HYPERTHYROIDISM (THYROTOXICOSIS)

Workup

This disorder is the result of an excessive concentration of circulating thyroid hormone. Hyperthyroidism may be primary (common), secondary (rare), iatrogenic, paraneoplastic (lung cancer, testicular cancer, choriocarcinoma, and hydatiform mole) or secondary to patient abuse of replacement hormone preparations. Once this disorder is suspected, the diagnosis is usually easily confirmed by ordering appropriate diagnostic tests.

Primary hyperthyroidism refers to excessive thyroxine (T4) and/or triiodothyronine (T3) secretion secondary to abnormal thyroid stimulation, thyroid hyperfunctioning nodules, or ectopic malignant thyroxine secretion. Secondary hyperthyroidism is the result of abnormal, excessive thyroid stimulating hormone (TSH) release and stimulation of the thyroid resulting in excessive T4 release. Excessive TSH production may be secondary to pituitary pathology or hypothalamic pathology resulting in excess thyrotropin releasing hormone (TRH) production, which will stimulate the pituitary gland to secrete excessive amounts of TSH. Overtreatment of hypothyroidism, either by physician or patient abuse, results in iatrogenic disease. The antiarrythmic agent amiodarone may also cause hyperthyroidism.

Symptoms of hyperthyroidism include heat intolerance, irritability, weight loss, frequent bowel movements, proximal muscle weakness, tremulousness, anxiety, fever, and fatigue. Menstruating females often suffer oligomenorrhea. Physical findings include tachycardia, a widened pulse pressure, eye findings (lid lag, exophthalmos), goiter, thyroid bruit upon auscultation, a thrill with palpation of the thyroid, brisk reflexes, pretibial myxedema, and a systolic murmur. Patients afflicted with this disorder may exhibit electrocardiographic abnormalities to include sinus tachycardia and atrial fibrillation. In fact, hyperthyroidism should be ruled out in all patients with new onset atrial fibrillation. Apathetic hyperthyroidism refers to hyperthyroidism that is asymptomatic except for cardiac findings and occurs in the elderly. Cardiac symptoms may include congestive heart failure, which is often refractory to therapy, tachycardia, and a widened pulse pressure.

Associated lab abnormalities include an extremely depressed TSH level, an elevated free T4 and/or free T3 which are characteristic of primary hyperthyroidism. Secondary hyperthyroidism is characterized by elevated levels of TSH,  freeT4 and/or free T3 levels. If the free T4 level is normal but symptoms of hyperthyroidism are present along with a suppressed TSH, T3 toxicosis should be considered and a serum free T3 level should be determined if not ordered initially. The profile of a low TSH with normal free T4 and free T3 levels is consistent with subclinical hyperthyroidism. In acutely ill patients, euthyroid sick syndrome may manifest as a low to low normal TSH, low T3, and a normal T4 level. Medications associated with low TSH levels include glucocorticoids, octreotide, dopamine, dobutamine, and amiodarone. Hypercalcemia may result from hyperthyroidism-associated bone disease, and osteoporosis is a potential long-term complication if effective therapy is not administered. Hyperthyroid-induced hepatosteatosis may result in elevation of liver function tests to include the alkaline phosphatase, ALT and AST values.

Primary hyperthyroidism may be secondary to one of several different pathologies, which are listed in order of decreasing frequency:

GRAVES DISEASE: This is the most common form of hyperthyroidism and is characterized by the triad of exophthalmos, diffuse goiter, and hyperthyroidism. This is an autoimmune disorder, and diagnosis is confirmed by finding the above triad plus the presence of serum antibodies (TSH receptor antibodies composed of thyroid-stimulating immunoglobulin and the TSH receptor-blocking antibodies) or the characteristic elevated diffuse uptake of iodine 123 on uptake testing. The presence of pretibial myxedema is also indicative of Graves disease as the underlying cause of hyperthyroidism.

TOXIC NODULAR GOITER (toxic adenoma and toxic multinodular goiter): This form of hyperthyroidism may be the result of a single or multiple autonomously hyperfunctioning nodules. This disorder usually occurs in thyroid glands that have been enlarged for prolonged periods of time. These nodules are benign. When patients with this condition are exposed to iodine (radiocontrast, amiodarone), they may suffer clinical worsening of their disease (jodbasedow effect).

THYROIDITIS: These are transient forms of hyperthyroidism (subacute ,painless and postpartum). Subacute thyroiditis is a painful condition that often follows a respiratory illness and is secondary to thyroid follicle disruption with release of stored thyroid hormone. Postpartum disease is generally painless and lasts approximately one to three months. Because this disorder is transient, antithyroid agents (methimazole or propylthiouracil) are unnecessary and are ineffective. Aspirin 650 mg PO QID may relieve the pain, and if aspirin is ineffective, prednisone 20-40 mg PO QD may offer relief. Symptoms of hyperthyroidism may be controlled with propranolol 20-40 mg PO QID, but the medication should be discontinued after a few weeks and the patient monitored for signs of hyperthyroidism.

THYROTOXICOSIS FACTITIA: This is hyperthyroidism that occurs secondary to ingestion of exogenous thyroxine preparations. In persons ingesting exogenous thyroxine, the serum thyroglobulin level will be extremely low.

TROPHOBLASTIC TUMORS (rare): Hyperthyroidism results when trophoblastic tumors secrete excessive amounts of beta hCG greater than 100,00 mIU/mL. Hyperthyroidism occurs because beta hCG has a similar alpha subunit to that of TSH and binds to TSH receptors on thyroid follicular cells.

STRUMA OVARII (rare): This uncommon disorder occurs when thyroid rests within the ovary become hyperplastic. This disorder is characterized by a low TSH, an elevated T4, low thyroid radioisotope uptake on thyroid scanning, and detection of pelvic radioisotope uptake when the gamma scanner is directed at the pelvis during thyroid scanning.

Thyroid radioiodine uptake may be helpful in establishing the cause of hyperthyroidism. Radioiodine uptake will be elevated in Graves disease (homogeneous uptake of 35-100%), toxic nodular goiter (heterogeneous uptake 20-60%), toxic adenoma (increased uptake of 20-60% in area of nodule). Conversely, the uptake of radioiodine will be low in cases of subacute thyroiditis, postpartum thyroiditis, struma ovarii, and overdosing of exogenous thyroid hormone (iatrogenic or factitious hyperthyroidism). Radioiodine uptake testing should not be performed within 8 weeks of the patient receiving intravenous iodinated contrast medium for other radiographic testing as the prior iodine-containing contrast will saturate the thyroid and prevent uptake of the iodine 123 even if the thyroid is hyperactive. Pregnancy is a definite contraindication to iodine 123 uptake testing.

Thyroid storm is a life-threatening form of hyperthyroidism, and this disorder is characterized by signs and symptoms or a history of hyperthyroidism plus fever and a change in mental status. Therapy includes propylthiouracil (150 mg PO STAT followed by 100-150 mg PO TID) and iodides to block thyroid hormone release (SSKI 10 drops QD or sodium iodide 0. 5 grams by slow intravenous drip Q 6-8 hours). Iodine should only be administered 1-2 hours after thyroid-blocking agents (propylthiouracil) have been given. Decadron (4 mg intravenously Q 6 hours) reduces serum T3 levels. Beta blockade with propranolol (30-60 mg PO Q 8 hours) or intravenous esmolol will help control heart rate. Supportive measures include fluids and determining the cause (infection, trauma). Fever should not be treated with cooling mattresses, and Tylenol is ineffective. Fever may be controlled with Demerol (25-50 mg intravenously Q 6 hours) and chlorpromazine (25-50 mg intravenously Q 6 hours).

Therapy for hyperthyroidism depends on the etiology. Commonly used therapies for Graves disease include radioablation or medical therapy with propylthiouracil (50-150 mg PO TID/QID) or methimazole (5-20 mg PO BID/TID) plus beta blockade for symptom control. Therapy may be continued for a period of approximately 6 months to two years and then discontinued to see if remission has occurred. If hyperthyroidism persists, therapy may be continued indefinitely or radioablation of the thyroid may be offered to the patient.  Patients should be monitored post ablation for the development of a hypothyroid state. Thyroidectomy is a uncommon form of therapy in appropriate cases.