Hypothyroidism clinical manifestations

Clinical manifestations of overt hypothyroidism are usually obvious though minor deficiencies may be more easily missed they may have pronounced adverse effects on patients well-being. The diagnosis nowadays should always be confirmed biochemically (with detection of low serum T4 and high TSH levels), and highly sensitive and specific immunoassays are now readily available in most countries. 

There is no discrete target tissue for thyroid hormones virtually every cell in the body is affected by thyroid hormones in some way. These hormones are intimately involved in the maintenance of normal function in virtually every cell type, including cellular responsiveness to other hormones, to the availability of metabolic substrates, to growth factors, and so on. Thyroid dysfunction can produce dramatic changes in the metabolism of proteins, carbohydrates, and lipids at the cellular level that can have repercussions for the operation of the cardiovascular, gastrointestinal, musculoskeletal, reproductive, and nervous systems. Some of the clinical manifestations of thyroid dysfunction are presented next in the discussions of hypothyroid and hyperthyroid states. 

The clinical manifestations of hyperthyroidism and hypothyroidism are listed in Table 31-2. From a pharmacotherapeutic standpoint, hyperthyroidism is treated with drugs that attenuate the synthesis and effects of thyroid hormones. Hypothyroidism is usually treated by thyroid hormone administration (replacement therapy). The general aspects and more common forms of hyperthyroidism and hypothyroidism are discussed here, along with the drugs used to resolve these primary forms of thyroid dysfunction. 

Hypothyroidism describes the clinical state arising from a deficiency in thyroid hormone. Toxicity resulting in hypothyroidism is manifested at several organ systems as... 

Thyroid hypofunction is the most common hormonal deficiency in the general population (Roberts and Ladenson, 2004). The prevalence of hypothyroidism seems to rise with age, and is clearly higher in middle age and the elderly in relation to the younger population. However, hypothyroidism in aged people may go unnoticed because of its paucity of clinical manifestations, or because many of the chnical signs and symptoms are unspecific and may be confounded with the normal ageing process (Di ez, 1998). We herein review the main chnical aspects of this common condition in middle age and in the elderly. 

Table 106.2 Clinical manifestations of hypothyroidism in middle age and the elderly...

The most extreme manifestation of untreated hypothyroidism is myxedema coma, which even if detected early and appropriately treated, carries a mortality rate of 30 to 60%. Myxedema coma is a misnomer. Most patients exhibit neither the myxedema nor coma. Patients with myxedema coma usually have longstanding hypothyroidism with the classic symptoms of hypothyroidism. Decompensation into myxedema coma may occur when the homeostatic mechanisms of the severely hypothyroid patient are subject to a stressful precipitating event (e.g., infection, trauma, some medications, stroke, surgery). The principal manifestation of myxedema coma is a deterioration of mental status (apathy, confusion, psychosis, but rarely coma). Other common clinical features include hypothermia, diastolic hypertension (early), hypotension (late), hypoventilation, hypoglycemia, and hyponatremia. If myxedema coma is suspected, the patient is usually admitted to an intensive care unit for pulmonary and cardiovascular support... 

Many of the manifestations of thyroid hyperactivity resemble sympathetic nervous system overactivity (especially in the cardiovascular system), although catecholamine levels are not increased. Changes in catecholamine-stimulated adenylyl cyclase activity as measured by cAMP are found with changes in thyroid activity. Possible explanations include increased numbers of 13 receptors or enhanced amplification of the 13 receptor signal. Other clinical symptoms reminiscent of excessive epinephrine activity (and partially alleviated by adrenoceptor antagonists) include lid lag and retraction, tremor, excessive sweating, anxiety, and nervousness. The opposite constellation of effects is seen in hypothyroidism (Table 38-4). 

Cardiovascular Effects Thyroid hormones directly and indirectly influence cardiac function, and cardiovascular manifestations are prominent clinical consequences of thyroid disease. In hyperthyroidism, there is tachycardia, increased stroke volume, increased cardiac index, cardiac hypertrophy, decreased peripheral vascular resistance, and increased pulse pressure. In hypothyroidism, there is bradycardia, decreased cardiac index, pericardial effusion, increased peripheral vascular resistance, decreased pulse pressure, and elevation of mean arterial pressure. 

Despite the relatively detailed understanding of iodine metabolism and the action of THs at the molecular level, their action on the human nervous system remains poorly understood. At the clinical interface, the neuromuscular manifestations of THs are quite common. Their incidence depends primarily on how extensively and rigorously the symptoms are sought. Overall, neuromuscular dysfunction occurs in 20—80% of cases (Aminoff, 2002). In hypothyroidism, it is as high as 79%, and in hyperthyroidism it is 67%. The predominant symptoms are sensorimotor axonal neuropathy in both extremes of thyroid dysfunction. Most of these resolve with treatment for the thyroid condition. Although not documented, most patients with thyroid disease often complain of neuromuscular-type symptoms. 

Despite these promising clinical data, the toxicities, cost, and complexities of administration have limited the use of radioimmunotherapy. The murine antibodies induce an immune response. This may manifest as acute infusion reactions and human anti-murine antibodies (HAMA), which occur in approximately 2% of patients treated with Y ibritumomab tiuxetan and 9% of patients treated with I tositumomab. Myelosuppression 6-9 weeks after administration is common. Ten percent of patients treated with I tositumomab develop hypothyroidism [92]. The most feared complication of radioimmunotherapy is treatment-related myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). Rates of these late, generally incurable toxicities range 1.5—2.5% for Y ibritumomab tiuxetan and 3.5—6.4% for tositumomab [63, 93, 94]. Because ionizing radiation is teratogenic, radioimmunotherapy is contraindicated in all stages of pregnancy. 

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