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Thyroid function tests

thyroid function tests, thyroid function tests normal values
Thyroid function tests TFTs is a collective term for blood tests used to check the function of the thyroid

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-stimulating hormone

Thyroid-stimulating hormone TSH, thyrotropin is generally increased in hypothyroidism and decreased in hyperthyroidism, making it the most important test for early detection of both of these conditions The result of this assay is suggestive of the presence and cause of thyroid disease, since a measurement of elevated TSH generally indicates hypothyroidism, while a measurement of low TSH generally indicates hyperthyroidism However, when TSH is measured by itself, it can yield misleading results, so additional thyroid function tests must be compared with the result of this test for accurate diagnosis

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

History

First-generation TSH assays were done by radioimmunoassay and were introduced in 1965 There were variations and improvements upon TSH radioimmunoassay, but their use declined as a new immunometric assay technique became available in the middle of the 1980s The new techniques were more accurate, leading to the second, third, and even fourth generations of TSH assay, with each generation possessing ten times greater functional sensitivity than the last Third generation immunometric assay methods are typically automated Fourth generation TSH immunometric assay has been developed for use in research

Current status

Third generation TSH assay is the current requirement for modern standards of care At present, TSH testing in the United States is typically carried out with automated platforms using advanced forms of immunometric assay Nonetheless, there is currently no international standard for measurement of thyroid-stimulating hormone

Interpretation

Accurate interpretation takes a variety of factors into account, such as the thyroid hormones ie thyroxine T4 and triiodothyronine T3, current medical status such as pregnancy, certain medications like propylthiouracil, temporal effects including circadian rhythm and hysteresis, and other past medical history

Thyroid hormones

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 It is usually slightly elevated in pregnancy secondary to increased levels of thyroid binding globulin TBG

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, 55 11, 123 μg/dL
60 140, 160 nmol/L

Free thyroxine

Free thyroxine fT4 is generally elevated in hyperthyroidism and decreased in hypothyroidism

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 07, 08 14, 15, 18 ng/dL
9, 10, 12 18, 23 pmol/L
Infant 0–3 d 20 50 ng/dL
26 65 pmol/L
Infant 3–30 d 09 22 ng/dL
12 30 pmol/L
Child/Adolescent
31 d – 18 y
08 20 ng/dL
10 26 pmol/L
Pregnant 05 10 ng/dL
65 13 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

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, 75 175, 181 ng/dL
09, 11 25, 27 nmol/L

Free triiodothyronine

Free triiodothyronine fT3 is generally elevated in hyperthyroidism and decreased in hypothyroidism

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 30 70 pg/mL
31 77 pmol/L
Children 2–16 y 30 70 pg/mL
15 152 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 30 mg/L

Thyroglobulin

Reference ranges:

Lower limit Upper limit Unit
15 30 pmol/L
1 20 μg/L

Other binding hormones

  • Transthyretin prealbumin
  • Albumin

Protein binding function

Thyroid hormone uptake

Thyroid hormone uptake Tuptake or T3 uptake is a measure of the unbound thyroxine binding globulins in the blood, that is, the TBG that is unsaturated with thyroid hormone Unsaturated TBG increases with decreased levels of thyroid hormones It is not directly related to triiodothyronine, despite the name T3 uptake

Reference ranges:

Patient type Lower limit Upper limit Unit
Females 25 35 %
In pregnancy 15 25 %
Males 25 35 %

Other protein binding tests

  • Thyroid Hormone Binding RatioTHBR
  • Thyroxine-binding index TBI

Mixed parameters

Free thyroxine index

The Free Thyroxine Index FTI or T7 is obtained by multiplying the total T4 with T3 uptake FTI is considered to be a more reliable indicator of thyroid status in the presence of abnormalities in plasma protein binding 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

Patient type Lower limit Upper limit Unit
Females 18 50
Males 13 42

Structure parameters

Derived structure parameters that describe constant properties of the overall feedback control system may add useful information for special purposes, eg in diagnosis of nonthyroidal illness syndrome or central hypothyroidism

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 GT is elevated in hyperthyroidism and reduced in hypothyroidism

GT is calculated with

G ^ T = β T D T + [ T S H ] 1 + K 41 [ T B G ] + K 42 [ T B P A ] [ F T 4 ] α T [ T S H ] }_=D_+1+K_+K_} \over }}}

or

G ^ T = β T D T + [ T S H ] [ T T 4 ] α T [ T S H ] }_=D_+} \over }}}

α T } : Dilution factor for T4 reciprocal of apparent volume of distribution, 01 l−1
β T } : Clearance exponent for T4 11e-6 sec−1
K41: Dissociation constant T4-TBG 2e10 l/mol
K42: Dissociation constant T4-TBPA 2e8 l/mol
DT: EC50 for TSH 275 mU/l

Lower limit Upper limit Unit
141 867 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

GD is obtained with

G ^ D = β 31 K M 1 + [ F T 4 ] 1 + K 30 [ T B G ] [ F T 3 ] α 31 [ F T 4 ] }_=K_+1+K_} \over }}}

or

G ^ D = β 31 K M 1 + [ F T 4 ] [ T T 3 ] α 31 [ F T 4 ] }_=K_+} \over }}}

α 31 } : Dilution factor for T3 reciprocal of apparent volume of distribution, 0026 l−1
β 31 } : Clearance exponent for T3 8e-6 sec−1
KM1: Dissociation constant of type-1-deiodinase 5e-7 mol/l
K30: Dissociation constant T3-TBG 2e9 l/mol

Lower limit Upper limit Unit
20 40 nmol/s

TSH index

Jostel's TSH index JTI or TSHI helps to determine thyrotropic function of anterior pituitary on a quantitative level It is reduced in thyrotropic insufficiency and in certain cases of non-thyroidal illness syndrome

It is calculated with

T S H I = L N T S H + 01345 ∗ F T 4

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

s T S H I = T S H I − 27 / 0676

Parameter Lower limit Upper limit Unit
TSHI 13 41
sTSHI -2 2

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 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

Effects of drugs

Drugs can profoundly affect thyroid function tests Listed below is a selection of important effects

Effects of some drugs on Tests of Thyroid function
Cause Drug Effect on hormone concentrations Effect on structure parameters
Inhibited TSH secretion Dopamine, L-DOPA, glucocorticoids, somatostatin ↓T4; ↓T3; ↓TSH ↔SPINA-GT; ↓JTI
Inhibited synthesis or release of thyroid hormone Iodine, lithium ↓T4; ↓T3; ↑TSH ↓SPINA-GT; ↔JTI
Inhibited conversion of T4 to T3 Step-up hypodeiodination Amiodarone, glucocorticoids, propranolol, propylthiouracil, radiographic contrast agents ↓T3; ↑rT3; ↓, ↔, ↑T4 and fT4; ↔, ↑TSH ↓SPINA-GD
Inhibited binding of T4/T3 to serum proteins Salicylates, phenytoin, carbamazepine, furosemide, nonsteroidal anti-inflammatory agents, heparin in vitro effect ↓T4; ↓T3; ↓fT4E, ↔, ↑fT4; ↔TSH ↓T4/fT4 ratio
Stimulated metabolism of iodothyronines Phenobarbital, phenytoin, carbamazepine, rifampicin ↓T4; ↓fT4; ↔TSH
Inhibited 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, perphenazine ↑T4; ↑T3; ↔fT4; ↔TSH ↔SPINA-GT; ↔SPINA-GD; ↔JTI; ↑T4/fT4 ratio
Decrease in concentration of T4-binding proteins Androgens, glucocorticoids ↓T4; ↓T3; ↔fT4; ↔TSH ↔SPINA-GT; ↔SPINA-GD; ↔JTI; ↓T4/fT4 ratio

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

See also

  • Reference ranges for 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
  • Long-acting thyroid stimulator LATS

References

  1. ^ Dayan CM February 2001 "Interpretation of thyroid function tests" Lancet 357 9256: 619–24 doi:101016/S0140-67360004060-5 PMID 11558500 
  2. ^ a b c d e f g h i j k l m n o p q r s t u v 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, DC, 20372-5300 Archived 25 December 2011 at the Wayback Machine
  3. ^ a b c d e f Spencer, Carole 1 January 2013 "Assay of Thyroid Hormones and Related Substances" Thyroid Disease Manager Retrieved 5 November 2013 
  4. ^ a b c d e f g Toft, Anthony; Beckett, Geoffrey 2005 Werner & Ingbar’s The Thyroid: A Fundamental & Clinical Text 9th ed Philadelphia, PA: Lippincott Williams & Wilkins pp 329–344 ISBN 0-7817-5047-4 
  5. ^ Hoermann, Rudolf; Midgley, John E M; Larisch, Rolf; Dietrich, Johannes W 22 December 2017 "Recent Advances in Thyroid Hormone Regulation: Toward a New Paradigm for Optimal Diagnosis and Treatment" Frontiers in Endocrinology 8 doi:103389/fendo201700364  |access-date= requires |url= help
  6. ^ Spencer, Carole; Takeuchi, Michael; Kazarosyan, Margarita 1996 "Current status and performance goals for serum thyrotropin TSH assays" Clinical Chemistry Clinical Chemistry 42 1: 141–145 Retrieved 5 November 2013 
  7. ^ Hoermann, Rudolf; Midgley, John E M; Larisch, Rolf; Dietrich, Johannes W "Homeostatic Control of the Thyroid–Pituitary Axis: Perspectives for Diagnosis and Treatment" Frontiers in Endocrinology 6: 177 doi:103389/fendo201500177 PMC 4653296  PMID 26635726 
  8. ^ Leow, Melvin Khee-Shing "A Review of the Phenomenon of Hysteresis in the Hypothalamus–Pituitary–Thyroid Axis" Frontiers in Endocrinology 7: 64 doi:103389/fendo201600064 PMC 4905968  PMID 27379016 
  9. ^ Dayan, Colin 24 February 2001 "Interpretation of thyroid function tests" PDF The Lancet Bristol: The Lancet Publishing Group 357: 619–624 doi:101016/s0140-67360004060-5 PMID 11558500 Retrieved 5 November 2013 
  10. ^ a b c d e f g h i j k l m n o Table 4: Typical reference ranges for serum assays Archived July 1, 2011, at the Wayback Machine - Thyroid Disease Manager
  11. ^ a b c d e f g h 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
  12. ^ 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:101373/clinchem2007101428 PMID 18593963 
  13. ^ a b c d e f g h i j Free T4; Thyroxine, Free; T4, Free UNC Health Care System
  14. ^ Derived from molar values using molar mass of 77687 g/mol
  15. ^ a b c d Reference range list from Uppsala University Hospital "Laborationslista" Artnr 40284 Sj74a Issued on April 22, 2008
  16. ^ a b c d e f g h i j Derived from mass values using molar mass of 77687 g/mol
  17. ^ a b c d Derived from mass values using molar mass of 65098 g/mol
  18. ^ 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 doi:101515/JPEM20011491635 PMID 11795654 
  19. ^ 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:101186/1472-6823-8-13 PMC 2576461  PMID 18851740 CS1 maint: Multiple names: authors list link
  20. ^ a b 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:101385/ENDO:27:3:283 PMID 16230785 
  21. ^ a b 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:101097/MCG0b013e318254ea8a PMID 22874844 
  22. ^ a b 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:103389/fendo201600057 PMC 4899439  PMID 27375554 
  23. ^ 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 
  24. ^ 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
  25. ^ a b 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:101097/MD0000000000002640 PMC 4753882  PMID 26871787 
  26. ^ a b c d e f g 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 71 4: 529–34 doi:101111/j1365-2265200903534x PMID 19226261 
  27. ^ 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:101210/jcem8253945 PMID 9141558 
  28. ^ 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:101210/jcem84116080 PMID 10566629 
  29. ^ 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 
  30. ^ Chatzitomaris, Apostolos; Hoermann, Rudolf; Midgley, John E; Hering, Steffen; Urban, Aline; Dietrich, Barbara; Abood, Assjana; Klein, Harald H; Dietrich, Johannes W 20 July 2017 "Thyroid Allostasis–Adaptive Responses of Thyrotropic Feedback Control to Conditions of Strain, Stress, and Developmental Programming" Frontiers in Endocrinology 8 doi:103389/fendo201700163 PMC 5517413  PMID 28775711 

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
  • Interpretation of thyroid function tests by Dayan, Colin M 2001 The Lancet, Vol 357

CDC laboratory procedure manuals

The Centers for Disease Control and Prevention has published the following laboratory procedure manuals for measuring thyroid-stimulating hormone:

  • Thyroid Stimulating Hormone TSH University of Washington Medical Center September 2011 Method: Access 2 Beckman Coulter
  • Thyroid Stimulating Hormone TSH Collaborative Laboratory Services September 2011 Method: Access 2 Beckman Coulter
  • Thyroid Stimulating Hormone TSH September 2009 Method: Access 2 Beckman Coulter
  • Lab 18 Thyroid Stimulating Hormone 2001-2002 Method: Microparticle Enzyme Immunoassay
  • Lab 18 TSH - Thyroid Stimulating Hormone 1999-2000 Method: Microparticle Enzyme Immunoassay

Beckman Coulter procedure manuals

Beckman Coulter provides the equipment and reagents used in the 2009-2011 CDC manuals, and has published the following manuals for performing the procedure:

  • HYPERsensitive hTSH - 3rd generation 2010 Hosted by the University of California, San Francisco
  • Reference 33820 - HYPERsensitive hTSH 3rd generation and Fast hTSH 2nd generation
  • http://wwwtsh3rdgenerationcom 2010 Hosted by manufacturer]

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