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Endocrinol Metab Clin N Am 36 (2007) 595–615

Madhuri Devdhar, MD, Yasser H. Ousman, MD*, Kenneth D. Burman, MD
Washington Hospital Center, 110 Irving Street, NW, Room 2A-72, Washington, DC 20010-2975 USA

Hypothyroidism is one of the most common disorders encountered in an endocrine office practice. Hypothyroidism results from reduced thyroid hormone actions at the peripheraltissues. This reduction in thyroid hormone action is, in the vast majority of cases, secondary to reduced thyroid hormone synthesis and secretion by the thyroid gland. Occasionally, peripheral resistance to thyroid hormone is the culprit. The availability of sensitive biochemical tests and effective therapies has simplified the diagnosis and management of this endocrine condition. This articlereviews the epidemiology, etiology, clinical presentation, diagnosis, and treatment of hypothyroidism. We emphasize some of the more recent issues, such as combination thyroid hormone therapy, management of hypothyroidism during pregnancy, and the management of subclinical hypothyroidism.

Epidemiology Hypothyroidism is a relatively common disorder. The prevalence of hypothyroidism increases withage, and the disorder is nearly 10 times more common in females than in males. Hypothyroidism is particularly common in areas of iodine deficiency. Individuals who have thyroid peroxidase antibodies and those who have thyroid-stimulating hormone (TSH) values that are in the upper normal range are at increased risk for developing hypothyroidism. The prevalence of overt hypothyroidism varies accordingto different surveys between 0.1 and 2% [1]. Subclinical hypothyroidism is more prevalent and can be seen in as many as 15% of older women. In the United States National Health and Nutrition Examination Survey (NHANES III), the
* Corresponding author. E-mail address: yasser.ousman@medstar.net (Y.H. Ousman). 0889-8529/07/$ - see front matter Ó 2007 Elsevier Inc. All rights reserved.doi:10.1016/j.ecl.2007.04.008 endo.theclinics.com



et al

prevalence of overt hypothyroidism was found to be 0.3%;prevalence of subclinical hypothyroidism was found to be 4.3% [2]. Etiology A summary of the most common causes of hypothyroidism is given in Box 1. Resistance to thyroid hormones Hypothyroidism may be transient or permanent, central, or primary. Central hypothyroidism canaccompany disorders of the hypothalamic-pituitary axis, leading to reduced TSH secretion or reduced biological activity of TSH. As a result, there is reduction in thyroid stimulation by the TSH and, secondarily, reduced thyroid hormone synthesis and secretion. Primary hypothyroidism refers to a defect in the thyroid gland resulting in reduced synthesis and secretion of thyroid hormones. Centralhypothyroidism Central hypothyroidism is classically divided into secondary hypothyroidism, where the defect is in the pituitary gland, and tertiary hypothyroidism, where the defect is in the hypothalamus. From a practical point of view,

Box 1. Causes of hypothyroidism Central hypothyroidism Pituitary tumors, metastasis, hemorrhage, necrosis, aneurysms Surgery, trauma Infiltrative disorders Infectiousdiseases Chronic lymphocytic hypophysitis Other brain tumors Congenital abnormalities, defects in thyrotropin releasing hormone, TSH, or both Primary hypothyroidism Chronic autoimmune thyroiditis Subacute, silent, postpartum thyroiditis Iodine deficiency, iodine excess Thyroid surgery, I-131 treatment, external irradiation Infiltrative disorders Drugs Agenesis and dysgenesis of the thyroid HYPOTHYROIDISM


the end result is the same: a reduction in the release of biologically active TSH. A variety of disorders can cause central hypothyroidism. In clinical practice, pituitary adenomas are the most common. Less prevalent conditions include pituitary apoplexy and infiltrative disorders of the hypothalamuspituitary axis, such as sarcoidosis, tuberculosis, and other granulomatous...
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