Thyroid Disorders PDF

Thyroid Disorders INTRO DUCTIO N Thyroid disorders involve thyroid hormone production or secretion and result in alterations in metabolic stability. THYROID HORMONE PHYSIOLOGY  The thyroid hormones thyroxine (T4) and triiodothyronine (T3) are forme...

Thyroid Disorders INTRO DUCTIO N Thyroid disorders involve thyroid hormone production or secretion and result in alterations in metabolic stability. THYROID HORMONE PHYSIOLOGY  The thyroid hormones thyroxine (T4) and triiodothyronine (T3) are formed within thyroglobulin, a large glycoprotein synthesized in the thyroid  cell. Inorganic iodide enters the thyroid follicular cell and is oxidized by thyroid peroxidase and covalently bound (organified) to tyrosine residues of thyroglobulin.  Iodinated tyrosine residues mono-iodo-tyrosine (MIT) and diiodotyrosine (DIT) combine (couple) to form iodothyronines in reactions catalyzed by thyroid peroxidase. Thus, two molecules of DIT combine to form T4, and MIT and DIT join to form T3.  Proteolysis within thyroid cells releases thyroid hormone into the bloodstream. T4 and T3 are transported by thyroid binding globulin (TBG),  transthyretin, and albumin. Only the unbound (free) thyroid hormone can diffuse into cells, elicit biologic effects, and regulate thyroid stimulating hormone (TSH) secretion from the pituitary.  T4is secreted solely from the thyroid, but 3 cm in diameter).  In multinodular goiter, follicles with autonomous function coexist with normal or even nonfunctioning follicles. Thyrotoxicosis occurs when autonomous follicles generate more thyroid hormone than is required.  Painful subacute (granulomatous or de Quervain) thyroiditis often develops after a viral syndrome, but rarely has a specific virus been identified in thyroid parenchyma.  Painless (silent, lymphocytic, or postpartum) thyroiditis is a common cause of thyrotoxicosis. Its etiology is not fully understood; autoimmunity may underlie most cases.  Thyrotoxicosis factitia is hyperthyroidism due to ingestion of exogenous thyroid hormone. This may occur when thyroid hormone is used for inappropriate indications, excessive doses are used for accepted medical indications, there is accidental ingestion, or it is used surreptitiously.  Amiodarone may induce thyrotoxicosis (2%–3% of patients), overt hypothyroidism (5% of patients), subclinical hypothyroidism (25% of patients),or euthyroid hyperthyroxinemia. Because of amiodarone’s high iodine content (37% by weight), increased thyroid hormone synthesis commonly exacerbates thyroid dysfunction in patients with preexisting thyroid disease. Amiodarone also causes a destructive thyroiditis with leakage of thyroglobulin and thyroid hormones. CLINICAL PRESENTATION  Symptoms of thyrotoxicosis include nervousness, anxiety, palpitations, emotional lability, easy fatigability, heat intolerance, weight loss concurrent with increased appetite, increased frequency of bowel movements, proximal muscle weakness (noted on climbing stairs or arising from a sitting position), and scanty or irregular menses in women. 13   Physical signs include warm, smooth, moist skin, and unusually fine hair; separation of the ends of the fingernails from the nail beds (onycholysis); retraction of the eyelids and lagging of the upper lid behind the globe upon downward gaze (lid lag); tachycardia at rest, widened pulse pressure, and systolic ejection murmur; occasional gynecomastia in men; fine tremor of the protruded tongue and outstretched hands; and hyperactive deep tendon reflexes. Thyromegaly is usually present.  Graves’ disease is manifested by hyperthyroidism, diffuse thyroid enlargement, and extrathyroidal findings of exophthalmos, pretibial myxedema, and thyroid acropachy. In severe disease, a thrill may be felt and a systolic bruit may be heard over the gland.  In subacute thyroiditis, patients have severe pain in the thyroid region, which often extends to the ear. Systemic symptoms include fever, malaise, myalgia, and signs and symptoms of thyrotoxicosis. The thyroid gland is firm and exquisitely tender on physical examination.  Painless thyroiditis has a triphasic course that mimics painful subacute thyroiditis. Most patients present with mild thyrotoxic symptoms; lid-retraction and lid lag are present, but exophthalmos is absent. The thyroid gland may be diffusely enlarged without tenderness.  Thyroid storm is a life-threatening medical emergency characterized by decompensated thyrotoxicosis, high fever (often >39.4°C [103°F]), tachycardia, tachypnea, dehydration, delirium, coma, nausea, vomiting, and diarrhea. Precipitating factors include infection, trauma, surgery, radioactive iodine (RAI) treatment, and withdrawal from antithyroid drugs. DIAGNOSIS  Elevated 24 hour radioactive iodine uptake (RAIU) indicates true hyperthyroidism: the patient’s thyroid gland is overproducing T4, T3, or both (normal RAIU 10%–30%). A low RAIU indicates that excess thyroid hormone is not a consequence of thyroid gland hyperfunction but is likely caused by thyroiditis, struma ovarii, follicular cancer, or exogenous thyroid hormone ingestion.  In thyrotoxic Graves’ disease, there is an increase in the overall hormone production rate with a disproportionate increase in T3 relative to T4 (Table 1). Saturation of TBG is increased due to elevated serum levels of T4and T3, which is reflected in elevated T3resin uptake. As a result, concentrations of free T4, free T3, and the free T4 and T3 indices are increased to an even greater extent than the measured serum total T4 and T3concentrations. The TSH level is undetectable due to negative feedback by elevated levels of thyroid hormone at the pituitary. In patients with symptomatic disease, measurement of serum free T4, total T4, total T3, and TSH will confirm the diagnosis of thyrotoxicosis. If the patient is not pregnant or lactating, an increased 24 hour RAIU indicates that the thyroid gland is inappropriately using iodine to produce more thyroid hormone when the patient is thyrotoxic. 14   For toxic adenomas, because there may be isolated elevation of serum T3 with autonomously functioning nodules, a T3 level must be measured to rule out T3toxicosis if the T4level is normal. If autonomous function is suspected but the TSH is normal, the diagnosis can be confirmed by failure of the autonomous nodule to decrease iodine uptake during exogenous T3administration sufficient to suppress TSH.  In multinodular goiters, a thyroid scan shows patchy areas of autonomously functioning thyroid tissue.  TSH induced hyperthyroidism is diagnosed by evidence of peripheral hypermetabolism, diffuse thyroid gland enlargement, elevated free thyroid hormone levels, and elevated serum immunoreactive TSH concentrations. Because the pituitary gland is extremely sensitive to even minimal elevations of free T4, a “normal” or elevated TSH level in any thyrotoxic patient indicates inappropriate production of TSH.  TSH secreting pituitary adenomas are diagnosed by demonstrating lack of TSH response to TRH stimulation, inappropriate TSH levels, elevated TSH α subunit levels, and radiologic imaging.  In subacute thyroiditis, thyroid function tests typically run a triphasic course in this self-limited disease. Initially, serum T4 levels are elevated due to release of preformed thyroid hormone. The 24 hour RAIU during this time is