Laboratory Assessment of Thyroid Function: Integrated Diagnostic Pathways for Laboratory Technicians and Endocrinology Specialists

Abdullah Mohammed Almarshud (1) , Badour Mayof Alanazi (2) , Norah Saad Almutairi (3) , Mehad Abdulkreem Abdulhameed Alkhifi (4) , Marwah Ahmed Muqtiri (5) , Hashim Saad Aldukhayni (6) , Amal Ali Soliman Gahtani (7) , Nasser Najem Alothman (8) , Abdullah Al-Ghamdi (9) , Amin Ibrahim Ahmed Otaif (10) , Mohammed Aqeel Mohammed Alsharari (2)
(1) Qassim Health Cluster Alrabieia,Ministry of Health, Saudi Arabia,
(2) Ministry Of Health, Saudi Arabia,
(3) Maternity And Child Hospital,Ministry of Health, Saudi Arabia,
(4) Prince Mohammed Bin Abdulaziz Hospital In Riyadh,Ministry of Health, Saudi Arabia,
(5) Regional Laboratory & Central Blood Bank In Jizan,Ministry of Health, Saudi Arabia,
(6) King Khalid Hospital Alkharj,Ministry of Health, Saudi Arabia,
(7) Jazan Regional Laboratory,Ministry of Health, Saudi Arabia,
(8) Tumaer General Hospital , Ministry of Health, Saudi Arabia,
(9) King Abdullah Bisha Hospital,Ministry of Health, Saudi Arabia,
(10) Ma'taq Al-Asm Health Center,Ministry of Health, Saudi Arabia

Abstract

Background: Thyroid hormones regulate metabolism, cardiovascular function, and neuropsychiatric health. Even minor deviations in thyroid status can lead to multisystem disorders, making thyroid function tests (TFTs) essential in clinical practice.


Aim: To outline integrated diagnostic pathways for thyroid function assessment, emphasizing laboratory procedures, interpretive frameworks, and quality control for accurate diagnosis and monitoring.


Methods: A comprehensive review of thyroid physiology, etiologic categories, epidemiologic drivers, and laboratory methodologies was conducted. The article details specimen handling, immunoassay principles, interference factors, and quality management systems to ensure reliable TFT results.


Results: TSH remains the primary screening marker due to its sensitivity, but FT4 and FT3 measurements are critical in subclinical disease, central hypothyroidism, and treatment monitoring. Interfering factors—such as heterophile antibodies, binding protein abnormalities, and medications—can distort results, necessitating confirmatory strategies like equilibrium dialysis or mass spectrometry. Quality assurance through internal/external QC and patient-based monitoring minimizes analytical errors. Clinical interpretation must integrate physiologic context, comorbidities, and exposure history to avoid misdiagnosis.


Conclusion: Accurate thyroid diagnostics require a multidisciplinary approach combining physiologic insight, rigorous laboratory practice, and contextual interpretation. Understanding assay limitations and interference mechanisms is vital for preventing diagnostic errors and optimizing patient care.

Full text article

Generated from XML file

References

Brochmann H, Bjøro T, Gaarder PI, Hanson F, Frey HM. Prevalence of thyroid dysfunction in elderly subjects. A randomized study in a Norwegian rural community (Naerøy). Acta endocrinologica. 1988 Jan:117(1):7-12

Feingold KR, Ahmed SF, Anawalt B, Blackman MR, Boyce A, Chrousos G, Corpas E, de Herder WW, Dhatariya K, Dungan K, Hofland J, Kalra S, Kaltsas G, Kapoor N, Koch C, Kopp P, Korbonits M, Kovacs CS, Kuohung W, Laferrère B, Levy M, McGee EA, McLachlan R, Muzumdar R, Purnell J, Rey R, Sahay R, Shah AS, Singer F, Sperling MA, Stratakis CA, Trence DL, Wilson DP, Spencer CA. Assay of Thyroid Hormones and Related Substances. Endotext. 2000

Koulouri O, Moran C, Halsall D, Chatterjee K, Gurnell M. Pitfalls in the measurement and interpretation of thyroid function tests. Best practice & research. Clinical endocrinology & metabolism. 2013 Dec:27(6):745-62. doi: 10.1016/j.beem.2013.10.003.

Rivas AM, Lado-Abeal J. Thyroid hormone resistance and its management. Proceedings (Baylor University. Medical Center). 2016 Apr:29(2):209-11

Pearce EN, Farwell AP, Braverman LE. Thyroiditis. The New England journal of medicine. 2003 Jun 26:348(26):2646-55

Antonelli A, Ferrari SM, Corrado A, Di Domenicantonio A, Fallahi P. Autoimmune thyroid disorders. Autoimmunity reviews. 2015 Feb:14(2):174-80. doi: 10.1016/j.autrev.2014.10.016.

Roberts CG, Ladenson PW. Hypothyroidism. Lancet (London, England). 2004 Mar 6:363(9411):793-803

Franklyn JA, Boelaert K. Thyrotoxicosis. Lancet (London, England). 2012 Mar 24:379(9821):1155-66. doi: 10.1016/S0140-6736(11)60782-4.

Haugen BR, Alexander EK, Bible KC, Doherty GM, Mandel SJ, Nikiforov YE, Pacini F, Randolph GW, Sawka AM, Schlumberger M, Schuff KG, Sherman SI, Sosa JA, Steward DL, Tuttle RM, Wartofsky L. 2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer: The American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer. Thyroid : official journal of the American Thyroid Association. 2016 Jan:26(1):1-133. doi: 10.1089/thy.2015.0020.

Tanner M, Kent N, Smith B, Fletcher S, Lewer M. Stability of common biochemical analytes in serum gel tubes subjected to various storage temperatures and times pre-centrifugation. Annals of clinical biochemistry. 2008 Jul:45(Pt 4):375-9. doi: 10.1258/acb.2007.007183.

Mardell R, Gamlen TR. Discrepant results for free thyroxin by radioimmunoassay and dialysis procedures explained. Clinical chemistry. 1982 Sep:28(9):1989

Ercan M, Fırat Oğuz E, Akbulut ED, Yilmaz M, Turhan T. Comparison of the effect of gel used in two different serum separator tubes for thyroid function tests. Journal of clinical laboratory analysis. 2018 Jul:32(6):e22427. doi: 10.1002/jcla.22427.

Keffer JH. Preanalytical considerations in testing thyroid function. Clinical chemistry. 1996 Jan:42(1):125-34

Philippe J, Dibner C. Thyroid circadian timing: roles in physiology and thyroid malignancies. Journal of biological rhythms. 2015 Apr:30(2):76-83. doi: 10.1177/0748730414557634.

Soldin OP, Chung SH, Colie C. The Use of TSH in Determining Thyroid Disease: How Does It Impact the Practice of Medicine in Pregnancy? Journal of thyroid research. 2013:2013():148157. doi: 10.1155/2013/148157.

Fisher DA. Physiological variations in thyroid hormones: physiological and pathophysiological considerations. Clinical chemistry. 1996 Jan:42(1):135-9

Soh SB, Aw TC. Laboratory Testing in Thyroid Conditions - Pitfalls and Clinical Utility. Annals of laboratory medicine. 2019 Jan:39(1):3-14. doi: 10.3343/alm.2019.39.1.3.

Spencer CA, Schwarzbein D, Guttler RB, LoPresti JS, Nicoloff JT. Thyrotropin (TSH)-releasing hormone stimulation test responses employing third and fourth generation TSH assays. The Journal of clinical endocrinology and metabolism. 1993 Feb:76(2):494-8

Van Houcke SK, Van Uytfanghe K, Shimizu E, Tani W, Umemoto M, Thienpont LM. IFCC international conventional reference procedure for the measurement of free thyroxine in serum: International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) Working Group for Standardization of Thyroid Function Tests (WG-STFT)(1). Clinical chemistry and laboratory medicine. 2011 Aug:49(8):1275-1281. doi: 10.1515/CCLM.2011.639.

Soukhova N, Soldin OP, Soldin SJ. Isotope dilution tandem mass spectrometric method for T4/T3. Clinica chimica acta; international journal of clinical chemistry. 2004 May:343(1-2):185-90

Thienpont LM, Van Uytfanghe K, Marriott J, Stokes P, Siekmann L, Kessler A, Bunk D, Tai S. Feasibility study of the use of frozen human sera in split-sample comparison of immunoassays with candidate reference measurement procedures for total thyroxine and total triiodothyronine measurements. Clinical chemistry. 2005 Dec:51(12):2303-11

Thienpont LM, Van Uytfanghe K, Beastall G, Faix JD, Ieiri T, Miller WG, Nelson JC, Ronin C, Ross HA, Thijssen JH, Toussaint B, IFCC Working Group on Standardization of Thyroid Function Tests. Report of the IFCC Working Group for Standardization of Thyroid Function Tests; part 3: total thyroxine and total triiodothyronine. Clinical chemistry. 2010 Jun:56(6):921-9. doi: 10.1373/clinchem.2009.140228.

Ross HA, Menheere PP, Endocrinology Section of SKML (Dutch Foundation for Quality Assessment in Clinical Laboratories), Thomas CM, Mudde AH, Kouwenberg M, Wolffenbuttel BH. Interference from heterophilic antibodies in seven current TSH assays. Annals of clinical biochemistry. 2008 Nov:45(Pt 6):616. doi: 10.1258/acb.2008.008066.

Zouwail SA, O'Toole AM, Clark PM, Begley JP. Influence of thyroid hormone autoantibodies on 7 thyroid hormone assays. Clinical chemistry. 2008 May:54(5):927-8. doi: 10.1373/clinchem.2007.099770.

Sapin R, Gasser F, Schlienger JL. Familial dysalbuminemic hyperthyroxinemia and thyroid hormone autoantibodies: interference in current free thyroid hormone assays. Hormone research. 1996:45(3-5):139-41

Ohba K, Noh JY, Unno T, Satoh T, Iwahara K, Matsushita A, Sasaki S, Oki Y, Nakamura H. Falsely elevated thyroid hormone levels caused by anti-ruthenium interference in the Elecsys assay resembling the syndrome of inappropriate secretion of thyrotropin. Endocrine journal. 2012:59(8):663-7

Loh TP, Kao SL, Halsall DJ, Toh SA, Chan E, Ho SC, Tai ES, Khoo CM. Macro-thyrotropin: a case report and review of literature. The Journal of clinical endocrinology and metabolism. 2012 Jun:97(6):1823-8. doi: 10.1210/jc.2011-3490.

Cartwright D, O'Shea P, Rajanayagam O, Agostini M, Barker P, Moran C, Macchia E, Pinchera A, John R, Agha A, Ross HA, Chatterjee VK, Halsall DJ. Familial dysalbuminemic hyperthyroxinemia: a persistent diagnostic challenge. Clinical chemistry. 2009 May:55(5):1044-6. doi: 10.1373/clinchem.2008.120303. E

Stockigt JR, Lim CF. Medications that distort in vitro tests of thyroid function, with particular reference to estimates of serum free thyroxine. Best practice & research. Clinical endocrinology & metabolism. 2009 Dec:23(6):753-67. doi: 10.1016/j.beem.2009.06.004.

Stevenson HP, Archbold GP, Johnston P, Young IS, Sheridan B. Misleading serum free thyroxine results during low molecular weight heparin treatment. Clinical chemistry. 1998 May:44(5):1002-7

Després N, Grant AM. Antibody interference in thyroid assays: a potential for clinical misinformation. Clinical chemistry. 1998 Mar:44(3):440-54

Krasowski MD. Educational Case: Hemolysis and Lipemia Interference With Laboratory Testing. Academic pathology. 2019 Jan-Dec:6():2374289519888754. doi: 10.1177/2374289519888754.

Clark PM, Holder RL, Haque SM, Hobbs FD, Roberts LM, Franklyn JA. The relationship between serum TSH and free T4 in older people. Journal of clinical pathology. 2012 May:65(5):463-5. doi: 10.1136/jclinpath-2011-200433.

Koulouri O, Gurnell M. How to interpret thyroid function tests. Clinical medicine (London, England). 2013 Jun:13(3):282-6. doi: 10.7861/clinmedicine.13-3-282.

Hoermann R, Eckl W, Hoermann C, Larisch R. Complex relationship between free thyroxine and TSH in the regulation of thyroid function. European journal of endocrinology. 2010 Jun:162(6):1123-9. doi: 10.1530/EJE-10-0106.

Surks MI, Ortiz E, Daniels GH, Sawin CT, Col NF, Cobin RH, Franklyn JA, Hershman JM, Burman KD, Denke MA, Gorman C, Cooper RS, Weissman NJ. Subclinical thyroid disease: scientific review and guidelines for diagnosis and management. JAMA. 2004 Jan 14:291(2):228-38

Gurnell M, Halsall DJ, Chatterjee VK. What should be done when thyroid function tests do not make sense? Clinical endocrinology. 2011 Jun:74(6):673-8. doi: 10.1111/j.1365-2265.2011.04023.x.

Ylli D, Klubo-Gwiezdzinska J, Wartofsky L. Thyroid emergencies. Polish archives of internal medicine. 2019 Aug 29:129(7-8):526-534. doi: 10.20452/pamw.14876.

Popoveniuc G, Chandra T, Sud A, Sharma M, Blackman MR, Burman KD, Mete M, Desale S, Wartofsky L. A diagnostic scoring system for myxedema coma. Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists. 2014 Aug:20(8):808-17. doi: 10.4158/EP13460.OR.

Walker HK, Hall WD, Hurst JW, Dunlap DB. Thyroid Function Tests. Clinical Methods: The History, Physical, and Laboratory Examinations. 1990

Ting MJM, Zhang R, Lim EM, Ward BK, Wilson SG, Walsh JP. Familial Dysalbuminemic Hyperthyroxinemia as a Cause for Discordant Thyroid Function Tests. Journal of the Endocrine Society. 2021 Apr 1:5(4):bvab012. doi: 10.1210/jendso/bvab012.

Díaz S, Cárdenas H, Brandeis A, Miranda P, Salvatierra AM, Croxatto HB. Relative contributions of anovulation and luteal phase defect to the reduced pregnancy rate of breastfeeding women. Fertility and sterility. 1992 Sep:58(3):498-503

Olateju TO, Vanderpump MP. Thyroid hormone resistance. Annals of clinical biochemistry. 2006 Nov:43(Pt 6):431-40

Rasool R, Unar A, Jafar TH, Chanihoon GQ, Mubeen B. A Role of Thyroid Hormones in Acute Myocardial Infarction: An Update. Current cardiology reviews. 2023:19(1):e280422204209. doi: 10.2174/1573403X18666220428121431.

Nademanee K, Piwonka RW, Singh BN, Hershman JM. Amiodarone and thyroid function. Progress in cardiovascular diseases. 1989 May-Jun:31(6):427-37

Wiersinga WM. Propranolol and thyroid hormone metabolism. Thyroid : official journal of the American Thyroid Association. 1991 Summer:1(3):273-7

Heyma P, Larkins RG, Perry-Keene D, Peter CT, Ross D, Sloman JG. Thyroid hormone levels and protein binding in patients on long-term diphenylhydantoin treatment. Clinical endocrinology. 1977 May:6(5):369-76

Hershman JM, Craane TJ, Colwell JA. Effect of sulfonylurea drugs on the binding of triiodothyronine and thyroxine to thyroxine-binding globulin. The Journal of clinical endocrinology and metabolism. 1968 Nov:28(11):1605-10

Rootwelt K, Ganes T, Johannessen SI. Effect of carbamazepine, phenytoin and phenobarbitone on serum levels of thyroid hormones and thyrotropin in humans. Scandinavian journal of clinical and laboratory investigation. 1978 Dec:38(8):731-6

Mohamedali M, Reddy Maddika S, Vyas A, Iyer V, Cheriyath P. Thyroid disorders and chronic kidney disease. International journal of nephrology. 2014:2014():520281. doi: 10.1155/2014/520281.

Heinen E, Herrmann J, Mosny D, Moreno F, Teschke R, Krüskemper HL. Inhibition of peripheral deiodination of 3, 5, 3'-triiodothyronine: an adverse effect of propylthiouracil in the treatment of T3-thyrotoxicosis. Journal of endocrinological investigation. 1981 Jul-Sep:4(3):331-4

Zhang S, Wang W, Zhao H, He F, Zhong K, Yuan S, Wang Z. Status of internal quality control for thyroid hormones immunoassays from 2011 to 2016 in China. Journal of clinical laboratory analysis. 2018 Jan:32(1):. doi: 10.1002/jcla.22154.

Hu LT, Wang ZG. Internal quality control practice of thyroid disease related tests and imprecision analysis in China. Clinical laboratory. 2014:60(2):301-8

Kinns H, Pitkin S, Housley D, Freedman DB. Internal quality control: best practice. Journal of clinical pathology. 2013 Dec:66(12):1027-32. doi: 10.1136/jclinpath-2013-201661.

James D, Ames D, Lopez B, Still R, Simpson W, Twomey P. External quality assessment: best practice. Journal of clinical pathology. 2014 Aug:67(8):651-5. doi: 10.1136/jclinpath-2013-201621.

Zhang Y, Wang HL, Xie YH, He DH, Zhou CQ, Kong LR. Practical application of the patient data-based quality control method: the potassium example. Biochemia medica. 2024 Feb 15:34(1):010901. doi: 10.11613/BM.2024.010901.

Valenstein PN, Stankovic AK, Souers RJ, Schneider F, Wagar EA. Document control practices in 120 clinical laboratories. Archives of pathology & laboratory medicine. 2009 Jun:133(6):942-9

Wadhwa V, Rai S, Thukral T, Chopra M. Laboratory quality management system: road to accreditation and beyond. Indian journal of medical microbiology. 2012 Apr-Jun:30(2):131-40. doi: 10.4103/0255-0857.96647.

Lunn G, Lawler Chemical Resistance Of Gloves G. Laboratory safety. Current protocols in protein science. 2002 Aug:Appendix 2():A.2A.1-A.2A.35. doi: 10.1002/0471140864.psa02as28.

Tait FN, Mburu C, Gikunju J. Occupational safety and health status of medical laboratories in Kajiado County, Kenya. The Pan African medical journal. 2018:29():65. doi: 10.11604/pamj.2018.29.65.12578.

Authors

Abdullah Mohammed Almarshud
Amalmarshud@Moh.Gov.Sa (Primary Contact)
Badour Mayof Alanazi
Norah Saad Almutairi
Mehad Abdulkreem Abdulhameed Alkhifi
Marwah Ahmed Muqtiri
Hashim Saad Aldukhayni
Amal Ali Soliman Gahtani
Nasser Najem Alothman
Abdullah Al-Ghamdi
Amin Ibrahim Ahmed Otaif
Mohammed Aqeel Mohammed Alsharari
Almarshud, A. M., Badour Mayof Alanazi, Norah Saad Almutairi, Mehad Abdulkreem Abdulhameed Alkhifi, Marwah Ahmed Muqtiri, Hashim Saad Aldukhayni, … Mohammed Aqeel Mohammed Alsharari. (2025). Laboratory Assessment of Thyroid Function: Integrated Diagnostic Pathways for Laboratory Technicians and Endocrinology Specialists. Saudi Journal of Medicine and Public Health, 2(2), 2599–2618. https://doi.org/10.64483/202522437

Article Details

Similar Articles

<< < 4 5 6 7 8 > >> 

You may also start an advanced similarity search for this article.

Most read articles by the same author(s)