2/7/2020 Diagnosis of and screening for hypothyroidism in nonpregnant adults - UpToDate

Author: Douglas S Ross, MD

Section Editor: David S Cooper, MD
Deputy Editor: Jean E Mulder, MD

Contributor Disclosures

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

Literature review current through: Jun 2020. | This topic last updated: Sep 16, 2019.

INTRODUCTION

The diagnosis of hypothyroidism relies heavily upon laboratory tests because of the lack of
specificity of the typical clinical manifestations. Primary 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. Secondary (central)
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.
Screening for hypothyroidism during pregnancy and in neonates is reviewed separately. (See
"Hypothyroidism during pregnancy: Clinical manifestations, diagnosis, and treatment", section on
'Screening' and "Clinical features and detection of congenital hypothyroidism", section on
'Newborn screening'.)

The major clinical manifestations, causes, and treatment of hypothyroidism and the diagnosis
and management of subclinical hypothyroidism are discussed separately. (See "Clinical
manifestations of hypothyroidism" and "Disorders that cause hypothyroidism" and "Treatment of
primary hypothyroidism in adults" and "Subclinical hypothyroidism in nonpregnant adults".)

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, there is an age-related shift
towards higher TSH concentrations in older patients, and 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'.)

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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 blacks than in whites or
Mexican-Americans.

Thus, a significant proportion of the United States population has laboratory evidence of thyroid
disease, suggesting that routine screening could be useful. (See 'Screening' below.)

CLINICAL FEATURES

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 1). 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. In the majority of patients with chronic autoimmune thyroiditis, thyroid
peroxidase (TPO) antibodies are elevated. A variety of metabolic abnormalities may be present
including hypercholesterolemia, macrocytic anemia, elevated creatine kinase, and hyponatremia
[9]. The symptoms, signs, and metabolic abnormalities of hypothyroidism are discussed in more
detail elsewhere. (See "Clinical manifestations of hypothyroidism".)

DIAGNOSIS

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

● Primary hypothyroidism is characterized by a high serum TSH concentration and a low

serum free T4 concentration. Patients with a high serum TSH concentration and a normal
serum free T4 concentration may have subclinical hypothyroidism. (See "Subclinical

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hypothyroidism in nonpregnant adults", section on 'Diagnosis' and "Subclinical

hypothyroidism in nonpregnant adults", section on 'Differential diagnosis'.)

● Central hypothyroidism is characterized by a low serum T4 concentration and a serum TSH

concentration that is not appropriately elevated. In this setting, differentiation must be made
between pituitary (secondary hypothyroidism) and hypothalamic (tertiary hypothyroidism)
disorders. (See "Central hypothyroidism", section on 'Diagnosis'.)

Primary hypothyroidism — Primary thyroid disease accounts for over 95 percent of cases of
hypothyroidism.

In most patients with symptoms or signs suggestive of hypothyroidism (table 2), the serum TSH
should be the initial test. If the serum TSH concentration is elevated, the TSH measurement
should be repeated along with a serum free T4 to make the diagnosis of hypothyroidism (table
3).

● If the repeat serum TSH value is still high and the serum free T4 is low, consistent with
primary hypothyroidism, replacement therapy with T4 should be initiated. (See "Treatment of
primary hypothyroidism in adults".)

● If the repeat serum TSH value is still high but the serum free T4 value is within the normal
range, indicating subclinical hypothyroidism, the decision about T4 replacement is made on
a case-by-case basis and depends partly upon the degree of TSH elevation. (See
"Subclinical hypothyroidism in nonpregnant 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
'Secondary and tertiary (central) hypothyroidism' below.)

We define an elevated serum TSH as a TSH concentration above the upper limit of the normal
TSH reference range, which is typically 4 to 5 mU/L in most laboratories. Presently there is
considerable 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, independent of the presence of antithyroid antibodies [10], or in obesity [11]. 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 morbid obesity. This topic is reviewed in detail separately. (See
"Laboratory assessment of thyroid function", section on 'Serum TSH'.)

Secondary and tertiary (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

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(tertiary hypothyroidism) or pituitary (secondary hypothyroidism) disease [12,13]. Central

hypothyroidism is much less common than primary hypothyroidism.

Secondary and tertiary hypothyroidism should be suspected in the following circumstances:

● 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

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. Thus, we measure both serum TSH and free T4 if pituitary or
hypothalamic disease is suspected (eg, a young woman with amenorrhea and fatigue). We also
measure free T4 if the patient has convincing symptoms of hypothyroidism despite a normal
TSH result. In patients with central hypothyroidism, the serum free T4 value is low-normal to low
and serum TSH may be frankly low, inappropriately normal (for the low T4), or slightly high (7 to
15 mU/L) due to secretion of biologically inactive TSH (table 3) [14].

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 or thyroid
hormone, recovery from nonthyroidal illness, and TSH-secreting pituitary adenomas (table 4).
High serum TSH concentrations may also occur in primary adrenal insufficiency [15] and
factitiously in rare patients who have antibodies to the murine immunoglobulins used in the
assay [16], or complexes of TSH bound to immunoglobulin G (IgG) [17].

Resistance to TSH or thyroid hormone — An elevated TSH concentration may rarely be due
to resistance to TSH secondary to alterations in the TSH receptor [18], 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 (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

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manifestations of hypothyroidism; however, most such patients are euthyroid. (See "Impaired
sensitivity to thyroid hormone" and "Disorders that cause hypothyroidism".)

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".)

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

The clinical evaluation of a patient with biochemical evidence of 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. Physical examination may, in some cases, reveal thyroid
enlargement (goiter) or an old thyroidectomy scar. (See "Disorders that cause hypothyroidism".)

Thyroid peroxidase antibodies — Chronic autoimmune hypothyroidism (Hashimoto's

thyroiditis) is the most common cause of primary hypothyroidism in iodine sufficient areas of the
world. 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 serological feature being the presence of high serum concentrations of antibodies to
thyroid peroxidase (TPO) and thyroglobulin. Serum concentrations of TPO autoantibodies are
elevated in more than 90 percent of patients [19].

We do not routinely measure TPO antibodies in patients with primary overt hypothyroidism,
because almost all have chronic autoimmune 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

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● Subclinical hypothyroidism, painless (silent) thyroiditis, or postpartum thyroiditis, to predict

the likelihood of progression to permanent overt hypothyroidism

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.

SCREENING

"Screening" refers to the measurement of thyroid function tests in asymptomatic patients at risk
of having thyroid disease who are presently not known to have thyroid disease. 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'.)

There are two strategies for screening asymptomatic individuals: screening all individuals over a
certain age (when risk of hypothyroidism increases), or screening only those individuals with
clinical risk factors for hypothyroidism. In the absence of data supporting any screening strategy,
we suggest screening patients at increased risk for hypothyroidism, including but not limited to
patients with goiter, history of autoimmune disease, previous radioactive iodine therapy, and/or
head and neck irradiation, family history of thyroid disease, and use of medications that may
impair thyroid function (table 2).

We recommend measurement of serum TSH as a screening test for hypothyroidism.

Effectiveness — There are no clinical trials evaluating the effectiveness of screening for
hypothyroidism. A computer decision model that evaluated a hypothetical cohort of women and
men 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) [20]. 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.

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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 85th birthday and again three years later [21]. 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:

● Twelve percent had hypothyroidism 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.

Candidates for screening — All patients with symptoms of hypothyroidism (table 1) should be
evaluated for hypothyroidism. Screening of asymptomatic individuals is controversial [22,23]. In
the absence of data showing any benefit of population-based screening, we suggest not
routinely measuring thyroid function in asymptomatic, nonpregnant individuals.

As an alternative, we suggest screening for hypothyroidism in patients with laboratory or

radiologic abnormalities that could be caused by hypothyroidism, patients with risk factors for
hypothyroidism (eg, patients with goiter, history of autoimmune disease, previous radioactive
iodine therapy and/or head and neck irradiation, family history of thyroid disease), and patients
taking drugs that may impair thyroid function (table 2). 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")

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● 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')

● High serum muscle enzyme concentrations

● Macrocytic anemia (see "Approach to the adult with anemia", section on 'Macrocytic
anemia')

● Pericardial or pleural effusions (see "Diagnostic evaluation of pleural effusion in adults:

Additional tests for undetermined etiology", section on 'History')

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

● Pituitary or hypothalamic disorders (see "Central hypothyroidism")

● History of autoimmune diseases

The universal screening of asymptomatic pregnant women for hypothyroidism during the first
trimester of pregnancy is controversial. This topic is reviewed in detail elsewhere. In brief, we
suggest a targeted approach to screening pregnant women. We favor screening pregnant
women if they are from an area of moderate to severe iodine insufficiency, have symptoms of
hypothyroidism, a family or personal history of thyroid disease, or a personal history of thyroid
peroxidase (TPO) antibodies, type 1 diabetes, head and neck radiation, recurrent miscarriage,
morbid obesity, or infertility. (See "Hypothyroidism during pregnancy: Clinical manifestations,
diagnosis, and treatment", section on 'Screening'.)

Screening tests — Third-generation serum TSH assays are both more sensitive and specific
than serum free T4 measurements for detecting primary hypothyroidism in ambulatory patients
(see "Laboratory assessment of thyroid function"). Although the normal range for serum free T4
concentrations is wide (approximately 0.8 to 1.8 ng/dL [10 to 36 pmol/L]), each person has an
endogenous setpoint dictating the optimum concentration for that individual. TSH secretion
increases when the serum free T4 concentration falls below that level. (See "Thyroid hormone
synthesis and physiology", section on 'Regulation of thyroid hormone production'.)

Primary thyroid disease accounts for over 95 percent of cases of hypothyroidism. As a result,
measurement of serum TSH (rather than free T4 or total T4) is an excellent screening test for
hypothyroidism in ambulatory patients [24]. There are, however, three settings in which
measurement of serum TSH may not be a useful tool for the diagnosis of hypothyroidism:

● If pituitary or hypothalamic disease is known or suspected.

● In hospitalized patients, since there are many other factors in acutely or chronically ill
euthyroid patients that influence TSH secretion. (See "Thyroid function in nonthyroidal
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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 analogues (such as octreotide). Drugs that increase TSH secretion
include dopamine antagonists (metoclopramide or domperidone), amiodarone, and oral
cholecystographic dyes (eg, sodium ipodate).

Because errors may be made when only TSH is measured in patients with secondary or central
hypothyroidism or TSH-mediated hyperthyroidism, some experts recommend that both serum
TSH and free T4 be measured in all patients for screening purposes.

This approach adds considerable cost to screening and is likely to pick up few cases of
unsuspected pituitary disease. As a result, many laboratories are using strategies such as the
following to limit unnecessary laboratory testing:

● Serum TSH normal – No further testing performed

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

Screening inpatients is a more difficult problem and is not recommended unless thyroid disease
is strongly suspected since changes in thyroid hormones, binding proteins, and TSH
concentrations occur in severe nonthyroidal illness. (See "Thyroid function in nonthyroidal
illness".)

Recommendations by expert groups — Screening recommendations from major groups have

been conflicting.

● The American Academy of Family Physicians (AAFP) recommends periodic assessment of

thyroid function in older women [25].

● The American College of Physicians (ACP) suggests that office screening of women older
than 50 years may be indicated [26].

● 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 [27].

● The United States Preventive Services Task Force found insufficient evidence to assess the
benefits and harms of screening [28,29].

Recommendations for screening pregnant women are discussed separately. (See

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

● 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 1). 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. Serum concentrations of thyroid peroxidase
(TPO) autoantibodies are elevated in more than 90 percent of patients with hypothyroidism
due to chronic autoimmune hypothyroidism (Hashimoto's thyroiditis). (See 'Clinical features'
above and "Clinical manifestations of hypothyroidism".)

● The diagnosis of hypothyroidism is based primarily upon laboratory testing. In most patients
with symptoms suggestive of hypothyroidism, the serum thyroid-stimulating hormone (TSH)

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should be the initial test. If the serum TSH concentration is elevated, the TSH measurement
should be repeated along with a serum free thyroxine (T4) to make the diagnosis of
hypothyroidism (table 3). If the repeat serum TSH value is still high and the serum free T4 is
low, suggesting primary hypothyroidism, replacement therapy with T4 should be initiated.
(See 'Diagnosis' above and "Treatment of primary hypothyroidism in adults".)

Patients with a high serum TSH concentration and a normal serum free T4 concentration
may have subclinical hypothyroidism. (See 'Diagnosis' above and 'Primary hypothyroidism'
above.)

● If central hypothyroidism is suspected (eg, presence of pituitary or hypothalamic disease), or

if the patient has convincing symptoms of hypothyroidism despite a normal TSH result, we
measure serum TSH and free T4. In patients with central hypothyroidism, the serum free T4
value is low-normal or low and serum 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 'Diagnosis' above and "Central hypothyroidism".)

● The differential diagnosis of an elevated serum TSH concentration includes resistance to

TSH, recovery from nonthyroidal illness, and a TSH-secreting pituitary adenoma. (See
'Differential diagnosis' above.)

● 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. We do not routinely measure TPO antibodies in patients with primary
overt hypothyroidism, because almost all have chronic autoimmune thyroiditis. (See
'Identifying the cause' above.)

● We suggest not performing population-based screening for hypothyroidism (Grade 2C). As

an alternative, we prefer to screen individuals who are at increased risk for hypothyroidism
(table 2). (See 'Candidates for screening' above.)

TSH is the most sensitive test for detecting primary hypothyroidism in ambulatory patients.
However, TSH alone may not be a useful tool for the diagnosis of hypothyroidism if pituitary
or hypothalamic disease is known or suspected; in hospitalized patients, since there are
many other factors in acutely or chronically ill euthyroid patients that influence TSH
secretion; and in patients receiving drugs or with underlying diseases that affect TSH
secretion (table 4). (See "Thyroid function in nonthyroidal illness".)

● The universal screening of asymptomatic pregnant women for hypothyroidism during the
first trimester of pregnancy is controversial. We suggest a targeted approach rather than
universal screening (Grade 2C). We favor screening pregnant women if they are from an
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area of moderate to severe iodine insufficiency, have symptoms of hypothyroidism, a family

or personal history of thyroid disease, or a personal history of TPO antibodies, type 1
diabetes, morbid obesity, head and neck radiation, recurrent miscarriage, or infertility. (See
"Hypothyroidism during pregnancy: Clinical manifestations, diagnosis, and treatment",
section on 'Screening'.)

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