Hypothyroidism

P Terranova, University of Kansas Medical Center, Kansas City, MO, USA

2014 Elsevier Inc. All rights reserved.

Introduction 1
Definition 1
Classification 1
Consequences 1
Associated Disorders 1
Etiology 2
Epidemiology 2
Pathophysiology 2
Signs and Symptoms 2
Standard Therapies 2
Animal Models 3
References 3

Introduction

Hypothyroidism is considered an underactive thyroid and is characterized by a decrease in the serum concentrations of the thyroid
hormones thyroxin (T4) and triiodothyronine (T3). The secretion of T3 and T4 occurs in thyroid gland follicles by a process
controlled by thyroid stimulating hormone (TSH), a protein secreted from the anterior pituitary. The secretion of TSH from the
anterior pituitary is regulated by thyrotropin releasing hormone (TRH), a tripeptide produced in the hypothalamus. Thus, TRH
secreted from the hypothalamus stimulates pituitary secretion of TSH, which subsequently stimulates the thyroid gland to secrete
thyroid hormones. When serum concentrations of T3/T4 are decreased, TSH secretion is increased by a reduction in negative
feedback. In most clinical cases (99%) hypothyroidism is due to an abnormality of the thyroid (primary hypothyroidism);
however, reduced secretion of TSH accounts for some hypothyroidism (<1%). While peripheral resistance to the thyroid hormones
is rare, when it occurs it is referred to as severe generalized thyroid hormone resistance.

Definition

Hypothyroidism is characterized by a decrease in thyroid hormone secretion resulting in a reduction in the metabolic effects
mediated by this hormone.

Classification

Hypothyroidism is an endocrine disorder of the thyroid gland. It is characterized by a reduction in the secretion of thyroid
hormone largely due to iodine deficiency, autoimmune disease or iatrogenic causes. Hypothyroidism is more likely to occur in
women over 60 years of age.

Consequences

Thyroid hormone deficiency results in a reduction in the metabolic rate of all tissues and organs. Symptoms may include weakness,
lethargy and intolerance to cold. Hypothyroidism may also be associated with myxedema, a skin condition characterized by an
atrophied epidermal layer and hyperkeratosis in areas of abrasion. The dermis exhibits edema due to the infiltration of muco-
polysaccharides, hyaluronic acid, and chondroitin sulfate. The gastric mucosa may be reduced, as evidenced by a decrease in acid
secretion.

Change History: August 2014. P Terranova added keywords, abstract, new references, and made changes to the text.

Reference Module in Biomedical Research http://dx.doi.org/10.1016/B978-0-12-801238-3.05078-9 1

2 Hypothyroidism

Associated Disorders

Temporary hypothyroidism may develop from viral thyroiditis, silent thyroiditis, and postpartum thyroiditis.

Etiology

Hypothyroidism results from acquired thyroid disease, through hereditary mechanisms, or from abnormalities in the
hypothalamicpituitary axis. Most hypothyroidism is due to an autoimmune condition in which the thyroid is attacked by
endogenous antibodies that cause the destruction of the thyroid hormone producing parts of the gland (Hashimotos disease).
Hypothyroidism may occur as a result of treatment for Graves disease (hyperthyroidism). Pharmacological agents, such as iodides
and thionamides, used to treat hyperthyroidism may cause hypothyroidism, making it necessary to monitor the response to these
agents. Idiopathic hypothyroidism, a common condition, may develop slowly. Hereditary hypothyroidism, which is rare, is
associated with a mutation in the beta form of the thyroid hormone receptor that renders it inactive. Thus, a generalized
insensitivity to thyroid hormones develops resulting in marked hypothyroidism. Hypothyroidism may also be secondary to an
underproduction of thyroid stimulating hormone.

Epidemiology

Hypothyroidism occurs in about 2% of adult women. It is approximately tenfold less common in men than in women Primary
hypothyroidism accounts for about 95% of all cases, occurring mainly in women over 60 years of age.

Pathophysiology

Disorders involving the hypothalamus and/or pituitary may decrease the function of the thyroid. For example, a pituitary tumor
may shunt blood carrying TRH from the hypothalamus away from the TSH producing cells in the pituitary. This results in less TSH
being secreted, and therefore a decrease in the production of triiodothyronine (T3) and thyroxin (T4). Most commonly,
hypothyroidism is caused by a malfunction of the thyroid gland itself. Hashimotos disease, also referred to as autoimmune
thyroiditis, is the main cause of thyroid hypofunction. Viral infection, radiation treatment of the neck, and surgical removal of the
thyroid are other causes of thyroid hypofunction. In Hashimotos disease, anti-thyroid antibodies destroy the hormone producing
regions of the thyroid resulting in reduced secretion of T3 and T4.

Signs and Symptoms

The most common signs and systems of hypothyroidism are cold intolerance, fatigue and weight gain. Patients may present with
complaints of lethargy, sleepiness, memory impairment, slowed speech, a shortened attention span, and recent personality
changes. Hypothyroid patients may have muscle weakness, cramps with some joint pain, and delayed tendon reflexes. Carpal
tunnel syndrome may be present. Hypothyroid patients may also experience nausea and constipation and exercise intolerance.
Other signs include a hoarse voice, bradycardia, and mild hypertension. Women may exhibit menstrual irregularities, and both
men and women may exhibit decreased libido and fertility. The skin is usually dry and rough, especially in the axillae, there maybe
non-pitting edema in the hands, face and ankles, hair loss and brittle nails, and periorbital swelling and a round face. Because low
serum levels of thyroid hormones are always associated with high circulating levels of TSH, the latter is considered the most
definitive diagnostic feature for hypothyroidism.

Standard Therapies

Agent Name Discussion

L-T4 (levo- Hormone replacement therapy with L-T4, is the standard treatment for hypothyroidism. The dosage depends on the severity of the
thyroxin) condition, age of the patient, and medical condition.
 Hypothyroidism 3

Animal Models

Studies with thyroid hormone receptor knockout animals indicate the importance of hormone receptor corepressors in hypothy-
roidism (Wondisford, 2003). Moreover, knockout models provide insight into the physiological consequences of hypothyroidism
(Brent, 2000).

References
Brent GA (2000) Tissue-specific actions of thyroid hormone: Insights from animal models. Reviews in Endocrine and Metabolic Disorders 1: 2733.
Wondisford FE (2003) Thyroid hormone action: Insight from transgenic mouse models. Journal of Investigative Medicine 51(4): 215220.

Further Reading
Biondi B and Wartofsky L (2014) Treatment with throid horone. Endocrine Reviews 35: 433512.
Caturegli P, DeRimigis A, and Rose NR (2014) Hashimoto thyroiditis: Clinical and diagnostic criteria. Autoimmunity Reviews 13: 391397.
Griffin JE (2000) The thyroid. In: Griffin JE and Ojeda SR (eds.) Textbook of endocrine physiology, vol. 4pp. 303327. New York: Oxford University Press.
Shapiro LE and Surks MI (2001) Hypothyroidism. In: Becker KL (ed.) Principles and practice of endocrinology and metabolism, vol. 3pp. 445454. Philadelphia: Lippincott Williams
and Wilkins.

Relevant Websites

http://www.endocrineweb.com/hypo2.html Hypothyroidism Diagnosis, Tests, and Treatments for Hypothyroidism.

http://www.thyroid.org/what Hypothyroidsim. The American Thydoid Association.