Overview and Risk Factors
Hypothyroidism is a condition in which the thyroid gland fails to secrete sufficient thyroxine (T4) and triiodothyronine (T3). The disease may reflect intrinsic thyroid dysfunction (primary hypothyroidism), or it may result from insufficient stimulation of the thyroid gland by thyroid-stimulating hormone (TSH) due to a malfunction in the hypothalamic-pituitary axis (secondary hypothyroidism).
Clinical manifestations may be subtle and nonspecific, including weakness, fatigue, and weight gain. However, chronic or severe disease can manifest with goiter, dull facial expression, drooping eyelids, hoarse speech, thinning or dry, brittle hair, dry skin, myxedema (swelling of the skin and soft tissues), menstrual disorders, bradycardia, pericardial effusion, constipation, depression, paresthesias, ataxia, and anemia.
Hypothyroidism affects about 5 million Americans. The most common cause worldwide is iodine deficiency. However, in the United States, where iodized salt is commonly used, most cases are due to autoimmune thyroiditis (Hashimoto's disease), in which CD8+ lymphocytes and antithyroid antibodies impair the normal functioning of the thyroid gland. Other causes include drugs (lithium, amiodarone), genetic mutations of thyroglobulin and thyroid peroxidase molecules, congenital hypothyroidism, neck surgery, and radiothyroid ablation therapy. Hypothyroidism may also result from hypothalamic or pituitary disorders, such as pituitary tumors, postpartum pituitary necrosis, and head trauma, in which the production or release of TSH is impaired.
Some, but not all, patients with hypothyroidism develop a goiter. The clinical presentation of goiter depends on its size and location and may include cough, dyspnea and wheezing due to tracheal compression, dysphagia due to esophageal compression, hoarseness resulting from laryngeal nerve compression, and Horner's syndrome if the cervical sympathetic chain is involved.
Myxedema coma is a life-threatening complication manifested by mental status changes, often accompanied by hypotension, hypothermia, hypoventilation, and, though rarely, coma. (Its name is actually a misnomer, because patients typically exhibit neither the nonpitting swelling of the skin referred to as myxedema nor coma.) Precipitants of myxedema coma include infection, myocardial infarction, stroke, trauma (including surgery and burns), hypoglycemia, hyponatremia, hemorrhage, noncompliance with thyroid medications, and various drugs (eg, beta-blockers, sedatives, narcotics, and phenothiazines).
Risk Factors
- Gender. The majority of cases occur in women.
- Age. Risk of hypothyroidism and myxedema coma increases with age.
- Genetics. Hypothyroidism is associated with several polymorphisms in the genes for human leukocyte antigen (HLA), T-cell antigen receptors, and other immunomodulatory molecules.
- Obesity is an important risk factor.
Diagnosis and Treatment
Diagnosis
Because clinical presentation is highly variable, diagnosis relies on laboratory testing. Several factors may lead to altered thyroid test results in the absence of thyroid disease. These include malnutrition, chronic illness, diabetic ketoacidosis, drugs, and pregnancy.
Initial laboratory testing includes serum TSH and free T4 levels.
- Serum TSH is increased in primary hypothyroidism. This is the most sensitive test for primary hypothyroidism, but it is less useful for secondary hypothyroidism, in which TSH is usually decreased, but may also be normal or elevated.
- Serum free T4 is decreased.
Further laboratory testing may be useful in selected cases.
- Thyrotropin-releasing hormone is elevated in primary hypothyroidism.
- Thyroid autoantibodies are present in Hashimoto's thyroiditis.
- Radioactive iodine uptake will be low in cases of hypothyroidism. However, this study is more useful for evaluating cases of hyperthyroidism.
- Elevated cholesterol, triglycerides, and creatine phosphokinase may occur.
Radioimaging can evaluate the size, shape, and iodine distribution of the thyroid gland and evaluate for compression of vital structures.
Fine needle aspirate can confirm the diagnosis and rule out cancer.
Treatment
In most cases, hypothyroidism requires lifelong thyroid hormone replacement (L-thyroxine). The usual regimen begins at 50μg per day and increases by 25 to 50 μg per day every 4 to 8 weeks until a maintenance dose is reached. The dose is adjusted until an appropriate TSH level is attained.
Iodine deficiency is treated with potassium iodide.
Myxedema coma is treated initially with intravenous L-thyroxine, L-triiodothyronine, and corticosteroids, followed by maintenance doses of oral thyroid hormones.
Nutritional Considerations
Genetic factors apparently account for approximately 80% of the risk for autoimmune thyroid disease, leaving a role for environmental factors such as diet in many cases. Individuals and populations ingesting inadequate amounts of iodine appear to be particularly at risk, as do patients with celiac disease.
The use of iodized salt is a well-accepted public health strategy for decreasing the incidence of iodine deficiency disorders.1 Although mild iodine deficiency in a population results in enlarged thyroid glands, evidence of clinical hypothyroidism does not necessarily follow.2 Conversely,even mildly to moderately excessive iodine intake (>220 μg/day) through foods, dietary supplements, topical medications, and/or iodinated contrast media3 can increase risk for hypothyroidism.4 Iodine excess causes a hypothyroid state partly because of a decrease in the sodium/iodide symporter5 that is responsible for transport of iodide into thyrocytes, a fundamental step in thyroid hormone biosynthesis.6
Hypothyroidism is not uncommonly found in patients with celiac disease (CD);7 for example, 8% of patients with CD were found to be hypothyroid in one study.8 The prevalence of autoantibodies to the thyroid is significantly higher in patients with undiagnosed celiac disease than in celiac patients on a gluten-free diet.9,10 These autoantibodies appear to be gluten-dependent, disappearing after adoption of a gluten-free diet.9 Although evidence is limited, clinical trials found that most patients who strictly followed a gluten-free diet for one year experienced a normalization of subclinical hypothyroidism11 and reduced need for thyroxine.12
Iron deficiency may also contribute to thyroid disease risk. Although Western, meat-eating populations have greater iron stores than non-Western populations, some individuals may experience poor iron status. Plasma thyroxine and triiodothyronine concentrations were significantly lower in women with iron-deficiency anemia, compared with controls.13 Iron-deficiency anemia blunts the effect of iodine supplementation on thyroid function, and iron supplementation improves it.14 However, iron supplements should be taken apart from levothyroxine (see below).
When thyroid medication is used, it should be taken on an empty stomach. Meals can delay gut absorption of levothyroxine, with a particularly noticeable effect from high-fiber meals.15,16 Both calcium carbonate and iron supplements can significantly reduce absorption of levothyroxine and reduce its effectiveness.17,18 This may have particular relevance for older women, who are more likely to need thyroid hormone replacement and to take calcium supplements.
Orders
See Basic Diet Orders chapter.
Dietitian should instruct patient on ways to avoid diet-medication interactions that may influence TSH and T3.
What to Tell the Family
Hypothyroidism is common and treatable, in most cases with excellent outcome. Prevention of hypothyroidism requires adequate dietary intake of iodine and selenium at recommended levels. Patients who live in countries where iodine and selenium are scarce may need supplements of these minerals. In patients with established hypothyroidism, hormone replacement is needed to normalize T3 and TSH levels.
References
1. Delange F, Burgi H, Chen ZP, Dunn JT. World status of monitoring iodine deficiency disorders control programs. Thyroid. 2002;12:915-924.
2. Thomson CD. Selenium and iodine intakes and status in New Zealand and Australia. Br J Nutr. 2004;91:661-672.
3. Pennington JA. A review of iodine toxicity reports. J Am Diet Assoc. 1990; 90:1571-1581.
4. Laurberg P, Bulow Pedersen I, Knudsen N, Ovesen L, Andersen S. Environmental iodine intake affects the type of nonmalignant thyroid disease.
Thyroid. 2001;11:457-469.
5. Wolff J. Physiology and pharmacology of iodized oil in goiter prophylaxis.
Medicine (Baltimore). 2001;80:20-36.
6.Ferreira AC, Lima LP, Araujo RL, et al. Rapid regulation of thyroid sodium-iodide symporter activity by thyrotrophin and iodine. J Endocrinol. 2005;184:69-76.
7. Cardenas A, Kelly CP. Celiac sprue. Semin Gastrointest Dis. 2002;13:232-244.
8. Ansaldi N, Palmas T, Corrias A et al. Autoimmune thyroid disease and celiac disease in children. J Pediatr Gastroenterol Nutr. 2003;37:63-66.
9. Ventura A, Neri E, Ughi C, Leopaldi A, Citta A, Not T. Gluten-dependent diabetes-related and thyroid-related autoantibodies in patients with celiac disease. J Pediatr. 2000;137:263-265.
10. Bonamico M, Anastasi E, Calvani L, et al. Endocrine autoimmunity and function in adolescent celiac patients: importance of the diet. J Pediatr Gastroenterol Nutr. 1997;24:463.
11. Sategna-Guidetti C, Volta U, Ciacci C, et al. Prevalence of thyroid disorders in untreated adult celiac disease patients and effect of gluten withdrawal: an Italian multicenter study. Am J Gastroenterol. 2001;96:751-757.
12. Valentino R, Savastano S, Tommaselli AP, et al. Prevalence of coeliac disease in patients with thyroid autoimmunity. Horm Res. 1999;51:124-127.
13. Beard JL, Borel MJ, Derr J. Impaired thermoregulation and thyroid function in iron-deficiency anemia. Am J Clin Nutr. 1990;52:813-819.
14. Zimmermann MB, Kohrle J. The impact of iron and selenium deficiencies on
iodine and thyroid metabolism: biochemistry and relevance to public health. Thyroid. 2002;12:867-878.
15. Liel Y, Harman-Boehm I, Shany S. Evidence for a clinically important adverse effect of fiber-enriched diet on the bioavailability of levothyroxine in adult hypothyroid patients. J Clin Endocrinol Metab. 1996;81:857-859.
16. Benvenga S, Bartolone L, Squadrito S, et al. Delayed intestinal absorption of levothyroxine. Thyroid. 1995;5:249-253.
17. Singh N, Singh PN, Hershman JM. Effect of calcium carbonate on the absorption of levothyroxine. JAMA. 2000;283:2822-2825.
18. Campbell NR, Hasinoff BB, Stalts H, Rao B, Wong NC. Ferrous sulfate reduces thyroxine efficacy in patients with hypothyroidism. Ann Intern Med. 1992;117:1010-1013.
