Chapter: Modern Pharmacology with Clinical Applications: Thyroid and Antithyroid Drugs

Thyrotoxicosis

Thyrotoxicosis is any condition in which the body tis-sues are exposed to supraphysiological concentrations of thyroid hormones.

THYROTOXICOSIS

 

Thyrotoxicosis is any condition in which the body tis-sues are exposed to supraphysiological concentrations of thyroid hormones. This designation is preferred to the term hyperthyroidism to describe this disorder be-cause its origin may not result from excessive thyroid gland secretion. Thyrotoxicosis factitia arises from the ingestion of excessive quantities of thyroid hormone rather than from overactivity of the thyroid gland. The term hyperthyroidism is reserved for disorders that re-sult from overproduction of hormone by the thyroid it-self. This distinction is important because only condi-tions caused by hyperthyroidism respond to treatment with agents that decrease iodine uptake, thyroid hor-mone production, and the release of thyroid hormone, and only these conditions may require permanent ra-dioactive or surgical ablation of the gland.

 

The manifestations of hyperthyroidism depend on the severity of the disease, the age of the patient, the presence or absence of extrathyroidal manifestations, and the specific disorder producing the thyrotoxicosis. Of the various types of hyperthyroidism, only two are common: Graves’ disease and toxic multinodular goiter. Less common causes include toxic adenoma and post-partum thyroiditis, among others.

 

Graves’ disease, the most common type of hyperthy-roidism, is an autoimmune disease that is characterized by the presence of TSH receptor–stimulating antibodies (TSAB) that bind to the TSH receptors (TSHR) on thy-roid follicular cells. These TSABs mimic TSH in stimu-lating growth of the thyroid gland (diffuse goiter) and by causing an increase in synthesis and secretion of T4 and T3. In these patients, serum concentrations of T4, T3, and TSAB are elevated, while TSH levels are sup-pressed. Additional symptoms of Graves’ disease may include infiltrative ophthalmopathy (exophthalmos) and occasionally infiltrative dermopathy. Both of these are also thought to result from an autoimmune process.

In older patients toxic multinodular goiter typically presents as longstanding asymptomatic multinodular goiters. Functional autonomy of the nodules develops over time by an unknown mechanism and causes the disease to move from the nontoxic to the toxic phase. The onset of hyperthyroidism is gradual, and the symp-toms are usually milder than those of Graves’ disease.

 

Toxic adenoma (Plummer’s disease) is less common and is caused by one or more autonomous adenomas of the thyroid gland. These autonomously secreting tu-mors occur in an intrinsically normal thyroid gland and result from point mutations in the TSHRs on thyroid follicular cells. These point mutations lead to constitu-tive activation of the TSHR in the absence of TSH. Tumor growth is progressive over many years, and with growth, a progressively larger share of thyroid hormone secretion is assumed by the adenoma; TSH secretion is inhibited, while the remainder of the gland is unstimu-lated and may atrophy. Continued autonomous growth results in excessive secretion of T4 and T3 and thyrotox-icosis.

 

 

Clinical Manifestations of Thyrotoxicosis

 

The signs and symptoms of thyrotoxicosis, regardless of the cause, may include the following: increased basal metabolic rate, heat intolerance, tachycardia, widened pulse pressure, cardiac arrhythmias, skeletal muscle weakness, muscle wasting, tremor, hyperreflexia, emo-tional instability, nervousness, insomnia, change in men-strual pattern, frequent bowel movements (occasionally diarrhea), and weight loss despite an increased appetite. In addition, very frequent manifestations of all forms of thyrotoxicosis, irrespective of the underlying cause, are retraction of the upper eyelid (evident as the presence of a rim of sclera between the lid and the limbus) and lid lag. These ocular manifestations appear to be due largely to increased adrenergic stimulation and are ameliorated by adrenergic antagonists and reversed promptly upon successful treatment of the thyrotoxico-sis. These eye signs do not indicate Graves’ infiltrative ophthalmopathy and are not accompanied by protru-sion of the eyes.

 

In Graves’ disease, the autoimmune processes medi-ate the enlargement of the thyroid gland, the infiltrative ophthalmopathy with exophthalmos, and the dermopa-thy and thereby distinguish Graves’ disease from other causes of thyrotoxicosis.

 

Thyrotoxic Crisis, or Thyroid Storm

 

Thyrotoxic crisis, thyroid storm, or accelerated hyper-thyroidism is an extreme accentuation of thyrotoxicosis. Although uncommon, this serious complication of hy-perthyroidism usually occurs in association with Grave’s disease and occasionally with toxic multinodular goiter.

If unrecognized, it is invariably fatal. Thyroid storm is usually abrupt in onset and occurs in patients whose pre-existing thyrotoxicosis has been treated incompletely or not at all.Thyrotoxic crisis may be related to cytokine re-lease and an acute immunological disturbance caused by a precipitating condition, such as trauma, surgery, dia-betic ketoacidosis, toxemia of pregnancy, or parturition. Although the serum thyroid hormone levels may not be appreciably greater than those in uncomplicated thyro-toxicosis, the clinical picture is severe hypermetabolism with fever, profuse sweating, tachycardia, arrhythmias, and so on. Pulmonary edema or congestive heart failure may also develop. With progression of the disorder, apa-thy, stupor, and coma may supervene, and hypotension can develop. There are no foolproof criteria by which se-vere thyrotoxicosis complicated by some other serious disease can be distinguished from thyrotoxic crisis in-duced by that disease. In any event, the differentiation between these alternatives is of no great significance be-cause treatment of the two is the same, directed at sys-temic support and amelioration of the thyrotoxicosis.

 

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