Laboratory assessment of thyroid function

INTRODUCTION — Secretion of the thyroid hormones T4 (thyroxine) and T3 (triiodothyronine) is regulated by pituitary thyroid-stimulating hormone (TSH) (figure 1 and figure 2). TSH secretion, in turn, is controlled through negative feedback by thyroid hormones (see "Thyroid hormone synthesis and physiology"). There is a negative log-linear relationship between serum free T4 and TSH concentrations [1]. This means that very small changes in serum free T4 concentrations induce very large reciprocal changes in serum TSH concentrations. As a result, thyroid function is best assessed by measuring serum TSH, assuming steady-state conditions and the absence of pituitary or hypothalamic disease. Nevertheless, direct measurement of serum thyroid hormone levels is still important since it may be difficult in some patients to be certain about the state of pituitary and hypothalamic function.

This topic review will provide an overview of thyroid function testing. More detailed discussions of serum TSH and free thyroid hormone measurements, abnormalities in thyroid hormone binding proteins, and the effects of drugs and nonthyroidal illness on thyroid function tests are discussed separately. (See "Drug interactions with thyroid hormones" and "Thyroid function in nonthyroidal illness" and "Diagnosis of and screening for hypothyroidism in nonpregnant adults" and "Diagnosis of hyperthyroidism".)

LABORATORY TESTS USED TO ASSESS THYROID FUNCTION — Thyroid function is assessed by one or more of the following tests:

●Serum TSH concentration

●Serum total T4 and T3 concentrations

●Serum free T4 and T3 concentrations

There are multiple methods for measuring TSH, total T4 and total T3, and free T4 and free T3 [2]. In most hospital or clinical laboratories in the United States, a "full" set of thyroid function tests usually includes an automated immunometric chemiluminescent third-generation TSH level, an automated "direct" competitive-binding chemiluminescent free T4, and a total T3 or free T3 assay [2]. Most clinical laboratories also offer a total T4 assay. Other assays are costly and require referral to a reference laboratory.

Assay interference with biotin ingestion — Patients taking biotin should hold the supplement for two days prior to assessing thyroid function and longer if they are taking more than 10 mg a day.

Some automated assays for measurement of thyroid tests utilize a biotin-streptavidin separation system [3]. Patients who are ingesting 5 to 10 mg of biotin (eg, marketed over the counter to prevent hair loss) can have spurious results in these assays. Biotin may cause falsely low values in immunometric assays (eg, used to measure TSH), and falsely high values in competitive binding assays (eg, used to measure free T4, T3, and free T3, and TSH receptor-binding inhibitor immunoglobulin [TBII or TBI]) [4,5]. (See "Diagnosis of hyperthyroidism", section on 'Differential diagnosis' and "Subclinical hyperthyroidism in nonpregnant adults", section on 'Differential diagnosis'.)

Serum TSH

●Assays – Third-generation TSH chemiluminometric assays, currently in wide use, have detection limits of approximately 0.01 mU/L. They can therefore provide detectable TSH measurements even in mild hyperthyroidism [6]. Because of the considerably lower detection limit, even with poor quality control, serum TSH values in patients with overt hyperthyroidism are easily distinguished from those in euthyroid patients [7].

Second-generation TSH immunometric assays have detection limits of approximately 0.1 mU/L, and they are still used in some laboratories as screening tests to distinguish hyperthyroidism from euthyroidism and to assess the degree of hypothyroidism [8]. However, values near or at the detection limit do not distinguish the degree of hyperthyroidism, and poor quality control in many laboratories can lead to erroneous values [9].

●Reference range – There is considerable controversy as to the appropriate upper limit of normal for serum TSH. Most laboratories have used values of approximately 4.5 to 5.0 mU/L. Although age-adjusted reference ranges for TSH are not routinely reported by clinical laboratories, we and others favor using aged-based normal ranges for TSH [10].

•Age-related increase in TSH – The distribution of TSH values in the population differs by age. In an analysis of 16,533 individuals in the National Health and Nutrition Examination Survey III (NHANES III), there was an age-related shift toward higher TSH concentrations in older patients, which persisted when those with positive antithyroid antibodies were excluded [11]. For example, the 97.5 centile for TSH in adults aged 20 to 29 years, or over age 80, was 3.56 and 7.49 mU/L, respectively. Seventy percent of the individuals in the older group with a TSH greater than 4.5 mU/L were within the normal range for their age. Similar age-associated increases in serum TSH concentrations were found in other prospective cohort studies [10,12-14].

Controversy exists as to whether patients with serum TSH values between 5 and 10 mU/L with normal free T4 levels (subclinical hypothyroidism) require treatment. If age-adjusted normal ranges for TSH were employed, 60 percent of women diagnosed with subclinical hypothyroidism would be considered euthyroid [15]. (See "Subclinical hypothyroidism in nonpregnant adults".)

•Optimal TSH and cardiovascular and skeletal outcomes – Higher TSH levels within the normal reference range may be associated with health (eg, cardiovascular, skeletal) benefits rather than health problems in older adults [16,17]. As an example, in a systematic review and meta-analysis of individual patient data, TSH levels between the 60^th and the 80^th percentile of the normal reference range (median 1.9 to 2.9 mU/L) were associated with the lowest risk of cardiovascular disease and mortality [16]. These data suggest that the determination of optimal TSH levels should include an assessment of cardiovascular and skeletal outcomes.

•Other factors that may impact TSH reference range – A weight-related shift upward in the reference range for TSH among people with class II or class III obesity has been reported [18]. The NHANES III study found that persons of African descent have a TSH distribution that is shifted downward, so that 3 to 4 percent of healthy Black individuals have a serum TSH <0.4 mU/L [19].

A monograph published by the National Academy of Clinical Biochemistry argued that the upper limit of normal of the euthyroid reference range should be reduced to 2.5 mU/L because 95 percent of rigorously screened euthyroid volunteers have serum values between 0.4 and 2.5 mU/L [20]. However, a population study from Germany, which excluded patients with a positive family history, goiter, nodules, or positive antithyroid peroxidase (TPO) antibodies, found a normal reference range of 0.3 to 3.63 mU/L [21]. The use of 2.5 or 3.63 mU/L as the upper limit of normal for serum TSH will increase substantially the number of patients in the United States diagnosed with subclinical hypothyroidism, and treatment may result in adverse outcomes, especially in the older adult population. Until there are data demonstrating an adverse biologic significance for age-adjusted serum TSH values between 2.5 to 3.5 mU/L and the age-adjusted upper limit of normal, the wisdom of labeling such patients as hypothyroid is questionable.

Serum total T4 and T3

●Assays – Serum total T4 is usually measured by automated competitive binding chemiluminometric assays. Older competitive binding radioimmunoassays are still available. Virtually all (99.97 percent) of serum T4 is bound to TBG (thyroxine-binding globulin), transthyretin (also called TBPA [thyroxine-binding prealbumin]), and albumin. Serum total T4 assays measure both bound and unbound ("free") T4.

Serum total T3 is also usually measured by automated competitive binding chemiluminescent assays. T3 is less tightly bound to TBG and TBPA but more tightly bound to albumin than T4.

●Reference range – Normal ranges vary among laboratories; a typical reference range for total T4 is 4.6 to 11.2 mcg/dL (60 to 145 nmol/L). The normal range for total T3 is even more variable among laboratories than that for total T4; a typical range is approximately 75 to 195 ng/dL (1.1 to 3 nmol/L).

Serum free T4 and T3 — The free hormone hypothesis states that the unbound or free hormone is the fraction that is available for uptake into cells and interaction with nuclear receptors [22]. The bound hormone, on the other hand, represents a circulating storage pool that is not immediately available for uptake into cells.

Since drugs and illness can alter concentrations of binding proteins or interaction of the binding proteins with T4 or T3 (table 1), the free and total hormone concentrations may not be concordant. An example is estrogen-induced TBG excess, in which total T4 concentrations are high due to increased TBG-bound hormone, but the physiologically important free T4 concentrations are normal (see "Euthyroid hyperthyroxinemia and hypothyroxinemia"). It is therefore necessary to estimate free hormone concentrations.

●Assays – Most laboratories measure free T4 and free T3 by "direct" measurement.

•"Direct" free T4 – Direct free T4 measurements can be automated, and varying methodologies have been used by commercial laboratories [23]; however, none of these actually measure unbound T4 directly since free hormone represents only 0.03 percent of serum total T4. The perceived advantage of direct free T4 measurement is that confusion related to binding protein abnormalities is mitigated by providing values that allegedly take binding abnormalities into account. The disadvantage is that no currently available assay provides correct free T4 values for all the binding abnormalities that have been described. Direct free T4 measurements may be unreliable during pregnancy due to low albumin and other factors (see "Overview of thyroid disease and pregnancy") and in malnourished or critically ill patients due to low levels of binding proteins (see "Thyroid function in nonthyroidal illness"). The normal range also varies with the methodology used.

•"Direct" free T3 – Direct free T3 measurements use similar methodology and are increasingly available, but these assays demonstrate even higher variability than the free T4 assays, and we agree with American Thyroid Association guidelines that the use of total T3 measurements are more reliable [2,24].

•Free T4 index, calculated using the T3 uptake (or THBI) – This older method for estimating the free T4 concentration is still in use. Calculation of the free T4 index has the advantage that the clinician is given both a total T4 and a T3 uptake or thyroid hormone binding index (THBI), making it clear when the patient has a potential binding protein abnormality. The disadvantages are: (1) the calculation is poorly understood by many clinicians, and (2) the free T4 index, as with direct free T4 measurements, fails to give correct values for many described binding protein abnormalities. (See "Euthyroid hyperthyroxinemia and hypothyroxinemia".)

The traditional T3-uptake test is performed by incubating the patient's serum with radiolabeled T3 tracer and subsequently adding an insoluble substance (dextran-coated charcoal or "resin") that traps the remaining unbound radiolabeled T3. The value reported is the percent of tracer bound to the resin, which varies inversely with the number of available free binding sites for T3. The number of free binding sites is determined by both binding protein levels and endogenous hormone production.

The normal range varies considerably among laboratories. While many laboratories still report the actual measured value for the T3 uptake, it is preferable to calculate a THBI, which is simply a normalized T3-resin uptake value [25]:

The mean THBI is, therefore, by definition 1.00, with a normal range of approximately 0.83 to 1.16. Some laboratories call the THBI the thyroid hormone-binding ratio (THBR).

The free T4 index is calculated by "correcting" the total T4 by the T3 uptake or THBI:

If the index is calculated by using the T3-uptake, the result is a unitless number with a normal range distinct for the laboratory. If the index is calculated using the THBI, the index should have approximately the same normal range as the total T4 values for the laboratory.

The T3-uptake was designed to distinguish TBG excess and deficiency from hyperthyroidism and hypothyroidism:

-Hyperthyroidism – High serum total T4, high T3-uptake or THBI, high free T4 index

-TBG excess – High serum total T4, low T3-uptake or THBI, normal free T4 index

-Hypothyroidism – Low serum total T4, low T3-uptake or THBI, low free T4 index

-TBG deficiency – Low serum total T4, high T3-uptake or THBI, normal free T4 index

However, the index may not fully correct at the extremes of binding protein abnormalities.

•Equilibrium dialysis – Measurement of free T4 by equilibrium dialysis is available only in a few reference laboratories. The classic technique measures the distribution of free T4 at equilibrium across a dialysis membrane to estimate the unbound fraction. The method is too tedious and expensive for routine use. (See "Drug interactions with thyroid hormones", section on 'Drugs that affect thyroid hormone metabolism or clearance'.)

Reverse T3 — Reverse T3 (rT3) is an inactive metabolite of thyroxine. It is widely measured by alternative health practitioners to justify the use of T3 therapy and supplements thought to enhance the conversion of T4 to T3. It has extremely limited utility for conventional medical practitioners for assessing rare conditions such as consumptive hypothyroidism, MCT8 or SBP2 mutations, or possibly distinguishing central hypothyroidism from nonthyroidal illness in critically ill hospitalized patients [2,26].

CLINICAL USE OF THYROID FUNCTION TESTS — Thyroid function tests are used in a variety of clinical settings to evaluate thyroid dysfunction, assess the adequacy of levothyroxine therapy, and monitor the treatment of hyperthyroidism (table 2). Assuming steady-state conditions and the absence of pituitary or hypothalamic disease, thyroid function is best assessed by measuring serum TSH. However, measurement of serum TSH and thyroid hormone levels remains important in patients with symptoms of possible thyroid dysfunction since a normal serum TSH does not unequivocally exclude the possibility of central hypothyroidism or central hyperthyroidism from a TSH secreting tumor.

"Screening" refers to the measurement of thyroid function tests in asymptomatic patients at risk of having thyroid disease who are presently not known to have thyroid disease. There is some debate over the cost effectiveness of screening or case finding in apparently asymptomatic patients. This topic is reviewed in detail elsewhere. (See "Diagnosis of and screening for hypothyroidism in nonpregnant adults", section on 'Screening'.)

Evaluating for thyroid dysfunction

●Outpatient setting – When evaluation is performed in the outpatient setting, many laboratories use the following strategies to limit unnecessary laboratory testing:

•Serum TSH normal – No further testing performed

•Serum TSH high – Free T4 added to determine the degree of hypothyroidism

•Serum TSH low – Free T4 and T3 added to determine the degree of hyperthyroidism

We make two amendments to this strategy when used to assess possible thyroid dysfunction in an individual patient:

•We measure both serum TSH and free T4 if pituitary or hypothalamic disease is suspected (eg, a young woman with amenorrhea and fatigue).

•We measure serum free T4 if the patient has symptoms of hyper- or hypothyroidism despite a normal TSH result.

Serum TSH assays are both more sensitive and specific than serum free T4 measurements for outpatients if a single test is utilized [2,27]. However, some experts recommend that both serum TSH and free T4 be measured in all patients for evaluation purposes since errors may be made when only TSH is measured in patients with secondary or central hypothyroidism or TSH-mediated hyperthyroidism. This approach adds considerable cost to screening and is likely to pick up few cases of unsuspected pituitary disease. As an example, in a study of 4843 community-dwelling individuals, measuring a TSH only would have missed 3.8 percent of patients with an abnormal free T4, and 85 percent of these patients had only minimally high or low free T4 concentrations [28].

●Inpatient setting – Evaluating thyroid function in the inpatient setting is a more difficult problem, and it is not recommended unless thyroid disease is strongly suspected, since changes in thyroid hormones, binding proteins, and TSH concentrations occur in severe nonthyroidal illness (see "Thyroid function in nonthyroidal illness"). These changes may include [29]:

•Low concentrations of all three binding proteins

•High concentrations of free fatty acids that displace thyroid hormones from binding proteins

•Acquired central hypothyroidism

•The patient may be receiving medications that affect thyroid function (table 1)

While there are advocates for either serum TSH or free T4 being more useful in inpatients, most experts suggest that both serum TSH and free T4 or total T4 are necessary to assess thyroid function in hospitalized patients [30-32].

Monitoring levothyroxine therapy — One of the more common reasons for assessing thyroid function is to assess the adequacy of levothyroxine therapy.

●Primary hypothyroidism – Patients with primary hypothyroidism who are taking levothyroxine replacement therapy can be monitored by assessing the serum TSH only. In general, serum free T4 measurements are very insensitive for assessing the appropriateness of the levothyroxine dose. Doses of levothyroxine that are 40 percent higher than optimal may result in subnormal serum TSH concentrations, yet serum free T4 concentrations frequently remain within the normal range [33]. Conversely, some patients who take levothyroxine may have high free T4 and normal TSH levels, depending on the timing of blood testing and levothyroxine ingestion [34]. Nevertheless, free T4 measurements can be useful to determine appropriate dose increases or decreases when TSH is very high or low, respectively. (See "Treatment of primary hypothyroidism in adults", section on 'Initial monitoring and dose adjustments' and "Treatment of primary hypothyroidism in adults", section on 'Adjustment of maintenance dose'.)

Liothyronine (T3, Cytomel) is generally not recommended for treating hypothyroidism. However, in patients with persistent hypothyroid symptoms on levothyroxine monotherapy, T3 is sometimes added. In this setting, we do not routinely monitor T3 levels. With the currently available T3-containing preparations, there are wide fluctuations in T3 concentrations throughout the day due to its rapid gastrointestinal absorption and its relatively short half-life in the circulation (approximately one day), thus T3 measurement primarily reflects the elapsed time since ingestion of T3. (See "Treatment of primary hypothyroidism in adults", section on 'Monitoring combined therapy'.)

●Secondary hypothyroidism – The one setting in which the serum free T4 value should be used to titrate the thyroid hormone dose is in patients with secondary hypothyroidism due to pituitary or hypothalamic disease who have absent or impaired TSH release. In this situation, the free T4 level should be maintained in the upper 50 percent of the normal range. (See "Central hypothyroidism", section on 'Treatment'.)

●Thyroid cancer – The goal and requirement for monitoring are different in patients taking levothyroxine for suppression of TSH secretion to prevent recurrence of thyroid cancer. (See "Differentiated thyroid cancer: Overview of management", section on 'Thyroid hormone suppression'.)

●Thyroid nodules and goiter – Rarely, mild suppression of TSH with levothyroxine is used to prevent growth or regrowth of goitrous tissue. (See "Thyroid hormone suppressive therapy for thyroid nodules and benign goiter".)

Monitoring treatment of hyperthyroidism — During the early treatment of hyperthyroidism with antithyroid drugs, radioiodine, or surgery, serum TSH may remain subnormal for several weeks and rarely for several months. Initial monitoring of therapy, therefore, should consist of periodic clinical assessment, measurements of serum free T4, and often measurements of total T3 levels. Serum T3 concentrations may be disproportionately higher than serum T4 concentrations in many types of hyperthyroidism. Also, serum free T4 levels may normalize with antithyroid drug therapy, while serum T3 levels may remain persistently elevated. Once steady-state conditions are assured, measurement of serum TSH only can be used to assess the efficacy of therapy. (See "Graves' hyperthyroidism in nonpregnant adults: Overview of treatment", section on 'Monitoring after treatment'.)

ANTITHYROID ANTIBODIES — Several antibodies against thyroid antigens have been described in chronic autoimmune thyroiditis and Graves' disease. However, routine measurement of antithyroid antibodies is not necessary for the assessment of thyroid function.

●Thyroglobulin (Tg, formerly known as the colloid antigen) – Tg is synthesized by follicular cells and secreted into the lumen of the thyroid follicle, where it is stored as colloid. Patients with Hashimoto's thyroiditis or Graves' disease may have thyroglobulin antibodies, but thyroglobulin antibodies do not need to be measured to diagnose autoimmune thyroid disease. However, thyroglobulin antibodies can interfere with the measurement of serum thyroglobulin, and they are therefore always assessed when monitoring serum thyroglobulin levels in patients with differentiated thyroid cancer. (Thyroglobulin is used for the detection of residual, recurrent, or metastatic disease.) (See "Differentiated thyroid cancer: Role of serum thyroglobulin", section on 'Thyroglobulin antibodies'.)

●Thyroid peroxidase (TPO, formerly known as the microsomal antigen) – TPO catalyzes the iodination of tyrosine residues of Tg to form monoiodotyrosine and diiodotyrosine. Nearly all patients with Hashimoto's thyroiditis have high serum concentrations of TPO antibodies. Serum anti-TPO antibodies need not be measured in patients with overt primary hypothyroidism, because almost all have chronic autoimmune thyroiditis. However, a test for anti-TPO antibodies may be useful to predict the likelihood of progression to permanent overt hypothyroidism in patients with subclinical hypothyroidism. (See "Subclinical hypothyroidism in nonpregnant adults", section on 'Identifying the cause'.)

●The TSH receptor – Thyrotropin receptor antibodies (TRAbs) are classified as stimulating, blocking, or neutral. Stimulating antibodies (thyroid-stimulating immunoglobulins, TSI) cause Graves' disease. Thyroid receptor-blocking antibodies can cause hypothyroidism. Some patients will have a mixture of both antibodies, and, depending on the relative titers of these antibodies, they may fluctuate between hyperthyroidism and hypothyroidism. Neutral antibodies bind the receptor but do not stimulate or block function.

There are two methods for measuring TRAb:

•TSI assays measure only thyroid-stimulating antibodies

•TSH receptor-binding inhibitor immunoglobulin (TBII or TBI) assays measure stimulating, blocking, and neutral antibodies.

Third-generation TSI assays have been reported to have a sensitivity of 97 percent and a specificity of 99 percent for the diagnosis of Graves' disease [35]. However, sensitivity may be lower in patients with mild hyperthyroidism [36]. Some third-generation TBII assays are automated and less expensive but are not specific for stimulating antibodies.

Measurement of TRAb is unnecessary for establishing the cause of hyperthyroidism if a radioiodine uptake has been obtained. However, TRAb measurements are being used increasingly as an alternative to obtaining a radioiodine uptake when Graves' disease is suspected. TRAb measurements are also useful for assessing the likelihood of remission after a 12- to 18-month course of antithyroid drugs in patients with Graves' disease, and many experts will obtain a baseline measurement early in the course of antithyroid drug treatment. (See "Diagnosis of hyperthyroidism", section on 'Determining the etiology' and "Postpartum thyroiditis", section on 'Differential diagnosis' and "Thionamides in the treatment of Graves' disease", section on 'Evaluation prior to stopping therapy'.)

There are no commercial assays for blocking antibodies available in the United States, but one such assay is available in Europe. When considering the presence of blocking antibodies in patients with fluctuating hyper- and hypothyroidism (or initial hyperthyroidism, followed by hypothyroidism), a negative TSI level and a positive TBII level, or a TBII level that is considerably higher than the TSI level, is indirect evidence for the possible presence of blocking antibodies.

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SUMMARY AND RECOMMENDATIONS

●Laboratory tests to assess thyroid function – Thyroid function is assessed by one or more of the following tests:

•Serum thyroid-stimulating hormone (TSH) concentration

•Serum total thyroxine (T4) and triiodothyronine (T3) concentrations

•Serum free T4 and T3 concentrations

Very small changes in serum free T4 concentrations induce very large reciprocal changes in serum TSH concentrations (figure 1). As a result, thyroid function is best assessed by measuring serum TSH, assuming steady-state conditions and the absence of pituitary or hypothalamic disease. However, direct measurement of serum thyroid hormone levels remains important in many patients since it may be difficult in some patients to be certain about the state of pituitary and hypothalamic function. (See 'Laboratory tests used to assess thyroid function' above.)

●Assay interference with biotin – Patients taking biotin should hold the supplement for two days prior to assessing thyroid function and longer if they are taking more than 10 mg a day. (See 'Assay interference with biotin ingestion' above.)

●Clinical use of thyroid tests – Thyroid function tests are used in a variety of clinical settings to evaluate thyroid dysfunction, assess the adequacy of levothyroxine therapy in patients with hypothyroidism, and monitor the treatment of hyperthyroidism (table 2). (See 'Clinical use of thyroid function tests' above.)

●Evaluation of thyroid dysfunction – When evaluation is performed in the outpatient setting, many laboratories use the following strategies to limit unnecessary laboratory testing:

-Serum TSH normal – No further testing performed

-Serum TSH high – Free T4 added to determine the degree of hypothyroidism

-Serum TSH low – Free T4 and T3 added to determine the degree of hyperthyroidism

We make two amendments to this strategy when used to assess possible thyroid dysfunction in an individual patient:

-We measure both serum TSH and free T4 if pituitary or hypothalamic disease is suspected (eg, a young woman with amenorrhea and fatigue).

-We measure serum free T4 if the patient has symptoms of hyper- or hypothyroidism despite a normal TSH result. (See 'Evaluating for thyroid dysfunction' above.)

•Monitoring levothyroxine treatment – In patients with primary hypothyroidism who are taking levothyroxine replacement therapy, the serum TSH should be used to titrate the thyroid hormone dose. (See 'Monitoring levothyroxine therapy' above and "Treatment of primary hypothyroidism in adults", section on 'Initial monitoring and dose adjustments' and "Treatment of primary hypothyroidism in adults", section on 'Adjustment of maintenance dose'.)

In patients with secondary hypothyroidism due to pituitary or hypothalamic disease (absent or impaired TSH release), the serum free T4 value should be used to titrate the thyroid hormone dose. (See 'Monitoring levothyroxine therapy' above and "Central hypothyroidism", section on 'Treatment'.)

The goal and requirement for monitoring are different in patients taking levothyroxine for suppression of TSH secretion to prevent recurrence of thyroid cancer or growth or regrowth of goitrous tissue. (See "Thyroid hormone suppressive therapy for thyroid nodules and benign goiter" and "Differentiated thyroid cancer: Overview of management", section on 'Thyroid hormone suppression'.)

•Monitoring treatment of hyperthyroidism – Initial monitoring of hyperthyroidism treatment should consist of periodic clinical assessment, measurements of serum free T4, and often measurements of total T3 levels. During the early treatment of hyperthyroidism with antithyroid drugs, radioiodine, or surgery, serum TSH may remain subnormal for several weeks and rarely for several months. Once steady-state conditions are assured, measurement of serum TSH only can be used to assess the efficacy of therapy. (See 'Monitoring treatment of hyperthyroidism' above.)

●Antithyroid antibodies – Several antibodies against thyroid antigens have been described in chronic autoimmune thyroiditis. However, routine measurement of antithyroid antibodies is not necessary for the assessment of thyroid function. Measurement of thyrotropin receptor antibodies (TRAbs) can be useful in establishing a diagnosis of Graves' disease and assessing the likelihood of remission after a 12- to 18-month course of antithyroid drug therapy. (See 'Antithyroid antibodies' above.)