Introduction
Background
Hypothyroidism is a common endocrine disorder resulting from deficiency of thyroid hormone. It usually is a primary process in which the thyroid gland produces insufficient amounts of thyroid hormone. It can also be secondary, that is lack of thyroid hormone secretion due to the failure of either adequate thyrotropin (ie, thyroid-stimulating hormone [TSH]) secretion from the pituitary gland or thyrotropin-releasing hormone (TRH) from the hypothalamus (secondary or tertiary hypothyroidism). The patient's presentation may vary from asymptomatic to, rarely, coma with multisystem organ failure (myxedema coma). The most common cause in the Unites States is autoimmune thyroid disease (Hashimoto thyroiditis).
Cretinism refers to congenital hypothyroidism, which affects 1 per 4000 newborns.
Subclinical hypothyroidism, also referred to as mild hypothyroidism, is defined as normal serum free T4 levels with slightly high serum TSH concentration.
Pathophysiology
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 thyroxine (T4) daily and only small amounts of triiodothyronine (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 thyroid T4-5'-deiodinase activity. This, in turn, causes the thyroid to release more T3.
Because all metabolically active cells require thyroid hormone, the effects of hormone deficiency vary. Systemic effects are either due to derangements in metabolic processes or direct effects by myxedematous infiltration, that is accumulation of glucosaminoglycans in the tissues.
The myxedematous changes in the heart result in decreased contractility, cardiac enlargement, pericardial effusion, decreased pulse, and decreased cardiac output. In the GI tract, achlorhydria and decreased intestinal transit with gastric stasis can occur. Delayed puberty, anovulation, menstrual irregularities, and infertility are common. 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 due to a change in metabolic clearance. In addition, hypothyroidism may result in an increase in insulin resistance.
Frequency
United States
The Third National Health and Nutrition Examination Survey (NHANES III) of 17,353 individuals reflecting the US population reported hypothyroidism (defined as elevated TSH levels) in 4.6% of the population (0.3% overt and 4.3% subclinical).1 It is more common in women with small body size at birth and low body mass index during childhood.2
International
Iodine deficiency as a cause of hypothyroidism is more common internationally. The prevalence is reported as 2-5% depending on the study, increasing to 15% by age 75 years.
Mortality/Morbidity
In developed countries, death caused by hypothyroidism is uncommon.
Race
NHANES III reported that the prevalence of hypothyroidism (including subclinical) was higher in whites (5.1%) than in people of Hispanic descent (4.1%) or African Americans (1.7%). African Americans tend to have lower TSH values.1
Sex
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 reports of prevalence 2-8 times higher in females.
Age
The frequency of hypothyroidism, goiters, and thyroid nodules increases with age. Hypothyroidism is most prevalent in elderly populations, with 2% to as much as 20% of older age groups having some form of hypothyroidism. In the Framingham study, thyroid function was assessed in adults older than 60 years. The study found hypothyroidism (TSH >10 mIU/L) in 5.9% of women and 2.4% of men.
Clinical
History
Hypothyroidism commonly manifests as a slowing in physical and mental activity but may be asymptomatic. Symptoms and signs of this disease are often subtle and neither sensitive nor specific. Classic signs and symptoms such as cold intolerance, puffiness, decreased sweating, and coarse skin previously reported in 90-97% of patients may actually occur in only 50-64% of younger patients. Many of the more common symptoms are nonspecific and difficult to attribute to a specific cause. Individuals can also present with obstructive sleep apnea (secondary to macroglossia) or carpal tunnel syndrome. Women can present with galactorrhea and menstrual disturbances. Consequently, the diagnosis of hypothyroidism is based on clinical suspicion and confirmed by laboratory testing.
Myxedema coma is a severe form of hypothyroidism that results in an altered mental status, hypothermia, bradycardia, hypercarbia, and hyponatremia. Cardiomegaly, pericardial effusion, cardiogenic shock, and ascites may be present. Myxedema coma most commonly occurs in individuals with undiagnosed or untreated hypothyroidism that are subjected to an external stress such as cold exposure, surgery, infection, hypnotics, or other medical interventions.
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
- Feeling of fullness in the throat
- Painless thyroid enlargement
- Exhaustion
- Neck pain, sore throat, or both
- Low-grade fever
Physical
Signs found in hypothyroidism are usually subtle and require a careful physical examination. Often, many signs are dismissed as part of aging; however, consider a diagnosis of hypothyroidism when such signs are present.
Physical signs of hypothyroidism include the following:
- Hypothermia
- Weight gain
- Slowed speech and movements
- Dry skin
- Jaundice
- Pallor
- Coarse, brittle, strawlike hair
- Loss of scalp hair, axillary hair, pubic hair, or a combination
- Dull facial expression
- Coarse facial features
- Periorbital puffiness
- Macroglossia,
- Goiter
- Hoarseness
- Decreased systolic blood pressure and increased diastolic blood pressure
- Bradycardia
- Pericardial effusion
- Abdominal distension, ascites is uncommon.
- Nonpitting edema (myxedema)
- Pitting edema of lower extremities
- Hyporeflexia with delayed relaxation, ataxia, or both
Metabolic abnormalities associated with hypothyroidism include anemia, dilutional hyponatremia, hyperlipidemia, and reversible increase in creatinine.3
Causes
Worldwide, iodine deficiency remains the foremost cause of hypothyroidism. In the United States and other areas of adequate iodine intake, autoimmune thyroid disease is most common. The prevalence of antibodies is higher in women, and increases with age.
Primary hypothyroidism
- Autoimmune: The most frequent cause of acquired hypothyroidism is autoimmune thyroiditis (Hashimoto thyroiditis). The body recognizes 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. Up to 95% of affected individuals have circulating antibodies to thyroid tissue. Antimicrosomal or antithyroid peroxidase (anti-TPO) antibodies are found more commonly than antithyroglobulin antibodies (95% vs 60%). These antibodies may not be present early in the disease process and usually disappear over time.
- Postpartum thyroiditis: Up to 10% of postpartum women may develop lymphocytic thyroiditis in the 2-10 months after delivery. The frequency may be as high as 25% in women with type 1 diabetes mellitus. The condition is usually transient (2-4 mo) and can require a short course of treatment with levothyroxine (LT4), but postpartum patients with lymphocytic thyroiditis are at increased risk of permanent hypothyroidism. The hypothyroid state can be preceded by a short thyrotoxic state. High titers of anti-TPO antibodies during pregnancy have been reported to be 97% sensitive and 91% specific for postpartum autoimmune thyroid disease.
- Subacute granulomatous thyroiditis: Inflammatory conditions or viral syndromes may be associated with transient hyperthyroidism followed by transient hypothyroidism (de Quervain or painful thyroiditis, subacute thyroiditis). These are often associated with fever, malaise, and a painful and tender gland.
- Drugs: Medicationssuch as amiodarone, interferon alpha, thalidomide, lithium, and stavudine have also been associated with primary hypothyroidism.
- Iatrogenic
- Use of radioactive iodine for treatment of Graves disease generally results in permanent hypothyroidism within one year of therapy. The frequency 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.
- Thyroidectomy
- External neck irradiation (for head and neck neoplasms, breast cancer, or Hodgkin disease) may result in hypothyroidism and require monitoring.
- Rare: Rare causes include inborn errors of thyroid hormone synthesis.
- Iodine deficiency or excess: Worldwide Iodine deficiency is the most common cause of hypothyroidism. Excess iodine, as in radiocontrast dyes, amiodarone, health tonics, and seaweed, inhibits iodide organification and thyroid hormone synthesis. Most healthy individuals have a physiologic escape from this effect; however those with abnormal thyroid glands may not. These include patients with autoimmune thyroiditis, surgically treated Graves hyperthyroidism (subtotal thyroidectomy) and prior radioiodine therapy.4
Central hypothyroidism (secondary or tertiary) results when the hypothalamic-pituitary axis is damaged. Various causes should be considered.
- Pituitary adenoma
- Tumors impinging on the hypothalamus
- History of brain irradiation
- Drugs (eg, dopamine, lithium)
More on Hypothyroidism |
 Overview: Hypothyroidism |
| Differential Diagnoses & Workup: Hypothyroidism |
| Treatment & Medication: Hypothyroidism |
| Follow-up: Hypothyroidism |
| References |
| Next Page » |
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Further Reading
Keywords
thyroiditis, myxedema coma, cretinism, hypothyrosis, hypothyroidea, thyrotropin, TSH, tertiary hypothyroidism, thyrotropin releasing-hormone, TRH, thyroxine, T4, triiodothyronine, T3, Hashimoto disease, Hashimoto thyroiditis, primary hypothyroidism, secondary hypothyroidism, congenital hypothyroidism, cold intolerance, weight gain, menstrual disturbances, periorbital puffiness, goiter, autoimmune thyroiditis, iodine deficiency, de Quervain thyroiditis, subacute thyroiditis, postpartum autoimmune thyroid disease, amiodarone, interferon alpha, thalidomide, stavudine, central hypothyroidism, subclinical hypothyroidism
