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Diagnosis of hyperthyroidism
Author: Douglas S Ross, MD
Section Editor: David S Cooper, MD
Deputy Editor: Jean E Mulder, MD

All topics are updated as new evidence becomes available and our peer review process is complete.

Literature review current through: May 2022. | This topic last updated: Feb 15, 2022.

INTRODUCTION

The diagnosis of hyperthyroidism is usually evident in patients with unequivocal clinical and
biochemical manifestations of the disease. Other patients have fewer and less obvious clinical
signs but definite biochemical hyperthyroidism. Still others have little or no clinical
hyperthyroidism, and their only biochemical abnormality is a low serum thyroid-stimulating
hormone (TSH) concentration, a disorder called subclinical hyperthyroidism.

Following a brief discussion of the clinical manifestations of hyperthyroidism, the diagnosis and
evaluation of patients with hyperthyroidism will be presented here. An overview of the clinical
manifestations of hyperthyroidism, disorders that cause hyperthyroidism, the diagnosis of
hyperthyroidism during pregnancy, and subclinical hyperthyroidism are discussed in detail
separately.

● (See "Overview of the clinical manifestations of hyperthyroidism in adults".)

● (See "Disorders that cause hyperthyroidism".)
● (See "Hyperthyroidism during pregnancy: Clinical manifestations, diagnosis, and causes".)
● (See "Subclinical hyperthyroidism in nonpregnant adults".)

CLINICAL MANIFESTATIONS

Symptoms — Hyperthyroid symptoms are nonspecific and may be present in patients with

subclinical disease and absent in those with overt disease, especially older adults.

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Overt hyperthyroidism — Most patients with overt hyperthyroidism have a dramatic

constellation of symptoms. These symptoms characteristically include anxiety, emotional
lability, weakness, tremor, palpitations, heat intolerance, increased perspiration, and weight
loss despite a normal or increased appetite [1,2].

While the combination of weight loss and increased appetite is a characteristic finding, some
patients gain weight, in particular younger patients, due to excessive appetite stimulation [1].
Other symptoms that may be present include hyperdefecation (not diarrhea), urinary
frequency, oligomenorrhea or amenorrhea in women, and gynecomastia and erectile
dysfunction in men [3,4]. (See "Overview of the clinical manifestations of hyperthyroidism in
adults".)

Milder symptoms — Patients with mild hyperthyroidism and older patients often have
symptoms that are referable to one or only a few organ systems [5]. Isolated symptoms and
signs that should lead to evaluation for hyperthyroidism in patients of any age include
unexplained weight loss, new onset atrial fibrillation, myopathy, menstrual disorders, and
gynecomastia.

Other conditions that should suggest the possibility of hyperthyroidism include osteoporosis,
hypercalcemia, heart failure, premature atrial contractions, shortness of breath, and a
deterioration in glycemic control in patients with previously diagnosed diabetes. (See "Overview
of the clinical manifestations of hyperthyroidism in adults".)

Older patients — In older patients, cardiopulmonary symptoms such as tachycardia (or atrial
fibrillation), dyspnea on exertion, and edema may predominate [1,6-8]. They also tend to have
more weight loss and less of an increase in appetite [1]. The most dramatic example of this
phenomenon is "apathetic thyrotoxicosis," in which older patients have no symptoms except for
weakness and asthenia. (See "Overview of the clinical manifestations of hyperthyroidism in
adults", section on 'Geriatric hyperthyroidism'.)

Subclinical hyperthyroidism, defined as normal serum levels of free thyroxine (T4) and
triiodothyronine (T3) with a suppressed TSH level, is associated with a threefold increase in the
risk of atrial fibrillation in older persons ( figure 1). (See "Epidemiology of and risk factors for
atrial fibrillation" and "Subclinical hyperthyroidism in nonpregnant adults", section on 'Atrial
fibrillation'.)

Physical examination — The physical examination in patients with overt hyperthyroidism may

be notable for hyperactivity and rapid speech. Many patients have stare (lid retraction) and lid
lag, representing sympathetic hyperactivity. The skin is typically warm and moist, and the hair
may be thin and fine. Tachycardia is common, the pulse is irregularly irregular in patients with
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atrial fibrillation, systolic hypertension may be present, and the precordium is often
hyperdynamic [6]. Tremor, proximal muscle weakness, and hyperreflexia are other frequent
findings. Exophthalmos, periorbital and conjunctival edema, limitation of eye movement, and
infiltrative dermopathy (pretibial myxedema) occur only in patients with Graves' disease. (See
"Clinical features and diagnosis of Graves' orbitopathy (ophthalmopathy)" and "Pretibial
myxedema (thyroid dermopathy) in autoimmune thyroid disease".)

Thyroid size — The presence and size of a goiter depends upon the cause of the
hyperthyroidism. (See "Disorders that cause hyperthyroidism".)

● Thyroid enlargement ranges from minimal to massive in patients with Graves' disease or
toxic multinodular goiter. A nonpalpable thyroid occurs commonly in older patients with
Graves' disease. (See "Disorders that cause hyperthyroidism", section on 'Toxic adenoma
and toxic multinodular goiter' and "Overview of the clinical manifestations of
hyperthyroidism in adults", section on 'Geriatric hyperthyroidism'.)

● Patients with painless (silent or lymphocytic) thyroiditis may have no, minimal, or modest
thyroid enlargement. The absence of any thyroid enlargement should also suggest
exogenous hyperthyroidism or struma ovarii. (See "Exogenous hyperthyroidism" and
"Struma ovarii".)

● A single, palpable nodule raises the possibility of an autonomously functioning thyroid

adenoma. (See "Disorders that cause hyperthyroidism", section on 'Toxic adenoma and
toxic multinodular goiter'.)

● The thyroid is painful and tender in subacute (granulomatous) thyroiditis. (See "Subacute
thyroiditis".)

Laboratory tests

Thyroid function tests — All patients with primary hyperthyroidism have a low TSH. The
serum TSH concentration alone cannot determine the degree of biochemical hyperthyroidism;
serum free T4 and T3 are required to provide this information. However, in laboratories utilizing
serum TSH assays with detection limits of 0.01 mU/L (third generation), most patients with overt
hyperthyroidism have values <0.05 mU/L. (See "Laboratory assessment of thyroid function".)

Many patients with overt hyperthyroidism have high free T4 and T3 concentrations. In one
study, free T4 and free T3 levels were higher in males aged 20 to 39 years than similarly aged
females [9]. In some patients, however, only the serum T3 or serum T4 is elevated.

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In patients with subclinical hyperthyroidism, TSH is below normal (but more frequently >0.05
mU/L) and serum free T4, T3, and free T3 are normal. (See 'Diagnosis' below.)

Other — Patients with hyperthyroidism may have other nonspecific laboratory findings. As an

example, patients with hyperthyroidism tend to have low serum total, low-density (LDL), and
high-density lipoprotein (HDL) cholesterol concentrations, which increase after treatment. In
addition, the red blood cell mass may be increased in hyperthyroidism, but the plasma volume
is increased more, resulting in a normochromic, normocytic anemia. Serum alkaline
phosphatase and osteocalcin concentrations may be high, indicative of increased bone
turnover. (See "Overview of the clinical manifestations of hyperthyroidism in adults", section on
'Metabolic/Endocrine' and "Overview of the clinical manifestations of hyperthyroidism in
adults", section on 'Hematologic' and "Overview of the clinical manifestations of
hyperthyroidism in adults", section on 'Bone'.)

DIAGNOSIS

The diagnosis of hyperthyroidism is based upon thyroid function tests. In patients in whom
there is a clinical suspicion of hyperthyroidism, the best initial test is serum TSH. If the value is
normal, the patient is very unlikely to have primary hyperthyroidism. Many laboratories have
instituted algorithms in which serum free T4 and T3 are automatically measured if a low serum
TSH value is obtained [10]. If a laboratory is unable to add these determinations to a low TSH
value and it will be inconvenient for the patient to return for follow-up testing, it is reasonable
to order serum TSH, free T4, and T3 as initial tests in patients in whom the clinical suspicion of
hyperthyroidism is high. In addition, if hyperthyroidism is strongly suspected despite a normal
or elevated serum TSH value, serum free T4 and T3 should be measured. (See "Laboratory
assessment of thyroid function".)

Overt hyperthyroidism — The diagnosis of overt hyperthyroidism is usually straightforward.

Except for laboratory error or assay interference due to biotin ingestion, all patients with low
serum TSH and high free T4 and/or T3 concentrations have primary hyperthyroidism. (See
'Assay interference with biotin ingestion' below.)

T3-toxicosis — Most patients with overt hyperthyroidism caused by Graves' disease or nodular

goiter have greater increases in serum T3 than in serum T4, due both to a disproportionate
increase in thyroidal T3 secretion and increased extrathyroidal conversion of T4 to T3 [11].

Patients with T3-toxicosis by definition have symptoms and signs of hyperthyroidism but only
high serum T3 (and low TSH) concentrations. An occasional patient will have normal serum T3

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and free T4 levels but will have an elevated serum free T3 [12]. This pattern of test results tends
to occur early in the course of hyperthyroidism, a time at which most patients have relatively
few symptoms.

T4-toxicosis — The pattern of low TSH, high serum free T4, and normal T3 concentrations is
called T4-toxicosis. It may be found in patients with hyperthyroidism who have a concurrent
nonthyroidal illness that decreases extrathyroidal conversion of T4 to T3 [13]. Despite the
nonthyroidal illness, these patients remain hyperthyroid and their serum TSH concentrations
are low; with recovery from the nonthyroidal illness, serum T3 concentrations rise unless the
hyperthyroidism is recognized and treated. (See "Thyroid function in nonthyroidal illness".)

Amiodarone inhibits extrathyroidal conversion of T4 to T3 in all patients. Thus, patients with

amiodarone-induced hyperthyroidism may also have T4-hyperthyroidism (or at least have
serum T3 concentrations that are not as elevated as in patients with Graves' hyperthyroidism).
This pattern is present whether the hyperthyroidism is caused by amiodarone-induced
thyroiditis or iodide excess [14]. (See "Amiodarone and thyroid dysfunction".)

Subclinical hyperthyroidism — The availability of sensitive assays for TSH resulted in the

identification of patients who have low serum TSH concentrations (<0.4 mU/L) but normal
serum free T4, T3, and free T3 concentrations, a constellation of biochemical findings defined as
subclinical hyperthyroidism. Most of these patients have no clinical manifestations of
hyperthyroidism, and those symptoms that are present are mild and nonspecific. Many patients
have a multinodular goiter with autonomy (toxic nodular goiter) or mild Graves' disease. Most
patients are detected through routine screening of thyroid function. (See "Subclinical
hyperthyroidism in nonpregnant adults".)

TSH-induced hyperthyroidism — TSH-induced hyperthyroidism is a very rare cause of overt

hyperthyroidism, due to either a TSH-secreting pituitary adenoma or partial resistance to the
feedback effect of T4 and T3 on TSH secretion (due to defects in the T3-nuclear receptor)
[15,16]. These patients have normal or high serum TSH despite high free T4 and T3
concentrations. (See "TSH-secreting pituitary adenomas" and "Resistance to thyroid hormone
and other defects in thyroid hormone action".)

Critically ill patients — Rarely, patients with hyperthyroidism who are critically ill due to a
nonthyroidal illness have normal serum total T4 and normal or even low T3 concentrations.
Serum T4 and even free T4 concentrations may be normal because of decreased protein-
binding of T4, caused by either low serum concentrations of thyroxine-binding globulin,
displacement of T4 from binding proteins by endogenous metabolites or drugs, and other
factors. Similar results (low-normal serum T4, normal or low serum T3, and low serum TSH

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concentrations) are found in euthyroid patients in intensive care units. (See "Thyroid function in
nonthyroidal illness".)

Since critically ill hyperthyroid patients and many euthyroid critically ill patients have low serum
TSH concentrations, identification of those that are hyperthyroid may be difficult [17,18]. The
nonthyroidal illness may overshadow or mimic hyperthyroidism (by causing tachycardia,
tremor, weakness). Since many critically ill patients have low serum T4 and T3 concentrations, a
serum T4 value well within the normal range suggests the possible presence of
hyperthyroidism. The diagnosis is further supported by very low serum TSH values, eg, less
than 0.01 mU/L. In contrast, detectable but subnormal TSH values (eg, TSH 0.1 to 0.4 mU/L) in
an assay with a detection limit of 0.01 mU/L are more consistent with nonthyroidal illness alone
[17,18].

In critically ill patients with suspected hyperthyroidism (TSH <0.01 mU/L and normal serum T4),
antithyroid drug therapy should be instituted, with a plan for reassessment after recovery from
the nonthyroidal illness.

DIFFERENTIAL DIAGNOSIS

There are several situations in which the diagnosis of hyperthyroidism may be missed or
incorrectly suspected:

Euthyroid hyperthyroxinemia — The presence of hyperthyroidism may be incorrectly

suspected in patients who have one of several abnormalities in serum thyroid hormone-binding
proteins that result in high serum total (and sometimes free) T4 concentrations and normal (or
slightly high) T3 concentrations. These patients have normal TSH concentrations and are
euthyroid (euthyroid hyperthyroxinemia). (See "Euthyroid hyperthyroxinemia and
hypothyroxinemia".)

Low serum TSH without hyperthyroidism — There are other causes of the combination of low
serum TSH and normal free T4 and T3 concentrations other than subclinical hyperthyroidism:

● Central hypothyroidism – Some patients with central hypothyroidism have low serum TSH
and normal (but usually low-normal) free T4 and T3 concentrations. (See "Diagnosis of and
screening for hypothyroidism in nonpregnant adults" and "Central hypothyroidism".)

● Nonthyroidal illness – Euthyroid patients with nonthyroidal illness, especially those

receiving high-dose glucocorticoids or dopamine, may have low serum TSH but low or low-

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normal free T4 and very low serum T3 concentrations. (See "Thyroid function in
nonthyroidal illness".)

● Recovery from hyperthyroidism – Serum TSH concentrations may remain low for up to
several months after normalization of serum T4 and T3 concentrations in patients treated
for hyperthyroidism or recovering from hyperthyroidism caused by thyroiditis.

● The "physiologic" lowering of serum TSH in pregnancy. (See "Overview of thyroid disease
and pregnancy", section on 'hCG and thyroid function'.)

● An altered set point of the hypothalamic-pituitary-thyroid axis in some otherwise healthy

older persons [19,20].

In hospitalized patients with detectable but subnormal serum TSH concentrations and normal
free T4 and T3 concentrations, a practical approach is to reevaluate the patient in four to eight
weeks. By that time, it should be apparent whether the low serum TSH value was due to
nonthyroidal illness or true thyroid dysfunction. (See "Thyroid function in nonthyroidal illness".)

Assay interference with biotin ingestion — Ingestion of 5 to 30 mg of biotin can cause

spurious results in thyroid test assays using biotin-streptavidin affinity systems in their design
[21-23]. Biotin will cause falsely low values in immunometric assays (eg, used to measure TSH),
and falsely high values in competitive binding assays (eg, used to measure T4, T3, and TSH
receptor-binding inhibitor immunoglobulin [TBII or TBI]). These biochemical findings suggest a
diagnosis of Graves' disease; however, discontinuation of biotin supplements results in
resolution of the biochemical abnormalities. Thyroid tests should be repeated at least two days
after discontinuation of biotin supplements.

DETERMINING THE ETIOLOGY

Our approach outlined below is consistent with the 2016 American Thyroid Association
guidelines for management of hyperthyroidism and other causes of thyrotoxicosis [24]. The
approach recommended by the 2018 European Thyroid Association guideline for the
management of Graves' hyperthyroidism places increased reliance on ultrasonography with
color-flow Doppler and measurement of thyroid artery flow velocity and peak systolic velocity
for the diagnosis of Graves' disease, and it limits the use of radioiodine imaging to those
patients with potential autonomous nodules, or those patients who elect treatment with
radioiodine [25].

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Our approach — Once the diagnosis of hyperthyroidism has been established, the cause of the
hyperthyroidism should be determined ( algorithm 1). (See "Disorders that cause
hyperthyroidism" and 'Thyroid tests' below and 'Thyrotropin receptor antibodies' below and
'Radioiodine uptake' below.)

The diagnosis may be obvious on presentation; a patient with new-onset ophthalmopathy, a

large non-nodular thyroid, and moderate to severe hyperthyroidism has Graves' disease.
However, if the diagnosis is not apparent based on the clinical presentation, diagnostic testing
is indicated and can include the following, depending on available expertise and resources:

● Measurement of thyrotropin receptor antibodies (TRAb, measured by TSI or TBII [TBI]

assays)
● Determination of the radioactive iodine uptake ( table 1)
● Measurement of thyroidal blood flow on ultrasonography

Without nodular thyroid disease — For a nonpregnant, hyperthyroid patient without a

nodular thyroid and without obvious clinical manifestations of Graves' disease (eg, without
ophthalmopathy), measurement of TRAb, determination of radioactive iodine uptake, or
assessment of thyroidal blood flow on ultrasonography are acceptable options to distinguish
Graves' disease from other causes of hyperthyroidism ( algorithm 1). We typically measure
TRAb first (see 'Thyrotropin receptor antibodies' below). If the antibodies are positive, it
confirms the diagnosis of Graves' disease. If negative, it does not distinguish among the
etiologies, as TRAb may not be elevated in patients with mild Graves' disease [26,27]. In this
setting, we proceed with a radioactive iodine uptake. An alternative is to assess thyroidal blood
flow on ultrasound in those centers where expertise is available. (See 'Other tests' below.)

With nodular thyroid disease — For nonpregnant, hyperthyroid patients with physical

examination findings consistent with or suspicious for nodular thyroid disease, we obtain a
radioactive iodine uptake and scan as our initial test to distinguish toxic multinodular goiter
(multiple areas of focal increased and suppressed uptake) and toxic adenoma (focal increased
uptake) from Graves' disease (diffuse increased uptake) or to assess the functionality of nodules
that may coexist with Graves' disease ( algorithm 1). (See 'Radioiodine uptake' below.)

Radioactive iodine is contraindicated during pregnancy. Thus, for pregnant, hyperthyroid

women, we measure TRAb or assess thyroidal blood flow on ultrasonography (where expertise
is available). Hyperthyroidism during pregnancy is reviewed in detail separately. (See
"Hyperthyroidism during pregnancy: Clinical manifestations, diagnosis, and causes", section on
'Establishing the cause'.)

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Thyroid tests — Sometimes the pattern of thyroid function test abnormalities suggests a

specific diagnosis. As examples:

● If TSH is low and only serum T3 is high (normal free T4 concentration), the patient most
likely has Graves' disease or an autonomously functioning thyroid adenoma. This pattern
is more common in regions of marginal iodine intake than in the United States. Another
possibility is exogenous T3 (liothyronine) ingestion. T3-hyperthyroidism can also be seen
in patients taking antithyroid drugs [28]. A radioiodine scan can differentiate between
Graves' disease or autonomy and exogenous intake of T3. (See 'Radioiodine uptake'
below.)

● If TSH is low, free T4 is high, and T3 is normal, the patient may have hyperthyroidism with
concurrent nonthyroidal illness, amiodarone-induced thyroid dysfunction, or exogenous
T4 ingestion. Patients who ingest exogenous T4 (levothyroxine) may have high serum T4
and T3 concentrations, but the T3/T4 ratio is lower than that in most patients with Graves'
hyperthyroidism and toxic adenoma(s) whose T3/T4 ratio usually exceeds 20 (ng/mcg)
[29]. (See "Thyroid function in nonthyroidal illness" and "Amiodarone and thyroid
dysfunction".)

● If free T4 and T3 are elevated and serum TSH is normal or elevated, serum alpha subunit
and a pituitary magnetic resonance imaging (MRI) should be obtained to assess the
possibility of a TSH-producing pituitary tumor (see "TSH-secreting pituitary adenomas").
Patients with resistance to thyroid hormone have variable degrees of end-organ evidence
of hyperthyroidism and a family history of "hyperthyroidism" or genetic abnormalities in
the T3 receptor; commercial assays for genetic testing for thyroid hormone resistance are
available. (See "Resistance to thyroid hormone and other defects in thyroid hormone
action".)

The various causes of hyperthyroidism and the tests used to identify them are discussed in
more detail elsewhere. (See "Disorders that cause hyperthyroidism" and "Painless thyroiditis"
and "Subacute thyroiditis" and "Exogenous hyperthyroidism" and "Diagnostic approach to and
treatment of thyroid nodules" and "Clinical presentation and evaluation of goiter in adults".)

Radioiodine uptake — For nonpregnant, hyperthyroid patients with physical examination

suggesting nodular thyroid disease, we obtain a radioactive iodine uptake as our initial test to
determine the etiology of hyperthyroidism. Pregnancy and breastfeeding are absolute
contraindications to radionuclide imaging. However, in the unusual instance where radioiodine
uptake measurement is felt to be essential for a definitive diagnosis in a lactating woman,
breast milk can be pumped and discarded for five days after ingestion of iodine-123 (123I), then

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breastfeeding may be resumed [24]; breastfeeding should not be resumed if the iodine-131
(131I) isotope is used for determining the uptake.

From a pathogenetic viewpoint, hyperthyroidism results from two different mechanisms that
can be distinguished by the findings on the 24-hour radioiodine uptake ( table 1):

● Hyperthyroidism with a high (or normal) radioiodine uptake indicates de novo synthesis of
hormone ( image 1).

● Hyperthyroidism with a low (nearly absent) radioiodine uptake indicates either

inflammation and destruction of thyroid tissue with release of preformed hormone into
the circulation or an extrathyroidal source of thyroid hormone, such as in patients with
factitious thyrotoxicosis and in patients with struma ovarii, where the functioning thyroid
tissue is in the pelvis rather than the neck. Patients who have been exposed to large
amounts of iodine (eg, intravenous radiographic contrast, amiodarone) may also have a
misleading low radioiodine uptake, although a nearly absent level of uptake after iodine
exposure is common only with amiodarone. (See "Overview of thyroiditis" and "Exogenous
hyperthyroidism" and "Struma ovarii" and "Amiodarone and thyroid dysfunction".)

A radioiodine uptake and scan may be indeterminate in a patient with subclinical

hyperthyroidism due to an autonomous nodule ( image 2). A suppression scan may better
demonstrate an area of focal autonomy ( image 3). Suppression scans are reviewed in more
detail separately. (See "Diagnostic approach to and treatment of thyroid nodules", section on
'Thyroid scintigraphy'.)

Thyrotropin receptor antibodies — For pregnant, hyperthyroid patients and for nonpregnant,

hyperthyroid patients without nodular goiter and without obvious clinical manifestations of
Graves' disease (eg, without ophthalmopathy), we measure TRAb to determine the etiology of
hyperthyroidism. Graves' disease is caused by autoantibodies to the TSH (thyrotropin) receptor
that activate the receptor, thereby stimulating thyroid hormone synthesis and secretion as well
as thyroid growth (causing a diffuse goiter). The presence of TRAb in serum distinguishes the
disorder from other causes of hyperthyroidism.

In such situations where the clinical diagnosis is uncertain, TRAb, using third-generation assays,
have a sensitivity and specificity of 97 and 99 percent for diagnosing Graves' disease [27].
Therefore, in the presence of TRAb, it is reasonable to assume the diagnosis of Graves'
hyperthyroidism [26,30].

Note that there are two methods for measuring TRAb, and commercial laboratories in the
United States may refer to these assays as TBI or TBII (thyrotropin-binding inhibiting or
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thyrotropin-binding inhibitory immunoglobulin), and thyroid-stimulating immunoglobulin (TSI)

assays [27]. Third-generation TBI/TBII assays are competition-based assays that measure
inhibition of binding of a labeled, monoclonal, anti-human TRAb (or labeled TSH) to
recombinant TSH receptor. In contrast, TSI assays measure immunoglobulin-stimulated
increased cAMP production, eg, from Chinese hamster ovary cells transfected with human TSH
(hTSH) receptor.

When TRAb measurement is negative, we then obtain a radioiodine uptake and scan to
determine the etiology of the hyperthyroidism. Assessment of thyroid blood flow by
ultrasonography is an alternative approach, if expertise is available.

Other tests — Other measurements that help differentiate Graves' hyperthyroidism from

destruction-induced hyperthyroidism when a radioiodine uptake is contraindicated include a
serum T3/T4 ratio >20 (in standard units ng/mcg) [29] and a serum free T3/free T4 ratio >0.3 (SI
units) [31]. Additionally, assessment of quantitative thyroid blood flow by ultrasonography may
be helpful to differentiate Graves' hyperthyroidism from painless thyroiditis [32]. (See
"Hyperthyroidism during pregnancy: Clinical manifestations, diagnosis, and causes", section on
'Establishing the cause' and "Overview of the clinical utility of ultrasonography in thyroid
disease", section on 'Autoimmune thyroid disease'.)

SOCIETY GUIDELINE LINKS

Links to society and government-sponsored guidelines from selected countries and regions
around the world are provided separately. (See "Society guideline links: Hyperthyroidism".)

INFORMATION FOR PATIENTS

UpToDate offers two types of patient education materials, "The Basics" and "Beyond the
Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade
reading level, and they answer the four or five key questions a patient might have about a given
condition. These articles are best for patients who want a general overview and who prefer
short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more
sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading
level and are best for patients who want in-depth information and are comfortable with some
medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print
or e-mail these topics to your patients. (You can also locate patient education articles on a
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variety of subjects by searching on "patient info" and the keyword(s) of interest.)

● Basics topic (see "Patient education: Hyperthyroidism (overactive thyroid) (The Basics)")

● Beyond the Basics topics (see "Patient education: Hyperthyroidism (overactive thyroid)
(Beyond the Basics)" and "Patient education: Antithyroid drugs (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

● Signs and symptoms – Patients with hyperthyroidism may have symptoms that include
anxiety, emotional lability, weakness, tremor, palpitations, heat intolerance, increased
perspiration, and weight loss despite a normal or increased appetite. The physical
examination may be notable for hyperactivity and rapid speech. The presence and size of
a goiter depends upon the cause of the hyperthyroidism. Exophthalmos, periorbital and
conjunctival edema, limitation of eye movement, and infiltrative dermopathy (pretibial
myxedema) occur only in patients with Graves' disease. (See 'Clinical manifestations'
above.)

● Thyroid tests in primary hyperthyroidism – All patients with primary hyperthyroidism

have a low thyroid-stimulating hormone (TSH). Many patients with overt hyperthyroidism
have high free thyroxine (T4) and triiodothyronine (T3) concentrations. In some patients,
however, only the serum T3 or serum T4 is elevated.

In patients with subclinical hyperthyroidism, TSH is below normal (but frequently >0.05
mU/L) and serum free T4, T3, and free T3 are normal. Both overt and subclinical
hyperthyroidism are biochemical definitions since hyperthyroid symptoms are nonspecific
and may be present in patients with subclinical disease and absent in those with overt
disease, especially older adults. (See 'Thyroid function tests' above.)

● Suspected hyperthyroidism: Testing and diagnosis – In patients in whom

hyperthyroidism is suspected, serum TSH is the best initial test. If subnormal, serum free
T4 and T3 concentrations are run by most laboratories that offer a TSH reflex option. If
serum free T4 and T3 are not automatically measured when a low serum TSH value is
obtained but the index of suspicion for hyperthyroidism is high, a free T4 and T3 should be
ordered with the initial TSH measurement. (See 'Diagnosis' above.)

In the absence of laboratory error or assay interference, if serum TSH is low and free T4
and T3 are high, the diagnosis of hyperthyroidism is confirmed. (See 'Overt
hyperthyroidism' above and 'Assay interference with biotin ingestion' above.)

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● Identify cause of hyperthyroidism – Once the diagnosis of hyperthyroidism has been

established, the cause of the hyperthyroidism should be determined ( algorithm 1). The
diagnosis may be obvious on presentation; a patient with new-onset ophthalmopathy, a
large non-nodular thyroid, and moderate to severe hyperthyroidism has Graves' disease.
(See 'Our approach' above and "Disorders that cause hyperthyroidism".)

• Nonpregnant without nodular thyroid disease – For a nonpregnant, hyperthyroid

patient without a nodular thyroid and without obvious clinical manifestations of
Graves' disease (eg, without ophthalmopathy), measurement of TRAb (measured by TSI
or TBII [TBI] assays), determination of radioactive iodine uptake, or assessment of
thyroidal blood flow on ultrasonography are acceptable options to distinguish Graves'
disease from other causes of hyperthyroidism. We typically measure TRAb first. TRAb
should be measured using a third-generation assay. (See 'Our approach' above and
'Thyrotropin receptor antibodies' above.)

• Nonpregnant with nodular thyroid disease – For nonpregnant, hyperthyroid

patients with physical examination findings consistent with or suspicious for nodular
thyroid disease, we obtain a radioactive iodine uptake and scan as our initial test to
distinguish toxic multinodular goiter (multiple areas of focal increased and suppressed
uptake) and toxic adenoma (focal increased uptake) from Graves' disease (diffuse
increased uptake) or to assess the functionality of nodules which may coexist with
Graves' disease ( table 1). (See 'Our approach' above and 'Radioiodine uptake' above.)

• Pregnant or breastfeeding women – Radioactive iodine is contraindicated during

pregnancy and breastfeeding. Thus, for pregnant, hyperthyroid women, we measure
TRAb or assess thyroidal blood flow on ultrasonography (where expertise is available).
Hyperthyroidism during pregnancy is reviewed in detail separately. (See
"Hyperthyroidism during pregnancy: Clinical manifestations, diagnosis, and causes",
section on 'Establishing the cause'.)

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11. Laurberg P, Vestergaard H, Nielsen S, et al. Sources of circulating 3,5,3'-triiodothyronine in

hyperthyroidism estimated after blocking of type 1 and type 2 iodothyronine deiodinases. J
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12. Figge J, Leinung M, Goodman AD, et al. The clinical evaluation of patients with subclinical
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15. Wynne AG, Gharib H, Scheithauer BW, et al. Hyperthyroidism due to inappropriate
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16. Beck-Peccoz P, Chatterjee VK. The variable clinical phenotype in thyroid hormone resistance
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18. Franklyn JA, Black EG, Betteridge J, Sheppard MC. Comparison of second and third
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hyperthyroidism, patients receiving thyroxine therapy, and those with nonthyroidal illness.
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21. Barbesino G. Misdiagnosis of Graves' Disease with Apparent Severe Hyperthyroidism in a

Patient Taking Biotin Megadoses. Thyroid 2016; 26:860.

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Hormone and Nonhormone Assays in Healthy Adults. JAMA 2017; 318:1150.
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29. Amino N, Yabu Y, Miki T, et al. Serum ratio of triiodothyronine to thyroxine, and thyroxine-
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30. Vos XG, Smit N, Endert E, et al. Frequency and characteristics of TBII-seronegative patients
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32. Ota H, Amino N, Morita S, et al. Quantitative measurement of thyroid blood flow for
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67:41.
Topic 7847 Version 41.0

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GRAPHICS

Increased incidence of atrial fibrillation in

subclinical hyperthyroidism

Cumulative incidence of atrial fibrillation in subjects over age 60

years according to the serum concentration of TSH. The risk of atrial
fibrillation was increased almost threefold in the subjects with
marked suppression of TSH (left panel) as compared with those who
had normal serum TSH concentrations and were presumably
euthyroid (right panel); patients with slightly low serum TSH
concentrations (middle panel) had a lesser increase in risk.

TSH: thyroid-stimulating hormone.

Data from: Sawin CT, Geller A, Wolf PA, et al. Low serum thyrotropin concentrations
as a risk factor for atrial fibrillation in older persons. N Engl J Med 1994; 331:1249.

Graphic 55024 Version 4.0

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Determining the etiology of overt hyperthyroidism in nonpregnant, non-breast

Overt hyperthyroidism in nonpregnant, non-breastfeeding adults is defined by a low serum TSH with high fr
total T3) concentrations.

TRAb: thyrotropin receptor antibodies; TSI: thyroid-stimulating immunoglobulins; TBI/TBII: thyrotropin rece
immunoglobulin; RAIU: radioactive iodine uptake; TSH: thyroid-stimulating hormone; T4: thyroxine; T3: triio

* The presence of orbitopathy (ophthalmopathy) alone may be sufficient to diagnose Graves' disease.

¶ There is no formal definition of moderate to severe hyperthyroidism. A total T3 >300 ng/dL and/or free T4
moderate to severe disease.

Δ We obtain a baseline TSI after diagnosis of Graves' disease to guide therapy with thionamides.

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Graphic 133238 Version 1.0

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Causes of hyperthyroidism

Hyperthyroidism with a normal or high radioiodine uptake

Autoimmune thyroid disease

Graves' disease

Hashitoxicosis

Autonomous thyroid tissue (uptake may be low if recent iodine load led to iodine-
induced hyperthyroidism)

Toxic adenoma

Toxic multinodular goiter

TSH-mediated hyperthyroidism

TSH-producing pituitary adenoma

Non-neoplastic TSH-mediated hyperthyroidism

Human chorionic gonadotropin-mediated hyperthyroidism

Hyperemesis gravidarum

Trophoblastic disease

Hyperthyroidism with a near absent radioiodine uptake

Thyroiditis

Subacute granulomatous (de Quervain's) thyroiditis

Painless thyroiditis (silent thyroiditis, lymphocytic thyroiditis)

Postpartum thyroiditis

Amiodarone (also may cause iodine-induced hyperthyroidism)

Checkpoint inhibitor-induced thyroiditis

Radiation thyroiditis

Palpation thyroiditis

Exogenous thyroid hormone intake

Excessive replacement therapy

Intentional suppressive therapy

Factitious hyperthyroidism

Ectopic hyperthyroidism

Struma ovarii

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Metastatic follicular thyroid cancer

Major causes of hyperthyroidism according to the presence of a high or low radioiodine uptake.
High uptake indicates increased new hormone synthesis by the thyroid, whereas low uptake
indicates release of preformed hormone, exogenous ingestion, or extrathyroidal hormone
synthesis.

TSH: thyroid-stimulating hormone.

Graphic 76972 Version 6.0

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Autonomous thyroid nodule: Appearance on

thyroid scintigraphy

Iodine 123 (123-I) thyroid scan demonstrating an autonomous

("hot") nodule with suppression of isotope uptake elsewhere. The
total 24-hour isotope uptake was normal (12 percent).

SSN: suprastenal notch.

Courtesy of Douglas Ross, MD.

Graphic 79487 Version 4.0

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Indeterminate thyroid scan: Appearance on thyroid scintigraphy

123-I thyroid scan obtained to assess a palpable left thyroid nodule. The function of the nodule could not
be determined.

SSN: suprasternal notch; 123-I: iodine-123.

Courtesy of Douglas Ross, MD.

Graphic 51029 Version 5.0

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Thyroid suppression scan

123-I thyroid scan of an indeterminate thyroid nodule, after 4 weeks of T4 therapy. The nodule (outlined in
white) overlies an area of relatively increased isotope concentration, indicating autonomy, since uptake is
suppressed in the rest of the gland.

123-I: iodine-123; SSN: suprasternal notch; T4: levothyroxine.

Courtesy of Douglas Ross, MD.

Graphic 67109 Version 5.0

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Contributor Disclosures
Douglas S Ross, MD Consultant/Advisory Boards: Arbor Pharmaceuticals [Hypothyroidism];IBSA Pharma
Inc [Hypothyroidism];Medullary Thyroid Cancer Registry Consortium [Thyroid cancer];Spectrix
Therapeutics, LLC [Hypothyroidism].
All of the relevant financial relationships listed have been
mitigated. David S Cooper, MD No relevant financial relationship(s) with ineligible companies to
disclose. Jean E Mulder, MD No relevant financial relationship(s) with ineligible companies to disclose.

Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are
addressed by vetting through a multi-level review process, and through requirements for references to be
provided to support the content. Appropriately referenced content is required of all authors and must
conform to UpToDate standards of evidence.

Conflict of interest policy

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