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.
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, risk factors, and prevention of 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 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 thyroid eye disease" 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.
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 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 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-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].
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'.)
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 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 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 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.)
●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'.)
