På denne siden presenteres forskning som viser at TSH ikke er brukbart som måleenhet alene for å diagnostisere og behandle stoffskiftesykdommer

 

Alevizaki, M., Mantzou, E., Cimponeriu, A. T., Alevizaki, C. C., & Koutras, D. A. (2005). TSH may not be a good marker for adequate thyroid hormone replacement therapy. Wiener Klinische Wochenschrift, 117(18), 636-640.
Abstract: We conclude that patients with T4-treated hypothyroidism have lower T3 levels, lower T3/T4 ratio and lower SHBG than normal individuals with the same TSH, perhaps indicating relative tissue hypothyroidism in the liver. TSH levels used to monitor substitution, mostly regulated by intracellular T3 in the pituitary, may not be such a good indicator of adequate thyroid hormone action in all tissues.

 

Andersen S, Petersen KM, Brunn NH, Laurberg P (2002). Narrow individual variations in serum T4 and T3 in normal subjects: a clue to the understanding of subclinical thyroid disease. Journal of Clinical Endocrinology and Metabolism. 2002;87:1068–72.
Abstract: High individuality causes laboratory reference ranges to be insensitive to changes in test results that are significant for the individual. Our data indicate that each individual had a unique thyroid function. The individual reference ranges for test results were narrow, compared with group reference ranges used to develop laboratory reference ranges. Accordingly, a test result within laboratory reference limits is not necessarily normal for an individual. Our data indicate that the distinction between subclinical and overt thyroid disease (abnormal serum TSH and abnormal T4 and/or T3) is somewhat arbitrary.

 

Redigert av Professor of Internal Medicine James E. Griffin M.D. Diana and Richard C. Strauss Professor of Biomedical Research, and Chief of Clinical Endocrinology in the Department of Internal Medicine University of Texas Southwestern Medical Center at Dallas,Division of Neuroscience Oregon Regional Primate Research Center/Oregon Health Sciences University Sergio R. Ojeda M.D. Head Griffin James & Ojeda Sergio R, Text Book of Endocrine Physiology, Oxford University Press, 2000
Kapittel om stoffskiftesykdommer begynner på side 294 Det står blant annet at TSH ikke kan brukes som måleenhet alene for å sjekke stoffskiftefunksjonen. Det står også at ettersom grenseverdi/normalverdi hos friske mennesker for stoffskiftehormoner er så bred, kan man utmerket godt ha en stoffskiftesykdom selv om prøvene er normale.

 

2005 S. Karger AG, Basel Effects on bone mineral density by treatment of benign nodular goiter with mildly suppressive doses of L-thyroxine in a cohort women study.
Abstract
OBJECTIVES:
Thyroid diseases and their treatment may influence the osseous system. The influence that prolonged suppressive L-thyroxine (LT4) therapy may have on inducing subclinical hyperthyroidism on bone metabolism is still a matter of debate. The aim of the present study was to assess the effects of chronic LT4 treatment at mildly inhibiting serum thyroid-stimulating hormone (TSH) doses on bone mineral density (BMD) and biochemical bone remodeling markers in a cohort of women with benign nodular goiter, and to verify the efficacy of the treatment on nodule size
CONCLUSIONS:
This study suggests that at slightly suppressing TSH doses, LT4 therapy has no adverse effects on BMD in both pre- and postmenopausal women, while having an efficacy on nodule size comparable with that reported using an LT4 schedule able to maintain TSH near or below the assay sensitivity limit.

 

Becker DV, Bigos ST, Gaitan E, Morris JC, Rallison ML, Spencer CA, Sugarawa M, Van Middlesworth L, Wartofsky L. (1993). Optimal use of blood tests for assessment of thyroid function. Journal of the American Medical Association. 1993 Jun 2; 269: 273 ‘
Introduction: The decision to initiate (thyroid) therapy should be based on both clinical and laboratory findings and not solely on the results of a single laboratory test.

 

De Los Santos ET, Mazzaferri EL (1988). Sensitive thyroid-stimulating hormone assays: Clinical applications and limitations. Comprehensive Therapy. 1988; 14(9): 26-33.
Abstract: Interpretation of the TSH value should be made with a clear understanding of its limitations. At present, it is uncertain whether clinically euthyroid patients with autonomously functioning thyroid nodules, or with multinodular goiters, or patients taking thyroid hormone who have suppressed TSH values, are actually euthyroid at a cellular level. Other factors that affect TSH levels are the biologic variation in its secretion, the presence of heterophilic antibodies in a patient’s serum, and various drugs. The new ultrasensitive TSH assay does not yet replace other thyroid function tests, but it is clearly emerging as an important means of screening patients for thyroid dysfunction. It can usually separate patients with thyroid dysfunction from euthyroid individuals. Good clinical assessment is always necessary, and other thyroid function tests are often needed.

 

Després N, Grant A. (1998). Antibody interference in thyroid assays: a potential for clinical misinformation. Clinical Chemistry March 1998 vol. 44 no. 3 440-454.
Abstract: Measurements of thyrotropin and of total and free thyroxine and triiodothyronine are widely used diagnostic methods for thyroid function evaluation. However, some serum samples will demonstrate a nonspecific binding with assay reagents that can interfere with the measurement of these hormones. Several recent case reports have described the presence of such interferences resulting in reported abnormal concentrations of thyroid hormones inconsistent with the patient’s thyroid state. Circulating thyroid hormone autoantibodies, described in thyroid and nonthyroid disorders, are an important class of interference factor and can bind to hormone tracers used in various immunoassays.

 

Dickey RA, Wartofsky L, Feld S. (2005). Optimal thyrotropin level: normal ranges and reference intervals are not equivalent. Thyroid. 2005 Sep;15(9):1035-9
Abstract: This paper marshals arguments in support of a narrower, optimal or true normal range for thyrotropin (TSH) of 0.4 to 2.5 mIU/L, based on clinical results and recent information on the relatively stable and narrow range of values in patients without thyroid disease. The terminology used for TSH results is clarified in an attempt to help physicians interpret, explain, and respond to TSH test results for their patients.

 


Hoermann, R., Midgley, J. E., Giacobino, A., Eckl, W. A., Wahl, H. G., Dietrich, J. W., & Larisch, R. (2014)
. Homeostatic equilibria between free thyroid hormones and pituitary thyrotropin are modulated by various influences including age, body mass index and treatment. Clinical endocrinology.
Conclusions: TSH, FT4 and FT3 each have their individual, but also interlocking roles to play in defining the overall patterns of thyroidal expression, regulation and metabolic activity. Equilibria typical of the healthy state are not invariant, but profoundly altered, for example, by L-T4 treatment. Consequently, this suggests the revisitation of strategies for treatment optimization.
Tolkes slik av Thyroid UK sin rådgiver: July 2014
Thyroid UK advisors Rudolf Hoermann, John E.M. Midgley and Johannes W. Dietrich have just had a new research paper published in the Clinical Endocrinology Journal.

Dr John Midgley tells us:
«What it proves is that there is no such thing as a TSH range that is suitable for everyone, and that the range is different according to the effect of independent influences such as age, body mass, size of working thyroid volume and whether someone is on T4 or not.
The T4 therapy range is very much lower than the «normal» untreated and sits around the 1 or lower mark. The 3-4 upper level that works for the normal person is not satisfactory and can indicate undertreatment.
Also we’re finding that people with no thyroid working at all cannot easily regain normal FT3 with T4 alone and that TSH suppression often has to happen, and in some people no amount of T4 will regain normal FT3 levels. Recent reviews by the gurus now admit that some people cannot handle T4 only and regain health. Just thought you’d like to know that the avalanche is beginning.»


Holtorf, K. (2014).
Thyroid Hormone Transport into Cellular Tissue. Journal of Restorative Medicine, 3(1), 53-68. Chicago.
Abstract: New research is demonstrating that thyroid hormone transport across cellular membranes plays an important role in intracellular triiodothyronine (T3) levels of peripheral and pituitary tissues and is proving to have considerable clinical significance. Reduced T4 and T3 transport into the cells in peripheral tissues is seen with a wide range of common conditions, including insulin resistance, diabetes, depression, bipolar disorder, hyperlipidemia, chronic fatigue syndrome, fibromyalgia, neurodegenerative diseases, migraines, stress, anxiety, chronic dieting and aging, while the intracellular T3 level in the pituitary often remains unaffected.

 

Holtorf, K. (2014). Peripheral Thyroid Hormone Conversion and Its Impact on TSH and Metabolic Activity. Journal of Restorative Medicine, 3(1), 30-52.
Summary: Consequently, it is inappropriate to rely on a normal or low TSH as an adequate or sensitive indicator of normal or low tissue levels of T3 in the presence of any such conditions, making the TSH a poor marker for the body’s overall thyroid level.

 

Holtorf, K. (2012). Hormone Replacement Therapy in the Geriatric Patient: Current State of the Evidence and Questions for the Future. Estrogen, Progesterone, Testosterone, and Thyroid Hormone Augmentation in Geriatric Clinical Practice. This article, independently written and published, is a broad study of hormone replacement in geriatric patients. In the thyroid section, written by Kent Holtorf M.D ., it details the difference between serum thyroid hormone levels and tissue thyroid hormone levels, particularly in cases of chronic and acute stress.

 

Kalra S, Khandelwal, SK (2011). Why are our hypothyroid patients unhappy? Is tissue hypothyroidism the answer? Indian Journal of Endocrinology and Metabolism. 2011 July; 15(Suppl2): S95–S98.
Introduction: The improvements in laboratory diagnosis, follow-up, monitoring and treatment, however, have not necessarily improved satisfaction levels of patients. Many patients complain of persistent psychological symptoms after treatment. Others state that they do not feel normal. Some patients report inadequate weight loss or continuous weight gain in spite of normal TSH levels.
Conclusions: As we manage our patients with hypothyroidism, we not only have to maintain normal TSH levels, but also achieve symptomatic relief and satisfaction. We have to avoid being unsympathetic and dismissive of their complaints.

 

Pacchiarotti A, Martino E, Bartalena L, Aghini Lombardi F, Grasso L, Buratti L, Falcone M, Pinchera A (1986). Serum free thyroid hormones in subclinical hypothyroidism. Journal of Endocrinological Investigation. 1986 Aug;9(4):315-9.
Abstract: These results indicate that FT4 should be measured in addition to TSH for the diagnosis of impending thyroid failure, thus showing that in many cases patients with so-called subclinical hypothyroidism are actually already mild hypothyroid.

 

Pritchard, E.K. (2013). Reducing the Scope of Guidelines and Policy Statements in Hypothyroidism. Journal of Orthomolecular Medicine. Volume 28, Number 2, 2013. Abstract: Although practice guidelines and policy statements on hypothyroidism are generally effective, many patients do not respond to the prescribed treatment. Significantly, clinicians routinely face the conundrum of either following the guidelines, which are ineffective, or ethically prescribing alternative (but proscribed) treatment, which might bring and has brought severe punishment by boards of medicine or medical councils.

 

Rowsemitt, C. and Najarian, T. (2011) TSH is Not the Answer: Rationale for a New Paradigm to Evaluate and Treat Hypothyroidism, Particularly Associated with Weight Loss. Thyroid Science; 6(4): H1-16.
Conclusions: Treating to normalize thyroid hormone levels and eliminate hypothyroid symptoms results in the suppression of TSH. This is understood as a normal part of treatment once we accept that the thyroid set point has been lowered. This is not an argument to use thyroid hormones to increase metabolism above normal to achieve weight loss. Our goal is to correct the hypothyroid response in a weight loss patient and return him/her to normal metabolism so that the patient feels normal and is better able to lose weight and maintain that loss.

 

Ruhla, S., Arafat, A. M., Weickert, M. O., Osterhoff, M., Isken, F., Spranger, J., … & Möhlig, M. (2011). T3/rT3-ratio is associated with insulin resistance independent of TSH. Hormone and metabolic research, 43(02), 130-134.
Abstract: Here we show that the triiodothyronine/reverse triiodothyronine (T3/rT3- lab test ratio), which is supposed to reflect the tissue thyroid hormone metabolism, is significantly increased in insulin resistant subjects. This further supports a link between thyroid function and IR.

 

Sesmilo G, Simó O, Choque L, Casamitjana R, Puig-Domingo M (2011). Serum free triiodothyronine (T3) to free thyroxine (T4) ratio in treated central hypothyroidism compared with primary hypothyroidism and euthyroidism. Endocrinología y Nutrición. 2011 Jan;58(1):9-15
Conclusions: Treated patients with central hypothyroidism had a lower free T3 to free T4 ratio, similar free T3 levels and higher free T4 concentrations than euthyroid controls, whereas all these parameters were similar in central and primary hypothyroid patients treated with T4. The question of whether these findings translate into adequate tissue concentrations of free thyroid hormones in all tissues remains to be answered. Further studies should aim to determine whether clinical outcomes could be improved by a treatment achieving more physiological plasma concentrations.

 

Skinner GRB, Holmes D, Ahmad A, Davies JA, Benitez J (2000). Clinical Response to Thyroxine Sodium in Clinically Hypothyroid but Biochemically Euthyroid Patients. Journal of Nutritional and Environmental Medicine. Vol. 10, No. 2 , Pages 115-124. Conclusions: Clinically hypothyroid but biochemically euthyroid patients had favourable clinical response to thyroid replacement which correlated with the level of thyroid replacement. It is suggested that these findings be examined in a prospective placebo controlled clinical trial.

 

Skinner GR, Thomas R, Taylor M, Sellarajah M, Bolt S, Krett S, Wright A. (1997). Thyroxine should be tried in clinically hypothyroid but biochemically euthyroid patients. British Medical Journal: June 14; 314(7096).
Utdrag: We contend that an incremental three month trial of thyroxine treatment in clinically hypothyroid but biochemically euthyroid patients is a safe and reasonable strategy. The dangers of osteoporosis and cardiac catastrophe–particularly during a three month trial–are sometimes quoted, but these worries are unfounded and condemn many patients to years of hypothyroidism with its pathological complications and poor quality of life. We urge that the question of clinical hypothyroidism in biochemically euthyroid patients should be subjected to a formal clinical trial.

 

van den Beld, A.W., Visser, T., Feelders, R., Grobbee, R., Lamberts, W.J., (2005) Effect of Exogenous Thyroid Hormone Intake on the Interpretation of Serum TSH Results. The Journal of Clinical Endocrinology & Metabolism; 90 (12): 6403-6409.
Conclusions: In a population of independently living elderly men, higher FT4 and RT3 concentrations are associated with a lower physical function.

 

Wartofsky L, Dickey, R (2005). The Evidence for a Narrower Thyrotropin Reference Range Is Compelling. The Journal of Clinical Endocrinology & Metabolism. September 1, 2005 vol. 90 no. 9 5483-5488.
Abstract: Debate and controversy currently surround the recommendations of a recent consensus conference that considered issues related to the management of early, mild, or so-called subclinical hypothyroidism and hyperthyroidism. Intimately related to the controversy is the definition of the normal reference range for TSH. Recognition and establishment of a more precise and true normal range for TSH have important implications for both screening and treatment of thyroid disease in general and subclinical thyroid disease in particular.

 

Woeber, K. A. (2002). Levothyroxine therapy and serum free thyroxine and free triiodothyronine concentrations. Journal of endocrinological investigation, 25(2), 106-109. Abstract: These findings indicate that in hypothyroid patients L-T4-replacement, that is sufficient to maintain a normal serum TSH, is accompanied by a serum free T4 that is higher than that in untreated euthyroid patients or normal individuals and may not result in an appropriately normal serum free T3 concentration.

 

A. Mortoglou, H. Candiloros (2004)
The serum triiodothyronine to thyroxine (T3/T4) ratio in various thyroid disorders and after Levothyroxine replacement therapy Department of Endocrinology, Diabetes and Metabolism, Athens Medical Centre Hospital, Athens, Greece
Abstract: In order to examine the significance of differences in the triiodothyronine/thyroxine (T3/T4) ratio in the achievement of euthyroidism and in different thyroidal diseases, we studied 1050 subjects: 233 were euthyroid (Eu), 239 hypothyroid (Hypo) with initial TSH levels >15 mU/L, 273 hypothyroid on substitution therapy with L-thyroxine alone and TSH values of 0.35-3.5 mU/L, (hypoRx), 236 hyperthyroid (hyper) and 69 in the acute phase of subacute thyroiditis De Quervain’s (DQ). The ratio of T3/T4 was calculated using the conventional values. Results: The values of T3/T4 ratio in the various categories were: Eu= 15.89, Hypo= 24.12, hyper= 19.57, hypoRx= 13.42, DQ= 15.16. The T3/T4 ratio was lower in the hypoRx group than in the EU group (P <0.001), although neither TSH values nor T3 values showed any differences between these two groups, whereas T4 levels were significantly higher in the hypoRx group (Eu= 7.99±1.46, hypoRx = 9.11±1.58, P< 0.001). The T3/T4 ratio in the DQ group was comparable to that of the Eu group, but significantly lower than the hyper group (P=0.95 between Eu and DQ, P<0.001 between DQ and hyper).

Conclusions: These findings indicate that in hypothyroid patients, L-T4-replacement that is sufficient to maintain a normal serum TSH is accompanied by a serum T4 that is higher than in normal individuals and may not result in an appropriately normal serum T3 concentration. In Thyrotoxicosis, a ratio of total T3/T4 >18.9 suggests Graves’ disease or toxic multinodular goiter whereas T3/T4 <16 suggests thyroiditis (subacute or silent).

Eur J Endocrinol. 2013 Hoermann R, Midgley JE, Larisch R, Dietrich JW.
Is pituitary TSH an adequate measure of thyroid hormone-controlled homoeostasis during thyroxine treatment?
Abstract
OBJECTIVE:
In recognition of its primary role in pituitary-thyroid feedback, TSH determination has become a key parameter for clinical decision-making. This study examines the value of TSH as a measure of thyroid hormone homoeostasis under thyroxine (T(4)) therapy.
CONCLUSION:
The data reveal disjoints between FT(4)-TSH feedback and T(3) production that persist even when sufficient T(4) apparently restores euthyroidism. T(4) treatment displays a compensatory adaptation but does not completely re-enact normal euthyroid physiology. This invites a study of the clinical consequences of this disparity.

 

Endocrine Abstracts (2010) 21 OC5.6, Graham Leese & Robert Flynn, University of Dundee, Tayside, UK Is it safe for patients taking thyroxine to have a low but not suppressed serum TSH concentration?

Conclusion: People on long-term thyroxine with a high or suppressed TSH are at increased risk of cardiovascular disease, dysrhythmias and fractures. People with a low but not suppressed TSH did not have an increased risk of these outcomes in this study. It may be safe for patients treated with thyroxine to have a low but not suppressed serum TSH concentration.
Rakesh Nair, Shriraam Mahadevan,1 R. S. Muralidharan, and S. Madhavan, Indian J Endocrinol Metab. 2014 Does fasting or postprandial state affect thyroid function testing?
Abstract
BACKGROUND: Thyroid stimulating hormone (TSH) levels vary with the time of the day and probably in relation to food. In this study, we addressed the question of whether a fasting or non-fasting sample would make a clinically significant difference in the interpretation of thyroid function tests.
RESULTS:
TSH was suppressed in all subjects after food irrespective of the fasting levels. Free T4 values did not change significantly. This resulted in reclassification of 15 out of 20 (75%) subjects as subclinical hypothyroidism (SCH) based on fasting values whose TSH values were otherwise within range in the postprandial sample. This may have an impact on the diagnosis and management of hypothyroidism especially where even marginal changes in TSH may be clinically relevant as in SCH and in pregnancy.
CONCLUSION:
TSH levels showed a statistically significant decline postprandially in comparison to fasting values. This may have clinical implications in the diagnosis and management of hypothyroidism, especially SCH.

 

Science Daily:Date: March 15, 2010; Source: Society for Endocrinology May be safe for patients taking thyroxine to have lower TSH levels than currently recommended, new research shows
Summary: New research shows that it may be safe for patients taking thyroxine replacement to have low but not suppressed thyroid stimulating hormone (TSH) levels. The research shows for the first time that it may be safe for patients to take slightly higher doses of thyroxine than are currently recommended.

 

ARTHUR S. WEISSBEIN, CAPTAIN, MC, USA†, and JOHN D. LAWSON, MAJOR, MC, USA PARADOXICAL LENGTHENING OF MUSCLE CONTRACTION TIME IN HYPOTHYROID PATIENTS GIVEN SMALL DOSES OF l-TRIIODOTHYRONINE, THYROXINE AND DESICCATED THYROID
Received: August 04, 1959
Published Online: July 01, 2013
ABSTRAC: Since the prolongation of the Achilles reflex associated with myxedema is shortened during treatment with thyroid hormone, it was surprising to find that when small doses of thyroid hormone were administered to hypothyroid patients, the reflex time became longer rather than shorter. Further investigation revealed that this paradoxical response occurred in all patients who were hypothyroid by standard tests of thyroid function. Several borderline hypothyroid patients were also studied. The results thus far suggest that this paradoxical muscular response may possibly provide a means for detection of milder degrees of hypothyroidism than are demonstrable by the standard clinical tests now employed. The test was standardized on 40 hypothyroid patients. It was found that the most economical and simple method consists of recording the duration of the Achilles reflex contraction time within twenty-four hours after administration of 25 μg. of l-triiodothyronine (liothyronine) in fractional doses.