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Background

The thyroid panel is often referred to as thyroid function tests.  The usual panel includes the following tests:

Additional tests may include:

OUTLINE

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Clinical Utility  
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CLINICAL UTILITY CHARACTERIZATION

Strategies for thyrotropin use to monitor patients with treated thyroid carcinoma.

Ladenson PW.

Division of Endocrinology and Metabolism, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

Thyroid 1999 May;9(5):429-33 Abstract quote

Detection of residual and recurrent thyroid carcinoma requires long-term monitoring of patients with serum thyroglobulin measurement and radioiodine scanning during temporary thyrotropin (TSH) stimulation.

Recombinant thyrotropin (rTSH) permits these studies to be performed without the morbidity associated with withdrawal of thyroid hormone therapy. A protocol for rTSH use is proposed, beginning with measurement of serum thyroglobulin during TSH suppression. Patients at significant risk of recurrence with a low initial thyroglobulin level then have rTSH stimulation testing. Patients with positive rTSH-stimulated thyroglobulin concentrations and/or radioiodine scans can then be directed for appropriate therapy. The previously studied 2-dose rTSH protocol with imaging at 48 hours after 131I dosing requires Monday-through-Friday testing in most settings, but new regimens may be established. rTSH-stimulated testing may be less accurate in patients with thyroglobulin autoantibodies and those with residual normal thyroid tissue, and is generally unnecessary when there is other evidence of residual disease.

Physicians should consider patients' pretest probability of disease in deciding whether and how often to perform rTSH-stimulated testing after primary treatment for thyroid carcinoma.

Clinical experience with recombinant human thyroid-stimulating hormone (rhTSH): serum thyroglobulin measurement.

Pacini F, Lippi F.

Department of Endocrinology and Metabolism, Universita degli Studi di Pisa, Italy.

J Endocrinol Invest 1999;22(11 Suppl):25-9 Abstract quote

Only normal or neoplastic thyroid follicular cells produce and secrete the prohormone, thyroglobulin (Tg). For some 25 years, elevated serum concentrations of Tg therefore have been employed as a post-operative marker for well-differentiated thyroid carcinoma.

The aim of serum Tg measurement is to identify patients requiring: A) further testing to confirm the presence and to determine the stage, site and functionality of tumour; and/or B) further treatment. Serum Tg testing has the advantages of superior sensitivity to radioiodine whole-body scanning (WBS), lack of false positive readings, simplicity, speed, low cost, precision and wide availability. However, major limitations of serum Tg testing are interference by serum anti-Tg antibodies and decreased sensitivity during THST. To obviate this last drawback, the use of recombinant human thyroid-stimulating hormone (rhTSH) has been clinically investigated as a preparative adjunct to serum Tg testing in the diagnostic follow-up of well-differentiated thyroid cancer.

A large, multicentre international Phase III study now has confirmed evidence from earlier Phase I/II and Phase III trials and established the safety and efficacy of rhTSH in stimulating Tg release by residual and neoplastic thyroid tissue. This confirmatory study has clearly shown that 1) rhTSH administration significantly increases sensitivity of serum Tg measurement in patients on THST; and 2) by permitting sensitive diagnostic follow-up with serum Tg measurement and/or radioiodine WBS during THST, rhTSH administration improves patient comfort and quality of life compared to THST withdrawal. Thus use of the drug in diagnostic follow-up recently has received regulatory approval in the United States, and such approval is pending in the European Union. With regulatory approval, rhTSH is likely to gain an important role as a preparative adjunct to serum Tg testing in everyday practice.

Diagnosis of thyroid disease in hospitalized patients: a systematic review.

Attia J, Margetts P, Guyatt G.

Department of Internal Medicine, McMaster University, Hamilton, Ontario, Canada.

Arch Intern Med 1999 Apr 12;159(7):658-65 Abstract quote

BACKGROUND: The optimal approach for the diagnosis of hypothyroidism and hyperthyroidism in hospitalized patients is controversial.

OBJECTIVES: To estimate the prevalence of undiagnosed thyroid disease among inpatients, review the usefulness of clinical signs and symptoms, and elucidate the characteristics of the sensitive thyrotropin (thyroid-stimulating hormone) (sTSH) test in this population.

METHODS: We undertook a systematic review of the literature by conducting a MEDLINE search covering January 1966 through December 1996. Searching was conducted in duplicate and independently. Specific inclusion and exclusion criteria were predetermined.

RESULTS: Prevalence of thyroid disease among inpatients is approximately 1% to 2% and is similar to the outpatient population. Absence of clinical features of thyroid disease lowers the pretest likelihood and makes screening even less useful. Presence of clinical features, especially those specific for thyroid disease (eg, goiter), may increase the pretest likelihood and increase the yield of testing. Acute illness reduces the specificity of second-generation sTSH tests for thyroid disease. The positive likelihood ratio associated with an abnormal sTSH test result in ill inpatients is about 10 compared with about 100 in outpatients.

CONCLUSION: In unselected general medical, geriatric, or psychiatric inpatient populations, sTSH testing provides a low yield of true-positive and many false-positive results.

American Thyroid Association guidelines for detection of thyroid dysfunction.

Ladenson PW, Singer PA, Ain KB, Bagchi N, Bigos ST, Levy EG, Smith SA, Daniels GH, Cohen HD.

The Johns Hopkins University School of Medicine, Baltimore, MD 21287-0003, USA.

Arch Intern Med 2000 Jun 12;160(11):1573-5 Abstract quote

OBJECTIVE: To define the optimal approach to identify patients with thyroid dysfunction.

PARTICIPANTS: The 8-member Standards of Care Committee of the American Thyroid Association prepared a draft, which was reviewed by the association's 780 members, 50 of whom responded with suggested revisions.

EVIDENCE: Relevant published studies were identified through MEDLINE and the association membership's personal resources.

CONSENSUS PROCESS: Consensus was reached at group meetings. The first draft was prepared by a single author (P.W.L.) after group discussion. Suggested revisions were incorporated after consideration by the committee.

CONCLUSIONS: The American Thyroid Association recommends that adults be screened for thyroid dysfunction by measurement of the serum thyrotropin concentration, beginning at age 35 years and every 5 years thereafter. The indication for screening is particularly compelling in women, but it can also be justified in men as a relatively cost-effective measure in the context of the periodic health examination. Individuals with symptoms and signs potentially attributable to thyroid dysfunction and those with risk factors for its development may require more frequent serum thyrotropin testing.

Practical application of recombinant thyrotropin testing in clinical practice.

Ladenson PW, Ewertz ME, Dickey RA.

Division of Endocrinology and Metabolism, Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287-0003, USA

Endocr Pract 2001 May-Jun;7(3):195-201 Abstract quote

OBJECTIVE: To review the indications for use of recombinant thyrotropin (rTSH) and outline the details of implementation of rTSH diagnostic testing in patients with treated thyroid cancer.

METHODS: We discuss the results of published clinical trials that have compared rTSH-stimulated testing with conventional withdrawal of thyroid hormone suppressive therapy. Appropriate candidates for rTSH testing are described, and the typical schedule for rTSH testing and follow-up is presented. An overview of coding and documentation for reimbursement is also provided.

RESULTS: Clinical studies have found no significant difference in the combined sensitivity of (131)I scans and serum thyroglobulin measurements for detection of recurrent thyroid cancer after rTSH stimulation versus withdrawal of thyroid hormone therapy. As expected, patients have fewer symptoms and a more favorable mood state after use of rTSH. Patients with thyroid cancer who have undergone total or near-total thyroidectomy followed by 131I ablation can be considered for rTSH testing. For low-risk patients, two cycles of rTSH testing 1 to 2 years apart, followed by testing every 3 to 5 years, are recommended. For moderate- to high-risk patients who have undergone one cycle of negative levothyroxine-withdrawal testing, two cycles of rTSH testing at a 6- to 12-month interval, followed by testing every 1 to 3 years for at least the first decade of follow-up, are recommended. Most commercial insurance, Medicare, and Medicaid carriers now cover rTSH, either in a prescription drug plan or under major medical benefits.

CONCLUSION: Radioiodine scanning and serum thyroglobulin measurement after intramuscular injection of rTSH are valuable new monitoring options in patients with treated thyroid cancer, avoiding the adverse effects of hypothyroidism.

Thyroxine treatment in patients with symptoms of hypothyroidism but thyroid function tests within the reference range: randomised double blind placebo controlled crossover trial.

Pollock MA, Sturrock A, Marshall K, Davidson KM, Kelly CJ, McMahon AD, McLaren EH.

BMJ 2001 Oct 20;323(7318):891-5 Abstract quote

Objectives: To determine whether thyroxine treatment is effective in patients with symptoms of hypothyroidism but with thyroid function tests within the reference range, and to investigate the effect of thyroxine treatment on psychological and physical wellbeing in healthy participants.

Design: Randomised double blind placebo controlled crossover trial.

Setting: Outpatient clinic in a general hospital. Participants: 25 patients with symptoms of hypothyroidism who had thyroid function tests within the reference range, and 19 controls.

Methods: Participants were given thyroxine 100 &mgr;g or placebo to take once a day for 12 weeks. Washout period was six weeks. They were then given the other to take once a day for 12 weeks. All participants were assessed physiologically and psychologically at baseline and on completion of each phase.

Main outcome measures: Thyroid function tests, measures of cognitive function and of psychological and physical wellbeing. Results: 22 patients and 19 healthy controls completed the study. At baseline, patients' scores on 9 out of 15 psychological measures were impaired when compared with controls. Patients showed a significantly greater response to placebo than controls in 3 out of 15 psychological measures. Healthy participants had significantly lower scores for vitality when taking thyroxine compared to placebo (mean (SD) 60 (17) v 73 (16), P<0.01). However, patients' scores from psychological tests when taking thyroxine were no different from those when taking placebo except for a poorer performance on one visual reproduction test when taking thyroxine. Serum concentrations of free thyroxine increased and those of thyroid stimulating hormone decreased in patients and controls while they were taking thyroxine, confirming compliance with treatment. Although serum concentrations of free triiodothyronine increased in patients and controls taking thyroxine, the difference between the response to placebo and to thyroxine was significant only in the controls.

Conclusions: Thyroxine was no more effective than placebo in improving cognitive function and psychological wellbeing in patients with symptoms of hypothyroidism but thyroid function tests within the reference range. Thyroxine did not improve cognitive function and psychological wellbeing in healthy participants.

Serum thyroglobulin concentrations and (131)i whole-body scan results in patients with differentiated thyroid carcinoma after administration of recombinant human thyroid-stimulating hormone.

David A, Blotta A, Bondanelli M, Rossi R, Roti E, Braverman LE, Busutti L, Uberti EC.

Section of Endocrinology, Department of Biomedical Sciences and Advanced Therapies, University of Ferrara, Ferrara.

J Nucl Med 2001 Oct;42(10):1470-5 Abstract quote

The use of recombinant human thyroid-stimulating hormone (rhTSH) has recently become available as an alternative diagnostic tool to assess the persistence and recurrence of differentiated thyroid carcinoma (DTC) in patients on thyroid hormone-suppressive therapy (THST) after near-total or total thyroidectomy and ablative doses of (131)I. We report the results of rhTSH administration in patients who were monitored for DTC.

METHODS: Thirty-three adult DTC patients (13 men, 20 women; mean age +/- SE, 45.6 +/- 2.31 y; age range, 21-65 y) underwent diagnostic follow-up after rhTSH administration at a dose of 0.9 mg once a day for 2 d. Whole-body scanning and serum thyroglobulin (Tg) measurement were performed after rhTSH administration. Patients were divided into 2 groups depending on serum Tg concentrations on THST: 29 patients had Tg concentrations of <2 ng/mL (group A) and 4 patients had Tg values of >2 ng/mL (group B).

RESULTS: In group A, Tg values remained at <2 ng/mL in 25 patients and increased from 1.1 +/- 0.14 ng/mL to 22.0 +/- 5.75 ng/mL (mean +/- SE) in 4 patients after rhTSH administration. Whole-body scanning did not reveal any uptake of (131)I in the 25 patients without an increase in Tg, whereas (131)I uptake was evident in 2 of the 4 patients with a rise in Tg. In group B, Tg values increased in all 4 patients from 17.3 +/- 6.35 ng/mL to 55.3 +/- 12.75 ng/mL, and (131)I uptake was evident in 3 of the 4 patients. No major adverse effects were reported after rhTSH administration.

CONCLUSION: Our results show that the measurement of serum Tg concentrations after rhTSH has a higher diagnostic value than whole-body scanning in detecting the persistence of thyroid tissue. Therefore, rhTSH should be administered in TSH-suppressed patients with basal serum Tg concentrations of <2 ng/mL because the increment in serum Tg concentrations may reveal the persistence of thyroid tissue in these patients.

 

INTERFERING DISEASES OR SUBSTANCES THAT ALTER LEVELS CHARACTERIZATION

Thyroid function in patients with chronic renal failure.

Lim VS.

Nephrology Division, Department of Internal Medicine, University of Iowa Hospitals, Iowa City, IA, USA.

Am J Kidney Dis 2001 Oct;38(4 Suppl 1):S80-4 Abstract quote

Chronic renal failure affects thyroid function in multiple ways, including low circulating thyroid hormone concentration, altered peripheral hormone metabolism, disturbed binding to carrier proteins, possible reduction in tissue thyroid hormone content, and increased iodine store in thyroid glands.

Both plasma triiodothyronine (T(3)) and thyroxine (T(4)) are reduced. The low serum T(3) is not due to increased T(3) degradation or to decreased thyroidal T(3) secretion but is a result of impaired extrathyroidal T(4) to T(3) conversion. The reduction in T(4) is attributed to the presence of circulating inhibitors, which impair binding of T(4) to thyroxine-binding globulin. Despite decreased circulating T(4) and T(3), thyroid-stimulating hormone (TSH) is not elevated. This absence of TSH elevation is not due to dysfunction of the hypothalamo-pituitary axis, because truly hypothyroid renal failure patients can mount a high TSH response.

Thyroid hormone losses during hemodialysis and peritoneal dialysis are trivial and do not require replacement. Serum inorganic iodide and thyroidal iodine content are increased in renal failure patients, and thyroid gland enlargement is frequently encountered. Experiments performed to correct the low serum T(3) level by administration of small doses of LT(3) to renal failure patients resulted in lesser nitrogen balance, greater leucine flux, and protein degradation.

We speculate that the low thyroid state in uremia serves to defend against protein wasting and that misguided attempts to replete thyroid hormone stores may worsen protein malnutrition.

Henry JB. Clinical Diagnosis and Management by Laboratory Methods. Twentieth Edition. WB Saunders. 2001.


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Last Updated 1/14/2003

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