T4	Aluminium hydroxide, Ferrous sulfate, Cholestyramine, Colestipol, Iron sucralfate, Soybean preparations, Kayexalate	↓T4; ↓fT4; ↑TSH
Increase in concentration of T4-binding proteins	Estrogen, Clofibrate, Opiates (heroin, methadone), 5-Fluorouracil, Perphenzazine	↑T4; ↑T3; ↔fT4; ↔TSH
Decrease in concentration of T4-binding proteins	Androgens, Glucocorticoids	↓T4; ↓T3; ↔fT4; ↔TSH

↓: reduced serum concentration; ↑: increased serum concentration; ↔: non change; TSH: Thyroid-stimulating hormone; T₃: Total triiodothyronine; T₄: Total thyroxine; fT₄: Free thyroxine; fT₃: Free triiodothyronine; rT₃: Reverse triiodothyronine

TTSI

The Thyrotroph Thyroid Hormone Sensitivity Index (TTSI, also referred to as Thyrotroph T4 Resistance Index or TT4RI) was developed to enable fast screening for resistance to thyroid hormone.^[21][22] Somewhat similar to the TSH Index it is calculated from equilibrium values for TSH and FT4, however with a different equation.

Lower limit	Upper limit	Unit
100	150

See also

• Reference ranges for blood tests#Thyroid hormones

Reference ranges for blood tests, sorted by mass and molar concentration, with thyroid function tests marked in purple boxes in left half of diagram.

References

1. Dayan CM (February 2001). "Interpretation of thyroid function tests". Lancet. 357 (9256): 619–24. doi:10.1016/S0140-6736(00)04060-5. PMID 11558500.
2. 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
3. Table 4: Typical reference ranges for serum assays Archived July 1, 2011, at the Wayback Machine. - Thyroid Disease Manager
4. 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.
5. 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.
6. Free T4; Thyroxine, Free; T4, Free UNC Health Care System
7. Derived from molar values using molar mass of 776.87 g/mol
8. Reference range list from Uppsala University Hospital ("Laborationslista"). Artnr 40284 Sj74a. Issued on April 22, 2008
9. Derived from mass values using molar mass of 776.87 g/mol
10. Derived from mass values using molar mass of 650.98 g/mol
11. 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. doi:10.1515/JPEM.2001.14.9.1635. PMID 11795654.
12. Dietrich JW, Stachon A, Antic B, Klein HH, Hering S (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 Endocr Disord. 8: 13. doi:10.1186/1472-6823-8-13. PMC 2576461. PMID 18851740.
13. Rosolowska-Huszcz D, Kozlowska L, Rydzewski A (August 2005). "Influence of low protein diet on nonthyroidal illness syndrome in chronic renal failure". Endocrine. 27 (3): 283–8. doi:10.1385/ENDO:27:3:283. PMID 16230785.
14. Liu S, Ren J, Zhao Y, Han G, Hong Z, Yan D, Chen J, Gu G, Wang G, Wang X, Fan C, Li J (2012). "Nonthyroidal Illness Syndrome: Is it Far Away From Crohn's Disease?". J Clin Gastroenterol. 47 (2): 153–9. doi:10.1097/MCG.0b013e318254ea8a. PMID 22874844.
15. Dietrich, Johannes W.; Landgrafe-Mende, Gabi; Wiora, Evelin; Chatzitomaris, Apostolos; Klein, Harald H.; Midgley, John E. M.; Hoermann, Rudolf (9 June 2016). "Calculated Parameters of Thyroid Homeostasis: Emerging Tools for Differential Diagnosis and Clinical Research". Frontiers in Endocrinology. 7: 57. doi:10.3389/fendo.2016.00057. PMC 4899439. PMID 27375554.
16. Dietrich, J. W. (2002). Der Hypophysen-Schilddrüsen-Regelkreis. Berlin, Germany: Logos-Verlag Berlin. ISBN 978-3-89722-850-4. OCLC 50451543. 3897228505
17. 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.
18. Fan, S; Ni, X; Wang, J; Zhang, Y; Tao, S; Chen, M; Li, Y; Li, J (February 2016). "Low Triiodothyronine Syndrome in Patients With Radiation Enteritis: Risk Factors and Clinical Outcomes an Observational Study.". Medicine. 95 (6): e2640. doi:10.1097/MD.0000000000002640. PMC 4753882. PMID 26871787.
19. Jostel A, Ryder WD, Shalet SM (October 2009). "The use of thyroid function tests in the diagnosis of hypopituitarism: definition and evaluation of the TSH Index". Clin. Endocrinol. (Oxf). 71 (4): 529–34. doi:10.1111/j.1365-2265.2009.03534.x. PMID 19226261.
20. Burtis CA, Ashwood ER, Bruns DE. Tietz Textbook of Clinical Chemistry and Molecular Diagnostics, 5th edition. Elsevier Saunders. p. 1920. ISBN 978-1-4160-6164-9.
21. Yagi H, Pohlenz J, Hayashi Y, Sakurai A, Refetoff S (1997). "Resistance to thyroid hormone caused by two mutant thyroid hormone receptors beta, R243Q and R243W, with marked impairment of function that cannot be explained by altered in vitro 3,5,3'-triiodothyroinine binding affinity". J. Clin. Endocrinol. Metab. 82: 1608–14. doi:10.1210/jcem.82.5.3945. PMID 9141558.
22. Pohlenz J, Weiss RE, Macchia PE, Pannain S, Lau IT, Ho H, Refetoff S (1999). "Five new families with resistance to thyroid hormone not caused by mutations in the thyroid hormone receptor beta gene". J. Clin. Endocrinol. Metab. 84: 3919–28. doi:10.1210/jcem.84.11.6080. PMID 10566629.

Further reading

• American Thyroid Association: Thyroid Function Tests. Posted on June 4, 2012, seen on January 9, 2013.
• Thyroid function panel - Lab Tests Online

External links

• SPINA Thyr: Open source software for calculating GT and GD