eMedicine Specialties > Endocrinology > Thyroid

Hashimoto Thyroiditis

Author: Stephanie L Lee, MD, PhD, Fellow, Association of Clinical Endocrinology; Director of Thyroid Nodule and Cancer Center, Associate Chief, Section of Endocrinology, Diabetes and Nutrition, Boston Medical Center; Associate Professor, Department of Medicine, Boston University School of Medicine
Coauthor(s): Sylvester Odeke, MD, FACE, Assistant Professor of Medicine, Department of Internal Medicine, Division of Endocrinology and Metabolism, Brody School of Medicine, East Carolina University; Steven B Nagelberg, MD, Clinical Professor, Department of Medicine, Division of Endocrinology and Metabolism, Drexel University College of Medicine
Contributor Information and Disclosures

Updated: Apr 10, 2009

Introduction

Background

Hashimoto thyroiditis (or Hashimoto's thyroiditis) is part of the spectrum of autoimmune thyroid diseases (AITDs). By strict criteria, it is a histologic diagnosis first described by Hakaru Hashimoto, a Japanese surgeon working in Berlin, Germany. His report was based on the examination of 4 postoperative cases that he published in 1912. He is also credited with introducing the term struma lymphomatosa in reference to the syndrome.

Pathophysiology

Hashimoto's thyroiditis is characterized by the destruction of thyroid cells by various cell- and antibody-mediated immune processes. The initiating process is not well understood.^1,2,3 The thyroid gland is typically goitrous but may be atrophic or normal in size. Antibodies binding to and blocking the thyroid-stimulating hormone (TSH) receptor have also been described and may contribute to further impairment in thyroid function. The result is inadequate thyroid hormone production and secretion, although initially, preformed thyroxine (T4) and triiodothyronine (T3) may "leak" into the circulation from damaged cells.

Patients with Hashimoto's thyroiditis have antibodies to various thyroid antigens, the most frequently detected of which include anti – thyroid peroxidase (anti-TPO), antithyroglobulin (anti-Tg), and to a lesser extent, TSH receptor-blocking antibodies. Nevertheless, a small percentage of patients with Hashimoto's thyroiditis (approximately 10-15%) may be antibody negative.

Other antithyroid antibodies found in AITD (including Hashimoto's thyroiditis) include thyroid-stimulating antibody and cytotoxic antibody.

Other variants of AITD include the following conditions:

• Atrophic thyroiditis
• Juvenile thyroiditis⁴
• Postpartum thyroiditis
• Silent thyroiditis
• Focal thyroiditis

Frequency

United States

Hashimoto's thyroiditis is the most common cause of hypothyroidism in the United States after age 6 years, with the incidence estimated to be 1.3% in a series of 5000 children aged 11-18 years. In adults, incidence is estimated to be 3.5 per 1000 per year in women and 0.8 per 1000 per year in men. Incidence may be as high as 6% in the Appalachian region. In the Colorado Thyroid Disease Prevalence Study, involving 25,862 adults, the prevalence of elevated TSH in symptomatic and asymptomatic adults was 9.5%, with a greater percentage of those involved being women. The prevalence of hypothyroidism and of thyroid disease in general increases with age.

International

Worldwide, the most common cause of hypothyroidism is iodine deficiency. However, Hashimoto's thyroiditis remains the most common cause of spontaneous hypothyroidism in areas of adequate iodine intake. 

The annual incidence of Hashimoto's thyroiditis worldwide is estimated to be 0.3-1.5 cases per 1000 persons.^5,6

Mortality/Morbidity

Morbidity related to Hashimoto's thyroiditis typically results from failure to make the diagnosis of hypothyroidism or to institute l-thyroxine replacement therapy in adequate doses, or from failure on the part of the patient to take the replacement medication.

The increased prevalence of lipid disorders in association with untreated hypothyroidism has the potential to increase morbidity from coronary artery disease.

Race

No significant race predilection has been identified for Hashimoto's thyroiditis.

Sex

The incidence of Hashimoto's thyroiditis is estimated to be 10-15 times higher in females.

Age

The most commonly affected age range in Hashimoto's thyroiditis is 30-50 years, with the peak incidence in men occurring 10-15 years later. The overall incidence of hypothyroidism increases with age in men and women.

Clinical

History

• Hypothyroidism is usually insidious in onset, with signs and symptoms slowly progressing over months to years. Most commonly, patients do not relate a history suggestive of transient hyperthyroidism secondary to increased T4 and T3 levels resulting from thyrocyte destruction. The time course is influenced by the rapidity of onset and the severity of the clinical state of hypothyroidism. The history may be suggestive of other autoimmune associations.
  • The presentation of patients with hypothyroidism may be subclinical, without any symptoms, and may be found simply from routine screening of thyroid function. The usual finding is an elevated TSH level. The early compensatory increase in TSH tends to maintain a nearly normal thyroid function and keeps the patient in a euthyroid state.
  • Patients most commonly present with nonspecific symptoms suggestive of overt hypothyroidism.
  • Patients with long-standing, severe hypothyroidism could present in myxedema coma, precipitated by some major stress or infection.
• The most common and early presenting symptoms of hypothyroidism, such as fatigue, constipation, dry skin, and weight gain, are nonspecific. Weight gain due to hypothyroidism is usually no greater than 10% of the baseline euthyroid weight and is mostly attributable to fluid accumulation in interstitial tissues.
• Other symptoms of hypothyroidism include the following:
  • Cold intolerance
  • Voice hoarseness and pressure symptoms in the neck from thyroid enlargement
  • Slowed movement and loss of energy
  • Decreased sweating
  • Mild nerve deafness
  • Peripheral neuropathy
  • Menstrual irregularities (typically menorrhagia, infertility, and loss of libido) - Increased prolactin secondary to increased thyrotropin-releasing hormone (TRH) leads to decreased luteinizing hormone (LH) and follicle-stimulating hormone (FSH) and to decreased response to gonadotropin-releasing hormone (GnRH). The result is anovulatory cycles with menstrual irregularities.
  • Galactorrhea - This may occur because of the increased prolactin levels.
  • Depression, dementia, and other psychiatric disturbances
  • Memory loss
  • Sleep apnea and daytime somnolence - Obstructive sleep apnea in hypothyroidism is thought to be partly caused by hypofunction of upper airway muscles and weakness of the diaphragm.
  • Joint pains and muscle cramps
  • Hair loss from an autoimmune process directed against the hair follicles

Physical

• Findings
  • Puffy face and periorbital edema typical of hypothyroid facies
  • Cold, dry skin, which may be rough and scaly - Skin may appear yellow but does not involve the sclera, which distinguishes it from the yellowing of jaundice due to hypercarotenemia.
  • Peripheral edema of hands and feet, typically nonpitting
  • Thickened and brittle nails (may appear ridged)
  • Hair loss involving the scalp, the lateral third of the eyebrows, and possibly skin, genital, and facial hair
  • Bradycardia
  • Elevated blood pressure (typically diastolic hypertension) - Most often, blood pressure is normal or even low.
  • Diminished deep tendon reflexes and the classic prolonged relaxation phase, most notable and initially described at the Achilles tendon (although it may be present in other deep tendon reflexes as well)
  • Macroglossia
  • The thyroid gland is typically enlarged, firm, and rubbery, without any tenderness or bruit. It may be normal in size or not palpable at all.
  • Voice hoarseness
  • Slow speech
  • Impairment in memory function
  • Peripheral neuropathy - This may be a mononeuropathy (as exemplified by carpal tunnel syndrome) or a polyneuropathy resulting from the involvement of several peripheral nerves, manifesting as paresthesia
  • Ataxia from cerebellar dysfunction has been documented in hypothyroidism.

Causes

Causes of primary hypothyroidism include the following: 

• Postradioactive iodine (I-131) therapy for hyperthyroidism
• Total or subtotal thyroidectomy
• Radiation therapy for head and neck cancers and lymphoma - Hypothyroidism from radiation injury to the thyroid usually manifests 2-7 years or more after therapy.
• Iodine deficiency, which may be attributable to dietary factors or to inefficient iodine conservation due to intrathyroid and peripheral tissue deiodinase enzyme deficiency
• Congenital disorders of thyroid hormone synthesis
• Intrathyroid defects (eg, iodide transporter defect, thyroid peroxidase defect, thyroglobulin defect) - Other causes of congenital hypothyroidism include thyroid gland agenesis and dysgenesis.
• Transient hypothyroid phase of subacute thyroiditis (de Quervain disease)
• Transient hypothyroid phase of postpartum thyroiditis
• Infiltrative diseases of the thyroid
  • Progressive systemic sclerosis (scleroderma) can cause hypothyroidism from immune and nonimmune mechanisms. The nonimmune mechanism is due to severe fibrosis involving the thyroid gland.
  • Hemochromatosis in the primary and secondary forms, amyloidosis and sarcoidosis. These conditions may also cause central (secondary) hypothyroidism from pituitary infiltration. Hypothyroidism due to sarcoidosis is rare.
  • Fibrous invasive thyroiditis (Riedel struma) is a disorder of fibrous tissue proliferation affecting multiple organs. Hypothyroidism develops in 30-40% of patients with Riedel struma because of loss of thyroid parenchyma.
• Iodine excess, iodine-containing medications, and iodine-containing radiographic contrast agents
• Drugs
  • Antithyroid drugs (eg, propylthiouracil, methimazole, carbimazole)
  • Lithium inhibits thyroidal iodide transport and release of T4 and T3 and may cause hypothyroidism. Lithium may also cause chronic autoimmune thyroiditis with hypothyroidism in 20-40% of patients. Up to 50% of lithium-treated patients may develop a lithium-induced goiter after 2 years of therapy.
  • Amiodarone has a large iodine content, making up nearly 40% of each 200 mg tablet, and can cause hyperthyroidism and hypothyroidism. (It most commonly causes hypothyroidism.) Amiodarone also inhibits peripheral T4-to-T3 conversion; therefore, patients may have an elevated T4 level but remain euthyroid with a normal TSH level.
  • Interferon alpha may induce thyroid autoimmunity in 10-20% of patients. It leads to production of anti-Tg, anti-TPO, and TSH receptor – blocking antibodies. Patients can present with hypothyroidism, hyperthyroidism, or a biphasic thyrotoxicosis-hypothyroidism pattern of silent thyroiditis.⁷
  • Aminoglutethimide is a rare cause of thyroid goiter and hypothyroidism.
  • Phenytoin, carbamazepine, and rifampin increase the hepatic clearance of levothyroxine by induction of cytochrome P-450 enzymes. This can lead to an increased levothyroxine requirement in patients on replacement therapy. Therapy with any of these medications can also precipitate hypothyroidism in patients with decreased thyroid reserve.
• Central (secondary or tertiary) hypothyroidism
  • Diseases, surgical procedures, or irradiation of the pituitary gland can cause abnormal TSH secretion. Postpartum necrosis of the pituitary gland (Sheehan syndrome) can also lead to TSH deficiency and cause central hypothyroidism. TSH deficiency may occur in isolation, but it most commonly occurs with other tropic hormone deficiencies, such as corticotropin and gonadotropin deficiencies.
• Diseases of the hypothalamus (eg, tumorous or granulomatous conditions) and hypothalamic destruction after cranial irradiation can cause TRH deficiency and lead to central hypothyroidism.
  • In central hypothyroidism, the TSH level is most often within the reference range, being immunologically reactive but not biologically active. The diagnosis is usually supported by the presence of symptoms of hypothyroidism, along with a low T4 level in the face of a TSH level that may be low or within the reference range.

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