Thyrotoxicosis (Hyperthyroidism)

Introduction

Thyrotoxicosis results when tissues are exposed to excessive levels of T4 , T3 , or both. TSH-secreting pituitary tumors release biologically active hormone that is unresponsive to normal feedback control. The tumors may cosecrete prolactin or growth hormone; therefore, patients may present with amenorrhea, galactorrhea, or signs of acromegaly.

• In Graves disease, hyperthyroidism results from the action of thyroid-stimulating antibodies (TSAb) directed against the thyrotropin receptor on the surface of thyroid cell. These immunoglobulins bind to the receptor and activate the enzyme adenylate cyclase in the same manner as TSH.

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.
• 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.
• Graves disease is manifested by hyperthyroidism, diffuse thyroid enlargement, and extrathyroidal findings of exophthalmos, pretibial myxedema, and thyroid acropachy.

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 or hormone ingestion.
• 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 thyrotoxic Graves disease, there is an increase in the overall hormone production.

TREATMENT

Goals of Treatment: Eliminate excess thyroid hormone; minimize symptoms and long-term consequences; and provide individualized therapy based on the type and severity of disease, patient age and gender, existence of nonthyroidal conditions, and response to previous therapy.

Nonpharmacologic Therapy

Surgical removal of the thyroid gland should be considered in patients with a large gland (>80 g), severe ophthalmopathy, or lack of remission on antithyroid drug treatment.

• If thyroidectomy is planned, propylthiouracil (PTU) or methimazole is usually given until the patient is biochemically euthyroid (usually 6–8 weeks), followed by addition of iodides (500 mg/day) for 1–14 days before surgery to decrease vascularity of the gland. Levothyroxine may be added to maintain the euthyroid state while thionamides are continued.

Pharmacologic Therapy

PTU and methimazole block thyroid hormone synthesis. Usual initial doses include PTU 300 to 600 mg daily (usually in three or four divided doses) or methimazole 30 to 60 mg daily given in three divided doses. Evidence exists that both drugs can be given as single daily dose. Typical daily maintenance doses are PTU 50 to 300 mg and methimazole 5 to 30 mg. Continue therapy for 12 to 24 months to induce long-term remission.

Potassium iodide is available as a saturated solution (SSKI, 38 mg iodide per drop) or as Lugol solution, containing 6.3 mg of iodide per drop.

• Typical starting dose of SSKI is 3 to 10 drops daily (120–400 mg) in water or juice. When used to prepare a patient for surgery, it should be administered 7 to 14 days preoperatively
• Propranolol doses required to relieve adrenergic symptoms vary, but an initial dose of 20 to 40 mg orally four times daily is effective for most patients (heart rate<90beats/min). Younger or more severely toxic patients may require 240 to 480 mg/day.

General supportive measures, including acetaminophen as an antipyretic (aspirin or other nonsteroidal anti-inflammatory drugs may displace bound thyroid hormone), fluid and electrolyte replacement, sedatives, digoxin, antiarrhythmics, insulin, and antibiotics should be given as indicated.