endocrine and metabolic disorders
Hyperthyroidism
Etiology of Hyperthyroidism
Hyperthyroidism may result from increased Synthesis and Release of Thyroid Hormones (thyroxine [T4] and triiodothyronine [T3]) from the thyroid, caused by thyroid stimulators in the blood or by autonomous thyroid hyperfunction. It can also result from excessive release of thyroid hormone from the thyroid without increased synthesis. Such release is commonly caused by the destructive changes of various types of thyroiditis. Themost common causesoverall include Graves disease Multinodular goiter Thyroiditis Single, autonomous, hyperfunctioning "hot" nodule Graves disease (toxic diffuse goiter),the most common cause of hyperthyroidism, is characterized by hyperthyroidism and one or more of the following: Goiter Proptosis None Infiltrative dermopathy Graves disease is caused by an autoantibody against the thyroid receptor for thyroid-stimulating hormone (TSH); unlike most autoantibodies, which are inhibitory, this autoantibody is stimulatory, thus causing continuous synthesis and secretion of excess T4 and T3. Graves disease (like Hashimoto Thyroiditis ) sometimes occurs with other autoimmune disorders, including type 1 The pathogenesis of infiltrative ophthalmopathy (responsible for the exophthalmos in Graves disease) is poorly understood but may result from immunoglobulins directed to the TSH receptors in the orbital fibroblasts and fat that result in release of proinflammatory cytokines, inflammation, and accumulation of glycosaminoglycans. Ophthalmopathy may also occur before the onset of hyperthyroidism or as late as 20 years afterward and frequently worsens or abates independently of the clinical course of hyperthyroidism. Typical ophthalmopathy in the presence of normal thyroid function is called euthyroid Graves disease. Toxic solitary or multinodular goiter (Plummer disease)sometimes results from TSH receptor gene mutations causing continuous thyroid activation. Patients with toxic nodular goiter have none of the autoimmune manifestations or circulating antibodies observed in patients with Graves disease. Also, in contrast to Graves disease, toxic solitary and multinodular goiters usually do not remit. includes subacute granulomatous thyroiditis, Hashimoto Thyroiditis , and Inappropriate TSH secretionis a rare cause. Patients with hyperthyroidism have essentially undetectable TSH except for those with a TSH-secreting anterior pituitary adenoma or pituitary resistance to thyroid hormone. TSH levels are high, and the TSH produced in both disorders is biologically more active than normal TSH. An increase in the alpha-subunit of TSH in the blood (helpful in differential diagnosis) occurs in patients with a TSH-secreting pituitary adenoma. Drug-induced hyperthyroidismcan result fromamiodarone, checkpoint inhibitors used in cancer therapy,alemtuzumabused in treatment of multiple sclerosis, or interferon-alfa, which may induce thyroiditis with hyperthyroidism and other thyroid disorders. Although more commonly causing hypothyroidism,lithiumcan rarely cause hyperthyroidism. Patients receiving these drugs should be closely monitored. Thyrotoxicosis factitiais hyperthyroidism resulting from intentional or accidental overingestion of thyroid hormone. Excess iodine ingestioncauses hyperthyroidism with a low thyroid radioactive iodine uptake. It most often occurs in patients with underlying nontoxic nodular goiter (especially older patients) who are given drugs that contain iodine (eg,amiodarone) or who undergo radiologic studies using iodine-rich contrast agents. The etiology may be that the excess iodine provides substrate for functionally autonomous (ie, not under TSH regulation) areas of the thyroid to produce hormone. Hyperthyroidism usually persists as long as excess iodine remains in the circulation. Gestational Trophoblastic Disease (molar pregnancy) and choriocarcinoma Nonautoimmune autosomal dominant hyperthyroidismmanifests during infancy. It results from mutations in the TSH receptor gene that produce continuous thyroid stimulation. Metastatic thyroid canceris a possible cause. Overproduction of thyroid hormone occurs rarely from functioning metastatic follicular carcinoma, especially in pulmonary metastases. Struma ovariidevelops when ovarian teratomas contain enough thyroid tissue to cause true hyperthyroidism. Radioactive iodine uptake occurs in the pelvis, and uptake by the thyroid is usually suppressed. 