Although Thyroid Patient Advocacy has, on numerous occasions, asked the Royal College of Physicians and the British Thyroid Association et all. to show research/studies to back up their Policy Statement on the Diagnosis and Management of Primary Hypothyroidism ….that the use of sensitive and specific blood tests as the only method for the precise diagnosis of thyroid dysfunction and for the monitoring of treatment with approved medications …” they have failed to produce any.

The recommended TSH reference ranges are:

America 0.3 – 3.0
Sweden 0.3 2.5
Belgium 0.3 2.5
Germany 0.3 2.5
Australia 0.3 2.5

So why was it decided by the BTA/RCP to recommend 0.5 to 10.0 in the UK?

There is no question that the interpretation of the Thyroid Stimulating Hormone (TSH) test remains controversial. The TSH result is relied on by most mainstream doctors to detect and monitor thyroid problems. Touted as the “gold standard” for diagnosis and management of thyroid conditions, this test is considered sacrosanct by the majority of doctors.

The National Academy of Clinical Biochemistry (NACB) issued new guidelines in 2002 for the diagnosis and monitoring of thyroid disease. They reported that the then current TSH reference range (approximately 0.5 to 5.5) may be too wide and may include people with thyroid disease. When more sensitive screening was done, which excluded people with thyroid disease, 95% of the population tested had a TSH level between 0.4 and 2.5. So the NACB recommended reducing the reference range to that, indicating that anything below or above that could be a sign of thyroid disease.

The American Association of Clinical Endocrinologists (AACE) in their Guidelines (January 2003) called for doctors to “consider treatment for patients who test outside the boundaries of a narrower margin based on a target TSH level of 0.3 to 3″. Their statement also said: “the AACE believes the new range will result in proper diagnosis for millions of Americans who suffer from a mild thyroid disorder, but have gone untreated until now.”

Yet, over 9 years later, the majority of testing laboratories still use the old reference range of 0.05 to 5.5, and flag results as abnormal only if they are outside that reference range.

Yet, the British Thyroid Association and the Royal College of Physicians insist that doctors should not give a diagnosis if TSH is within the reference range of 0.5 to 10.0, even though Dr Anthony Toft, (ex President of the British Thyroid Association and Royal College of Physicians, Edinburgh) stated in the British Thyroid Foundation newsletter (Issue No. 23) that normal range for TSH is 0.15 3.5.
It is surely not unreasonable to expect that doctors throughout the UK would agree as to what the results of their gold standard test means instead of leaving tens of thousands continuing to suffer symptoms of hypo-thyroidism without the benefit of a diagnosis or corrective thyroid hormone replacement for those who need it.

THE FOLLOWING REFERENCES SHOW THAT THE TSH SERUM MEASUREMENT ALONE IS NOT SUFFICIENT FOR DIAGNOSIS AND FOLLOW-UP OF THYROID DEFICIENCY AND THAT THE RECOMMENDED RANGE IN THE UK IS TOO WIDE.

Claim: TSH is the first line test to do. It is sufficient to diagnose all forms of eu-, hypo- and hyperthyroidism. No other test is necessary for the diagnosis.

Facts: TSH is often insufficient on its own to diagnose between eu-, hypo- and hyperthyroidism, particularly to diagnose milder, borderline states of hypothyroidism. Other tests are necessary, as is a complete clinical evaluation (medical history, actual complaints, physical examination) of the patient.

Doubts on the usefulness of the serum TSH test alone for diagnosis

Over reliance on laboratory tests without clinical evaluation may lead to considerable diagnostic errors

1. Nicoloff JT, Spencer CA. The use and misuse of the sensitive thyrotropin assay. J Clin Endocrinol Metab. 1990;71:553-8.

2. De Los Santos ET, Mazzaferri EL. Sensitive thyroid-stimulating hormone assays: Clinical applications and limitations. Compr Ther. 1988; 14(9): 26-33.

3. Becker DV, Bigos ST, Gaitan E, Morris JCrd, rallison ML, Spencer CA, Sugarawa M, Van Middlesworth L, Wartofsky L. Optimal use of blood tests for assessment of thyroid function. JAMA 1993 Jun 2; 269: 273 (the decision to initiate therapy shoul be based on both clinical and laboratory findings and not solely on the results of a single laboratory test)

4. Rippere V. Biochemical victims: False negative diagnosis through overreliance on laboratory resultsa personal report. Med Hypotheses. 1983; 10(2): 113.

Discussions and controversy in medical associations and journals on the TSH reference range

5. 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;291:22838 (conclusions of a consensus panel of the Endocrine Society, the American Thyroid Association,and American Association of Clinical Endocrinology. Although the panel concluded that there was good data that patients with slight elevations of TSH above 4.5 may progress to overt hypothyroidism, and that levothyroxine therapy would prevent symptoms, they did not agree that early treatment provided any benefit!)

6. Dickey RA, Wartofsky L, Feld S. Optimal thyrotropin level: normal ranges and reference intervals are not equivalent. Thyroid. 2005 Sep;15(9):1035-9

7. Wartofsky L, Dickey RA. The evidence for a narrower thyrotropin reference range is compelling. J Clin Endocrinol Metab. 2005 Sep;90(9):5483-8 (remarkable article of which a lot of the following information is extracted)

8. Gharib H, Tuttle RM, Baskin HJ, Fish LH, Singer PA, McDermott MT. Subclinical thyroid dysfunction: a joint statement on management from the American Association of Clinical Endocrinologists, the American Thyroid Association, and The Endocrine Society. J Clin Endocrinol Metab. 2005;90:5815

9. Surks MI. Commentary: subclinical thyroid dysfunction: a joint statement on management from the American Association of Clinical Endocrinologists, the American Thyroid Association, and The Endocrine Society. J Clin Endocrinol Metab. 2005;90:5867

10. Ringel MD, Mazzaferri EL. Editorial: subclinical thyroid dysfunction: can there be a consensus about the consensus? J Clin Endocrinol Metab. 2005;90:58890

11. Pinchera A. Subclinical thyroid disease: to treat or not to treat? Thyroid. 2005;15:12

Studies that show that the serum TSH reference range of 0.1-5.1 mU/liter for a POPULATION is too large

Studies indicating a population mean value of 1.5 mU/liter for an iodine-sufficient population

12. Vanderpump MPJ, Tunbridge WMG, French JM, Appleton D, Bates D, Clark F, Grimley Evans J, Hasan DM, Rodgers H, Tunbridge F. The incidence of thyroid disorders in the community: a twenty-year follow-up of the Whickham Survey. Clin Endocrinol (Oxf). 1995;43:5568

13. Hollowell JG, Staehling NW, Flanders WD, Gunter EW, Spencer CA, Braverman LE. Serum TSH, T4, and thyroid antibodies in the United States population (1988 to 1994): National Health and Nutrition Examination Survey (NHANES III). J Clin Endocrinol Metab. 2002; 87:48999
14. Andersen S, Petersen KM, Brunn NH, Laurberg P. Narrow individual variations in serum T4 and T3 in normal subjects: a clue to the understanding of subclinical thyroid disease. J Clin Endocrinol Metab. 2002;87:106872

15. Demers LM, Spencer CA. Laboratory medicine practice guidelines: laboratory support for the diagnosis and monitoring of thyroid disease. Clin Endocrinol (Oxf). 2003;58:13840

16. Baloch Z, Carayon P, Conte-Devolx B, Demers LM, Feldt-Rasmussen U, Henry JF, LiVosli VA, Niccoli-Sire P, John R, Ruj J, Smyth PP, Spencer CA, Stockigt JR, Guidelines Committee, National Academy of Clinical Biochemistry 2003 Laboratory medicine practice guidelines. Laboratory support for the diagnosis and monitoring of thyroid disease. Thyroid. 2003 Jan;13(1):3-126

A longitudinal study in diabetics where a baseline TSH levels above the 1.53 mU/liter predicted subsequent thyroid dysfunction, whereas no thyroid dysfunction if TSH levels < 1.53 mU/liter, the reference range for diabetics should then be 0.4-1.52 mU/liter

17. Warren RE, Perros P, Nyirenda MJ, Frier BM. Serum thyrotropin is a better predictor of future thyroid dysfunction than thyroid autoantibody status in biochemically euthyroid patients with diabetes: implications for screening. Thyroid. 2004;14:8537

If the serum TSH reference range would be based upon a cohort of truly normal individuals with no personal or family history of thyroid dysfunction, no visible or palpable goiter, not taking any medication, who are seronegative for thyroid preoxidase antibodies, and whose blood samples are drawn fasting in the morning hours (0610 h), the TSH reference range would become 0.42.5 mU/L (Demers & co, Baloch & co.)

18. Demers LM, Spencer CA. Laboratory medicine practice guidelines: laboratory support for the diagnosis and monitoring of thyroid disease. Clin Endocrinol (Oxf). 2003;58:13840

19. Hollowell JG, Staehling NW, Flanders WD, Gunter EW, Spencer CA, Braverman LE. Serum TSH, T4, and thyroid antibodies in the United States population (1988 to 1994): National Health and Nutrition Examination Survey (NHANES III). J Clin Endocrinol Metab. 2002; 87:48999

20. Baloch Z, Carayon P, Conte-Devolx B, Demers LM, Feldt-Rasmussen U, Henry JF, LiVosli VA, Niccoli-Sire P, John R, Ruj J, Smyth PP, Spencer CA, Stockigt JR, Guidelines Committee, National Academy of Clinical Biochemistry 2003 Laboratory medicine practice guidelines. Thyroid. 2003 Jan;13(1):3-126

When data for subjects with positive TPOAb or a family history of autoimmune thyroid disease are excluded, the normal reference interval becomes much tighter, i.e. 0.42.0 mU/liter. This tighter reference range may certainly be more applicable to African-Americans, who have a lower mean TSH

21. Hollowell JG, Staehling NW, Flanders WD, Gunter EW, Spencer CA, Braverman LE. Serum TSH, T4, and thyroid antibodies in the United States population (1988 to 1994): National Health and Nutrition Examination Survey (NHANES III). J Clin Endocrinol Metab. 2002; 87:48999
22. Demers LM, Spencer CA. Laboratory medicine practice guidelines: laboratory support for the diagnosis and monitoring of thyroid disease. Clin Endocrinol (Oxf). 2003;58:13840

Publications with data to support a more narrow reference range for serum TSH that would be obtained when persons with diffuse hypoechogenicity of the thyroid on ultrasound, a condition that precedes thyroid peroxidase antibody positivity in autoimmune thyroid disease, would be excluded

23. Pedersen OM, Aardal NP, Larssen TB, Varhaug JE, Myking O, Vik-Mo H. The value of ultrasonography in predicting autoimmune thyroid disease. Thyroid. 2000;10:2519
For the American Association of Clinical Endocrinologists the revised reference TSH range is 0.33.0 mU/L

24. American Association of Clinical Endocrinologists. American Association of Clinical Endocrinologists medical guidelines for clinical practice for the evaluation and treatment of hyperthyroidism and hypothyroidism. Endocr Pract. 2002;8:45769

Ethnic differences: the mean TSH level in African-Americans is 1.18 mU/liter, in contrast to a mean of 1.40 mU/liter in Caucasians, due to the greater frequency of autoimmune thyroid disease in whites (12.3%) than in blacks (4.3%), which may have unjustifiedly skewed the upper end of the TSH curve (NHANES data). For African-Americans, the TSH reference range should therefore be lower than in whites

25. Hollowell JG, Staehling NW, Flanders WD, Gunter EW, Spencer CA, Braverman LE. Serum TSH, T4, and thyroid antibodies in the United States population (1988 to 1994): National Health and Nutrition Examination Survey (NHANES III). J Clin Endocrinol Metab. 2002;87:4899

A study, which suggests that the serum TSH cut-off point between hypo- and euthyroidism is 2, not 4 or 5.5

26. Michalopoulou G, Alevizaki M, Piperingos G, Mitsibounas D, Mantzos E, Adampoulos P, Koutras DA. High serum cholesterol levels in persons with ‘high-normal’ TSH levels: Should one extend the definition of subclinical hypothyroidism? Eur J Endocrinol. 1998 Feb;138(2):141-5(Treating TPO antibody-positive hypercholesterolemic patients with TSH levels between 2-4 mU/L with low dose levothyroxine normalizes TSH levels and improves the lipid profile)

In 2003, the National Academy of Clinical Biochemistry (NACB) has reduced the upper limit of the reference range from 5.5 to 4.1 mU/L, but stating also that “greater than 95% of healthy, euthyroid subjects have a serum TSH concentration between 0.4 2.5 mU/L“. “.. patients with a serum TSH >2.5 mU/L, when confirmed by repeat TSH measurement made after 3 to 4 weeks, may be in the early stages of thyroid failure, especially if thyroid peroxidise antibodies are detected

27. Baloch Z, Carayon P, Conte-Devolx B, Demers LM, Feldt-Rasmussen U, Henry JF, LiVosli VA, Niccoli-Sire P, John R, Ruj J, Smyth PP, Spencer CA, Stockigt JR, Guidelines Committee, National Academy of Clinical Biochemistry 2003 Laboratory medicine practice guidelines. Thyroid. 2003 Jan;13(1):3-126

Supporters of the recommendations of the consensus panel (Endocrine Society, American Association of Clinical Endocrinologists, American Thyroid Association) promote a target TSH range of 1.01.5 mU/liter in patients already receiving T4 therapy

28. Baloch Z, Carayon P, Conte-Devolx B, Demers LM, Feldt-Rasmussen U, Henry JF, LiVosli VA, Niccoli-Sire P, John R, Ruj J, Smyth PP, Spencer CA, Stockigt JR, Guidelines Committee, National Academy of Clinical Biochemistry 2003 Laboratory medicine practice guidelines. Thyroid. 2003 Jan;13(1):3-126

The lower end of the normal or reference range for TSH lies between 0.2 and 0.4 mU/liter, as indicated by a number of clinical studies

29. Baloch Z, Carayon P, Conte-Devolx B, Demers LM, Feldt-Rasmussen U, Henry JF, LiVosli VA, Niccoli-Sire P, John R, Ruj J, Smyth PP, Spencer CA, Stockigt JR, Guidelines Committee, National Academy of Clinical Biochemistry 2003 Laboratory medicine practice guidelines. Thyroid. 2003 Jan;13(1):3-126

30. Parle JV, Franklyn JA, Cross KW, Jones SC, Sheppard MC. Prevalence and follow-up of abnormal thyrotrophin (TSH) concentrations in the elderly in the United Kingdom. Clin Endocrinol (Oxf). 1991;34:77-83

31. Warren RE, Perros P, Nyirenda MJ, Frier BM. Serum thyrotropin is a better predictor of future thyroid dysfunction than thyroid autoantibody status in biochemically euthyroid patients with diabetes: implications for screening. Thyroid. 2004;14:8537

32. Canaris GJ, Manowitz NR, Mayor G, Ridgway EC. The Colorado thyroid disease prevalence study. Arch Intern Med. 2000;160:52634

33. Sawin CT, Geller A, Kaplan MM, Bacharach P, Wilson PW, Hershman JM. Low serum thyrotropin (thyroid stimulating hormone) in older persons without hyperthyroidism. Arch Intern Med. 1991;151:1658

34. Hershman JM, Pekary AE, Berg L, Solomon DH, Sawin CT Serum thyrotropin and thyroid hormone levels in elderly and middle-aged euthyroid persons. J Am Geriatr Soc. 1993;41:8238
35. Parle JV, Maisonneuve P, Sheppare MC, Boyle P, Franklyn JA. Prediction of all-cause and cardiovascular mortality in elderly people from one low serum thyrotropin result: a 10-year cohort study. Lancet. 2001;358:8615

The TSH reference range for an INDIVIDUAL is narrower than the reference range for a population

The value of a population-based reference range is limited when the individual patient-based reference range (i.e. his personal reference range) is narrow

36. Fraser CG, Harris EK. Generation and application of data on biological variation in clinical chemistry. Crit Rev Clin Lab Sci. 1989;27:40937

37. Harris EK. Effects of intra- and interindividual variation on the appropriate use of normal ranges. Clin Chem. 1974;20:153542

The individual TSH reference ranges are remarkably narrow within a relatively small segment of the population reference range, i.e. confined to only 25% of a range of 0.35.0 mU/liter.

A shift in the TSH value of the individual outside of his or her individual reference range, but still within the population reference range, would not be normal for that individual. For example, an individual (as in Andersons series) with a personal range of 0.51.0 mU/liter would be at subphysiological thyroid hormone levels at the population mean TSH of 1.5 mU/liter (as explained by Wartofsky 2005)

38. Andersen S, Petersen KM, Brunn NH, Laurberg P. Narrow individual variations in serum T4 and T3 in normal subjects: a clue to the understanding of subclinical thyroid disease. J Clin Endocrinol Metab. 2002;87:106872

Studies of twins have data to support that each of us has a genetically determined optimal free T4 (FT4)-TSH set point or relationship

39. Demers LM, Spencer CA. Laboratory medicine practice guidelines: laboratory support for the diagnosis and monitoring of thyroid disease. Clin Endocrinol (Oxf). 2003;58:13840

40. Meikle AW, Stringham JD, Woodward MG, Nelson JC. Hereditary and environmental influences on the variation of thyroid hormones in normal male twins. J Clin Endocrinol Metab. 1988 ; 66:58892

A measured TSH difference of 0.75 mU/liter can already be significant in a patient. The NACB guideline 8 states that “the magnitude of difference in TSH values that would be clinically significant when monitoring a patients response to therapy is 0.75 mU/liter. Greater TSH fluctuations in a specific patient may mean that s/he becomes hypothyroid or hyperthyroid.
41. Baloch Z, Carayon P, Conte-Devolx B, Demers LM, Feldt-Rasmussen U, Henry JF, LiVosli VA, Niccoli-Sire P, John R, Ruj J, Smyth PP, Spencer CA, Stockigt JR, Guidelines Committee, National Academy of Clinical Biochemistry 2003 Laboratory medicine practice guidelines. Thyroid. 2003 Jan;13(1):3-126

A serum TSH that rises in a given individual from a set point of 1.0 to 3.5 is likely to be abnormally elevated and imply early thyroid failure. A minor change in serum free T4 results in an amplified change in TSH to outside of the usual population-based reference range, although the free T4 is still within its own population-based reference range, because of the the log-linear relationship between TSH and free T4. In the case of subclinical hypothyroidism, for example, a slight drop in free T4 results in an amplified and inverse response in TSH secretion (as explained by Wartofsky 2005)

42. Cooper DS. Subclinical hypothyroidism. N Engl J Med. 2001;345:2605

43. Ayala A, Wartofsky L. Minimally symptomatic (subclinical) hypothyroidism. Endocrinologist. 1997;7:4450

There is a 3-fold difference between the average daily maximal TSH (3) and minimal TSH (1 mIU/ml)

89. Brabant G, Prank K, Ranft U, Schuermeyer T, Wagner TO, Hauser H, Kummer B,
44. Feistner H, Hesch RD, von zur Muhlen A. Physiological regulation of circadian and pulsatile thyrotropin secretion in normal man and woman. J Clin Endocrinol Metab. 1990 Feb;70(2):403-9

Conclusion: TSH reference range is too large => need for narrower ranges

45. Pain RW. Simple modifications of three routine in vitro tests of thyroid function. Clin Chem. 1976; 22(10): 1715-8.

46. Dickey RA, Wartofsky L, Feld S. Optimal thyrotropin level: normal ranges and reference intervals are not equivalent. Thyroid. 2005 Sep;15(9):1035-9

47. Wartofsky L, Dickey RA. The evidence for a narrower thyrotropin reference range is compelling. J Clin Endocrinol Metab. 2005 Sep;90(9):5483-8

Other arguments that may explain why the TSH test alone is not the only test
The TSH test is insufficient to diagnose all forms of hypothyroidism, including the borderline forms.

The frequency of abnormal TSH values

48. Canaris GJ, Manowitz NR, Mayor G, Ridgway EC. The Colorado thyroid disease prevalence study. Arch Intern Med. 2000;160:52634

49. Warren RE, Perros P, Nyirenda MJ, Frier BM. Serum thyrotropin is a better predictor of future thyroid dysfunction than thyroid autoantibody status in biochemically euthyroid patients with diabetes: implications for screening. Thyroid. 2004;14:8537

Longitudinal studies indicating a rate of progression of mild thyroid failure into overt hypothyroidism of about 5% per year (50% or more in 10 years!): they have to be treated
50. Vanderpump MPJ, Tunbridge WMG, French JM, Appleton D, Bates D, Clark F, Grimley Evans J, Hasan DM, Rodgers H, Tunbridge F. The incidence of thyroid disorders in the community: a twenty-year follow-up of the Whickham Survey. Clin Endocrinol (Oxf). 1995; 43:5568

51. Parle JV, Franklyn JA, Cross KW, Jones SC, Sheppard MC. Prevalence and follow-up of abnormal thyrotrophin (TSH) concentrations in the elderly in the United Kingdom. Clin Endocrinol (Oxf). 1991;34:7783

52. Huber G, Staub J-J, Meier C, Mitrache C, Guglielmetti M, Huber P, Braverman LE. Prospective study of the spontaneous course of subclinical hypothyroidism: prognostic value of thyrotropin, thyroid reserve, and thyroid antibodies. J Clin Endocrinol Metab. 2002;87:32216

53. Kabadi UM. Subclinical hypothyroidism: natural course of the syndrome during a prolonged follow-up study. Arch Intern Med. 1993;153:957-61

The pituitary 5-deiodinase type 2 that converts thyroxine into triiodothyronine (T3), is different than the liver and kidney 5-deiodinase type 1 that provides the T3 for the rest of the body. This difference may explain why TSH secretion and thus serum TSH secreted by the pituitary gland may be normal, while the rest of the body may be in a thyroid deficient state.

54. Koenig RJ, Leonard JL, Senator D, Rappaport N, Watson A, Larsen PR. Regulation of thyroxine 5′-deiodinase activity by 3,5,3′-triiodothyronine in cultured anterior pituitary cells. Endocrinology. 1984 Jul;115(1):324-9.

In fasting, hypothyroidism or selenium deficiency for example, the 5-deiodinase of the pituitary gland increases or remains unchanged, while that of the liver decreases.

55. Suda AK, Pittman CS, Shimizu T, Cambers JB. The production and metabolism of 3,5,3′-triiodothyronine and 3,3′,5′-triiodothyronine in normal and fasting subjects. J Clin Endocrinol Metab. 1978 Dec;47(6):1311-9

56. Larsen PR, Silva JE, Kaplan MM. Relationships between circulating and intracellular thyroid hormones: Physiological and clinical implications. Endocr Rev. 1981 Winter;2(1):87-102.

57. Chanoine JP, Safran M, Farwell AP, Tranter P, Ekenbarger DM, Dubord S, Arthur JR, Beckett GJ, Braverman LE Dubord S, Alex S, Arthur JR, Beckett GJ, Braverman LE, Leonard JLl. Selenium deficiency and type II 5′-deiodinase regulation in the euthyroid and hypothyroid rat: evidence of a direct effect of thyroxine. Endocrinology. 1992 Jul;131(1):479-84

A normal or low serum TSH may reflect in elderly persons hypothyroidism in peripheral tissues, and not anymore eu- or hyperthyroidism, because the pituitary gland has aged. Progressively with increasing age, the serum TSH test becomes less reliable as a diagnostic test.

58. Urban RJ. Neuroendocrinology of aging in the male and female. Endocrinol Metab Clin North Am. 1992;21(4): 921-31.

Necessity for other tests than the TSH to diagnosis thyroid dysfunction, e.g. the serum free T4

59. Ladenson PW. Diagnosis of hypothyroidism. In Werner and Ingbar’s The Thyroid, 7th edition, Braverman LE and Utiger RE, Lippincott-Raven Publishers, Philadelphia. 1996; 878-82

60. Pacchiarotti A, Martino E, Bartalena L, Aghini Lombardi F, Grasso L, Buratti L, Falcone M, Pinchera A. Serum free thyroid hormones in subclinical hypothyroidism. J Endocrinol Invest. 1986 Aug;9(4):315-9

61. Surks MI, Chopra IJ, Mariosh CN, Nicoloff JT, Salomon DH. American Thyroid Association guidelines for use of laboratory tests in thyroid disorders. JAMA. 1990 Mar 16;263(11):1529-32

62. Davis JR, Black EG, Sheppard MC. Evaluation of a sensitive chemiluminescent assay for TSH in the follow-up of treated thyrotoxicosis. Clin Endocrinol Oxf. 1987; 27(5): 563-70

Serum thyroid hormone levels may not reflect the cellular thyroid status

63. Escobar del Rey F, Ruiz de Ona C, Bernal J, Obregon MJ, Morreale de Escobar G. Generalized deficiency of 3, 5, 3′-triiodothyronine in tissues from rats on a low iodine intake, despite normal circulating T3 levels. Acta Endocrinol (Copenh) 1989; 120: 490-8

Need to analyse valuable indicators of peripheral activity such as the serum levels of plasma binding proteins SHBG, TBG, CBG, or of thyroid-dependent enzymes such as alkaline phosphatase, osteocalcin

64. Smallridge RC. Metabolic, physiologic, and clinical indexes of thyroid function. In Werner and Ingbar’s The Thyroid, 7th edition, Braverman LE and Utiger RP, Lippincott-Raven Publishers, Philadelphia, 1996

65. Foldes J, Tarjan G, Banos C, Nemeth J, Varga F, Buki B. Biologic markers in blood reflecting thyroid hormone effect at peripheral tissue level in patients receiving levothyroxine replacement for hypothyroidism. Exp Clin Endocrinol. 1992; 99(3): 129-3

Conditions or factors that DEPRESS the serum TSH

Aging

66. Urban RJ. Neuroendocrinology of aging in the male and female. Endocrinol Metab Clin North Am. 1992;21(4): 921-31

67. Sawin CT, Geller A, Kaplan MM, Bacharach P, Wilson PW, Hershman JM. Low serum thyrotropin (thyroid-stimulating hormone) in older persons without hyperthyroidism. Arch Intern Med. 1991; 151(1): 165-8

Fasting
68. Croxson MS, Hall TD, Kletzky OA, Jaramillo JE, Nicoloff OA. Decreased serum thyrotropin induced by fasting. J Clin Endocrinol Metab. 1977; 45: 560

69. Borst GC, Osburne RC, O’Brian JT, Georges LP, Burman KD. Fasting decreases thyrotropin responsiveness to thyrotropin-releasing hormone: A potential cause of misinterpretation of thyroid function tests in the critically ill. J Clin Endocrinol Metab. 1983 Aug;57(2):380-3

70. Campbell GA, Kurcz M, Marshall S, Meites J. Effects of starvation in rats on serum levels of follicle stimulating hormone, luteinizing hormone, thyrotropin, growth hormone and prolactin; response to LH-releasing hormone and thyrotropin-releasing hormone. Endocrinology. 1977; 100(2): 580-7

71. Opstad PK. The thyroid function in young men during prolonged physical stress and the effect of energy and sleep deprivation. Clin Endocrinol. 1984; 20: 657-69.

Strenuous physical exercise

72. Scanlon MF, Toft AD. Regulation of thyrotropin secretion. In Werner and Ingbar’s The Thyroid, 7th edition

Pregnancy (first trimester)

73. Braverman LE and Utiger RE, Lippincott-Raven Publisers, Philadelphia. 1996; 220-40.
Depression and anxiety disorders

74. Bartalena L, Placidi GF, Martino E, Falcone M, Pellegrini L, Dell’Osso L, Pacchiarotti A, Pinchera A. Nocturnal serum thyrotropin (TSH) surge and the TSH response to TSH-releasing hormone: dissociated behavior in untreated depressives. Clin Endocrinol Metab. 1990 Sep;71(3):650-5.

75. Rupprecht R, Rupprecht C, Rupprecht M, Noder M, Mahlstedt J. Triiodothyronine, thyroxine, and TSH response to dexamethasone in depressed patients and normal controls. Biol Psychiatry. 1989;25(1): 22-32.

76. Maeda K, Yoshimoto Y, Yamadori A. Blunted TSH and unaltered PRL responses to TRH following repeated administration of TRH in neurological patients: A replication of neuroendocrine features of major depression. Biol Psychiatry. 1993; 33(4): 277-83.

77. Duval F, Macher JP, Mokrani MC. Difference between evening and morning thyrotropin responses to protirelin in major depressive episode. Arch Gen Psychiatry. 1990; 47(5): 443-8.

78. Loosen PT, Prange AJ Jr. erum thyrotropin response to thyrotropin-releasing hormone in psychiatric patients: A review. Am J Psychiatry 1982; 139(4): 405-16.

Non-thyroidal diseases: diabetes mellitus, Cushings syndrome, renal failure, cancer, myocardial infarction, AIDS, post-traumatic syndromes, chronic alcoholic liver disease, other illnesses

79. Devos P. Rationele keuze van schildklierfunctie tests. Tijdschr Geneesk. 1990; 46(8): 591-9

80. Alexander CM, Kaptein EM, Lum SMC, Spencer CA, Kumar K, Nicoloff JT. Pattern of recovery of thyroid hormone indices associated with treatment of diabetes mellitus. J Clin Endocrinol Metab. 1982; 54: 362-366

81. Andrade SF, Kanitz-Ml, Povoa H Jr. Study of thyrotropic reserve in diabetics of adult type. Acta-Biol Mod Ger 1977; 36(10): 1479-81

82. Gonzalez C, Montoya-E, Jolin T. Effect of streptozotocin diabetes on the hypothalamic pituitary thyroid axis in the rat. Endocrinology 1980; 107(6): 2099-103

83. Rossi GL, Bestetti GE, Tontis DK, Varini M. Reverse hemolytic plaque assay study of luteinizing and follicle-stimulating hormone and thyrotropin secretion in diabetic rat pituitary glands. Diabetes 1989; 38(10): 1301-6

84. Adriaanse R, Brabant G, Endert E, Wiersinga W. Pulsatile thyrotropin secretion in patients with Cushing’s syndrome. Metabolism. 1994 Jun;43(6):782-6

85. Beyer HK-, Schuster P, Pressler H. Studies on hypothalamic pituitary thyroid regulation in hemodialysis patients. Nuklearmedizin 1981;20(1):19-24

86. Kokei S, Inoue T, lino S. Serum free thyroid hormones and response of TSH to TRH in nonthyroidal illnesses. Nippon Naibunpi Gakkai Zasshi. 1986; 62(11): 1231-43

87. De Marinis L, Mancini A, Masala R, Torlontano M, Sandric S, Barbarino A. Evaluation of pituitary-thyroid axis response to acute myocardial infarct. J Endocrinol Invest. 1985; 8(6): 519-22

88. Rondanelli M, Solerte SG, Fioravanti M, Scevola K, et al. Circadian secretory pattern of growth hormone, insulin-like growth factor type I, cortisol, adrenocorticotropic hormone, thyroid-stimulating hormone, and prolactin during HIV infection. AIDS Res Hum Retroviruses. 1997; 13(14): 1243-9.

89. Wintemitz WW, Dzur JA. Pituitary failure secondary to head trauma. Case report. J Neurosurg. 1976; 44(4): 504-5

90. Dzur JA, Wintemitz WW. Posttraumatic hypopituitarism: Anterior pituitary insufficiency secondary to head trauma. South Med J. 1976; 69(10): 1377-9

91. Modigliani E, Periac P, Perret G, Hugues JN, Coste T. TRH response in 53 patients with chronic alcoholism. Ann Med Interne Paris. 1979; 130(5):297-302

92. Ekman AC, Vakkuri 0, Ekman M, Leppalusto J, Ruckonen A, Knip M. Ethanol decreases nocturnal plasma levels of thyrotropin and growth hormone but not those of thyroid hormones or protection in man. J Clin Endocrinol Metab. 1996; 81(7):2627-32

93. Bacci V, Schussler GC, Kaplan TB. The relationschip between serum triidothyronine and thyrotropin during systemic illness. J Clin Endocrinol Metab. 1982; 54:1229-35

94. Hamblin PS, Dyer SA, Mohr VS, Le Grand BA, Lim CF, Tuxen DV, Topliss DJ, Stockigt JR. Relationship between thyrotropin and thyroxine changes during recovery from severe hypothyroxinemia of critical illness. J Clin Endocrinol Metab. 1986 Apr;62(4):717-22

95. Bermudez F, Sucks MI, Opperheimer JH. High incidence of decreased serum triiodothyronine concentration in patients with nonthyroidal disease. J Clin Endocrinol Metab. 1975; 41: 27-40.

Medications: thyroid therapy, estroprogestative birth control pills, progestogens, anti-infammatory agents (incl. glucocorticoids and aspirin), antidepressants, L-Dopa, bromocriptine, neuroleptica, anti-hypertensives, antiarrhythmics (amiodarone), hypolipemic agents, IGF-1, somatostatin, etc.

96. Franklyn JA, Black EG, Betteridge J, Sheppard MC. Comparison of second and third generation methods for measurement of serum thyrotropin in patients with overt hyperthyroidism, patients receiving thyroxine therapy, and those with nonthyroidal illness. J Clin Endocrinol Metab. 1994;78(6):1368-71

97. Gow SM, Caldwell G, Toft AD, Seth J, Hussey AJ, Sweeting VM, Beckett GJ. Relationship between pituitary and other target organ responsiveness in hypothyroid patients receiving thyroxine replacement. J Clin Endocrinol Metab. 1987;64(2):364-70

98. Custro N, Scafidi V Costanzo G, Corsello FP. Variations in the serum levels of thyroid hormones and TSH after intake of a dose of L-thyroxine in euthyroid subjects and in adequately treated hypothyroid patients. Bull Soc Ital Biol Sper. l989; 65(11):1045-52

99. England ML, Hershman JM. Serum TSH concentration as an aid to monitoring compliance with thyroid hormone therapy in hypothyroidism. Am J Med Sci. 1986 Nov;292(5):264-6

100. Chopra U, Carlson HE, Solomon DH. Comparison of inhibitory effects of 3,5,3′-triiodothyronine (T3), thyroxine (T4), 3,3,’,5′-triiodothyronine (rT3,), and 3,3′-diiodothyronine (T2) on thyrotropin-releasing hormone-induced release of thyrotropin in the rat in vitro. Endocrinology. 1978; 103(2): 393-402

101. Fraser WD, Biggart EM, O’Reilly DS, Gray HW, McKillop JH, Thomson JA. Are biochemical tests of thyroid function of any value in monitoring patients receiving thyroxine replacement? Br Med J (Clin Res Ed). 1986 Sep 27;293(6550): 293-808

102. Cooper DS, Walker H, Rodbard D, Maloof F. Peripheral responses to thyroid hormone before and after L-thyroxine therapy in patients with subclinical hypothyroidism. J Clin Endocrinol Metab. 1981 Dec;53(6):1238-42

103. Saberi M, Utiger RD. Serum thyroid hormone and thyrotropin concentrations during thyroxine and triiodothyronine therapy. J Clin Endocrinol Metabol. 1974;39:923-7

104. Rey Stocker I, Zufferey MM, Lemarchand MT, Rais M. The sensibility of the hypophysis, the gonads and the thyroid before and after the administration of oral contraceptives. A resume. Pediatr Ann. 1981;10(12):15-20.

105. Lemarchand-Beraud T. Influence of estrogens on pituitary responsiveness to LHRH and TRH in human. Reymond M, Berthier C. Ann Endocrinol Paris. 1977; 38(6): 379-82.

106. El-Etreby MF, Graf KJ, Gunzel P, Neumann F. Evaluation of effects of sexual steroids on the hypothalamic-pituitary system of animals and man. Arch Toxicol Suppl. 1979;2:11-39

107. Prank K, Ranft U, Bergmann P, Schuermeyer T, Hesch RD, von Zur Muhlen A. Circadian and pulsatile TSH secretion under physiological and pathological conditions. Horm Metab Res Suppl. 1990; 23:12-7

108. Kourides IA, Ridgeway EC, Weintraub BD, Maloof F. The effect of glucocorticoid administation on human pituitary secretion of thyrotropin and prolactin. J Clin Endocrinol Metab. 1976; 43:338-46.

109. Atterwill CK, Catto LC, Heal DJ, Holland CW, Dickens TA, Jones CA. The effects of desipramine (DMI) and electroconvulsive shock (ECS) on the function of the hypothalamo-pituitary-thyroid axis in the rat. Psychoneuroendocrinology. 1989;14(5):339-46

110. Kaptein EM, Kletzsky OA, Spencer CA, NicoloffJT. Effects of prolonged dopamine infusion on anterior pituitary function in normal males. J Clin Endocrinol Metab 1980; 51:488-91

111. Samuels MH, Kramer P, Wilson D, Sexton F. Effect ofnaloxone infusions on pulsatile thyrotropin secretion. J Clin Endocrinol Metab. 1994;78(5):129-32.

112. Burger A, Nicod DP, Lemarchaud-Beraud T, Vallotton MB. Effect of amiodarone on serum triiodothyronine, reverse triiodothyronine, thyroxine and thyrotropin. J Clin Invest 1976; 58: 255-9

113. Davis PJ, Davis FB, Utiger RD, Kulaga SF Jr. Changes in serum thyrotropin (TSH) in man during halofenate administration. J Clin Endocrinol Metab 1976; 43(4): 873-81

114. Trainer PI, Holly 1, Medbak S, Rais LH, Besser GM. The effect of recombinant IGF-1 on anterior pituitary function in healthy volunteers. Clin Endocrinol (Chef) 1994; 41(6): 801-7.

Toxic foods: MSG, alcohol

115. Bakke JL, Lawrence N, Bennett J, Robinson S, Bowers CY. Late endocrine effects of administering monosodium glutamate to neonatal rats. Neuroendocrinology 1978; 26(4): 220-8.

116. Greeley GH Jr, Nicholson GF, Kizer JS. A delayed LH/FSH rise after gonadectomy and a delayed serum TSH rise after thyroidectomy in monosodium-L-glutamate (MSG)-treated rats. Brain Res 1980; 195(1):111-22

117. Modigliani E, Periac P, Perret G, Hugues JN, Coste T. TRH response in 53 patients with chronic alcoholism. Ann Med Interne Paris. 1979; 130(5): 297-302

Thyroid diseases: hyperthyroidism, Graves-Basedow disease, nodular goiter, thyroiditis, secondary or tertiary hypothyroidism, congenital hypothyroidism

118. Spencer CA, Lai-Rosenfeld AO, Guttler RB, LoPresti J, Marcus AO, Nimalasuriya A, Eigen A, Doss RC, Green BJ, Nicoloff JT. Thyrotropin secretion in thyrotoxic and thyroxine-treated patients: assessment by a sensitive immunoenzymometric assay. J Clin Endocrinol Metab. 1986 Aug;63(2):349-55

119. Yeo PP, Loh KC. Subclinical thyrotoxicosis. Adv Intern Med. 1998; 43: 501-32

120. Chanson P. Insuffisance thyrotropic. Rev Prat. 1998 15; 48(18): 2023-6

121. Petersen PH, RosleffF, Rasmussen J, Hobolth N. Studies on the required analytical quality of TSH measurements in screening for congenital hypothyroidism. Scand J Clin Lab Invest Suppl. 1980;155: 5-93.

122. Fofanova 0V, Takamura N, Kinoshita E, Yoshimoto M, Tsuji Y, Peterkova VA, Evgrafov 0V, Dedov II, Goncharov NP, Yamashita S. Rarity of PIT1 involvement in children from Russia with combined pituitary hormone deficiency. Am J Med Genet 1998; 77(5): 360-5.

FACTORS that ELEVATE the serum TSH

Neonatus, stress emotional arousal, cold exposure, sleep deprivation, adrenal insufficiency, recovery from severe illness, congenital malformations

123. Hashimoto H, Sato F, Kubo M, Ohki T. Maturation of the pituitary-thyroid axis during the perinatal period. Endocrinol Jpn 1991;38(2):151-7

124. Gendrel D, Feinstein MC, Grenier J, Roger M, Ingrand J, Chaussain JL, Canlorbe P, Job JC. Falsely elevated serum thyrotropin (TSH) in newborn infants: Transfer from mothers to infants of a factor interfering in the TSH radioimmunoassay. J Clin Endocrinol Metab 1981;52(1):62-5.

125. Armario A, Lopez Calderon A, Jolin T, Castellanos JM. Sensitivity of anterior pituitary hormones to graded levels of psychological stress. Life Sci 1986; 39(5): 471-5

126. Reed HL, Silverman ED, Shakir KM, Dons R, Burman KD, O’Brian JT. Changes in serum triiodothyronine (TQ kinetics after prolonged Antarctic residence: The polar T3 syndrome. J Clin Endocrinol Metab. 1990; 70(4): 965-74

127. Sadamatsu M, Kato N, Iida H, Takahashi S, Sakaue K, Takahashi K, Hashida S, Ishikawa E. The 24-hour rhythms in plasma growth hormone, prolactin and thyroid stimulating hormone: effect of sleep deprivation. J Neuroendocrinol. 1995 Aug;7(8):597-606

128. Sjoberg S, Wemer S. Increased level of TSH can be a sign of adrenal cortex failures: Not necessarily of thyroid gland disease. Lakartidningen 1999; 96(5):464-5

129. De Nayer P, Dozin B, Vandeput Y, Bottazzo FC, Crabbe J. Altered interaction between triiodothyronine and its nuclear receptors in absence of cortisol: A proposed mechanism for increased thyrotropin secretion in corticoid deficiency states. Eur J Clin Invest. 1987 Apr;17(2):106-8

130. Oakley GA, Muir T, Ray M, Girdwood RW, Kennedy R, Donaldson MD. Increased incidence of congenital malformations in children with transient thyroid-stimulating hormonal elevation on neonatal screening. J Pediatr. 1998; 132(4): 573-4

Medications: iodine, antithyroidea, , lithium, neuroleptica (haloperidol, chlorpromazine), cimetidine, sulfapyridine, clomifen, antidepressants (sertraline), antihistaminic agents, cholestograhic agents, etc.

131. Devos P. Rationele keuze van schildklierfunctie tests. Tijdschr Geneesk. 1990;46(8):591-9

132. Kleinmann RE, Vagenakis AG, Braverman LE. The effect of iopanoic acid on the regulation of thyrotropin secretion in euthyroid subjects. J Clin Endocrinol Metab. 1980;51(2): 399-403

133. Mc Caven KC, Garber JR, Spark R. Elevated serum thyrotropin in thyroxine-treated patients with hypothyroidism given sertraline. N Engl J Med. 1997; 337(14):1010-1

134. Brown CG, Harland RE, Major IR, Atterwill CK. Effects of toxic doses of a novel histamine (H2) antagonist on the rat thyroid gland. Food Chem Toxicol. 1987; 25(10):787-94

Auto-immune thyroiditis and hypothyroidism: primary, iodine-deficient, thyroid hormone resistance

135. Devos P. Rationele keuze van schildklierfunctie tests. Tijdschr Geneesk. 1990;46(8): 591-9

136. Missler U, Gutekunst R, Wood WG. Thyroglobulin is a more sensitive indicator of iodine deficiency than thyrotropin: Development and evaluation of dry blood spot assays for thyrotropin and thyroglobulin in iodine- deficient geographical areas. Eur J Clin Chem Clin Biochem 1994; 32(3): 137-43

137. Volpe R. Subacute (de Quervain’s) thyroiditis. J Clin Endocrinol Metab. 1979 Mar;8(1):81-95

138. Massoudi MS, Meilahn EN, Orchard TJ, Foley TP Jr, Kuller LH, Costantino JP, Buhari AM. Thyroid function and perimenopausal lipid and weight changes: the Thyroid Study in Healthy Women (TSH-W). J Womens Health. 1997 Oct;6(5):553-8

139. Smallridge RC, Parker RA, Wiggs EA, Rajagopal KR, Fein HG. Thyroid hormone resistance in a large kindred: physiologic, biochemical, pharmacologic, and neuropsychologic studies. Am J Med. 1989 Mar;86(3):289-96

TSH-secreting tumors (rare)

140. Smallridge RC. Thyrotropin-secreting pituitary tumors, Endocrinol Metab Clin North Am 1987 Sep;16(3):765-92

FACTORS that ELEVATE or DEPRESS serum TSH

Physiological serum TSH fluctuations

141. Brabant G, Prank K, Ranft U, Schuermeyer T, Wagner TO, Hauser H, Kummer B, Feistner H, Hesch RD, von zur Muhlen A. Physiological regulation of circadian and pulsatile thyrotropin secretion in normal man and woman. J Clin Endocrinol Metab. 1990 Feb;70(2):403-9

142. Brabant G, Prank K, Ranft U, Bergmann P, Schuermeyer T, Hesch RD, von zur Muhlen A. Circadian and pulsatile TSH secretion under physiological and pathophysiological conditions. Horm Metab Res Suppl. 1990;23:12-7

143. Goichot B, Brandenberger G, Schlienger JL. Secretion of thyrotropin during states of wakefulness and sleep. Physiological data and clinical applications. Presse Med. 1996;25(21):980-4

144. Rao ML, Gross G, Strebel B, Halaris A, Huber G, Braunig P, Marler M. Circadian rhythm of tryptophan, serotonin, melatonin, and pituitary hormones in schizophrenia. Biol Psychiatry. 1994;1:35(3): 151-63

145. Rose SR, Nisula BC. Circadian variation of thyrotropin in childhood. J Clin Endocrinol Metab. 1989; 68(6):1086-90

146. Scanlon MF, Weetman AP, Lewis M, Pourmand M, Rodriguez Arnao MD, Weightman DR, Hall R. Dopaminergic modulation of circadian thyrotropin rhythms and thyroid hormone levels in euthyroid subjects. J Clin Endocrinol Metab. 1980 Dec;51(6):1251-6

147. Rom Bugoslavskaia ES, Shcherbakova VS. Seasonal characteristics of the effect of melatonin on thyroid function. Bull Eksp Biol Med. 1986;101(3):268-9

Variations in the biological activity of TSH

148. Beck-Peccoz P, Persani L. Variable biological activity of thyroid stimulating hormone. Eur J Endocrinol. 1994 Oct;131(4):331-40

149. Maes M, Mommen K, Hendrickx D, Peeters D, D’Hondt P, Ranjan R, De Meyer F, Scharpe S. Components of biological variation of TSH, TT3, FT4, PRL, cortisol and testosterone in healthy volunteers. Clin Endocrinol (Oxf). 1997 May;46(5):587-98

150. Hiromoto M, Nishikawa M, Ishihara T, Yoshikawa N, Yoshimura M, Inada M. Bioactivity of thyrotropin (TSH) in patients with central hypothyroidism: Comparison between the in vivo 3,5,3′- triiodo-thyronine response to TSH and in vitro bioactivity of TSH. J Clin Endocrinol Metab. 1995 Apr;80(4):1124-8

TSH test kit imperfections

151. Rasmussen AK, Hilsted L, Perrild H, Christiansen E, Siersbaek-Nielsen K, Feldt-Rasmussen U. Discrepancies between thyrotropin (TSH) meaasurement by four sensitive immunometric assays. Clin Chim Acta. 1997 Mar 18;259(1-2):117-28

152. Libeer JC, Simonet L, Gillet R. Analytical evaluation of twenty assays for determination of thyrotropin (TSH). Ann Biol Clin Paris. 1989; 47(1): 1-11

153. Spencer CA, Takeuchi M, Kazarosyan M, MacKenzie F, Beckett GJ, Wilkinson E. Interlaboratory/intermethod differences in functional sensitivity of immunometric assays of thyrotropin (TSH) and impact on reliability of measurement of subnormal concentrations of TSH. Clin Chem. 1995 Mar;41(3):367-74

154. Faber J, Gam A, Siersbaek Nielsen K. Improved sensitivity of serum thyrotropin measurements: Studies on serum sex hormone-binding globulin in patients with reduced serum thyrotropin. Acta Endocrinol Copenh 1990; 123(5): 535-40

155. Laurberg P. Persistent problems with the specificity of immunometric TSH assays. Thyroid. 1993 Winter;3(4):279-83

156. Schlienger JL, Sapin R, Grunenberger F, Gasser F, Pradignac A. Thyrotropin assay by chemiluminescence in the diagnosis of dysthyroidism with low thyrotropin and normal thyroid hormones levels. Pathol Biol Paris. 1993; 41(5): 463-8

157. Spencer C, Eigen A, Shen D, Duda M, Qualls S, Weiss S, Nicoloff J. Specificity of sensitive assays of thyrotropin (TSH) used to screen for thyroid disease in hospitalized patients. Clin Chem. 1987 Aug;33(8):1391-6

158. Spencer CA, Challand GS. Interference in a radioimmunoassay for human thyrotropin. Clin Chem 1977;23(3): 584-8

159. Kahn BB, Weintraub BD, Csako G, Zweig MH. Factitious elevation of thyrotropin in a new ultra-sensitive assay: Implications for the use of monoclonal antibodies in ‘sandwich’ immuno-assay. J Clin Endocrinol Metab. 1988 Mar;66(3):526-33

160. Kourides IA, Weintraub BD, Martorana MAL, Maloof F. Alpha subunit contamination of human albumin preparations: Interference in radioimmunoassay. J Clin Endocrinol Metab. 1976; 43(4): 919-23

161. Bartlett WA, Browning MC, Jung RT. Artefactual increase in serum thyrotropin concentration caused by heterophilic antibodies with specificity for IgG of the family Bouidea. Clin Chem. 1986; 32(12): 22(4-9)

162. Csako G, Weintraub BD, Zweig MH. The potency of immunoglobulin antibodies in a monoclonal immunoradiometric assay for thyrotropin. Clin Chem. 1988 Jul;34(7):1481-3

163. Seghers J, Schruers F, De Nayer P, Beckers C. Interference in thyrotropin (TSH) determination: Falsely elevated TSH values in a transplanted patient. Eur J Nucl Med. 1989; 15(4): 194-6

164. Spencer C, Eigen A, Shen D, Duda M, Quails S, Weiss S, Nicoloff J. Specificity of sensitive assays of thyrotropin (TSH) used to screen for thyroid disease in hospitalized patients. Clin Chem. 1987;33(8):1391-6

165. Ealey PA, Marshall NJ, Ekins RP. Time-related thyroid stimulation by thyrotropin and thyroid-stimulating antibodies, as measured by the cytochemical section bioassay. J Clin Endocrinol Metab. 1981;52(3): 483-7

Doubts on the adequateness of measuring the serum TSH as a help to monitor a thyroid treatment ( follow-up) The serum TSH test for follow-up: The risk of misinterpretation increases when monitoring the treatment of hyper- or hypothyroidism

166. Talbot JN, Duron F, Feron R. Aubert P, Milhaud G. Thyroglobulin, thyrotropin and thyrotropin binding inhibiting immunoglobulins assayed at the withdrawal of antithyroid drug therapy as predictors of relapse of Graves’ disease within one year. J Endocrinol Invest. 1989; 12(9): 589-95
In 36-47 % of cinically euthyroid patients receiving adequate long-term thyroid therapy for hypothyroidism, an undetectable serum TSH is found

167. Franklyn JA, Black EG, Betteridge J, Sheppard MC. Comparison of second and third generation methods for measurement of serum thyrotropin in patients with overt hyperthyroidism, patients receiving thyroxine therapy, and those with nonthyroidal illness. J Clin Endocrinol Metab 1994; 78(6): 1368-71

168. Gow SM, Caldwell G, Toft AD, Seth J, Hussey AJ, Sweeting VM, Beckett GJ. Relationship between pituitary and other target organ responsiveness in hypothyroid patients receiving thyroxine replacement. J Clin Endocrinol Metab. 1987; 64(2): 364-70

After intake of thyroid hormones, the serum TSH is transitorily depressed within 60 minutes and remains low for up to 9 hours after intake

169. Chopra U, Carlson HE, Solomon DH. Comparison of inhibitory effects of 3,5,3′-triiodothyronine (T3), thyroxine (T4), 3,3,’,5′-triiodothyronine (rT3,), and 3,3′-diiodothyronine (T2) on thyrotropin-releasing hormone-induced release of thyrotropin in the rat in vitro. Endocrinology. 1978;103(2):393-402

Some patients who exhibit reversion of an initially high TSH level back into the reference range, are found to subsequently develop mild thyroid failure

170. Calaciura F, Motta RM, Miscio G, Fichera G, Leonardi D, Carta A, Trichitta V, Tassi V, Sava L, Vigneri R. Subclinical hypothyroidism in early childhood: a frequent outcome of transient neonatal hyperthyrotropinemia. J Clin Endocrinol Metab. 2002;87:320914

Supporters of the recommendations of the consensus panel promote a target TSH range of 1.01.5 mU/liter in patients already receiving T4 therapy, whereas they refuse to accept TSH levels of 310 mU/liter as abnormal in patients not receiving T4 therapy.

171. Baloch Z, Carayon P, Conte-Devolx B, Demers LM, Feldt-Rasmussen U, Henry JF, LiVosli VA, Niccoli-Sire P, John R, Ruj J, Smyth PP, Spencer CA, Stockigt JR, Guidelines Committee, National Academy of Clinical Biochemistry 2003 Laboratory medicine practice guidelines. Thyroid. 2003 Jan;13(1):3-126

The lower end of the normal or reference range for TSH lies between 0.2 and 0.4 mU/liter, as indicated by a number of clinical studies

172. Baloch Z, Carayon P, Conte-Devolx B, Demers LM, Feldt-Rasmussen U, Henry JF, LiVosli VA, Niccoli-Sire P, John R, Ruj J, Smyth PP, Spencer CA, Stockigt JR, Guidelines Committee, National Academy of Clinical Biochemistry 2003 Laboratory medicine practice guidelines. Thyroid. 2003 Jan;13(1):3-126

173. Parle JV, Franklyn JA, Cross KW, Jones SC, Sheppard MC. Prevalence and follow-up of abnormal thyrotrophin (TSH) concentrations in the elderly in the United Kingdom. Clin Endocrinol (Oxf). 1991;34:77-83

174. Warren RE, Perros P, Nyirenda MJ, Frier BM. Serum thyrotropin is a better predictor of future thyroid dysfunction than thyroid autoantibody status in biochemically euthyroid patients with diabetes: implications for screening. Thyroid. 2004;14:8537

175. Canaris GJ, Manowitz NR, Mayor G, Ridgway EC. The Colorado thyroid disease prevalence study. Arch Intern Med. 2000;160:52634

176. Sawin CT, Geller A, Kaplan MM, Bacharach P, Wilson PW, Hershman JM. Low serum thyrotropin (thyroid stimulating hormone) in older persons without hyperthyroidism. Arch Intern Med. 1991;151:1658

177. Hershman JM, Pekary AE, Berg L, Solomon DH, Sawin CT Serum thyrotropin and thyroid hormone levels in elderly and middle-aged euthyroid persons. J Am Geriatr Soc. 1993;41:8238

178. Parle JV, Maisonneuve P, Sheppare MC, Boyle P, Franklyn JA. Prediction of all-cause and cardiovascular mortality in elderly people from one low serum thyrotropin result: a 10-year cohort study. Lancet. 2001;358:8615