7/23/2017 Hypothyroidism: Practice Essentials, Background, Pathophysiology

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Hypothyroidism
Updated: Mar 16, 2017
Author: Philip R Orlander, MD; Chief Editor: George T Griffing, MD more...

OVERVIEW

Practice Essentials
Hypothyroidism is a common endocrine disorder resulting from deficiency of thyroid hormone. In the
United States and other areas of adequate iodine intake, autoimmune thyroid disease (Hashimoto
disease) is the most common cause of hypothyroidism; worldwide, iodine deficiency remains the
foremost cause.

The image below depicts the hypothalamic-pituitary-thyroid axis.

The hypothalamic-pituitary-thyroid axis. Levels of circulating thyroid hormones are regulated by a complex
feedback system involving the hypothalamus and pituitary gland.

See 21 Hidden Clues to Diagnosing Nutritional Deficiencies, a Critical Images slideshow, to help
identify clues to conditions associated with malnutrition.

Signs and symptoms

Hypothyroidism commonly manifests as a slowing in physical and mental activity but may be
asymptomatic. Symptoms and signs are often subtle and neither sensitive nor specific.

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The following are symptoms of hypothyroidism:

Fatigue, loss of energy, lethargy

Weight gain
Decreased appetite
Cold intolerance
Dry skin
Hair loss
Sleepiness
Muscle pain, joint pain, weakness in the extremities
Depression
Emotional lability, mental impairment
Forgetfulness, impaired memory, inability to concentrate
Constipation
Menstrual disturbances, impaired fertility
Decreased perspiration
Paresthesia and nerve entrapment syndromes
Blurred vision
Decreased hearing
Fullness in the throat, hoarseness

The following are symptoms more specific to Hashimoto thyroiditis:

Feeling of fullness in the throat

Painless thyroid enlargement
Exhaustion
Transient neck pain, sore throat, or both

Physical signs of hypothyroidism include the following:

Weight gain
Slowed speech and movements
Dry skin
Jaundice
Pallor
Coarse, brittle, straw-like hair
Loss of scalp hair, axillary hair, pubic hair, or a combination
Dull facial expression
Coarse facial features
Periorbital puffiness
Macroglossia
Goiter (simple or nodular)
Hoarseness
Decreased systolic blood pressure and increased diastolic blood pressure
Bradycardia
Pericardial effusion
Abdominal distention, ascites (uncommon)
Hypothermia (only in severe hypothyroid states)
Nonpitting edema (myxedema)
Pitting edema of lower extremities
Hyporeflexia with delayed relaxation, ataxia, or both

Myxedema coma is a severe form of hypothyroidism that most commonly occurs in individuals with
undiagnosed or untreated hypothyroidism who are subjected to an external stress. Features are as
follows:
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Altered mental status

Hypothermia
Bradycardia
Hypercarbia
Hyponatremia
Cardiomegaly, pericardial effusion, cardiogenic shock, and ascites may be present

See Clinical Presentation for more detail.

Diagnosis
Third-generation thyroid-stimulating hormone (TSH) assays are generally the most sensitive
screening tool for primary hypothyroidism. [1] If TSH levels are above the reference range, the next
step is to measure free thyroxine (T4) or the free thyroxine index (FTI), which serves as a surrogate of
the free hormone level. Routine measurement of triiodothyronine (T3) is not recommended.

Results in patients with hypothyroidism are as follows:

Elevated TSH with decreased T4 or FTI

Elevated TSH (usually 4.5-10.0 mIU/L) with normal free T4 or FTI is considered mild or
subclinical hypothyroidism

Abnormalities in the complete blood count and metabolic profile that may be found in patients with
hypothyroidism include the following [2] :

Anemia
Dilutional hyponatremia
Hyperlipidemia
Reversible increases in creatinine [2]
Elevations in transaminases and creatinine kinase

No universal screening recommendations exist for thyroid disease for adults. The American Thyroid
Association recommends screening at age 35 years and every 5 years thereafter, with closer attention
to patients who are at high risk, such as the following [3] :

Pregnant women
Women older than 60 years
Patients with type 1 diabetes or other autoimmune disease
Patients with a history of neck irradiation

See Workup for more detail.

Management

Monotherapy with levothyroxine (LT4) remains the treatment of choice for hypothyroidism. Aspects of
LT4 treatment are as follows:

Otherwise young and healthy patients can be started on LT4 at anticipated full replacement
doses
In elderly patients and those with known ischemic heart disease, begin with one fourth to one
half the expected dose and adjust the dose in small increments after no less than 4-6 weeks
For most cases of mild to moderate hypothyroidism, a starting LT4 dose of 50-75 µg daily will
suffice

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Clinical benefits begin in 3-5 days and level off after 4-6 weeks
Achieving a TSH level within the reference range may take several months
LT4 dosing changes should be made every 6-8 weeks until the patient’s TSH is in target range

After dose stabilization, patients can be monitored with annual clinical evaluations and TSH
monitoring. Patients should be monitored for symptoms and signs of overtreatment, which include the
following:

Tachycardia
Palpitations
Atrial fibrillation
Nervousness
Tiredness
Headache
Increased excitability
Sleeplessness
Tremors
Possible angina

In patients who continue to have symptoms (eg, weight gain, fatigue) despite normalization of their
TSH level, consideration should be given to causes other than hypothyroidism. In some cases,
however, the persistence of symptoms results from impaired conversion of T4 to T3 in the brain; these
patients may benefit from combination LT4/liothyronine (LT3) therapy. [4]

The updated guidelines on hypothyroidism issued by the American Thyroid Association in 2014
maintain the recommendation of levothyroxine as the preparation of choice for hypothyroidism, with
the following considerations: [5, 6]

If levothyroxine dose requirements are much higher than expected, consider evaluating for
gastrointestinal disorders such as Helicobacter pylori –related gastritis, atrophic gastritis, or
celiac disease; if such disorders are detected and effectively treated, re-evaluation of thyroid
function and levothyroxine dosage is recommended.
Initiation or discontinuation of estrogen and androgens should be followed by reassessment of
serum TSH at steady state, since such medications may alter levothyroxine requirement.
Serum TSH should be reassessed upon initiation of agents such as tyrosine kinase inhibitors
that affect thyroxine metabolism and thyroxine or triiodothyronine deiodination.
Serum TSH monitoring is advisable when medications such as phenobarbital, phenytoin,
carbamazepine, rifampin, and sertraline are started.
When deciding on a starting dose of levothyroxine, the patient’s weight, lean body mass,
pregnancy status, etiology of hypothyroidism, degree of TSH elevation, age, and general clinical
context, including the presence of cardiac disease, should be considered. The serum TSH goal
appropriate for the clinical situation should also be considered.
Thyroid hormone therapy should be initiated as an initial full replacement or as partial
replacement with gradual increments in the dose titrated upward using serum TSH as the goal.
Dose adjustments should be made upon significant changes in body weight, with aging, and
with pregnancy; TSH assessment should be performed 4-6 weeks after any dosage change.
Reference ranges of serum TSH levels are higher in older populations (eg, >65 years), so higher
serum TSH targets may be appropriate.

Updated recommendations concerning hypothyroidism treatment in pregnant women are as follows:

[5, 6]

Pregnant women with overt hypothyroidism should receive levothyroxine replacement therapy
with the dose titrated to achieve a TSH concentration within the trimester-specific reference
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range.
Serial serum TSH levels should be assessed every 4 weeks during the first half of pregnancy to
adjust levothyroxine dosing to maintain TSH within the trimester-specific range.
Serum TSH should be reassessed during the second half of pregnancy.
In women already taking levothyroxine, 2 additional doses per week of the current levothyroxine
dose, given as one extra dose twice weekly with several days’ separation, may be started as
soon as pregnancy is confirmed.

Treatment of myxedema coma is as follows:

Intravenous (IV) LT4 at a dose of 4 µg/kg of lean body weight, or approximately 200-250 µg, as
a bolus in a single or divided dose, depending on the patient’s risk of cardiac disease
After 24 hours, 100 µg LT4 IV, then 50 µg/day IV
Stress doses of IV glucocorticoids
Subsequent adjustment of the LT4 dose can be based on clinical and laboratory findings

See Treatment and Medication for more detail.

Background
Hypothyroidism is a common endocrine disorder resulting from deficiency of thyroid hormone. It
usually is a primary process in which the thyroid gland is unable to produce sufficient amounts of
thyroid hormone.

Hypothyroidism can also be secondary—that is, the thyroid gland itself is normal, but it receives
insufficient stimulation because of low secretion of thyrotropin (ie, thyroid-stimulating hormone [TSH])
from the pituitary gland. In tertiary hypothyroidism, inadequate secretion of thyrotropin-releasing
hormone (TRH) from the hypothalamus leads to insufficient release of TSH, which in turn causes
inadequate thyroid stimulation.

Worldwide, iodine deficiency remains the foremost cause of hypothyroidism. In the United States and
other areas of adequate iodine intake, autoimmune thyroid disease (Hashimoto disease) is the most
common cause. Hypothyroidism may also be drug-induced or otherwise iatrogenic. (See Etiology.)

The patient’s presentation may vary from asymptomatic to myxedema coma with multisystem organ
failure. Because nearly all metabolically active cells require thyroid hormone, deficiency of the
hormone has a wide range of effects. Classic signs and symptoms, such as cold intolerance,
puffiness, decreased sweating, and coarse skin, may not be present, especially in younger patients.
(See Presentation.)

Third-generation TSH assays are readily available and are generally the most sensitive screening tool
for primary hypothyroidism. The generally accepted reference range for normal serum TSH is 0.40-4.2
mIU/L.

If TSH levels are above the reference range, the next step would be to measure free thyroxine (T4).
Subclinical hypothyroidism, also referred to as mild hypothyroidism, is defined as normal serum levels
of free T4 and triiodothyronine (T3) with a slightly high serum TSH concentration. (See Workup.)

For hypothyroidism, thyroid hormone is administered to supplement or replace endogenous

production. In general, hypothyroidism can be adequately treated with a constant daily dose of
levothyroxine (LT4). (See Treatment and Medication.)

Congenital hypothyroidism, which affects 1 of every 4000 newborns, is due to congenital

maldevelopment of the thyroid (see Pediatric Hypothyroidism). This disorder is included in the

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newborn screening panel in the United States and many other countries, and it is readily treatable
once detected. Cretinism refers to severe hypothyroidism in an infant or child. This is classically the
result of maternal iodine deficiency, and thankfully is increasingly rare.

Pathophysiology
The hypothalamic-pituitary-thyroid axis governs thyroid hormone secretion (see the image below).

The hypothalamic-pituitary-thyroid axis. Levels of circulating thyroid hormones are regulated by a complex
feedback system involving the hypothalamus and pituitary gland.

Although hypothalamic or pituitary disorders can affect thyroid function, localized disease of the
thyroid gland that results in decreased thyroid hormone production is the most common cause of
hypothyroidism. Under normal circumstances, the thyroid releases 100-125 nmol of T4 daily and only
small amounts of T3. The half-life of T4 is approximately 7-10 days. T4, a prohormone, is converted to
T3, the active form of thyroid hormone, in the peripheral tissues by 5’-deiodination.

Early in the disease process, compensatory mechanisms maintain T3 levels. Decreased production of
T4 causes an increase in the secretion of TSH by the pituitary gland. TSH stimulates hypertrophy and
hyperplasia of the thyroid gland and 5’-deiodinase activity, thereby increasing T3 production.

Deficiency of thyroid hormone has a wide range of effects. Systemic effects are the result of either
derangements in metabolic processes or direct effects by myxedematous infiltration (ie, accumulation
of glucosaminoglycans in the tissues).

The hypothyroid changes in the heart result in decreased contractility, cardiac enlargement,
pericardial effusion, decreased pulse, and decreased cardiac output. In the gastrointestinal (GI) tract,
achlorhydria and prolonged intestinal transit time with gastric stasis can occur. Delayed puberty,
anovulation, menstrual irregularities, and infertility are common. TSH screening should be a routine
part of any investigation into menstrual irregularities or infertility.

Decreased thyroid hormone effect can cause increased levels of total cholesterol and low-density
lipoprotein (LDL) cholesterol and a possible change in high-density lipoprotein (HDL) cholesterol
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because of a change in metabolic clearance. In addition, hypothyroidism may result in an increase in

insulin resistance.

Etiology
In the United States and other areas of adequate iodine intake, autoimmune thyroid disease
(Hashimoto disease) is the most common cause of hypothyroidism. The prevalence of antibodies is
higher in women and increases with age.

Primary hypothyroidism
Types of primary hypothyroidism include the following:

Chronic lymphocytic (autoimmune) thyroiditis

Postpartum thyroiditis
Subacute (granulomatous) thyroiditis
Drug-induced hypothyroidism
Iatrogenic hypothyroidism

Chronic lymphocytic (autoimmune) thyroiditis

The most frequent cause of acquired hypothyroidism is chronic lymphocytic (autoimmune) thyroiditis
(Hashimoto thyroiditis). The body considers the thyroid antigens as foreign, and a chronic immune
reaction ensues, resulting in lymphocytic infiltration of the gland and progressive destruction of
functional thyroid tissue.

The majority of affected individuals will have circulating antibodies to thyroid tissue. Anti–thyroid
peroxidase (anti-TPO) antibodies are the hallmark of this disease. It should be noted that antibody
levels can vary over time, may not be present early in the disease process, and usually disappear
over time. Given this change in antibody concentration, it should be understood that the absence of
antibodies does not exclude the diagnosis of chronic lymphocytic (autoimmune) thyroiditis.

A study by Bothra et al reported that, compared with the general population, first-degree relatives of
persons with Hashimoto thyroiditis have a nine-fold greater risk of developing it. [7]

Postpartum thyroiditis

Up to 10% of postpartum women may develop lymphocytic thyroiditis (postpartum thyroiditis) in the 2-
12 months after delivery. The frequency may be as high as 25% in women with type 1 diabetes
mellitus. Although a short course of treatment with levothyroxine (LT4) may be necessary, the
condition is usually transient (2-4 months). However, patients with postpartum thyroiditis (anti-TPO–
positive) are at increased risk of permanent hypothyroidism or recurrence of postpartum thyroiditis
with future pregnancies.

The hypothyroid state can be preceded by a short thyrotoxic state. High titers of anti-TPO antibodies
during pregnancy have been reported to have high sensitive and specificity for postpartum
autoimmune thyroid disease.

In a 12-year longitudinal study, Stuckey et al found that hypothyroidism developed in 27 of 71 women

(38%) who had a past history of postpartum thyroid dysfunction (PPTD). In comparison, only 14 of
338 women (4%) who had not had PPTD developed hypothyroidism. [8]

Subacute granulomatous thyroiditis

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Also known as de Quervain disease, subacute granulomatous thyroiditis is a relatively uncommon

disease that occurs most frequently in middle-aged women. Disease features include low grade fever,
thyroid pain, dysphagia, and elevated erythrocyte sedimentation rate (ESR).

The disease is usually self-limited and does not normally result in longstanding thyroid dysfunction. It
is important to note that inflammatory conditions or viral syndromes may be associated with transient
hyperthyroidism followed by transient hypothyroidism (ie, de Quervain or painful thyroiditis and
subacute thyroiditis).

Drug-induced and iatrogenic hypothyroidism

The following medications reportedly have the potential to cause hypothyroidism:

Amiodarone
Interferon alfa
Thalidomide
Lithium
Stavudine
Oral tyrosine kinase inhibitors – Sunitinib, imatinib [9]
Bexarotene [10]
Perchlorate
Interleukin (IL)-2
Ethionamide
Rifampin
Phenytoin
Carbamazepine
Phenobarbital
Aminoglutethimide
Sulfisoxazole
p -Aminosalicylic acid
Ipilimumab

Use of radioactive iodine (I-131) for treatment of Graves disease generally results in permanent
hypothyroidism within 3-6 months after therapy. The frequency of hypothyroidism after I-131 treatment
is much lower in patients with toxic nodular goiters and those with autonomously functioning thyroid
nodules. Patients treated with radioiodine should be monitored for clinical and biochemical evidence
of hypothyroidism.

External neck irradiation (for head and neck neoplasms, breast cancer, or Hodgkin disease) may
result in hypothyroidism. Patients who have received these treatments require monitoring of thyroid
function.

Thyroidectomy of course results in hypothyroidism. Patients who undergo a thyroid lobectomy, with or
without isthmectomy, have an approximately 15-30% chance of developing thyroid insufficiency.

Genetics
Genome-wide association studies have suggested that a single-nucleotide polymorphism located near
the FOXE1 gene is associated with risk of developing thyroid disease and that the strongest
association is with hypothyroidism. Persons found to have GG at the described location had an odds
ratio (OR) of 1.35 for development of hypothyroidism, whereas persons found to have AG at the
location had an OR of 1.00, and persons found to have AA at the location had an OR of 0.74. [11]

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Approximately 10% of patients with congenital hypothyroidism have an error in thyroid hormone
synthesis. [12] Mutations in the TPO gene appear to be the most common error of hormone synthesis,
causing failure to produce adequate amounts of TPO. [13]

Mutations in the TSHR and PAX8 genes are known to cause congenital hypothyroidism without goiter.
[14, 15] Mutations in the TSHR gene can cause hypothyroidism due to insensitivity to TSH, though
most cases are notable for a clinically euthyroid state despite abnormal laboratory test results
(elevated TSH with normal serum thyroid hormone concentrations). Mutations in the PAX8 gene
cause hypothyroidism due to dysgenesis or agenesis of the gland .

Syndromic forms of hypothyroidism are also well described. Pendred syndrome is caused by a
mutation in the SLC26A4 gene, which causes a defect in the organification of iodine (ie, incorporation
into thyroid hormone), congenital sensorineural hearing loss, and, usually, an enlarged thyroid gland.
It is inherited in an autosomal recessive manner. [16]

Autoimmune polyendocrinopathy type I is caused by a mutation in the AIRE gene and is characterized
by the presence of Addison disease, hypoparathyroidism, and mucocutaneous candidiasis. A subset
of patients with this disease also have a high prevalence of autoimmune thyroiditis and
hypothyroidism and a novel mutation in the AIRE gene that is inherited in an autosomal dominant
fashion. [17] Autoimmune polyendocrinopathy type 2 (Schmidt syndrome) is associated with adrenal
insufficiency and hypothyroidism.

Iodine deficiency or excess

Worldwide, iodine deficiency is the most common cause of hypothyroidism. Excess iodine, as in
radiocontrast dyes, amiodarone, health tonics (herbal and dietary supplements), and seaweed, can
transiently inhibit iodide organification and thyroid hormone synthesis (the Wolff-Chiakoff effect). Most
healthy individuals have a physiologic escape from this effect. In patients with iodine overload, the
sodium-iodide symporter shuts down, and this allows intracellular iodine levels to drop and hormone
secretion to resume.

The Wolff-Chiakoff effect is short-lived because the sodium-iodide symporter is capable of rapidly
downregulation. However, exposure to excess iodine can produce more profound and sustained
hypothyroidism in individuals with abnormal thyroid glands (eg, from autoimmune thyroiditis, subtotal
thyroidectomy, or prior radioiodine therapy). [18]

Central hypothyroidism

Central hypothyroidism (secondary or tertiary) results when the hypothalamic-pituitary axis is

damaged. The following potential causes should be considered [19, 20] :

Pituitary adenoma
Tumors impinging on the hypothalamus
Lymphocytic hypophysitis
Sheehan syndrome
History of brain or pituitary irradiation
Drugs (eg, dopamine, prednisone, or opioids)
Congenital nongoiterous hypothyroidism type 4
TRH resistance
TRH deficiency

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Tumors in or around the pituitary cause impaired pituitary function by exerting pressure on normal
pituitary cells and thereby affect the secretion of TRH, TSH, or both. Radiation, hypophysitis, and
Sheehan syndrome cause death of these cells. Drugs such as dopamine and corticosteroids result in
decreased TSH secretion.

Congenital nongoiterous hypothyroidism type 4 is caused by a mutation in the TSHB gene and is
inherited in an autosomal recessive pattern. Patients have hypothyroidism and a low TSH level that
does not rise with administration of TRH. Many patients with this condition were the products of
consanguineous unions. [21]

TRH resistance is caused by a mutation in the TRHR gene and is inherited in an autosomal recessive
manner. Patients with this condition have hypothyroidism and, unsurprisingly, have insensitivity to
thyrotropin secretion. [22] That only a handful of cases of TRH resistance have been reported in the
literature suggests that this is a rare condition.

TRH deficiency is caused by mutation in the TRH gene and is inherited in an autosomal recessive
manner. [23] The index case was a girl evaluated for short stature who was found to have an isolated
deficiency of TRH. [24]

Epidemiology
The National Health and Nutrition Examination Survey (NHANES 1999-2002) of 4392 individuals
reflecting the US population reported hypothyroidism (defined as TSH levels exceeding 4.5 mIU/L) in
3.7% of the population. [25] Hypothyroidism is more common in women with small body size at birth
and low body mass index during childhood. [26]

Iodine deficiency as a cause of hypothyroidism is more common in less-developed countries. Routine

supplementation of salt, flour, and other food staples with iodine has decreased the rates of iodine
deficiency.

World Health Organization (WHO) data from 130 countries taken from January 1994 through
December 2006 found inadequate iodine nutrition in 30.6% of the population. The WHO recommends
urinary iodine concentrations between 100 and 199 μg/L in the general population and a range of 150-
249 μg/L in pregnant women. In developed countries, death caused by hypothyroidism is uncommon.

Age-related demographics
The frequency of hypothyroidism, goiters, and thyroid nodules increases with age. Hypothyroidism is
most prevalent in elderly populations, with 2-20% of older age groups having some form of
hypothyroidism. The Framingham study found hypothyroidism (TSH > 10 mIU/L) in 5.9% of women
and 2.4% of men older than 60 years. [27] In NHANES 1999-2002, the odds of having hypothyroidism
were 5 times greater in persons aged 80 years and older than in individuals aged 12-49 years. [25]

Sex-related demographics

Community studies use slightly different criteria for determining hypothyroidism; therefore, female-to-
male ratios vary. Generally, thyroid disease is much more common in females than in males, with
reported prevalences ranging from 2 to 8 times higher in females.

Race-related demographics

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NHANES 1999-2002 reported that the prevalence of hypothyroidism (including the subclinical form)
was higher in whites (5.1%) and Mexican Americans than in African Americans (1.7%). African
Americans tend to have lower median TSH values. [25]

Prognosis
Undertreatment of hypothyroidism leads to disease progression, with gradual worsening of symptoms
and further metabolic derangements. Ultimately, untreated hypothyroidism can cause profound coma
or even death. Untreated hypothyroidism in infants can cause irreversible mental retardation.

In most patients, fortunately, thyroid hormone treatment reverses the signs and symptoms of
hypothyroidism. With treatment, other secondarily affected laboratory values (eg, circulating lipid
levels and elevated prolactin levels) should improve.

Using disease-specific (ThyPRO questionnaire) and generic (36-item Short Form Health Survey [SF-
36]) measures of health-related quality of life (HRQL), Winther et al discovered that levothyroxine
treatment resulted in improvement in some, but not all, aspects of HRQL in patients with
hypothyroidism resulting from autoimmune thyroiditis. This included significant improvements in nine
of 13 ThyPRO scales after 6 weeks of therapy. [28]

Patient Education
Emphasize proper compliance at each visit. Clearly discuss the lifelong nature of hypothyroidism, the
need for lifelong levothyroxine therapy, the proper way to take medicine, and the need for TSH testing
at least annually.

Patients should take thyroid hormone as a single daily dose. Thyroid hormone is better absorbed in
the small bowel; therefore, absorption can be affected by malabsorptive states, small bowel disease
(eg, celiac sprue), and the patient’s age. Many drugs (eg, iron, calcium carbonate, calcium acetate
aluminum hydroxide, sucralfate, raloxifene, and proton pump inhibitors) can interfere with absorption
and therefore should not be taken within 2-4 hours of LT4 administration. [29]

Estrogen/progestin oral contraceptives and pregnancy are associated with changes in thyroid-binding
globulin. These changes may impact thyroid hormone dosing.

For patient education information, see the Thyroid & Metabolism Center as well as Thyroid Problems
and Chronic Fatigue Syndrome.

Clinical Presentation

References

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Contributor Information and Disclosures

Author

Philip R Orlander, MD Director and Professor, Division of Endocrinology, Associate Dean for
Educational Programs, Vice-Chair of Medicine for Education, Program Director, Internal Medicine
Residency Program, University of Texas Health Science Center at Houston

Philip R Orlander, MD is a member of the following medical societies: American Association of Clinical
Endocrinologists, American Diabetes Association, Endocrine Society, Texas Medical Association

Disclosure: Nothing to disclose.

Coauthor(s)

Jeena M Varghese, MD Assistant Professor, Division of Endocrinology, University of Texas Health

Science Center at Houston

Jeena M Varghese, MD is a member of the following medical societies: American Association of

Clinical Endocrinologists, American Thyroid Association, Endocrine Society

Disclosure: Nothing to disclose.

Lance M Freeman, MD Fellow, Division of Endocrinology, University of Texas Health Science Center
at Houston

Disclosure: Nothing to disclose.

Chief Editor

George T Griffing, MD Professor Emeritus of Medicine, St Louis University School of Medicine

George T Griffing, MD is a member of the following medical societies: American Association for the
Advancement of Science, International Society for Clinical Densitometry, Southern Society for Clinical
Investigation, American College of Medical Practice Executives, American Association for Physician
Leadership, American College of Physicians, American Diabetes Association, American Federation
for Medical Research, American Heart Association, Central Society for Clinical and Translational
Research, Endocrine Society

Disclosure: Nothing to disclose.

Acknowledgements

Anu Bhalla Davis, MD Assistant Professor, Department of Internal Medicine, Division of Diabetes,
Endocrinology, and Metabolism, University of Texas Medical School at Houston

Disclosure: Nothing to disclose.

Shikha Bharaktiya, MD Physician in Endocrinology, Diabetes, and Metabolism, Endocrinology Clinics

of Texas, PA

Disclosure: Nothing to disclose.

Arthur B Chausmer, MD, PhD, FACP, FACE, FACN, CNS Professor of Medicine (Endocrinology,
Adj), Johns Hopkins School of Medicine; Affiliate Research Professor, Bioinformatics and
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Computational Biology Program, School of Computational Sciences, George Mason University;

Principal, C/A Informatics, LLC

Arthur B Chausmer, MD, PhD, FACP, FACE, FACN, CNS is a member of the following medical
societies: American Association of Clinical Endocrinologists, American College of Endocrinology,
American College of Nutrition, American College of Physicians, American College of Physicians-
American Society of Internal Medicine, American Medical Informatics Association, American Society
for Bone and Mineral Research, Endocrine Society, and International Society for Clinical Densitometry

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical
Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Walter R Woodhouse, MD, MSA Associate Clinical Professor, Department of Family Practice,
Medical College of Ohio

Walter R Woodhouse, MD, MSA is a member of the following medical societies: American Academy
of Family Physicians, American Academy of Pain Medicine, and Society of Teachers of Family
Medicine

Disclosure: Nothing to disclose.

Frederick H Ziel, MD Associate Professor of Medicine, University of California, Los Angeles, David
Geffen School of Medicine; Physician-In-Charge, Endocrinology/Diabetes Center, Director of Medical
Education, Kaiser Permanente Woodland Hills; Chair of Endocrinology, Co-Chair of Diabetes
Complete Care Program, Southern California Permanente Medical Group

Frederick H Ziel, MD is a member of the following medical societies: American Association of Clinical
Endocrinologists, American College of Endocrinology, American College of Physicians, American
College of Physicians-American Society of Internal Medicine, American Diabetes Association,
American Federation for Medical Research, American Medical Association, American Society for
Bone and Mineral Research, California Medical Association, Endocrine Society, andInternational
Society for Clinical Densitometry

Disclosure: Nothing to disclose.

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