690 Hypothyroidism
○ Hashimoto’s thyroiditis is the most common
BASIC INFORMATION
DEFINITION
Hypothyroidism is a disorder caused by the
inadequate secretion of thyroid hormone.
SYNONYMS
Myxedema
ICD-10CM CODES
E03.9 Hypothyroidism, unspecified
E00.9 Congenital iodine-deficiency
syndrome, unspecified
E89.0 Postprocedural hypothyroidism
E03.2 Hypothyroidism due to medicaments
and other exogenous substances
E02 Subclinical iodine-deficiency
hypothyroidism
E03.0 Congenital hypothyroidism with
diffuse goiter
E03.1 Congenital hypothyroidism without
goiter
E03.3 Postinfectious hypothyroidism
E03.8 Other specified hypothyroidism
EPIDEMIOLOGY &
DEMOGRAPHICS
INCIDENCE/PREVALENCE: 1.5% to 2% of
women and 0.2% of men. Overall, about 1 in 300
persons in the United States has hypothyroidism.
PREDOMINANT AGE: Incidence of hypothyroid-
ism increases with age; among persons older than
60 yr, 6% of women and 2.5% of men have labora-
tory evidence of hypothyroidism (thyroid-stimulat-
ing hormone [TSH] more than twice normal level).
PHYSICAL FINDINGS & CLINICAL
PRESENTATION
the following signs and symptoms: fatigue,
lethargy, weakness, constipation, weight gain,
cold intolerance, muscle weakness, slow
speech, slow cerebration with poor memory.
color caused by carotenemia); nonpitting
edema in skin of eyelids and hands (myxede-
ma) secondary to infiltration of subcutaneous
tissues by a hydrophilic mucopolysaccharide
substance. (Fig. E1, A and B)
eyebrows.
thick and slow-moving lips.
(depending on the cause of the hypothyroidism).
effusion.
deep tendon reflexes, cerebellar ataxia, hear-
ing impairment, poor memory, peripheral
neuropathies with paresthesia.
muscular stiffness, weakness.
ETIOLOGY
1. Primary hypothyroidism (thyroid gland dys-
function): the cause of >90% of the cases of
hypothyroidism
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ALG
artery disease should be started with 12.5 to 25
cause of hypothyroidism after age 8 yr
○ Idiopathic myxedema (nongoitrous form of
Hashimoto’s thyroiditis)
○ Previous treatment of hyperthyroidism
(radioiodine therapy, subtotal thyroidectomy)
○ Subacute thyroiditis
○ Radiation therapy to the neck (usually for
malignant disease)
○ Iodine deficiency or excess
○ Drugs (lithium, para-aminosalicylate, sul-
fonamides, phenylbutazone, amiodarone,
thiourea)
○ Congenital (approximately one case per
4000 live births)
○ Prolonged treatment with iodides
2. Secondary hypothyroidism: pituitary dysfunc-
tion, postpartum necrosis, neoplasm, infiltra-
tive disease causing deficiency of TSH
3. Tertiary hypothyroidism: hypothalamic disease
(granuloma, neoplasm, or irradiation causing
deficiency of thyrotropin-releasing hormone)
4. Tissue resistance to thyroid hormone: rare
DIAGNOSIS
DIFFERENTIAL DIAGNOSIS
- and should be maintained in the upper half
drome, congestive heart failure, amyloidosis)
LABORATORY TESTS
has secondary or tertiary hypothyroidism, is
receiving dopamine or corticosteroids, or the
level is obtained after severe illness
4 plication of hypothyroidism is available under
hyperlipidemia, hyponatremia, and anemia
antibody titers: useful when autoimmune thy-
roiditis is suspected as the cause of the hypo-
thyroidism. The American Thyroid Association
recommends treatment of pregnant patients
with subclinical hypothyroidism and thyroid
peroxidase antibody (anti-TPO) positivity.
Fig. E1, C describes a strategy for the labora-
tory evaluation of patients with suspected
hypothyroidism
TREATMENT
NONPHARMACOLOGIC THERAPY
Patients should be educated regarding hypothyroid-
ism and its possible complications. Patients should
also be instructed about the need for lifelong treat-
ment and monitoring of their thyroid abnormality.
ACUTE GENERAL Rx
Start replacement therapy with levothyroxine
(L-thyroxine) 25 to 100 µg/day, depending on
the patient’s age and the severity of the disease.
Physiologic combinations of L-thyroxine plus lio-
thyronine do not offer any objective advantage
over L-thyroxine alone. The levothyroxine dose
may be increased every 6 to 8 wk, depending
on the clinical response and serum TSH level.
Elderly patients and patients with coronary
µg/day (higher doses may precipitate angina).
The average maintenance dose of levothyroxine
is 1.7 µg/kg/day (100 to 150 µg/day in adults).
The elderly may require <1 µg/kg/day, whereas
children generally require higher doses (up to
3 to 4 µg/kg/day). Pregnant patients also have
increased requirements. Estrogen therapy may
also increase the need for thyroxine. Women
with hypothyroidism should increase their levo-
thyroxine dose by approximately 30% as soon
as pregnancy is confirmed. Close monitoring
of serum thyrotropin levels and adjustment of
levothyroxine dose to maintain a TSH level of
4.0 mU per liter as upper limit is recommended
throughout pregnancy. Table E1 summarizes
conditions that alter levothyroxine requirements.
CHRONIC Rx
part of treatment. Patients should be evaluated
initially with office visit and TSH levels every 6
to 8 wk until the patient is clinically euthyroid
and the TSH level is normalized. The frequency
of subsequent visits and TSH measurement can
then be decreased to every 6 to 12 mo. Pregnant
patients should be checked every trimester.
-
tral hypothyroidism, measurement of serum
free thyroxine (free T4 level) is appropriate
of the normal range.
REFERRAL
Admission to the hospital intensive care unit is
recommended in all patients with myxedema
coma. Additional information on the diagnosis
and treatment of this life-threatening com-
“Myxedema Coma” in Section I.
PEARLS &
CONSIDERATIONS
COMMENTS
Subclinical hypothyroidism occurs in as many
as 15% of elderly patients and is characterized
by an elevated serum TSH and a normal free T4
level. Subclinical hypothyroidism is associated
with an increased risk of coronary heart disease
events and mortality, particularly in those with
a TSH concentration of 10 mU/L or greater.
Treatment is individualized. In general, replace-
ment therapy is recommended for all patients
with serum TSH >10 mU/L and with presence
of goiter or thyroid autoantibodies.
EVIDENCE
Available at www.expertconsult.com
SUGGESTED READINGS
Available at www.expertconsult.com
RELATED CONTENT
Hypothyroidism (Patient Information)
Myxedema Coma (Related Key Topic)
AUTHOR: FRED F. FERRI, M.D.
Hypothyroidism
EVIDENCE
Abstract[1]
Background:
Children born to women with low thyroid hormone levels have been re-
ported to have decreased cognitive function.
Methods:
We conducted a randomized trial in which pregnant women at a gesta-
tion of 15 weeks 6 days or less provided blood samples for measure-
ment of thyrotropin and free thyroxine (T4). Women were assigned to a
screening group (in which measurements were obtained immediately) or
a control group (in which serum was stored and measurements were
obtained shortly after delivery). Thyrotropin levels above the 97.5th
percentile, free T4 levels below the 2.5th percentile, or both were con-
sidered a positive screening result. Women with positive findings in the
screening group were assigned to 150 µg of levothyroxine per day. The
primary outcome was IQ at 3 years of age in children of women with
positive results, as measured by psychologists who were unaware of the
group assignments.
Results:
Of 21,846 women who provided blood samples (at a median gestational
age of 12 weeks 3 days), 390 women in the screening group and 404 in
the control group tested positive. The median gestational age at the start
of levothyroxine treatment was 13 weeks 3 days; treatment was ad-
justed as needed to achieve a target thyrotropin level of 0.1 to 1.0 mIU
per liter. Among the children of women with positive results, the mean IQ
scores were 99.2 and 100.0 in the screening and control groups, re-
spectively (difference, 0.8; 95% confidence interval [CI], −1.1 to 2.6; P
= 0.40 by intention-to-treat analysis); the proportions of children with an
IQ of less than 85 were 12.1% in the screening group and 14.1% in the
control group (difference, 2.1 percentage points; 95% CI, −2.6 to 6.7; P
= 0.39). An on-treatment analysis showed similar results.
Conclusions:
Antenatal screening (at a median gestational age of 12 weeks 3 days)
and maternal treatment for hypothyroidism did not result in improved
cognitive function in children at 3 years of age.
Current Controlled Trials Number:
. Funded by the Wellcome Trust UK and Compagnia di
San Paulo, Turin.
Abstract[2]
Context:
The incidence of postpartum thyroiditis (PPT) varies widely in the litera-
ture. Limited data exist concerning the hormonal status of women with
PPT at the end of the first postpartum year.
Objective:
Our aim was to conduct a large prospective study of the incidence and
clinical course of PPT.
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690.e1
Design:
A total of 4394 women were screened for thyroid function and thyroid
autoantibodies at 6 and 12 months postpartum. Women were classified
as being at high or low risk of having thyroid disease before any thyroid
testing.
Setting:
The study was conducted at two ambulatory clinics in southern Italy, an
area of mild iodine deficiency.
Patients:
A total of 4394 pregnant women were studied.
Intervention:
There was no intervention.
Main Outcome Measures:
We measured incidence, clinical presentation, and course of postpartum
thyroiditis.
Results:
The incidence of postpartum thyroiditis was 3.9% (169 of 4384). Women
classified as being at high risk for thyroid disease had a higher incidence
of PPT than women classified as low risk (11.1 vs. 1.9%; odds ratio,
6.69; 95% confidence interval, 4.63, 9.68). Eighty-two percent of the
169 women with PPT had a hypothyroid phase during the first postpar-
tum year. At the end of the first postpartum year, 54% of the 169 women
had persistent hypothyroidism.
Conclusions:
One of every 25 women in southern Italy developed PPT. Women at high
risk for thyroid disease have an increased rate of PPT. The high rate of
permanent hypothyroidism at 1 yr should result in a reevaluation of the
widely held belief that most women with PPT are euthyroid at the end of
the first postpartum year.
Evidence-Based References
1. Lazarus JH, et al.: Antenatal thyroid screening and childhood cognitive func-
tion, N Engl J Med 366:493–501, 2012.
2. Stagnaro-Green A, et al.: High rate of persistent hypothyroidism in a large-
scale prospective study of postpartum thyroiditis in southern Italy, J Clin
Endocrinol Metab 96:652–657, 2011.
SUGGESTED READINGS
Casey BM, et al.: Treatment of subclinical hypothyroidism or hypothyroxinemia in
pregnancy, N Engl J Med 376:815–825, 2017.
Gaitonde DY, et al.: Hypothyroidism: an update, Am Fam Phys 86(3):244–251,
2012.
, et al.: Subclinical hypothyroidism and the risk of coronary heart dis-
ease and mortality, JAMA 304(12):1365–1374, 2010.
Rugge JB, et al.: Screening and treatment of thyroid dysfunction: an evidence
review for the U.S. Preventive Services Task Force, Ann Intern Med 162:35–45,
2015.
Hypothyroidism 690.e2

A B

Suspected hypothyroidism

TSH, free T4

Normal/low TSH, low Elevated TSH, Elevated TSH, low free T4

free T4 normal/low free T4

Rule out secondary Rule out early Primary hypothyroidism

hypothyroidism hypothyroidism, Hashimoto‘s
(hypopituitarism) thyroiditis, subacute
thyroiditis, autoimmune
lymphocytic thyroiditis,
recovery from severe illness
MRI of pituitary
gland
C
FIG. E1 A and B,
of scleral pigmentation differentiates the carotenemia from jaundice. Both individuals demonstrate periorbital myxedema. The patient in B illustrates the loss of the
lateral aspect of the eyebrow, sometimes termed Queen Anne’s sign. That finding is not unusual in the age group that is commonly affected by severe hypothyroidism
and should not be considered to be a specific sign of the condition. C, Strategy for the laboratory evaluation of patients with suspected hypothyroidism. The principal
differential diagnosis is between primary and central hypothyroidism. The serum thyrotropin (TSH) concentration is the critical laboratory determination that, in general,
allows recognition of the cause of the disease. An exception is the individual with a recent history of thyrotoxicosis (and suppressed TSH), in whom a low free thyroxine
(T4) level may be associated with a reduced TSH level for several months after relief of the thyrotoxicosis. In patients with primary hypothyroidism, the absence of thyroid
peroxidase (TPO) antibodies raises a possible diagnosis of transient hypothyroidism after an undiagnosed episode of subacute or postviral thyroiditis. In such patients,
a trial of levothyroxine in reduced dosage after 4 months may reveal recovery of thyroid function, thus avoiding permanent levothyroxine replacement. MRI, Magnetic
resonance imaging; TRH, thyrotropin-releasing hormone. (From Melmed S, et al: Williams textbook of endocrinology, ed 12, Philadelphia, 2011, Saunders.)

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Hypothyroidism 690.e3

TABLE E1 Conditions That Alter Levothyroxine Requirements

Increased Levothyroxine Requirements

Pregnancy
Gastrointestinal Disorders
Mucosal diseases of the small bowel (e.g., sprue)
After jejunoileal bypass and small-bowel resection
Impaired gastric acid secretion (e.g., atrophic gastritis)
Diabetic diarrhea
Drugs That Interfere with Levothyroxine Absorption
Cholestyramine
Sucralfate
Aluminum hydroxide
Calcium carbonate
Ferrous sulfate
Drugs That Increase the Cytochrome P450 Enzyme (CYP3A4) Activity
Rifampin
Carbamazepine
Estrogen
Phenytoin
Sertraline
Drugs That Block T4-to-T3 Conversion
Amiodarone
Conditions That May Block Deiodinase Synthesis
Selenium deficiency
Cirrhosis
Decreased Levothyroxine Requirements
Aging (≥65 yr)
Androgen therapy in women

T4, Thyroxine; T3, triiodothyronine.

From Melmed S, et al: Williams textbook of endocrinology, ed 12, Philadelphia, 2011, Saunders.

Descargado para Anonymous User (n/a) en Universidad Nacional Autonoma de Mexico de ClinicalKey.es por Elsevier en abril 16, 2018.
Para uso personal exclusivamente. No se permiten otros usos sin autorización. Copyright ©2018. Elsevier Inc. Todos los derechos reservados.