Hyperthyroidism: A stepwise approach to management

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Applied Evidence

Hyperthyroidism: A stepwise approach to management

J Fam Pract. 2011 July;60(7):388-395

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References

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TABLE 2
Clinical and laboratory findings associated with common causes of hyperthyroidism^51-57

	Mechanism	Thyroid exam	Lab results	Radioactive iodine uptake
Graves’ disease	Antithyroid antibodies	Diffuse goiter	Low TSH; elevated T₃ and/or T₄; elevated thyroid antibodies	Diffusely increased
Toxic multinodular goiter	Iodine deficiency	Goiter with multiple nodules	Low TSH; elevated T₃ and/or T₄	Normal/increased uptake; "hot nodules" with suppression of extranodular tissue
Toxic adenoma	Benign thyroid hormone?secreting tumor; iodine deficiency	Palpable nodule	Low TSH; elevated T₃ and/or T₄	Normal/increased uptake; functioning "hot nodule" on scan with suppression of surrounding thyroid tissue
Subacute thyroiditis	Viral	Tender thyroid on palpation	Low TSH; elevated T₃ and/or T₄; elevated ESR; elevated thyroid antibodies	Low uptake with poor imaging of the thyroid on scan
Factitious hyperthyroidism	Excessive intake of exogenous thyroid hormone	Normal exam	Low TSH; elevated T₃ and/or T₄; low thyroglobulin level	Low or normal uptake
Secondary hyperthyroidism	Excessive pituitary TSH	Goiter	Elevated TSH; elevated T₃ and/or T₄	Diffusely increased uptake
ESR, erythrocyte sedimentation rate; T₃, triiodothyronine; T₄, thyroxine; TSH, thyroid-stimulating hormone.

Which laboratory tests to order, and what the results may mean

Rely on second- or third-generation TSH screening (normal=0.5-5 mIU/L), which is more sensitive and specific than measuring free T₄ (thyroxine) alone.⁶

Older patients usually have a higher normal TSH level. In one study, 70% of patients >80 years had a TSH >4.5 mIU/L.⁷

If the TSH level is low (<0.5 mIU/L), measure free T₃ (triiodothyronine) and free T₄ levels, which are elevated in hyperthyroidism, and are normal in subclinical hyperthyroidism.

Patients with Graves’ disease tend to have T₃ thyrotoxicosis with a T₃T₄ ratio >20.⁸ Isolated T₄ thyrotoxicosis is more commonly seen with nonthyroidal illness as a result of decreased conversion from T₄ to T₃, and also in amiodarone-induced hyperthyroidism.⁹

When further testing is needed (FIGURE). If the underlying cause of hyperthyroidism is not established on the basis of clinical findings (eg, diffuse goiter, myxedema, ophthalmopathy), order a 24-hour radioactive iodine (RAI) uptake test.¹⁰ Graves’ disease and toxic multinodular goiter exhibit increased RAI uptake that is diffuse and nodular, respectively. Subacute thyroiditis is associated with low RAI uptake (TABLE 2).

FAST TRACK

If the underlying cause of hyperthyroidism is not established on the basis of clinical findings, order a 24-hour radioiodine uptake test.

If RAI is contraindicated—eg, in pregnancy—testing for elevated levels of thyroid peroxidase antibodies (TPOab), TSH receptor antibodies (TRab), and thyroglobulin may help to differentiate Graves’ disease from multinodular goiter or uncover another autoimmune thyroid disorder.¹¹ If a patient’s TSH, T₄, and T₃ levels are all elevated, refer him or her for magnetic resonance imaging of the pituitary gland to look for a TSH-secreting adenoma.

FIGURE
Suspect hyperthyroidism? Order these tests^6-11

MRI, magnetic resonance imaging; RAI, radioactive iodine; T₃, triiodothyronine; T₄, thyroxine; TSH, thyroid-stimulating hormone.

Matching treatment to the underlying cause

RAI is usually the treatment of choice for patients without contraindications, although no randomized clinical trials have compared it with antithyroid medications or surgery.¹² Each modality has its own risks and benefits (TABLE 3), and treatment selection should be individualized.

TABLE 3
Comparison of treatment modalities for hyperthyroidism^12-21

	Antithyroid drugs*	Radioactive iodine*	Surgery
Recurrence rate	High recurrence rate; no permanent hypothyroidism	Usually permanent hypothyroidism; long-term use of levothyroxine is required	Subtotal thyroidectomy associated with higher rates of recurrence or persistence of hyperthyroidism than total thyroidectomy; permanent hypothyroidism; long-term use of levothyroxine is required
Preferred method within treatment modality	MMI is the preferred medication; PTU is used with pregnancy and severe hyperthyroidism not responding to MMI	High ablative dose is preferred in MNG, toxic nodule, cardiac disease, elderly; low calculated dose is preferred in patients with GO	No outcome differences for GO, whether thyroidectomy is total, bilateral subtotal, or unilateral total and contralateral subtotal
Setting	Outpatient	Outpatient	Inpatient
Risks	No surgical risks	No surgical risks	Reaction to anesthesia, recurrent laryngeal nerve palsy, hypoparathyroidism
Adverse effects	ATD adverse effects, including life-threatening agranulocytosis	Worsening of Graves’ ophthalmopathy; transient exacerbation of hyperthyroid symptoms	Permanent hypothyroidism; hypoparathyroidism; anesthesia complications
Safety in pregnancy	PTU is used in pregnancy	Contraindicated in pregnancy/lactation	If surgery is indicated in pregnancy, it is best performed in the second trimester
ATD, antithyroid drugs; GO, Graves’ ophthalmopathy; MMI, methimazole; MNG, toxic multinodular goiter; PTU, propylthiouracil. *Concomitant use of ATD and RAI is associated with a high failure rate and persistent or recurrent hyperthyroidism. Discontinue ATD 2 weeks before radioactive iodine treatment.

Radioactive iodine
In a 1990 survey, as many as 70% of specialists in the United States used RAI to treat hyperthyroidism, compared with just 22% of specialists in Europe.¹³ RAI is usually given in a single dose, and its maximal benefit is noted within 3 to 6 months. Two treatment methods are available: the ablative method and the gland-specific dosing method. Both have similar euthyroid state outcomes.¹⁴

The ablative method uses a high dose of RAI to achieve permanent hypothyroidism, necessitating lifelong levothyroxine replacement. This method is preferred for the elderly and for patients with cardiac disease, to achieve faster control of symptoms. It is also recommended for patients with toxic multinodular goiter and toxic nodules.