Hyperthyroidism is a hypermetabolic state resulting from excess thyroid hormone. Thyrotoxicosis is a general term for excess circulating and tissue hormone levels.

Thyrotoxicosis

• Patients with hyperthyroidism generally present with tachycardia, tremor, hyperreflexia, anxiety, irritability, emotional lability, panic attacks, heat intolerance, sweating, increased appetite, diarrhea, weight loss, menstrual dysfunction (oligomenorrhea, amenorrhea). Presentation may be different in elderly patients (see the following).
• Patients with Graves disease may present with exophthalmos, lid retraction, and lid lag (Graves ophthalmopathy). The following signs and symptoms of ophthalmopathy may be present: Blurring of vision, photophobia, increased lacrimation, double vision, and deep orbital pressure. Clubbing of fingers associated with periosteal new bone formation in other skeletal areas (Graves acropachy) and pretibial myxedema may also be noted.
• Clinical signs of hyperthyroidism in the elderly may be masked by manifestations of coexisting disease (e.g., new-onset atrial fibrillation, exacerbation of congestive heart failure).

• Graves disease (diffuse toxic goiter): 80% to 90% of all cases of hyperthyroidism
• Toxic multinodular goiter (Plummer disease)
• Toxic adenoma
• Iatrogenic and factitious
• Transient hyperthyroidism (subacute thyroiditis, Hashimoto thyroiditis)
• Rare causes: Hypersecretion of thyroid-stimulating hormone (TSH) (e.g., pituitary neoplasms), struma ovarii, ingestion of large amount of iodine in a patient with preexisting thyroid hyperplasia or adenoma (Jod-Basedow phenomenon), hydatidiform mole, carcinoma of thyroid, amiodarone therapy

• Anxiety disorder
• Pheochromocytoma
• Metastatic neoplasm
• Diabetes mellitus
• Premenopausal state

Suspected hyperthyroidism requires laboratory confirmation and identification of its etiology because treatment varies with cause. A detailed medical history will often provide clues to the diagnosis and etiology of the hyperthyroidism. Fig. 1 describes a diagnostic approach to suspected hyperthyroidism.

Figure 1 Hyperthyroidism.

RAIU, Radioactive iodine uptake; TSH, thyroid-stimulating hormone.

• Elevated free thyroxine (T₄)
• Elevated free triiodothyronine (T₃): Generally not necessary for diagnosis
• Low TSH (unless hyperthyroidism is a result of the rare hypersecretion of TSH from a pituitary adenoma). Serum TSH is the best test for diagnosis of thyrotoxicosis
• Thyroid autoantibodies useful in selected cases to differentiate Graves disease from toxic multinodular goiter (absent thyroid antibodies)

• 24-h radioactive iodine uptake (RAIU) is useful to distinguish hyperthyroidism from iatrogenic thyroid hormone synthesis (thyrotoxicosis factitia) and from thyroiditis (Box 1).
• An overactive thyroid shows increased uptake, whereas a normal underactive thyroid (iatrogenic thyroid ingestion, painless or subacute thyroiditis) shows normal or decreased uptake.
• The RAIU results also vary with the etiology of the hyperthyroidism:
  1. Graves disease: Increased homogeneous uptake
  2. Multinodular goiter: Increased heterogeneous uptake
  3. Hot nodule: Single focus of increased uptake
• RAIU is also generally performed before the therapeutic administration of radioactive iodine to determine the appropriate dose.

Patient education regarding thyroid disease and discussion of the therapeutic options. Avoidance of strenuous physical exercise, caffeine, and tobacco in patients with uncontrolled thyrotoxicosis. Patients should be informed that radioiodine, antithyroid drugs, and surgery are all reasonable treatment options for hyperthyroidism. It is crucial for the physician to have a detailed discussion with the patient about the benefits and risks relative to lifestyle, patients’ values, and coexisting conditions.

• Patients undergoing treatment with antithyroid drugs should be seen every 1 to 3 mo until euthyroidism is achieved and every 3 to 4 mo while they remain on antithyroid therapy. After treatment is stopped, periodic monitoring of thyroid function tests with TSH is recommended every 3 mo for 1 yr, then every 6 mo for 1 yr, then annually.
• Orbital decompression surgery can be used to correct Graves orbitopathy. The administration of the antioxidant selenium (100 mcg PO bid) has been recently reported as effective in improving quality of life, reducing ocular involvement, and slowing progression of the disease in patients with mild Graves orbitopathy. Its mechanism of action is believed to be an effect on the oxygen free radicals and cytokines that play a pathogenic role in Graves orbitopathy.

Successful treatment of hyperthyroidism requires lifelong monitoring for the onset of hypothyroidism or the recurrence of thyrotoxicosis.

• Endocrinology referral is recommended at the time of initial diagnosis and during treatment.
• Surgical referral in selected patients (see “Surgical Therapy”).
• Hospitalization of all patients with thyrotoxic storm.

• Elderly hyperthyroid patients may have only subtle signs (weight loss, tachycardia, fine skin, brittle nails). This form is known as apathetic hyperthyroidism and manifests with lethargy rather than hyperkinetic activity. An enlarged thyroid gland may be absent. Coexisting medical disorders (most commonly cardiac disease) may also mask the symptoms. These patients often have unexplained congestive heart failure, worsening of angina, or new-onset atrial fibrillation resistant to treatment. See the topic “Graves Disease” for additional information on diagnosis and treatment.
• Subclinical hyperthyroidism is defined as a normal serum-free thyroxine and free triiodothyronine levels with a TSH level suppressed below the normal range and usually undetectable. Prevalence in the general population is 1% to 2%. These patients usually do not present with signs or symptoms of overt hyperthyroidism. Subclinical hyperthyroidism is associated with an increased risk of atrial fibrillation and heart failure in older adults. Treatment options include observation or a therapeutic trial of low-dose antithyroid agents for 6 mo to attempt to induce remission. The American Thyroid Association and the American Association of Clinical Endocrinologists recommend treatment of patients with TSH levels <0.1 mIU if they are older than 65 or have associated comorbidities (osteoporosis, heart failure).
• Thyrotoxic periodic paralysis (TPP) is a hyperthyroidism-related hypokalemia and muscle-weakening condition resulting from a sudden shift of potassium into cells. Many patients do not have other symptoms of hyperthyroidism. Typical presentation involves an Asian adult male with acute fatigue and muscle weakness initially presenting in the lower extremities. Physical examination reveals decreased deep tendon reflexes, hypertension, and tachycardia. ECG often reveals U waves, high QRS voltage, and first-degree atrioventricular block. Additional laboratory testing reveals normal acid-base state, hypokalemia with low urinary potassium excretion (spot urinary potassium concentration <20 mEq/L from potassium shift into cells), hypophosphatemia, hypophosphaturia, and hypercalciuria. Electromyography during attacks shows low-amplitude compound muscle action potential of the tested muscle. Therapy consists of cautious potassium supplementation (increased risk of rebound hyperkalemia). Use of nonselective β-blockers (e.g., propranolol) to counteract hyperadrenergic activity, which may be causing TPP, may also be useful.

Hyperthyroidism (Patient Information)

Graves Disease (Related Key Topic)

Thyrotoxic Storm (Related Key Topic)