Hyperthyroidism and Other Causes of Thyrotoxicosis

Background

• Thyrotoxicosis is a clinical state characterized by excessive thyroid hormone levels.
• Hyperthyroidism is a form of thyrotoxicosis resulting from an inappropriately high synthesis and secretion of thyroid hormone by the thyroid gland. The most common causes of hyperthyroidism are Graves disease, toxic multinodular goiter, and toxic thyroid adenoma.
• Other causes of thyrotoxicosis that are not termed hyperthyroidism include subacute thyroiditis and excess intake of exogenous thyroid hormone.
• Complications of hyperthyroidism include thyroid storm (a life-threatening condition), cardiovascular complications such as heart failure and atrial fibrillation, and osteoporosis and fractures.
• Subclinical hyperthyroidism may be associated with cardiovascular and other complications similar to overt hyperthyroidism.

Evaluation

• Suspect thyrotoxicosis in patients with characteristic symptoms such as heat intolerance, increased sweating, palpitations, weight loss despite increased appetite, fatigue, fine tremors, anxiety, or poor concentration.
• On examination, the thyroid gland is often diffusely enlarged, with or without nodules, and there may be signs of tachycardia, heart failure, irregular heart rhythm, increased heart rate, lid lag, and hyperreflexia.
• A reliable interpretation of serum thyroid-stimulating hormone (TSH) tests requires an intact hypothalamic-pituitary-thyroid axis.
• In symptomatic patients or in those with signs of thyrotoxicosis, measure serum TSH. Measure free thyroxine (FT4), with or without total tri-iodothyronine (TT3), if the TSH is low.
  • Normal or elevated TSH usually excludes thyrotoxicosis.
  • Low TSH suggests thyrotoxicosis, but can also be seen with nonthyroidal illness, use of certain medications (such as levothyroxine, amiodarone, or lithium), or in the first trimester of pregnancy.
  • Elevated FT4 confirms thyrotoxicosis.
  • If TSH is low and FT4 is normal, check TT3 to evaluate for T3-thyrotoxicosis.
  • Normal FT4 and FT3 with low TSH suggests subclinical hyperthyroidism, lab error, hypothalamic or pituitary disease, nonthyroidal illness, or medication effects.
• For confirmed thyrotoxicosis:
  • Diagnose Graves disease in patients with characteristic clinical findings such as symmetrically enlarged thyroid and exophthalmos (Strong recommendation).
  • Consider measuring TSH receptor antibodies (TRAb) if the etiology is still unclear after thyroid scintigraphy.
  • If etiology of thyrotoxicosis is still uncertain in nonpregnant patients, perform radioactive iodine uptake to clarify different causes (Strong recommendation).
    • Do not perform a radioactive uptake in pregnant patients (Strong recommendation).
    • Single or multiple foci of increased uptake amid otherwise decreased uptake suggests toxic thyroid adenoma or toxic multinodular goiter.
    • Diffuse high uptake suggests Graves disease.
    • Low or absent uptake suggests thyroiditis or a nonthyroidal source of thyroid hormone.
    • Cold (hypofunctioning) or indeterminate nodules classified using thyroid scintigraphy should prompt a biopsy and evaluation for cancer.
  • Consider checking a serum thyroglobulin if exogenous thyroid hormone intake is suspected.
• Unusual causes to consider in the differential diagnosis include struma ovarii, choriocarcinoma, functional thyroid cancer metastases, and thyrotoxicosis factitia.

Management

• Prescribe beta-blockers for symptom relief from tachycardia, tremors, and anxiety (Strong recommendation).
• Treatment of hyperthyroidism usually depends on the underlying cause.
  • Treat Graves disease with antithyroid medications, radioactive iodine, or thyroidectomy (Strong recommendation).
  • Consider treating toxic multinodular goiter with radioactive iodine or thyroidectomy over antithyroid medications (Weak recommendation).
  • Consider treating toxic thyroid adenoma with radioactive iodine or thyroidectomy over antithyroid medications (Weak recommendation).
  • Treat acute (suppurative) thyroiditis with antibiotics (Strong recommendation).
  • Treat subacute painful thyroiditis with supportive care such as nonsteroidal anti-inflammatory drugs (NSAIDs) as first-line therapy or corticosteroids if patient fails to respond to NSAIDs or initially presents with moderate to severe pain or symptoms of thyrotoxicosis (Strong recommendation).
  • Treat painless (silent) thyroiditis with beta-blockers in patients with symptomatic thyrotoxicosis (Strong recommendation).
  • Treat amiodarone-induced type 1 thyrotoxicosis with methimazole (Strong recommendation) and treat amiodarone-induced type 2 thyrotoxicosis with corticosteroids. Occasionally both methimazole and corticosteroids are required if the type is uncertain. (Strong recommendation).
• Manage patients in thyroid storm in intensive care unit with beta-blockers, antithyroid drugs (ATDs), iodine, corticosteroids, aggressive cooling measures, and fluid replacement (Strong recommendation).
• Consider treating subclinical hyperthyroidism in patients > 65 years old, patients with hyperthyroid symptoms, and in patients with cardiac risk factors, heart disease, or osteoporosis according to same principles used in treating overt hyperthyroidism.
• During pregnancy:
  • Treat gestational hyperthyroidism and hyperemesis gravidarum-associated thyrotoxicosis with supportive therapy, without ATDs (Strong recommendation).
  • For pregnant women treated with antithyroid drugs, consider whether ATD can be discontinued, and if not, switch to propylthiouracil while attempting pregnancy and through the first trimester, then if ATD therapy still needed, switch to methimazole in second and third trimesters (Weak recommendation).
• Perioperative management in patients with hyperthyroidism depends on clinical status and the urgency of the procedure.
  • Surgery (thyroid or nonthyroid) in those with unrecognized or inadequately treated hyperthyroidism can precipitate thyroid storm.
  • Prior to any surgery, the goal is to achieve a euthyroid state.
    • Patients with moderate to severe hyperthyroidism should wait until hyperthyroidism is under control prior to proceeding to elective surgeries.
    • If the patient does not become euthyroid prior to thyroidectomy, if the need for surgery is urgent, or if the patient is allergic to antithyroid medication, premedication should include beta-blockers, potassium iodide, glucocorticoids, and possibly cholestyramine.