588 Buret

the follicular cells. Each follicle is surrounded by basement membrane, between the follicles are the parafollicular cells containing the calcitonin-secreting C cells. Te metabolism of virtually all nucleated cells of most tissues is controlled by the thyroid hormones. Te thyroid synthesizes two hormones: (1) Triiodothyronine (T3), which is the active hormone that acts at the cellular level and (2) L-thyroxine (T4), which is the prohormone. Iodine is an essential requirement for thyroid hormone synthesis. Inorganic iodide (obtained from dietary sources) is trapped by the gland by an enzyme-dependent system, oxidized, and incorporated into the glycoprotein thyroglobulin to form monoand diiodotyrosine and then T4 and T3. Globally, dietary iodine defciency is a major cause of thyroid disease. Te recommended daily intake of iodine is at least 140 µg. Dietary supplementation of salt and bread has limited the regions where endemic goiter still occurs, but surprisingly, iodine defciency is again a concern in Western countries, because adventitious iodine in dairy products is declining, with noniodoform disinfectants used in milk production, and non-iodized rock salt in place of iodized salt in cooking has become popular. In the US, iodine intakes have fallen, and it is uncertain that the iodine status for most pregnant woman is satisfactory, leading to calls for systematic iodine supplementation.41,42

Hypothyroidism Underactivity of the thyroid gland is usually primary, but can be secondary to diseases of the hypothalamic-pituitary axis, resulting in reduced TSH production and/or release. Hypothyroidism is one of the commonest endocrine disorders. Hypothyroidism can be either subclinical, or overt, with one large US population-based survey fnding the prevalence of subclinical disease to be 4.3% and that of overt disease 0.3%.43 Te overall UK prevalence for primary hypothyroidism is over 2% in women, but under 0.1% in men. Lifetime prevalence for an individual is higher, perhaps as high as 9% for women and 1% for men, with a mean age at diagnosis around 60 years. Te worldwide prevalence of subclinical hypothyroidism varies from 1% to 10%. TSH levels can usually accurately discriminate between hyperthyroidism, hypothyroidism, and euthyroidism (normal thyroid gland function). Exceptions are hypopituitarism and “sick euthyroid” syndrome when low levels (which normally imply hyperthyroidism) occur in the presence of low or normal T4 and T3 levels. As a single test of thyroid function TSH is sufciently sensitive in most circumstances, but for an accurate diagnosis of hypothyroidism, TSH plus the serum free T4 levels should be tested. When hyperthyroidism is suspected, the TSH as well as the free T4 and free T3 need to be checked. Antithyroid antibodies are common and may be destructive or stimulating or both. Destructive antibodies are directed against the microsomes or against the thyroglobulin. Te antigen for thyroid microsomal antibodies is the thyroid peroxidase (TPO) enzyme. TPO antibodies are found in up to 20% of the normal population, especially older women,

but only 10–20% of these develop overt hypothyroidism. TSH receptor IgG antibodies (TRAb) typically stimulate, but occasionally block, the receptor.

Primary Hypothyroidism: Etiology Atrophic (autoimmune) hypothyroidism is the most common cause of hypothyroidism. Te pathophysiology involves the development of antithyroid autoantibodies, leading to lymphoid infltration of the gland and eventual atrophy and fbrosis. It is far more common in women (with a 6:1 female-to-male ratio), and the incidence increases with age. Te condition is associated with other autoimmune disease such as pernicious anemia, vitiligo, and other endocrinopathies. Hashimoto’s thyroiditis is another form of autoimmune thyroiditis, more common in women and most commonly presenting in late middle age, that produces atrophic changes with regeneration, leading to goiter formation. TPO antibodies are present, often in very high titers (>1000 IU/L), and patients can be hypothyroid or euthyroid, although they may go through an initial toxic phase. Postpartum thyroiditis is usually a transient phenomenon following pregnancy, but such postpartum thyroiditis may be misdiagnosed as postnatal depression, emphasizing the need for thyroid function tests in this context. Dietary defciency of iodine is still common and in some areas endemic goiter is still a frequent occurrence. Efforts to prevent defciency by providing iodine in salt continue worldwide, but often with incomplete success. In India some 500 million have iodine defciency and about 2 million have cretinism. Cretinism (the preferred term is congenital hypothyroidism) is a condition of severely impaired physical and mental development and growth due to untreated congenital defciency of the thyroid hormones. Te most common cause is maternal hypothyroidism, which occurs as a consequence of dietary defciency of iodine. It has affected many people worldwide and continues to be a major public health problem in many countries. Iodine defciency remains the most common preventable cause of intellectual impairment and disability worldwide.44 Hypothyroidism may also result from the loss of the TSH-producing cells of the pituitary gland (secondary hypothyroidism). Although less common, it can be caused indirectly by a large, nonfunctioning pituitary adenoma.

Clinical Features Hypothyroidism produces many symptoms. Te alternative term myxoedema refers to the accumulation of mucopolysaccharide in the subcutaneous tissues. Te hypothyroid patient is the mirror image of the hyperthyroid patient.73 Patients are chronically fatigued, cold when others are comfortable, gaining weight without eating more, constipated, and bradycardic, with slowed reflexes. A slowed relaxation phase of the Achilles tendon reflex is an accurate physical