Diagnosis of and screening for hypothyroidism in nonpregnant adults

INTRODUCTION — 

The diagnosis of hypothyroidism relies heavily upon laboratory tests because of the lack of specificity of the typical clinical manifestations. Overt hypothyroidism is characterized by a high serum thyroid-stimulating hormone (TSH) concentration and a low serum free thyroxine (T4) concentration, whereas subclinical hypothyroidism is defined biochemically as a normal free T4 concentration in the presence of an elevated TSH concentration. Central (secondary or tertiary) hypothyroidism is characterized by a low serum T4 concentration and a serum TSH concentration that is not appropriately elevated.

This topic will review diagnosis of and screening for hypothyroidism in nonpregnant adults. The major clinical manifestations, causes, and treatment of hypothyroidism and the diagnosis and management of subclinical hypothyroidism are discussed separately. Screening for hypothyroidism during pregnancy and in neonates is also reviewed separately.

●(See "Clinical manifestations of hypothyroidism".)

●(See "Disorders that cause hypothyroidism".)

●(See "Treatment of primary hypothyroidism in adults".)

●(See "Subclinical hypothyroidism in nonpregnant adults".)

●(See "Hypothyroidism during pregnancy: Clinical manifestations, diagnosis, and treatment", section on 'Screening'.)

●(See "Clinical features and detection of congenital hypothyroidism", section on 'Newborn screening'.)

EPIDEMIOLOGY — 

In community surveys, the prevalence of overt hypothyroidism varies from 0.1 to 2 percent [1-5]. The prevalence of subclinical hypothyroidism is higher, ranging from 4 to 10 percent of adults, with possibly a higher frequency in older women [1,2,6,7]. However, the upper limit of normal for TSH shifts higher in older adults. Therefore, if age-adjusted normal ranges are used, the prevalence may not increase with old age. (See "Laboratory assessment of thyroid function", section on 'Serum TSH'.)

Hypothyroidism is five to eight times more common in women than men, and more common in women with small body size at birth and during childhood [5,8].

In the United States National Health and Nutrition Examination Survey (NHANES) III, 13,344 people without known thyroid disease or a family history of thyroid disease had measurements of serum TSH, T4, thyroglobulin antibodies, and thyroid peroxidase (TPO) antibodies with the following results [6]:

●Hypothyroidism was found in 4.6 percent (0.3 percent overt and 4.3 percent subclinical).

●Hyperthyroidism was found in 1.3 percent (0.5 percent overt and 0.7 percent subclinical).

●Serum TPO antibody concentrations were high in 11 percent.

●Mean serum TSH concentrations were significantly lower in Black Americans than in White Americans or Mexican Americans.

Thus, a significant proportion of the United States population has laboratory evidence of thyroid disease. (See 'Whom to test' below.)

WHOM TO TEST

Signs and/or symptoms of hypothyroidism present — All patients with symptoms and/or signs suggestive of hypothyroidism should be tested (table 1). (See "Clinical manifestations of hypothyroidism".)

●The clinical manifestations of hypothyroidism are highly variable, depending upon the age at onset and the duration and severity of thyroid hormone deficiency. Common symptoms of thyroid hormone deficiency include fatigue, cold intolerance, weight gain, constipation, dry skin, myalgia, and menstrual irregularities (table 2).

●Physical examination findings may include goiter (particularly in patients with iodine deficiency or goitrous chronic autoimmune thyroiditis [Hashimoto's thyroiditis]), bradycardia, diastolic hypertension, and a delayed relaxation phase of the deep tendon reflexes.

Screening in the absence of signs and/or symptoms of hypothyroidism — In the absence of data showing any benefit of population-based screening, we suggest not routinely measuring thyroid function in nonpregnant individuals without signs or symptoms of hypothyroidism. We instead measure TSH (or TSH and free T4, in selected cases) in individuals who are at increased risk for hypothyroidism.

●Increased risk for hypothyroidism – Patients with increased risk for hypothyroidism includes those with laboratory or radiologic abnormalities that could be caused by hypothyroidism, patients with risk factors for hypothyroidism (eg, patients with history of autoimmune disease, previous radioiodine therapy and/or head and neck irradiation, family history of thyroid disease), and patients taking drugs that may impair thyroid function (table 1).

As examples, thyroid function should be measured in patients with the following:

•Substantial hyperlipidemia or a change in lipid pattern, which occurs with increased frequency in hypothyroidism. (See "Lipid abnormalities in thyroid disease".)

•Hyponatremia, often resulting from inappropriate production of antidiuretic hormone, which is another laboratory manifestation of hypothyroidism. (See "Causes of hypotonic hyponatremia in adults", section on 'Hypothyroidism'.) (Related Lab Interpretation Monograph(s): "Low sodium in adults".)

•High serum muscle enzyme concentrations. (Related Lab Interpretation Monograph(s): "High skeletal muscle creatine kinase in adults".)

•Macrocytic anemia. (See "Diagnostic approach to anemia in adults", section on 'Macrocytosis (high MCV)'.) (Related Lab Interpretation Monograph(s): "Low hemoglobin, hematocrit in adults".)

•Pericardial or pleural effusions. (See "Diagnostic evaluation of the hemodynamically stable adult with a pleural effusion", section on 'History and examination'.)

•Previous thyroid injury (eg, radioiodine therapy, thyroid or neck surgery, external radiation therapy).

•Pituitary or hypothalamic disorders. (See "Central hypothyroidism".)

•History of autoimmune diseases.

•Malignancy treated with immunomodulatory therapy (eg, immune checkpoint inhibitors) or antiangiogenic tyrosine kinase inhibitors (eg, sunitinib, lenvatinib). (See "Drug interactions with thyroid hormones", section on 'Drugs that cause hypothyroidism' and "Overview of toxicities associated with immune checkpoint inhibitors", section on 'Hypothyroidism' and "Non-cardiovascular toxicities of molecularly targeted antiangiogenic agents", section on 'Thyroid dysfunction'.)

●Benefits and harms – The measurement of thyroid function tests in patients at risk of having thyroid disease who are presently not known to have thyroid disease and do not have symptoms of thyroid disease is controversial [9,10]. The primary benefit of screening for hypothyroidism is the detection of hypothyroidism before the occurrence of symptoms. Subclinical thyroid dysfunction is common in the adult population [6]. However, there is no evidence that early detection and treatment with T4 improves clinically important outcomes in individuals with hypothyroidism detected by screening. Although T4 replacement therapy has few side effects when properly dosed, overtreatment with thyroid hormone is common and may be associated with adverse skeletal and cardiovascular effects, particularly in older patients. (See "Subclinical hyperthyroidism in nonpregnant adults", section on 'Exogenous subclinical hyperthyroidism'.)

●Evidence of effectiveness – There are no clinical trials evaluating the effectiveness of screening for hypothyroidism. A computer decision model that evaluated a hypothetical cohort of individuals screened every five years beginning at age 35 years showed that screening for hypothyroidism was similarly cost effective as other accepted preventive practices (eg, breast cancer or hypertension screening) [11]. Benefit accrued mainly from the avoidance of symptoms of hypothyroidism when diagnosed and treated early and from the decrease in adverse cardiovascular outcomes associated with the lower serum cholesterol concentrations in treated hypothyroid patients. The cost effectiveness of screening was most favorable in older women.

●Recommendations of others – Screening recommendations from major groups are conflicting.

•The American Academy of Family Physicians (AAFP) does not recommend screening for hypothyroidism in asymptomatic adults [12].

•The American Thyroid Association (ATA) and the American Association of Clinical Endocrinologists (AACE) recommend measurement of TSH in any individual at risk for hypothyroidism (eg, personal history of type 1 diabetes or other autoimmune disease, family history of thyroid disease, history of neck radiation to the thyroid, history of thyroid surgery) and consideration of measurement of TSH in patients over the age of 60 years [13].

•The United States Preventive Services Task Force (USPSTF) found insufficient evidence to assess the benefits and harms of screening [14,15].

Special populations

●Asymptomatic pregnant women – The universal screening of asymptomatic pregnant women for hypothyroidism during the first trimester of pregnancy is controversial. This topic is reviewed in detail elsewhere. (See "Hypothyroidism during pregnancy: Clinical manifestations, diagnosis, and treatment", section on 'Screening'.)

●Older adults – We do not routinely screen asymptomatic older adults for hypothyroidism. Although hypothyroidism is common in older adults (eg, 5 to 15 percent in women over the age of 65 years), there is no evidence that it is associated with adverse outcomes in the oldest individuals when detected by screening alone. This was illustrated in a population-based, prospective study of 558 individuals in the Netherlands who were screened for hypothyroidism during the month of their 85^th birthday and again three years later [16]. Annual follow-up (for four years) was also performed to assess activities of daily living (ADLs), cognitive performance, and depressive mood with the following results:

•Hypothyroidism was identified in 12 percent at baseline (7 percent overt and 5 percent subclinical). Those with overt hypothyroidism were referred to their primary care clinician for further evaluation (although none were started on levothyroxine, as clinicians in the area do not routinely start treatment for disorders identified by screening only). None of the patients with subclinical hypothyroidism had progressed to overt hypothyroidism when retested at age 88 years.

•At baseline, there was no association between baseline serum TSH concentration and cognitive function, depressive symptoms, or disability in ADLs.

•All of the above measures of performance declined over time, but the decline was not accelerated in those with either subclinical or overt hypothyroidism. In fact, increasing serum TSH at baseline was associated with a slower decline in ability to perform "instrumental" ADLs (such as preparing one's own meals, shopping for groceries and personal items, managing one's money, using the telephone, and doing housework).

•Higher baseline TSH was also associated with lower all-cause and cardiovascular mortality, in spite of higher baseline serum cholesterol concentrations.

●Hospitalized or ill patients – Assessment of thyroid function is not recommended in hospitalized or ill patients unless thyroid disease is strongly suspected, since there are many other factors in acutely or chronically ill euthyroid patients that influence TSH secretion. This topic is reviewed in detail separately. (See "Thyroid function in nonthyroidal illness", section on 'Evaluation'.)

DIAGNOSTIC EVALUATION — 

Because of the lack of specificity of the typical clinical manifestations, the diagnosis of hypothyroidism is based primarily upon laboratory testing (algorithm 1).

●Initial test for most patients: TSH – For most patients with suspected hypothyroidism (table 1), the serum TSH should be the initial test (algorithm 1) [17]. TSH should not typically be measured in seriously ill patients unless there is a strong suspicion of thyroid dysfunction, since there are many other factors that influence TSH secretion in these patients. (See "Thyroid function in nonthyroidal illness".)

•If the TSH is elevated, it should be repeated along with a serum free T4 to make the diagnosis of primary hypothyroidism (table 3). (See 'Primary hypothyroidism' below.) (Related Lab Interpretation Monograph(s): "High thyroid-stimulating hormone (TSH) in adults".)

•If the TSH is normal but the patient has convincing symptoms of hypothyroidism, we measure a repeat serum TSH and a free T4 to assess for central hypothyroidism. (See 'Central hypothyroidism' below.)

Many laboratories use a "reflex to free T4" strategy. If the TSH is normal, no further testing is performed. If the TSH is abnormal, free T4 is automatically measured in the existing sample to aid in the interpretation of abnormal TSH. If the laboratory uses a reflexive free T4 testing strategy, repeat testing to confirm abnormal thyroid tests is warranted unless the diagnosis of hypothyroidism is certain based on history, physical examination, and clear thyroid test abnormalities (eg, a TSH >10 mU/L with low free T4).

●When to obtain TSH and free T4 as the initial tests – We obtain TSH and free T4 for initial testing in the following settings:

•Known or suspected pituitary or hypothalamic disease. Central hypothyroidism should be suspected in the following circumstances (see 'Central hypothyroidism' below):

-There is known hypothalamic or pituitary disease

-A mass lesion is present in the pituitary

-When symptoms and signs of hypothyroidism are associated with other hormonal deficiencies (eg, a young woman with amenorrhea and fatigue)

•Hospitalized or ill patients, when thyroid disease is strongly suspected. (See "Thyroid function in nonthyroidal illness".)

•In patients receiving drugs or with underlying diseases that affect TSH secretion (table 4). Drugs that can decrease TSH secretion include dopamine, high doses of glucocorticoids, and somatostatin analogs (such as octreotide). Drugs that increase TSH secretion include dopamine antagonists (metoclopramide or domperidone), amiodarone, and oral cholecystographic dyes (eg, sodium ipodate).

DIAGNOSIS

Primary hypothyroidism — Primary thyroid disease accounts for over 95 percent of cases of hypothyroidism. It is due to inadequate production of thyroid hormone caused by disease of the thyroid gland.

●Overt hypothyroidism – Overt hypothyroidism is characterized by a TSH above the upper limit of the normal TSH reference range and a free T4 below the lower limit of the normal reference range. (See "Treatment of primary hypothyroidism in adults".)

●Subclinical hypothyroidism – Subclinical hypothyroidism is characterized by a persistently elevated TSH and a normal free T4 (algorithm 1). Other causes of an elevated TSH must be excluded (table 4). (See "Subclinical hypothyroidism in nonpregnant adults", section on 'Diagnosis' and "Subclinical hypothyroidism in nonpregnant adults", section on 'Differential diagnosis'.)

It is important to differentiate overt and subclinical hypothyroidism because the decision to treat subclinical hypothyroidism is individualized. (See "Subclinical hypothyroidism in nonpregnant adults", section on 'Candidates for T4 replacement'.)

We define an elevated serum TSH as a TSH concentration above the upper limit of the normal TSH reference range, which is typically 4.5 mU/L in most laboratories. There is controversy over the appropriate upper limit of normal for serum TSH. Some experts have suggested that the true upper limit is only 2.5 or 3 mU/L in healthy individuals without thyroid disease, while others argue that the serum TSH distribution shifts towards higher values with age (eg, >70 years of age), independent of the presence of antithyroid antibodies [18], or in class 3 obesity (body mass index ≥40 kg/m²) [19]. In these cases, the upper limit of normal could be as high as 6 to 8 mU/L in healthy octogenarians, or as high as 7.5 mU/L in class 3 obesity. This topic is reviewed in detail separately. (See "Laboratory assessment of thyroid function", section on 'Serum TSH'.)

Central hypothyroidism — Thyrotropin-releasing hormone (TRH) and TSH are required for normal thyroid hormone secretion. Central hypothyroidism is due to insufficient stimulation of the thyroid gland by TSH, and it is caused by either hypothalamic (tertiary hypothyroidism) or pituitary (secondary hypothyroidism) disease [20,21]. Central hypothyroidism is much less common than primary hypothyroidism. (See "Central hypothyroidism", section on 'Etiology'.)

In patients with central hypothyroidism, the free T4 value is low-normal or low and TSH may be frankly low, inappropriately normal (for the low T4), or slightly high (5 to 10 mU/L) due to secretion of biologically inactive TSH (table 3). (See "Central hypothyroidism", section on 'Diagnosis'.)

In hypothyroidism caused by hypothalamic or pituitary disease, TSH secretion does not increase appropriately as T4 secretion falls. As a result, the symptoms and the serum free T4 value must be used to make the diagnosis. The clinical manifestations, diagnosis, differential diagnosis, and treatment of central hypothyroidism are reviewed in detail separately. (See "Central hypothyroidism".)

DIFFERENTIAL DIAGNOSIS — 

The differential diagnosis of an elevated serum TSH level includes resistance to TSH, resistance to thyroid hormone, recovery from nonthyroidal illness, and TSH-secreting pituitary adenomas (table 4). High serum TSH concentrations may also occur in primary adrenal insufficiency [22] and factitiously in rare patients who have antibodies to the murine immunoglobulins used in the assay [23], or complexes of TSH bound to immunoglobulin G (IgG) [24].

Resistance to TSH or thyroid hormone — An elevated TSH concentration may rarely be due to thyroidal resistance to TSH, secondary to alterations in the TSH receptor [25], failure of the cell to express the receptor at the cell surface, or to receptor-independent mechanisms. Many of these patients are euthyroid, while others are hypothyroid. Serum free T4 and triiodothyronine (T3) concentrations are typically normal or low. The thyroid gland is not enlarged. It may be difficult to distinguish subclinical hypothyroidism (common) from resistance to TSH (extremely rare). The presence of other family members expressing the same phenotype and ultimately a defect in the TSH receptor confirms the diagnosis of resistance to TSH. (See "Resistance to thyrotropin and thyrotropin-releasing hormone".)

Patients with mutations in the T3 receptor (generalized thyroid hormone resistance) have a normal or elevated TSH, but serum free T4 and T3 are also elevated. Some patients have manifestations of hypothyroidism; however, most such patients are clinically euthyroid. (See "Resistance to thyroid hormone and other defects in thyroid hormone action" and "Disorders that cause hypothyroidism".)

Recovery from nonthyroidal illness — Euthyroid patients with nonthyroidal illness may have transient elevations in serum TSH concentrations (up to 20 mU/L) during recovery from nonthyroidal illness. In patients with a recent illness, TSH and free T4 should be repeated four to six weeks after recovery. Few of these patients prove to have hypothyroidism when reevaluated after recovery from their illness. (See "Thyroid function in nonthyroidal illness".)

Medications — Drugs that may increase TSH include amiodarone, dopamine antagonists (eg, metoclopramide), oral cholecystogram dye (eg, sodium ipodate) (table 4).

Thyrotropin-secreting pituitary adenomas — TSH-secreting pituitary adenomas are a rare cause of hyperthyroidism. TSH-secreting adenomas secrete biologically active TSH in a more or less autonomous fashion. The characteristic biochemical abnormalities in patients with hyperthyroidism caused by a TSH-secreting adenoma are normal or high serum TSH concentrations and high serum total and free T4 and T3 concentrations. (See "TSH-secreting pituitary adenomas".)

IDENTIFYING THE CAUSE

Primary hypothyroidism — The most common cause of hypothyroidism in iodine-sufficient areas of the world is chronic autoimmune (Hashimoto's) thyroiditis. (See "Disorders that cause hypothyroidism", section on 'Primary hypothyroidism'.)

History and physical examination — The history should probe for other causes of hypothyroidism, including past treatment of hyperthyroidism with radioiodine, thyroidectomy, use of drugs that affect thyroid hormone synthesis, or iodine deficiency or excess (table 5). Physical examination may, in some cases, reveal thyroid enlargement (goiter) or an old thyroidectomy scar.

Thyroid peroxidase antibodies — If the history does not suggest an alternative cause, we assume that the patient has Hashimoto's thyroiditis. Additional laboratory testing is usually not required. Specifically, we do not routinely measure thyroid peroxidase (TPO) antibodies in patients with overt hypothyroidism because almost all have chronic autoimmune (Hashimoto's) thyroiditis.

However, many thyroid experts measure serum TPO antibodies in patients with (see "Clinical presentation and evaluation of goiter in adults", section on 'Initial testing' and "Subclinical hypothyroidism in nonpregnant adults", section on 'Identifying the cause'):

●Goiter, especially in the absence of hypothyroidism, to identify immunologically mediated goiter

●Subclinical hypothyroidism, painless (silent) thyroiditis, or postpartum thyroiditis, to predict the likelihood of progression to permanent overt hypothyroidism

Serum concentrations of TPO autoantibodies are elevated in more than 90 percent of patients with chronic autoimmune thyroiditis [26]. The two major forms of the disorder are goitrous autoimmune thyroiditis and atrophic autoimmune thyroiditis, with the common pathologic feature being lymphocytic infiltration and the common serologic feature being the presence of high serum concentrations of TPO antibodies and thyroglobulin. (See "Pathogenesis of Hashimoto's thyroiditis (chronic autoimmune thyroiditis)", section on 'Clinical phenotypes'.)

Sometimes TPO antibodies are measured concomitantly with TSH in patients who have symptoms of hypothyroidism and/or a goiter on physical examination, and TPO antibodies are found to be elevated in patients with normal thyroid function tests. These patients have chronic autoimmune thyroiditis but do not have hypothyroidism. They are more likely to develop hypothyroidism than antibody-negative individuals [7]. Such patients should have serum TSH measured annually.

Central hypothyroidism — Patients with biochemical evidence of central hypothyroidism require neuroradiologic studies (preferably magnetic resonance imaging [MRI]) to assess the hypothalamic-pituitary region and biochemical assessment for other pituitary hormone deficiencies, particularly secondary adrenal insufficiency. This topic is reviewed in detail separately. (See "Central hypothyroidism", section on 'Etiology' and "Central hypothyroidism", section on 'Evaluation'.)

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: Hypothyroidism".)

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 5^th to 6^th 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 10^th to 12^th 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 topics (see "Patient education: Hypothyroidism (underactive thyroid) (The Basics)")

●Beyond the Basics topics (see "Patient education: Hypothyroidism (underactive thyroid) (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

●Epidemiology – In community surveys, the prevalence of overt hypothyroidism varies from 0.1 to 2 percent. The prevalence of subclinical hypothyroidism ranges from 4 to 10 percent but may be overestimated in population-based studies, as the upper limit of normal for thyroid-stimulating hormone (TSH) shifts higher in older adults. Hypothyroidism is five to eight times more common in women than men. (See 'Epidemiology' above.)

●Whom to test

•Signs and/or symptoms of hypothyroidism present – All patient with signs and/or symptoms suggestive of hypothyroidism should be tested (table 2). (See 'Whom to test' above and "Clinical manifestations of hypothyroidism".)

•Screening in the absence of signs and/or symptoms of hypothyroidism – We suggest not performing population-based screening for hypothyroidism (Grade 2C). We instead measure TSH (or TSH and free thyroxine [T4], in selected cases) in individuals who are at increased risk for hypothyroidism (table 1). (See 'Screening in the absence of signs and/or symptoms of hypothyroidism' above.)

●Diagnostic evaluation

•Most patients: TSH – For most patients with suspected hypothyroidism (table 1), the TSH should be the initial test (algorithm 1). If the TSH is elevated, it should be repeated along with a free T4 to make the diagnosis of primary hypothyroidism (table 3). If the TSH is normal and the patient has convincing symptoms of hypothyroidism despite a normal TSH result, we also measure a repeat TSH along with a free T4. (See 'Diagnostic evaluation' above.)

TSH should not typically be measured in seriously ill patients unless there is a strong suspicion of thyroid dysfunction, since there are many other factors that influence TSH secretion in these patients.

•When to obtain TSH and free T4 as the initial tests – We measure both TSH and free T4 as the initial tests in the following settings (see 'Diagnostic evaluation' above):

-Known or suspected pituitary or hypothalamic disease.

-Hospitalized patients, when thyroid disease is strongly suspected. (See "Thyroid function in nonthyroidal illness".)

-Patients receiving drugs or with underlying diseases that affect TSH secretion (table 4).

●Diagnosis – The diagnosis of hypothyroidism is based primarily upon laboratory testing (algorithm 1).

•Primary hypothyroidism

-Overt hypothyroidism – Overt hypothyroidism is characterized by a TSH above the upper limit of the normal TSH reference range and a free T4 below the lower limit of the normal reference range. (See 'Diagnosis' above and "Treatment of primary hypothyroidism in adults".)

-Subclinical hypothyroidism – Subclinical hypothyroidism is characterized by an elevated TSH and a normal free T4. Other causes of an elevated TSH must be excluded (table 4). (See "Subclinical hypothyroidism in nonpregnant adults", section on 'Diagnosis' and "Subclinical hypothyroidism in nonpregnant adults", section on 'Differential diagnosis'.)

Older adults (eg, >70 years of age) and those with class 3 obesity (body mass index ≥40 kg/m²) may have a higher upper limit of normal for TSH. This shift in the upper limit of normal informs the diagnosis and management of subclinical hypothyroidism, particularly in older adults.

•Central hypothyroidism – In patients with central hypothyroidism, the free T4 is low-normal or low and TSH may be frankly low, inappropriately normal (for the low T4), or slightly high (5 to 10 mU/L) due to secretion of biologically inactive TSH (table 3). (See 'Central hypothyroidism' above and "Central hypothyroidism", section on 'Diagnosis'.)

●Differential diagnosis – The differential diagnosis of an elevated serum TSH concentration includes resistance to TSH, recovery from nonthyroidal illness, medications, and a TSH-secreting pituitary adenoma (table 4). (See 'Differential diagnosis' above.)

●Identifying the cause of hypothyroidism

•Primary hypothyroidism – The clinical evaluation of a patient with primary hypothyroidism should be directed toward confirming the presence and identifying the cause of the hormone deficiency (table 5). The history, for example, may uncover past treatment of hyperthyroidism with radioiodine or thyroidectomy, the use of drugs that affect thyroid hormone synthesis, or history of iodine deficiency or excess. If the history does not suggest an alternative cause, we assume that the patient has Hashimoto's thyroiditis. Additional laboratory testing is usually not required. Specifically, we do not routinely measure thyroid peroxidase (TPO) antibodies in patients with overt hypothyroidism because almost all have chronic autoimmune (Hashimoto) thyroiditis. (See 'Identifying the cause' above.)

•Central hypothyroidism – Patients with biochemical evidence of central hypothyroidism require neuroradiologic studies (preferably magnetic resonance imaging [MRI]) to assess the hypothalamic-pituitary region and biochemical assessment for other pituitary hormone deficiencies, particularly secondary adrenal insufficiency. (See "Central hypothyroidism", section on 'Etiology' and "Central hypothyroidism", section on 'Evaluation'.)