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Treatment of toxic adenoma and toxic multinodular goiter

Treatment of toxic adenoma and toxic multinodular goiter
Author:
Douglas S Ross, MD
Section Editor:
David S Cooper, MD
Deputy Editor:
Jean E Mulder, MD
Literature review current through: Jan 2024.
This topic last updated: Jun 22, 2023.

INTRODUCTION — Toxic adenoma and toxic multinodular goiter (MNG) are common causes of hyperthyroidism, second in prevalence only to Graves' disease. The prevalence of toxic nodular goiter increases with age and in the presence of iodine deficiency and may therefore be more common than Graves' disease in older populations in regions of iodine deficiency. Toxic adenoma and MNG are the result of focal and/or diffuse hyperplasia of thyroid follicular cells whose functional capacity is independent of regulation by thyroid-stimulating hormone (TSH). Twenty to 80 percent of toxic adenomas and some nodules of MNGs have somatic mutations of the TSH receptor gene that confers autonomous hyperactivity [1,2].

The treatment of toxic adenoma and MNG will be presented here. The clinical presentation, evaluation, and diagnosis of hyperthyroidism and of goiter, as well as the treatment of other causes of hyperthyroidism, are reviewed separately.

(See "Overview of the clinical manifestations of hyperthyroidism in adults".)

(See "Diagnosis of hyperthyroidism".)

(See "Disorders that cause hyperthyroidism".)

(See "Clinical presentation and evaluation of goiter in adults".)

(See "Graves' hyperthyroidism in nonpregnant adults: Overview of treatment".)

CONFIRM THE ETIOLOGY OF HYPERTHYROIDISM — Because the treatment of hyperthyroidism differs according to the etiology, the correct diagnosis of toxic adenoma or toxic multinodular goiter (MNG) must be made before therapy is instituted.

The diagnosis of toxic adenoma or MNG should be suspected in hyperthyroid (overt or subclinical) patients with physical examination or ultrasound findings consistent with or suspicious for nodular thyroid disease. For nonpregnant hyperthyroid patients with physical examination or ultrasound findings suggesting nodular thyroid disease, we obtain a radioiodine uptake scan as our initial test to distinguish toxic MNG and toxic adenoma from Graves' disease, or to assess the functionality of nodules, which may coexist with Graves' disease. Women of childbearing age who might be pregnant should have a negative pregnancy test prior to undergoing radioiodine scanning. (See "Diagnosis of hyperthyroidism", section on 'Our approach'.)

Radioiodine scanning is contraindicated during pregnancy. The diagnosis and evaluation of hyperthyroidism during pregnancy is reviewed separately. (See "Hyperthyroidism during pregnancy: Clinical manifestations, diagnosis, and causes".)

Toxic adenoma – A classic clinical presentation for toxic adenoma is a hyperthyroid patient with a palpable thyroid nodule that corresponds to an area of increased radioiodine concentration on thyroid scintigraphy; there should also be suppression of radioiodine uptake in surrounding and contralateral tissue if the TSH is subnormal (image 1).

Toxic MNG – A classical clinical presentation for toxic MNG is a hyperthyroid patient with a palpable nodular goiter or a thyroid ultrasound showing multiple nodules. The nodularity may only be appreciated on ultrasound. On thyroid scintigraphy, there are typically one or more focal areas of increased radioiodine uptake, which may or may not correspond to the nodules. Nonfunctioning ("cold") nodules are also present in some patients, and they should be evaluated in the same manner as a nonfunctioning solitary thyroid nodule, with the need for fine-needle aspiration (FNA) determined by nodule size and the presence of suspicious ultrasound characteristics (table 1). The prevalence of thyroid cancer in a patient with MNG is 3 to 10 percent, although many of these are microcarcinomas [3,4]. Periodic ultrasonography is also used to monitor nodule size accurately. (See "Diagnostic approach to and treatment of thyroid nodules", section on 'Evaluation'.)

In addition to hyperthyroid symptoms and goiter, some patients with MNG have obstructive symptoms (cough, dysphagia, dyspnea). Because MNGs usually grow very slowly over many decades, obstructive symptoms almost always develop insidiously. (See "Clinical presentation and evaluation of goiter in adults", section on 'Obstructive symptoms'.)

There are two clinical situations in which establishing the diagnosis of a toxic adenoma or MNG is more difficult:

First, the autonomously functioning tissue may be sufficiently diffuse that it is difficult to differentiate an MNG from Graves' disease by thyroid scintigraphy alone. When it is important to distinguish these disorders, a high serum concentration of thyrotropin receptor antibodies (TRAb) usually indicates Graves' disease; however, a low titer may not exclude the diagnosis in patients with very mild hyperthyroidism. (See "Diagnosis of hyperthyroidism", section on 'Determining the etiology'.)

Second, in iodine-induced hyperthyroidism, the exogenous iodine load can dilute the radioiodine tracer and result in both a low radioiodine uptake and a poor image on scintigraphy. Repeat scanning weeks or months later may be necessary. (See "Iodine-induced thyroid dysfunction", section on 'Iodine-induced hyperthyroidism'.)

INDICATIONS FOR TREATMENT

All patients with overt hyperthyroidism (low TSH with elevated free thyroxine [T4] and/or triiodothyronine [T3]) due to toxic adenoma or toxic multinodular goiter (MNG) require treatment.

The decision to treat when thyroid tests show subclinical hyperthyroidism (low serum TSH concentrations [<0.4 mU/mL] but normal serum free T4 and T3 concentrations) is based upon the risk for developing complications from subclinical hyperthyroidism (skeletal, cardiovascular) and the degree of TSH suppression. The management of patients with subclinical hyperthyroidism is reviewed in detail separately. (See "Subclinical hyperthyroidism in nonpregnant adults", section on 'Endogenous subclinical hyperthyroidism'.)

Patients with large goiters and symptoms of obstruction require treatment even if thyroid function is normal. (See "Treatment of benign obstructive or substernal goiter".)

THERAPEUTIC APPROACH — Treatment of hyperthyroidism due to toxic adenoma or toxic multinodular goiter (MNG) consists of both symptomatic relief with beta blockers and decreasing the production of thyroid hormone with radioiodine ablation or surgery [5]. Prolonged (probably lifelong) thionamide therapy is an increasingly popular option for patients who would like to avoid both radioiodine and surgery.

Symptom control — Beta blockers ameliorate many of the symptoms of hyperthyroidism [6]. They are often started as soon as the diagnosis of hyperthyroidism is made, even before obtaining a 24-hour radioiodine uptake or scan. In the absence of contraindications, we usually give atenolol (25 to 50 mg/day), which has the advantages of single-daily dosing and beta-1 selectivity, but all drugs of this class effectively reduce symptoms in patients with hyperthyroidism. Beta blockers may be tapered and discontinued after thyroid function tests have returned to normal. (See "Beta blockers in the treatment of hyperthyroidism".)

Decrease thyroid hormone synthesis — Surgery and radioiodine are the two most effective treatment options for permanently decreasing the production of thyroid hormone. Thionamides decrease thyroid hormone production but do not induce remission in hyperthyroidism secondary to nodular thyroid disease (ie, discontinuation results in recurrence of hyperthyroidism). Thionamides are often used to treat hyperthyroidism in patients with toxic adenoma or MNG in preparation for more definitive therapy with radioiodine or surgery, but they may also be used long term to treat hyperthyroidism due to toxic adenoma, and it may be the best option in patients with increased surgical risk and/or inability to comply with radiation safety guidelines. In centers where ultrasound-guided percutaneous ethanol injection, radiofrequency ablation (RFA), or interstitial laser photocoagulation are available, they are also options for patients who prefer to avoid radioiodine or surgery.

Choice of therapy — For patients with toxic adenoma or MNG, treatment options include surgery, radioiodine, prolonged (probably lifelong) thionamide therapy, or ultrasound-guided procedures such as RFA, laser, and ethanol ablation. In general, the choice among these options is based upon individual patient factors and regional availability of expertise. Lifelong thionamide therapy is an increasingly popular option. Our approach to management is consistent with the Hyperthyroidism Management Guidelines published by the American Thyroid Association (ATA) [7]:

We prefer surgery for patients with very large goiters (>80 g), symptoms or signs of compression/obstruction, the need for rapid return to euthyroidism, and coexisting thyroid cancer (or primary hyperparathyroidism). In the absence of one of these indications for surgery, radioiodine, antithyroid drugs, surgery, RFA (and similar procedures), and ethanol ablation are all options.

Radiation safety regulations in some states and countries advise mothers receiving radioiodine to severely limit the time spent with their infants for up to five days. As a result, if suitable childcare is unavailable, patients may opt to take thionamides for several years prior to receiving radioiodine, or may choose surgery, RFA, or ethanol ablation over radioiodine.

The individual patient's fears regarding radiation exposure, general anesthesia, or surgical complications often influence the decision, and some patients refuse both radioiodine and surgery. For them, prolonged thionamide therapy is acceptable as long as it is tolerated and the hyperthyroidism is controlled. Young women, however, need to be informed of the teratogenic effects of the thionamides. Percutaneous ethanol injection, RFA, or laser therapy, where available, are alternatives to prolonged thionamide therapy. (See 'Other therapies' below.)

In a randomized controlled trial of older adult patients with subclinical hyperthyroidism treated with radioiodine or antithyroid drugs, 19 patients had toxic nodular goiter treated with radioiodine and 21 were treated with methimazole. After five years, 9 radioiodine-treated patients were euthyroid on levothyroxine and 10 were euthyroid, while all 21 methimazole-treated patients were euthyroid on long-term methimazole therapy [8].

There are no randomized trials comparing radioiodine and surgery for the treatment of MNG or toxic adenoma. Both treatments resolve biochemical hyperthyroidism in most patients.

Surgery

Indications — Surgery is used more commonly for the treatment of patients with a toxic adenoma or MNG than it is for Graves' hyperthyroidism. It is indicated for patients with:

Obstructive goiters or very large goiters (>80 g)

Coexisting malignancy or primary hyperparathyroidism

Or patients who:

Need rapid and definitive correction of hyperthyroidism

Surgery could also be considered in children and adolescents and may be preferable in patients with coexistent, nonfunctioning nodules (as determined by scintigraphy) or nodular goiters that include both autonomous and nonfunctioning nodules, especially if the goiters are large [3,9-11]. These latter patients have a substantial decrease in the size of the autonomous nodules after radioiodine treatment, but because uptake may be suppressed in nonautonomous tissue, they may not have a reduction in nonautonomous nodules to the extent seen during radioiodine treatment of patients with nontoxic MNG. In addition, nodular thyroid tissue that remains following radioiodine treatment may develop calcifications over time, which may be interpreted as suspicious by radiologists on subsequent imaging and lead to thyroidectomy a decade or more after radioiodine treatment [11,12]. (See "Overview of the management of benign goiter".)

In retrospective studies, surgery successfully reduced goiter size, improved compressive symptoms, and corrected hyperthyroidism.

Goiter size – Total or near-total thyroidectomy results in correction of goiter in almost all patients, whereas radioiodine reduces thyroid volume by approximately 38 to 45 percent. As examples:

In a retrospective series of 581 patients with MNG, 13 percent had symptoms of cervical compression (choking, dysphagia, dyspnea) [13]. The majority of the patients with compressive symptoms were treated with thyroidectomy rather than radioiodine. All of those who had thyroidectomy had reduction in gland size and compressive symptoms, compared with only 46 percent of those who were treated with radioiodine.

In another retrospective series of 362 patients with MNG treated with surgery (53 percent), radioiodine (45 percent), or both (2 percent) between 1990 and 1999, reduction of goiter size was reported in 100 and 38 percent of patients treated with surgery and radioiodine, respectively [10].

Correction of hyperthyroidism – For rapid correction of hyperthyroidism, surgery is superior to radioiodine, as illustrated by the retrospective review described above (362 patients with MNG) [10]. One month after treatment, resolution of hyperthyroidism occurred in 96 and 6 percent of patients treated with surgery and radioiodine, respectively. However, with longer-term follow-up (mean 28 months), resolution of hyperthyroidism occurred in 84 percent of patients receiving radioiodine (average time to achieve resolution of hyperthyroidism was 5.4 months). Permanent hypothyroidism is almost inevitable after thyroidectomy.

Extent of resection — Surgery for toxic adenoma and MNG should only be performed by surgeons with expertise in thyroid surgery [7]. (See "Surgical management of hyperthyroidism", section on 'Extent of resection' and "Thyroidectomy".)

For patients with MNG, near-total or total thyroidectomy should be performed.

For patients with toxic adenoma without evidence of nodules in the contralateral lobe, ipsilateral lobectomy (or isthmusectomy if the adenoma is in the thyroid isthmus) is adequate.

For patients with toxic adenoma and a coexisting non-functioning nodule in the contralateral lobe, total thyroidectomy may be warranted. The decision should be based upon results of fine-needle aspiration (FNA) biopsy of the nonfunctioning nodule, its size, and surgical expertise.

Preoperative preparation — Patients with overt hyperthyroidism of any cause who are to undergo surgery should be treated with an antithyroid drug (ie, methimazole or carbimazole) until they are euthyroid. We typically avoid iodine in the preoperative preparation of patients with toxic adenoma and MNG owing to the increased risk of exacerbating hyperthyroidism. However, we rarely administer iodine to help lower thyroid hormone levels in hyperthyroid patients already taking methimazole who require urgent therapy (eg, severe hyperthyroidism or hyperthyroidism in the setting of myocardial infarction, stroke, or other severe comorbidity). Thionamides prevent the thyroid from using iodine as substrate for new hormone synthesis within two hours after the initial dose. Thus, thionamide therapy should therefore be started first and continued without interruption in divided doses because administration of iodine alone can exacerbate hyperthyroidism in these patients. (See "Surgical management of hyperthyroidism", section on 'Preoperative preparation' and "Iodine in the treatment of hyperthyroidism".)

Calcium and 25-hydroxyvitamin D should be measured and repleted if low or given prophylactically. (See "Surgical management of hyperthyroidism", section on 'Measures to prevent postoperative hypocalcemia'.)

Complications — Potential complications following near-total or total thyroidectomy include permanent hypoparathyroidism and recurrent laryngeal nerve injury, each reported in approximately 2 percent of patients [10,13]. A discussion of complications is reviewed in more detail elsewhere. (See "Surgical management of hyperthyroidism", section on 'Complications' and "Thyroidectomy", section on 'Complications'.)

Radioiodine therapy — We typically suggest radioiodine to patients who do not meet the surgical indications described above (see 'Indications' above). Radioiodine can be given as primary therapy to patients with mild, well-tolerated hyperthyroidism. In comparison, patients who are more symptomatic, older, or have underlying heart disease are usually pretreated with a thionamide before radioiodine administration. (See 'Thionamide administration' below.)

Pregnancy and breastfeeding are absolute contraindications to radioiodine therapy. In addition, radioiodine should not be administered for the treatment of toxic adenoma or MNG to women planning a pregnancy within four to six months, patients with coexisting thyroid cancer, or patients who are unable to comply with radiation safety guidelines. (See "Hyperthyroidism during pregnancy: Treatment" and "Radioiodine in the treatment of hyperthyroidism".)

Radioiodine is widely used for therapy of patients with toxic adenomas or MNGs [14]. Radioiodine is administered as an oral solution or capsule of sodium iodine 131 (131-I), which is rapidly concentrated in thyroid tissue. It induces extensive tissue damage, resulting in destruction of the adenoma or autonomous foci within 6 to 18 weeks. Radioiodine therapy not only ameliorates hyperthyroidism but also reduces the size of the adenomas [3,9]. As examples:

In a study of 62 patients treated with radioiodine for toxic adenoma, hyperthyroidism was controlled in all, usually in three months, and total thyroid volume decreased by 35 percent in three months and 45 percent in 24 months; five patients became hypothyroid during a three-year follow-up period [9].

In patients with MNG, treatment with radioiodine cured hyperthyroidism in 92 to 98 percent of patients; some patients required two doses [3,15].

In an Italian study of 153 patients with toxic multinodular goiter treated with a fixed dose of 15 millicuries (mCi), there was a 30 percent reduction in goiter size at one year, increasing to 50 percent or more by three years [16]; however, 22 percent of patients had regrowth of goitrous tissue. After a mean of 5.7 years, 62 percent of patients were euthyroid, 11 percent hyperthyroid, and 27 percent hypothyroid. In this study, 88 percent of patients had subclinical hyperthyroidism.

Unlike Graves' disease, in which the goal of radioiodine therapy is destruction of the gland with eventual hypothyroidism, most patients are euthyroid after radioiodine therapy because the radioiodine preferentially accumulates in the hyperfunctioning nodules [17]. In one series of 346 patients with toxic adenoma treated with 131-I, hypothyroidism was observed in 28, 46, and 60 percent of patients after 5, 10, and 20 years, respectively [18]. In a series of 265 patients with MNG, 59 of whom were pretreated with antithyroid drugs, hypothyroidism was observed in 32, 55, and 73 percent of patients after three months, one year, and eight years, respectively [15]. Higher rates of hypothyroidism are observed when patients are pretreated with antithyroid drugs. If the patient is pretreated with antithyroid drugs, radioiodine should ideally be given before the serum TSH concentration normalizes to prevent the accumulation of radioiodine into paranodular tissues, thereby minimizing the risk of hypothyroidism [19]. (See 'Pretreatment before radioiodine or surgery' below.)

Approximately 10 to 20 percent of patients fail to reach a euthyroid state following the first dose of radioiodine and require a second or subsequent dose. These patients typically have severe hyperthyroidism or large goiters. Dosing of radioiodine is reviewed in more detail separately. (See "Radioiodine in the treatment of hyperthyroidism", section on 'Dosing of radioiodine'.)

The development of Graves' disease in approximately 4 percent of patients is a rare sequela of radioiodine administration to patients with toxic nodular goiter. The subsequent and frequently more severe hyperthyroidism may be treated with additional radioiodine [20]. A general discussion of the adverse effects of radioiodine can be found elsewhere. (See "Radioiodine in the treatment of hyperthyroidism", section on 'Adverse effects'.)

With the increasing use of thyroid ultrasonography, another concern following radioiodine administration is that the autonomous nodules acquire suspicious ultrasonographic characteristics (hypoechogenicity and calcifications) that may lead to unnecessary procedures or surgery a decade or more following treatment [11,12].

Thionamide administration

Pretreatment before radioiodine or surgery — Thionamides should be used to control overt hyperthyroidism prior to surgery for toxic adenoma or MNG. Thionamides may be used to control overt hyperthyroidism prior to radioiodine in patients who are not tolerating hyperthyroid symptoms or who are at increased risk of hyperthyroid complications (eg, older patients and those with underlying cardiovascular disease). In addition, patients with symptomatic hyperthyroidism can be treated with an antithyroid drug to attain euthyroidism while considering options for definitive therapy. (See "Radioiodine in the treatment of hyperthyroidism", section on 'Pretreatment with methimazole' and "Surgical management of hyperthyroidism", section on 'Preoperative preparation'.)

In older patients or in those with heart disease, diabetes, or other comorbidities whose hyperthyroidism is mild, methimazole 5 or 10 mg once daily can be used. In comparison, those with larger goiters and more severe hyperthyroidism are usually started on 20 to 30 mg daily. Propylthiouracil should be avoided except during pregnancy, because of its greater degree of toxicity. When patients experience nausea on higher doses of methimazole, taking the pills with food or in divided doses may be helpful. (See "Thionamides in the treatment of Graves' disease", section on 'Dosing'.)

In patients undergoing surgery for toxic adenoma or MNG, methimazole should be discontinued immediately postoperatively. For patients being treated with radioiodine, methimazole should be discontinued three days before radioiodine is given [21]. In order to avoid exposure of normal thyroid tissue to radioiodine (which increases the risk of hypothyroidism), the TSH should ideally still be below normal when radioiodine is administered. Methimazole can be restarted three to seven days after radioiodine is administered and stopped once radioiodine has proved to be effective. If, however, the goal is to ablate autonomous tissue and reduce the size of autonomous and nonautonomous tissue in a toxic nodular goiter, allowing the TSH to increase during methimazole therapy may improve goiter shrinkage at the expense of a greater risk of hypothyroidism. (See "Treatment of benign obstructive or substernal goiter", section on 'Pretreatment with methimazole to increase the radioiodine uptake'.)

Long-term administration — Patients who do not want radioiodine, surgery, or other ultrasound-guided ablative procedures can be treated with long-term thionamide administration. However, in women who may subsequently desire a pregnancy, a discussion regarding the risks of becoming pregnant while on antithyroid drugs should precede a decision to use thionamides long term. (See "Hyperthyroidism during pregnancy: Treatment", section on 'Choice of thionamide'.)

For patients who choose long-term thionamide treatment, the initial dose is the same as for pretreatment before radioiodine or surgery (see 'Pretreatment before radioiodine or surgery' above). Thyroid function should be assessed at four- to six-week intervals by measurement of serum free T4 and TSH until the patient is stabilized. The dose of methimazole is tapered to a maintenance dose with the goal of maintaining euthyroidism. Thereafter, monitoring every three months is often initially required to make dose adjustments, but the interval can be extended to 6 to 12 months in patients on lifelong therapy.

Unlike Graves' hyperthyroidism, toxic nodules and MNG rarely resolve spontaneously with prolonged thionamide therapy. Toxic adenomas may undergo hemorrhage or infarction, leaving a patient euthyroid, but this is rare. Iodine-induced hyperthyroidism may be an exception because it can resolve in several months if the source of the iodine is discontinued. These patients can be treated with a thionamide alone. However, many clinicians still prefer radioiodine therapy or surgery because the patients are at risk for recurrent hyperthyroidism if given iodine again. (See "Iodine-induced thyroid dysfunction", section on 'Iodine-induced hyperthyroidism'.)

Other therapies — In countries where ultrasound-guided injection of ethanol and ultrasound-directed physical energy such as RFA are performed routinely, they are alternative treatment options for patients who are not candidates for or wish to avoid radioiodine, surgery, and prolonged thionamide therapy. Expertise in these approaches is rapidly increasing in the United States. Complications include burns on the skin, damage to the recurrent laryngeal nerve, and occasionally prolonged pain.

Ethanol injection – Ethanol injection of toxic adenomas under ultrasound guidance is a nonsurgical method of destroying the adenomas [22-25]. Ethanol is injected percutaneously using ultrasound guidance at weekly intervals for five to eight weeks. This form of therapy is not widely used in the United States. However, where available, it can be used when I-131 or surgery is not desirable and when the nodule is not too large (<5 mL in volume).

In one series of 117 patients with autonomous thyroid adenomas followed for an average of 2.5 years, all 40 patients with adenomas who had subclinical hyperthyroidism were cured, while 60 of 77 patients (80 percent) with hyperthyroidism (60 with a single adenoma and 17 with an MNG) also were cured [26]. No patient had recurrent hyperthyroidism. In a retrospective study in which radioiodine and ethanol injection were compared, reduction in adenoma volume was similar (67 percent for radioiodine versus 78 percent for ethanol) and radioiodine was more likely to result in hypothyroidism but also more likely to cure the hyperthyroidism [27]. The main adverse effect is local pain during and immediately after the procedure. Uncommon adverse effects include transient laryngeal nerve damage, abscess, and hematoma.

Radiofrequency ablation and laser therapy

Laser photocoagulation – Ultrasound-guided interstitial laser photocoagulation has been used to destroy autonomous nodules. In a randomized trial comparing laser and radioiodine therapy, both treatments resulted in a 44 to 48 percent reduction in nodule size, but only 47 percent of those receiving laser treatment were euthyroid at six months, compared with 87 percent in the radioiodine group [28].

RFA – In meta-analyses of observational studies, radiofrequency ablation (RFA) was effective in normalizing TSH in 57 to 71 to percent of patients with autonomous thyroid nodules [29,30]. RFA of thyroid nodules was superior to laser therapy in a meta-analysis that assessed nontoxic, solid thyroid nodules; RFA reduced nodule size by 76 percent, while laser reduced nodule size by only 50 percent [31]. In a multicenter study of RFA for toxic adenoma, 82 percent became euthyroid within the 20-month follow-up period [32]. An international consensus statement on the use of RFA provides extensive guidance for best practices [33]. While RFA has been used in some European countries for a decade, as its use increases in the United States and other countries, it is notable that there is a measurable learning curve for operator experience until 90 patients have been treated [34].

Monitoring after therapy

Radioiodine — After radioiodine treatment, patients require monitoring for hypothyroidism or persistent or recurrent hyperthyroidism. Measurement of serum TSH alone can be misleading in the early follow-up period because it can remain low for weeks or even months, even when the patient is biochemically euthyroid or even hypothyroid, with serum free T4 values well within or even below the normal range. Thus, the principal tests used to follow the immediate effect of treatment of hyperthyroidism are the serum free T4 and total T3 concentration. Thyroid tests (TSH, free T4, total T3) should be measured six to eight weeks after treatment and then at four- to eight-week intervals thereafter, depending upon the results of prior testing and change in thyroid size. If thyroid hormone is required, the dose may be less than full replacement owing to persistent autonomous thyroid function. Once steady-state conditions are assured, measurement of TSH is required to assess the efficacy of therapy. (See "Treatment of primary hypothyroidism in adults", section on 'Dose and monitoring'.)

Serum TSH should be measured at yearly intervals for the patient's lifetime because of the ongoing occurrence of hypothyroidism after radioiodine therapy.

Surgery — Beta blockers can be tapered following surgery. Monitoring for hypocalcemia after near-total or total thyroidectomy is necessary. The evaluation and management of post-thyroidectomy hypoparathyroidism is reviewed separately. (See "Differentiated thyroid cancer: Surgical treatment", section on 'Hypoparathyroidism' and "Thyroidectomy", section on 'Postoperative care'.)

For patients with MNG who had near-total or total thyroidectomy, thyroid hormone replacement (T4 [levothyroxine]) should be initiated at a dose of approximately 1.6 mcg/kg body weight daily. Older patients and those with coronary disease or multiple coronary risk factors should be treated with slightly less than full replacement dose (eg, start at approximately 80 percent of the calculated full replacement dose, then measure serum TSH in six to eight weeks and adjust the dose by 12 to 25 mcg/day if the TSH remains above the normal reference range). Serum TSH should be measured six to eight weeks after each dose adjustment. (See "Treatment of primary hypothyroidism in adults", section on 'Dose and monitoring'.)

Hypothyroidism is less common after lobectomy or isthmusectomy for toxic adenoma. In a meta-analysis of 32 studies, the overall risk of hypothyroidism following a lobectomy was 22 percent [35]. Serum TSH and free T4 levels should be measured four to six weeks after surgery. Thyroid hormone should be initiated only if the TSH rises and remains above normal.

Persistent or recurrent disease — For patients with persistent (beyond six months after initial treatment) or recurrent hyperthyroidism after radioiodine or surgery, we typically treat/re-treat with radioiodine. We prefer to avoid a second surgery in patients with inadequate initial surgery, due to an increased risk of surgical complications (hypoparathyroidism, recurrent laryngeal nerve damage). However, for patients who have persistent or recurrent hyperthyroidism after radioiodine, surgery is an alternative option.

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Hyperthyroidism".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

Basics topics (see "Patient education: Thyroid nodules (The Basics)" and "Patient education: Hyperthyroidism (overactive thyroid) (The Basics)" and "Patient education: Nodular goiter (The Basics)")

Beyond the Basics topics (see "Patient education: Thyroid nodules (Beyond the Basics)" and "Patient education: Hyperthyroidism (overactive thyroid) (Beyond the Basics)" and "Patient education: Antithyroid drugs (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

Confirm the etiology of hyperthyroidism – The treatment of hyperthyroidism differs according to the etiology. Therefore, the correct diagnosis of toxic adenoma or toxic multinodular goiter (MNG) must be made before therapy is instituted. (See 'Confirm the etiology of hyperthyroidism' above and "Diagnosis of hyperthyroidism", section on 'Determining the etiology'.)

Indications for treatment – All patients with overt hyperthyroidism due to toxic adenoma or MNG require treatment. The decision to treat when thyroid tests show subclinical hyperthyroidism is based upon the risk for developing complications from subclinical hyperthyroidism (skeletal, cardiovascular) and the degree of thyroid-stimulating hormone (TSH) suppression. (See 'Indications for treatment' above and "Subclinical hyperthyroidism in nonpregnant adults", section on 'Endogenous subclinical hyperthyroidism'.)

Treatment – The treatment of toxic adenoma and MNG consists of both symptomatic relief and decreasing the production of thyroid hormone.

Relieve symptoms – Assuming there are no contraindications to its use, we prescribe a beta blocker to patients with moderate-to-severe hyperadrenergic symptoms until euthyroidism is achieved by thionamides, radioiodine, or surgery. We typically start with atenolol 25 to 50 mg daily and increase the dose as needed (up to 200 mg daily) to reduce the pulse to less than 90 beats per minute (if blood pressure allows). (See 'Therapeutic approach' above and "Beta blockers in the treatment of hyperthyroidism".)

Decrease thyroid hormone production – For patients with toxic adenoma or MNG, treatment options include surgery, radioiodine, prolonged (probably lifelong) thionamide therapy, and ultrasound-guided procedures such as radiofrequency ablation (RFA) or ethanol ablation. Patients with symptoms or signs of compression/obstruction, a need for rapid return to euthyroidism, or coexisting thyroid cancer require surgery. In addition, for patients with very large goiters (>80 g), we suggest surgery (Grade 2C). In the absence of one of these indications for surgery, radioiodine, antithyroid drugs, or surgery are all options. (See 'Choice of therapy' above.)

The individual patient's fears regarding radiation exposure, general anesthesia, or surgical or procedural complications often influence the decision, and patients who prefer to avoid both radioiodine and surgery may choose prolonged thionamide as long as it is tolerated and the hyperthyroidism is controlled. Percutaneous ethanol injection, RFA, or laser therapy, where available, are alternatives to prolonged thionamide therapy. (See 'Decrease thyroid hormone synthesis' above and 'Choice of therapy' above.)

Pretreatment before radioiodine or surgery – Patients with overt hyperthyroidism of any cause who are to undergo surgery should be treated with an antithyroid drug (ie, methimazole or carbimazole) until they are euthyroid. Patients with significant symptoms of hyperthyroidism, older patients, or those with underlying cardiac disease are usually pretreated with a thionamide before radioiodine administration. (See 'Pretreatment before radioiodine or surgery' above and "Surgical management of hyperthyroidism", section on 'Preoperative preparation' and "Radioiodine in the treatment of hyperthyroidism", section on 'Pretreatment with methimazole'.)

Monitoring after treatment

Radioiodine – After radioiodine treatment, patients require monitoring for hypothyroidism or persistent or recurrent hyperthyroidism. Thyroid tests (TSH, free thyroxine [T4], total triiodothyronine [T3]) should be measured six to eight weeks after treatment and then at four- to eight-week intervals thereafter, depending upon the results of prior testing and change in thyroid size. (See 'Radioiodine' above.)

Surgery – For patients with MNG who had near-total or total thyroidectomy, thyroid hormone replacement (T4 [levothyroxine]) should be initiated at a dose of approximately 1.6 mcg/kg body weight daily. Older patients and those with coronary disease or multiple coronary risk factors should be treated with slightly less than full replacement dose (eg, 80 percent of the calculated full replacement dose). Serum TSH should be measured in six to eight weeks and the dose increased by 12 to 25 mcg/day if the TSH remains above the normal reference range. (See 'Surgery' above.)

Persistent or recurrent hyperthyroidism – For patients with persistent (beyond six months after initial treatment) or recurrent hyperthyroidism after radioiodine or surgery, we suggest retreatment/treatment with radioiodine (Grade 2C). We prefer to avoid a second surgery in patients with inadequate initial surgery, due to an increased risk of surgical complications (hypoparathyroidism, recurrent laryngeal nerve damage). However, for patients who have persistent or recurrent hyperthyroidism after radioiodine, surgery is an alternative option. (See 'Persistent or recurrent disease' above.)

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Topic 7873 Version 24.0

References

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