Nonthyroid surgery in the patient with thyroid disease

INTRODUCTION — Thyroid disease is common; the prevalence is higher in women and with increasing age. Thus, a significant number of patients who are undergoing surgery may have concomitant thyroid disease. Although most patients with well-compensated thyroid disease do not need special consideration prior to surgery, patients who have a newly diagnosed thyroid disorder around the time of surgery require a discussion of the risks and benefits of proceeding with surgery.

The issues surrounding thyroid disease in patients undergoing nonthyroid surgery are discussed here. The management of patients with hyperthyroidism undergoing thyroid surgery is reviewed separately. (See "Surgical management of hyperthyroidism", section on 'Preoperative preparation'.)

IS PREOPERATIVE MEASUREMENT OF TSH NECESSARY? — Despite the relatively high prevalence of thyroid disease in the general population, we believe there is no need to screen for thyroid disease during the preoperative medical consultation. (See "Preoperative medical evaluation of the healthy adult patient".)

However, if the history and physical examination are suggestive of thyroid disease, it is reasonable to try to make the diagnosis since it can have effects upon perioperative management. (See "Diagnosis of hyperthyroidism" and "Diagnosis of and screening for hypothyroidism in nonpregnant adults".)

For patients with known thyroid disease taking thyroid medication, monitoring of thyroid function on at least an annual basis is part of routine care. Adjustments in dosing are made as needed to maintain euthyroidism. In these patients with well-compensated thyroid disease, we and others believe that additional testing prior to surgery is unnecessary, as long as the patient is on a stable dose of medication and euthyroidism was documented within the past three to six months. (See "Treatment of primary hypothyroidism in adults", section on 'Dose and monitoring' and "Thionamides in the treatment of Graves' disease", section on 'Monitoring'.)

HYPOTHYROIDISM

Clinical manifestations that may impact perioperative outcome — Hypothyroidism affects many bodily systems that might influence perioperative outcome [1] (see "Clinical manifestations of hypothyroidism"):

●The systemic hypometabolism that is associated with hypothyroidism results in a decrease in cardiac output that is mediated by reductions in heart rate and contractility. (See "Cardiovascular effects of hypothyroidism".)

●Hypoventilation occurs because of respiratory muscle weakness and reduced pulmonary responses to hypoxia and hypercapnia. (See "Respiratory function in thyroid disease", section on 'Hypothyroidism'.)

●Decreased gut motility results in constipation and ileus.

●A variety of metabolic abnormalities can occur in hypothyroidism, including hyponatremia due to a reduction in free water clearance, reversible increases in serum creatinine, and reduced clearance of some drugs (eg, antiepileptics, anticoagulants, hypnotics, and opioids). Reduced clearance of vitamin K-dependent clotting factors, however, results in higher warfarin requirements during hypothyroidism and falling requirements during treatment with thyroid hormone.

●Patients with hypothyroidism have a decrease in red blood cell mass and a normochromic, normocytic anemia.

Defining the severity of hypothyroidism — Surgical outcomes vary with the degree of underlying hypothyroidism (see 'Surgical outcomes' below). In addition, one approach to management is to base therapeutic decisions on the severity of hypothyroidism (see 'Management' below). However, the definitions of mild, moderate, and severe hypothyroidism can be vague, and definitions may differ between experts or studies. We find the following definitions useful:

●Severe hypothyroidism – Includes patients with myxedema coma; with severe clinical symptoms of chronic hypothyroidism such as altered mentation, pericardial effusion, or heart failure; or those with very low levels of total thyroxine (T4) (eg, less than 1.0 mcg/dL) or free T4 (eg, less than 0.5 ng/dL) [2,3].

●Moderate hypothyroidism – Includes all other patients with overt hypothyroidism (elevated thyroid-stimulating hormone [TSH], low free T4) without the features of severe hypothyroidism.

●Mild hypothyroidism – Includes patients with subclinical hypothyroidism, defined biochemically as a normal serum free T4 concentration in the presence of an elevated serum TSH concentration.

Surgical outcomes — Observational studies evaluating surgical outcomes in patients with subclinical or overt hypothyroidism generally show few adverse effects in patients with mild (subclinical) or moderate hypothyroidism, but adverse outcomes increase with the severity of hypothyroidism.

●Mild (subclinical) hypothyroidism – There are few data on surgical outcomes in subclinical hypothyroid patients. In a prospective study comparing postoperative outcomes (after coronary artery bypass grafting [CABG]) in patients with known preoperative subclinical hypothyroidism (elevated TSH with normal free T4) and euthyroid patients, there were no significant differences in major adverse cardiovascular events or other outcomes (wound problems, mediastinitis, leg infection, respiratory complications) [4]. Similar results were reported in a study of outcomes after percutaneous transluminal coronary angioplasty [5].

However, a Chinese study of 548 patients with subclinical hypothyroidism compared with euthyroid controls found slight, statistically significant increases in impaired wound healing (3.7 versus 1.1 percent) and duration of inotropic support (4 versus 3 days) following coronary bypass surgery [6].

Another Chinese study of 123 patients with subclinical hypothyroidism and TSH >10 mIU/L found an increased incidence of postoperative infection following knee arthroplasty [7].

●Moderate overt hypothyroidism – Several studies have investigated the safety of general anesthesia and surgery in patients with untreated or inadequately treated hypothyroidism [2,8-13]. Surprisingly few adverse effects were reported, although the hypothyroid patients had a higher frequency of peri- and postoperative ileus, hypotension, hyponatremia, impaired wound healing, prolonged mechanical ventilation or reintubation, prolonged inotropic support, and central nervous system dysfunction than did the euthyroid patients. They also had less fever during serious infections and increased sensitivity to anesthesia and opiate pain medications.

As examples:

•One study investigated anesthetic and surgical outcomes in 59 hypothyroid patients and 59 paired euthyroid controls [2]. There were no differences between the groups in duration of surgery or anesthesia, lowest temperature and blood pressure recorded during surgery, need for vasopressors, time to extubation, fluid and electrolyte imbalances, incidence of arrhythmias, pulmonary and myocardial infarction, sepsis, need for postoperative respiratory assistance, bleeding complications, or time to hospital discharge.

•Another study investigated perioperative complications in 40 patients with mild to moderate hypothyroidism compared with 80 matched controls [8]. The hypothyroid patients had more intraoperative hypotension in noncardiac surgery and more heart failure in cardiac surgery. They also had more postoperative gastrointestinal and neuropsychiatric complications and were less likely to mount a fever with infection. However, in this study, there were no differences in perioperative blood loss; duration of hospitalization; or the prevalences of perioperative arrhythmia, hypothermia, hyponatremia, delayed anesthetic recovery, abnormal tissue integrity, impaired wound healing, pulmonary complications, or death.

•Retrospective and prospective studies of cardiac patients found no adverse outcomes in cardiac patients with mild to moderate hypothyroidism who had cardiac surgery or catheterization without thyroid replacement [9,13].

•In a Chinese study, 189 patients with known hypothyroidism and thyroid function tests consistent with overt hypothyroidism within two weeks of coronary artery surgery were compared with euthyroid controls [6]. Hypothyroidism was associated with impaired wound healing (11.8 versus 0.9 percent), increased mechanical ventilation (17 versus 15 hours) and reintubation (2.1 versus 0.4 percent), longer inotropic support (4 versus 3 days), and longer postoperative stay (4 versus 3 days).

●Severe hypothyroidism – Older case studies in the anesthesia literature reported intraoperative hypotension, cardiovascular collapse, and extreme sensitivity to opioids, sedatives, and anesthesia in undiagnosed patients with more severe hypothyroidism, including myxedema [14,15]. In some case reports, myxedema coma is described as a rare postoperative complication in patients with unrecognized severe hypothyroidism [16-19]. This represents a medical emergency with a high mortality rate. The hallmarks of myxedema coma are decreased mental status and hypothermia, but hypotension, bradycardia, hyponatremia, hypoglycemia, and hypoventilation are often present as well. (See "Myxedema coma".)

Management — In the absence of clinical trial data, the management of patients with recently diagnosed hypothyroidism who require surgery is based upon observational data and clinical experience. We base therapeutic decisions on the severity of hypothyroidism.

Subclinical hypothyroidism — We suggest not postponing surgery in patients with subclinical hypothyroidism (elevated serum TSH, normal free T4). This suggestion is based upon the studies in patients undergoing CABG and percutaneous transluminal coronary angioplasty (PTCA) described above [4,5]. (See 'Surgical outcomes' above.)

The degree of thyroid test abnormality that warrants treatment with levothyroxine is controversial. Selecting individuals for treatment of subclinical hypothyroidism is reviewed separately. (See "Subclinical hypothyroidism in nonpregnant adults", section on 'Management'.)

Moderate (overt) hypothyroidism — Our approach in patients with moderate hypothyroidism is based upon whether the surgery is urgent or elective and, in addition, upon the retrospective studies cited above [2,8]. (See 'Surgical outcomes' above.)

●Elective surgery – We suggest postponing elective surgery until the euthyroid state is restored.

●Urgent surgery – We suggest that patients with moderate, overt hypothyroidism undergo urgent surgery without delay, with the knowledge that minor perioperative complications might develop.

When a diagnosis of moderate hypothyroidism is made preoperatively, thyroid hormone replacement should be initiated as soon as the diagnosis is made. Generally, young patients are started on close to full replacement doses of levothyroxine (T4) (1.6 mcg/kg daily), while older patients or patients with cardiopulmonary disease are started on 25 to 50 mcg daily with an increase in dose every two to six weeks. (See "Treatment of primary hypothyroidism in adults", section on 'Initial dose'.)

Severe hypothyroidism — There is a lack of outcome data to direct the care of severely hypothyroid patients in the perioperative period. These patients should be considered high risk.

●Elective surgery – Elective surgery should be delayed until hypothyroidism has been treated.

●Urgent surgery – If emergency surgery must be performed in a patient with severe hypothyroidism, the patient should be treated as soon as the diagnosis is made. If there is concern about existing or precipitating myxedema coma (table 1), we prefer to treat patients with both triiodothyronine (T3) and T4 to rapidly normalize thyroid function (see "Myxedema coma"):

•T4 is given in a loading dose of 200 to 300 mcg intravenously followed by 50 mcg daily.

•T3 is given simultaneously in a dose of 5 to 20 mcg intravenously followed by 2.5 to 10 mcg every eight hours depending upon the patient's age and coexistent cardiac risk factors.

Use of an arterial line and Swan-Ganz catheter should be considered if cardiopulmonary disease exists.

•Consider adrenal insufficiency – Rarely, Addison disease will be present in a patient with primary hypothyroidism due to Hashimoto's thyroiditis. In addition, patients with central (secondary) hypothyroidism may have inadequate pituitary adrenal reserve as euthyroidism is restored. If the status of the pituitary adrenal axis is uncertain and deficiency is considered likely, patients should be given stress doses of corticosteroids until the integrity of the axis is ascertained. If the clinical situation permits (ie, surgery can be delayed for an hour), a cosyntropin stimulation test should be performed prior to administering steroids. If the results of the cosyntropin test are normal, stress steroids are not needed and can be discontinued if already given. (See "Diagnosis of adrenal insufficiency in adults", section on 'ACTH stimulation tests' and "Determining the etiology of adrenal insufficiency in adults", section on 'Establish the level of defect'.)

•Postoperative concerns – In the postoperative period, the patient's fluid and electrolyte status, especially the serum sodium, will need to be followed closely. In addition, a high index of suspicion for the development of an ileus, neuropsychiatric symptoms, and an infectious process without the presence of a fever is required.

Cardiovascular surgery — Patients with hypothyroidism who are scheduled to undergo cardiovascular interventions or surgery require special consideration. The risk of precipitating or worsening unstable coronary syndromes with thyroid hormones conflicts with the concern that untreated hypothyroidism might worsen heart failure or hypotension in the cardiac surgical patient [9,13]. (See 'Surgical outcomes' above.)

Angina is not an absolute contraindication to thyroid hormone replacement if the patient has symptomatic hypothyroidism. In patients with angina treated medically, the dose of T4 should begin with 25 micrograms/day and is increased 25 micrograms every two to six weeks, depending upon response. Most patients with angina have coronary artery revascularization first, and T4 is prescribed afterwards [1]. In most patients, angina has resolved after revascularization and before T4 has been prescribed, allowing the safe initial administration of a T4 dose that is approximately 50 to 75 percent of the full replacement dose based on body weight and adjusted four to six weeks later. (See "Treatment of primary hypothyroidism in adults", section on 'Older patients or those with coronary heart disease'.)

Preexisting hypothyroidism — Patients with a history of hypothyroidism receiving chronic T4 therapy who undergo surgery and are unable to eat for several days do not need to be given T4 parenterally. If oral intake cannot be resumed in five to seven days, then T4 should be given intravenously or intramuscularly. The dose should be approximately 70 to 80 percent of the patient's usual oral dose because that is approximately the fraction of oral T4 that is absorbed. We typically give 80 percent. (See "Treatment of primary hypothyroidism in adults", section on 'Surgical patients'.)

SUSPECTED HYPOTHYROIDISM IN HOSPITALIZED/SERIOUSLY ILL PATIENTS — Assessment of thyroid function in hospitalized or seriously ill patients can be difficult. Patients who are seriously ill often have abnormal thyroid function tests that may or may not be clinically significant [20]. These patients need to be distinguished from those who have clinically significant thyroid dysfunction. In general, thyroid function should not be assessed in seriously ill patients unless there is a strong suspicion of thyroid dysfunction. When thyroid dysfunction is suspected in critically ill patients, measurement of serum TSH alone is not appropriate for the evaluation of thyroid function. Instead, measurement of TSH, total T4, free T4, T3, and sometimes reverse T3 is necessary. (See "Thyroid function in nonthyroidal illness".)

The changes in thyroid function during critical illness include the following (figure 1):

●The majority of hospitalized patients have a low serum T3 concentration. Abnormalities in the T3 concentration have been noted in patients undergoing elective or emergency surgery, independent of the type of anesthesia.

●From 15 to 20 percent of hospitalized patients and up to 50 percent of patients in intensive care units have low serum T4 concentrations (low T4 syndrome).

●The serum TSH concentration may also be low.

Previously, these patients were thought to be euthyroid, and the term "euthyroid sick syndrome" was used to describe the laboratory abnormalities. The term "nonthyroidal illness" is now preferred since experimental data suggest that these patients develop acquired transient central hypothyroidism [21]. However, these changes may be adaptive rather than pathological in nature, and there is no evidence of benefit and some risk of harm by giving thyroid hormone to patients with nonthyroidal illness who have low serum T4 or T3 concentrations.

●Distinguishing nonthyroidal illness from primary hypothyroidism – In most critically ill patients with moderate or severe primary hypothyroidism, serum TSH will be well above the normal range (>20 mU/L) in association with a low free T4, and further management is as described above. (See 'Moderate (overt) hypothyroidism' above and 'Severe hypothyroidism' above.)

●Distinguishing nonthyroidal illness and central hypothyroidism – Patients with severe nonthyroidal illness may have transient adaptive central hypothyroidism, and in these patients, it may be difficult to distinguish nonthyroidal illness from true central hypothyroidism, particularly in patients with a history of hypothalamic or pituitary disease.

•Elective surgery – In this setting, nonurgent surgeries should be postponed, and clinical status and thyroid function tests (TSH, free T4) should be monitored every four to six weeks. In patients with transient central hypothyroidism due to nonthyroidal illness, thyroid tests should return to normal, whereas the thyroid test abnormalities will persist in patients with true central hypothyroidism. (See "Central hypothyroidism".)

•Urgent surgery – If the diagnosis of hypothyroidism is in doubt in a critically ill patient (because of the difficulty assessing thyroid function in this population) and surgery cannot be postponed, we treat with thyroid hormone replacement in the pre- and perioperative periods if there is clinical evidence to suggest a diagnosis of moderate to severe hypothyroidism (eg, bradycardia and hypothermia along with slow mentation, puffy face, a possible personal or strong family history of thyroid disease, or personal history of hypothalamic or pituitary disease or cranial irradiation).

In the absence of suspected myxedema coma, repletion should be cautious, beginning with approximately half the expected full replacement dose of T4 (0.8 mcg/kg for young patients and 25 to 50 mcg daily for older patients or patients with cardiopulmonary disease). We measure TSH and free T4 after four to six weeks, and further treatment decisions are based upon the results. In a patient with suspected central hypothyroidism, biochemical assessment of the pituitary adrenal axis should be performed, as described above. (See 'Severe hypothyroidism' above.)

HYPERTHYROIDISM

Clinical manifestations that may impact perioperative outcome — As with hypothyroidism, hyperthyroidism affects many bodily systems that might influence perioperative outcome (see "Overview of the clinical manifestations of hyperthyroidism in adults"):

●Patients with hyperthyroidism have an increase in cardiac output, due both to increased peripheral oxygen needs and increased cardiac contractility. Heart rate is increased, pulse pressure is widened, and peripheral vascular resistance is decreased. (See "Cardiovascular effects of hyperthyroidism".)

●Atrial fibrillation occurs in approximately 8 percent of patients with hyperthyroidism and is more common in older patients [22].

●Even subclinical hyperthyroidism is associated with increased rates of atrial ectopy and a threefold increased risk of atrial fibrillation. (See "Subclinical hyperthyroidism in nonpregnant adults", section on 'Atrial fibrillation'.)

●Dyspnea may occur for a variety of reasons, including increased oxygen consumption and carbon dioxide production, respiratory weakness, and decreased lung volume. (See "Respiratory function in thyroid disease", section on 'Hyperthyroidism'.)

●Weight loss is due primarily to increased calorigenesis and secondarily to increased gut motility and the associated hyperdefecation and malabsorption; these changes can cause the patient to be malnourished.

Management — Our recommendations for the management of nonthyroid surgery in hyperthyroid patients are based on studies of patients undergoing thyroidectomy, who are likely at higher risk for complications due to perioperative manipulation of the thyroid gland. We also base our management decisions on the severity of the hyperthyroidism.

●Subclinical hyperthyroidism is defined as a low TSH with normal free T4 and T3

●Overt hyperthyroidism is defined as a suppressed TSH with elevated free T4 and/or T3 concentrations

There are insufficient data to evaluate the risks of nonthyroid surgery in hyperthyroid patients, especially the risk of thyroid storm. A systemic literature review found 26 studies of patients having surgery while hyperthyroid, but only one study included patients undergoing nonthyroid surgery [23].  

Subclinical hyperthyroidism — In our experience, patients with subclinical hyperthyroidism can typically proceed with elective or urgent surgeries. Unless contraindicated, we typically administer a beta blocker (eg, atenolol 25 to 50 mg daily) preoperatively to older patients (>50 years), or younger patients with cardiovascular disease, especially atrial arrhythmias, and taper after recovery. (See "Beta blockers in the treatment of hyperthyroidism" and "Subclinical hyperthyroidism in nonpregnant adults", section on 'Management'.)

Overt hyperthyroidism — In patients with untreated or poorly controlled hyperthyroidism, an acute event such as surgery can precipitate thyroid storm, a potentially life-threatening condition. (See 'Thyroid storm' below.)

●Elective surgery – We suggest postponing all elective surgeries in patients with newly discovered, overt hyperthyroidism until the patient has achieved adequate control of their thyroid condition (normal free T4 and T3), which usually takes three to eight weeks.

●Urgent surgery – For overtly hyperthyroid patients in whom surgery cannot be postponed, preoperative treatment of hyperthyroidism should be initiated as soon as possible. (See 'Preoperative preparation for urgent surgery' below.)

In addition, the hyperthyroid patient requiring urgent surgery should be evaluated for possible cardiopulmonary disease, and the patient should be monitored for the possible development of arrhythmias, cardiac ischemia, and congestive heart failure [24]. Use of an arterial line and pulmonary artery catheter should be considered if cardiopulmonary disease exists. In the postoperative period, hyperthyroid patients are at increased risk of prolonged intubation due to increased basal oxygen consumption and respiratory muscle weakness.

Preoperative preparation for urgent surgery — Preoperative preparation typically includes beta blockers and, in patients with Graves' disease or toxic adenoma/multinodular goiter, thionamides. While thionamides alone are sufficient to achieve euthyroidism in approximately three to eight weeks, we suggest adding iodine (potassium iodide solution, SSKI, one to five drops three times daily) at least one hour after thionamides are administered, if hyperthyroidism is severe and the need for surgery is urgent [25]. Iodine will safely lower thyroid hormone concentrations in Graves' disease, but it should be used cautiously and only when hyperthyroidism is severe in patients with toxic adenoma/multinodular goiter since iodine can exacerbate hyperthyroidism in those patients unless iodine organification has been fully blocked by pretreatment with a thionamide.

Beta blockers — In the absence of contraindications, we administer a beta blocker preoperatively to patients with overt hyperthyroidism undergoing urgent nonthyroid surgery. The longer-acting beta blockers (eg, atenolol) are preferred in patients who are candidates for therapy because an oral dose taken one hour before surgery will usually maintain adequate beta blockade until the patient is able to take oral medications postoperatively [26].

●We typically start with atenolol 25 to 50 mg daily and increase the dose as needed to maintain the pulse rate below 80 beats/minute; up to 200 mg daily may be needed for the symptomatic treatment of hyperthyroidism and control of tachycardia.

●Intravenous propranolol (0.5 to 1 mg over 10 minutes followed by 1 to 2 mg over 10 minutes every few hours) can be used to control fever, hypertension, and tachycardia intraoperatively [27,28].

●Beta blockers should be continued until the patient's thyroid disease is under control.

Patients with relative contraindications to beta blockade may better tolerate beta-1-selective agents, such as atenolol or metoprolol, although even these drugs cannot be considered completely safe in patients with asthma or chronic obstructive pulmonary disease. (See "Treatment of hypertension in asthma and COPD", section on 'Beta blockers'.)

Calcium channel blockers can also be used for rate control in patients in whom beta blockers are contraindicated.

There are few data on the benefits of beta blocker administration to hyperthyroid patients undergoing nonthyroid surgery [29,30]. In hyperthyroid patients undergoing thyroid surgery, beta blockers administered preoperatively effectively control the clinical manifestations of hyperthyroidism and can be used for preoperative preparation of the hyperthyroid patient who cannot take thionamides or who needs urgent surgery, and there is insufficient time to render the patient euthyroid with thionamides [31-33]. As an example, in a randomized trial of methimazole versus metoprolol in 30 patients with newly diagnosed and untreated hyperthyroidism undergoing thyroid surgery, there was no difference in anesthesiologic or cardiovascular complications during surgery or in complications postsurgery [31]. The results of this trial suggest that serious perioperative complications are low in patients undergoing thyroid surgery who are treated preoperatively with beta blockers. However, case reports have documented the development of thyroid storm after surgery even when beta blockers have been used [34]. (See "Beta blockers in the treatment of hyperthyroidism".)

Thionamides — If hyperthyroidism is due to Graves' disease, toxic adenoma, or multinodular goiter, thionamides should be initiated with the aim of controlling hyperthyroidism in the postoperative period. Thionamides block de novo thyroid hormone synthesis but have no effect upon the release of preformed hormone from the thyroid gland and will therefore not have a significant effect on thyroid hormone levels over only a few preoperative days.

●Methimazole is usually preferred to propylthiouracil, except during the first trimester of pregnancy, because of its longer duration of action (allowing for single-daily dosing) and a lesser degree of toxicity. Dosing depends on the degree of hyperthyroidism (biochemical and clinical) and goiter size. (See "Thionamides in the treatment of Graves' disease", section on 'Initiation of therapy'.)

●Propylthiouracil (100 to 150 mg every six to eight hours) is preferred by some clinicians for the initial treatment of thyroid storm since it reduces T4-to-T3 conversion. (See "Thyroid storm", section on 'Thionamides'.)

●Patients who cannot take oral medications postoperatively will need rectal administration of thionamides, which should be ordered well in advance from the pharmacy (table 2).

The clinical use of thionamides, including dosing, monitoring, and adverse effects is reviewed separately. (See "Thionamides in the treatment of Graves' disease" and "Thionamides: Side effects and toxicities".)

Iodine — If hyperthyroidism is severe and the need for surgery is urgent, we also add potassium iodide solution (SSKI, one to five drops three times daily) one hour after thionamides.

Extreme caution is necessary before administering SSKI to a patient with known or suspected toxic adenoma/multinodular goiter since iodine, in the absence of a thionamide to block organification, may exacerbate the hyperthyroidism. Thionamide therapy should therefore be started first and continued without interruption, preferably in divided dosing. If the patient is unable to continue oral thionamides and has been loaded with iodine, hyperthyroidism may worsen. Thus, SSKI should not be used at all in a patient with toxic adenoma/multinodular goiter if the patient will be unable to continue oral or rectal thionamides. In patients with Graves' disease, however, exogenous iodine is unlikely to exacerbate hyperthyroidism by acting as substrate and therefore can be used in combination with thionamides and beta blockers, or, in patients with thionamide intolerance, with beta blockers alone. (See 'Intolerance to thionamides' below.)

Iodine blocks release of T4 and T3 from the gland and thereby shortens the time to achieving a euthyroid state. This effect, however, may be transient, and the use of iodine to block release of hormone beyond 10 days is not generally recommended; it can be started 10 days preoperatively for urgent procedures that are scheduled more than 10 days in the future but which cannot be delayed until the patient is chemically euthyroid following a thionamide.

Iopanoic acid (which is also rich in iodine) blocks both release of T4 and T3 from the gland and T4-to-T3 conversion but is not currently available in much of the world. Where available, iopanoic acid 500 mg daily added to a thionamide will reduce thyroid hormone levels more rapidly than other regimens. If iopanoic acid is available, the benefit of propylthiouracil over methimazole is moot (iopanoic acid is a more potent inhibitor of T4-to-T3 conversion), and methimazole should be used because of its longer duration of action. (See "Iodine in the treatment of hyperthyroidism" and "Iodinated radiocontrast agents in the treatment of hyperthyroidism".)

Intolerance to thionamides — Adverse effects of thionamides include common, minor side effects (eg, rash) and rare but serious adverse effects, such as agranulocytosis and hepatotoxicity. Although thionamide toxicity is uncommon, some patients are unable to continue thionamides because of side effects or because of allergy. (See "Thionamides: Side effects and toxicities".)

●Toxic adenoma/multinodular goiter – Patients with toxic adenoma/multinodular goiter who are intolerant or unable to take thionamides should be pretreated with beta blockers alone.

●Graves' disease – Patients with Graves' hyperthyroidism who are allergic to or are intolerant of thionamides can be treated with the combination of beta blockers and iodine.

●Severe hyperthyroidism – Patients with severe hyperthyroidism who are allergic to or unable to tolerate thionamides can treated with beta blockers, glucocorticoids (to inhibit conversion of T4 to T3), bile acid sequestrants (to reduce enterohepatic circulation of thyroid hormone), and, in patients with Graves' disease, iodine. (See "Thyroid storm", section on 'Thionamides'.)

Rarely, urgent thyroidectomy may be required prior to nonthyroidal surgery. (See "Surgical management of hyperthyroidism", section on 'Preoperative preparation'.)

Preexisting hyperthyroidism — Patients who are taking a thionamide preoperatively (whether chronic or recently started), who will not be able to take oral medications for longer than a day or two postoperatively, can be treated with rectal preparations. Most hospital pharmacies should be able to crush methimazole tablets and make a rectal suppository (table 2); if possible, the pharmacy should be given advanced notice. However, for patients well controlled on long-term methimazole therapy (TSH is normal), there is usually a delay of at least 7 to 10 days before patients develop recurrent hyperthyroidism after omission of treatment. In patients who have been on long-term treatment for more than 6 to 12 months, recurrence after stopping treatment may take weeks or months, especially if thyroid-stimulating immunoglobulins is no longer elevated. The decision to use rectal methimazole postoperatively, therefore, depends on the patient's clinical status and the availability of rectal preparations.

Thyroid storm — Patients with hyperthyroidism who are undergoing surgery are at risk for developing thyroid storm, a condition that usually occurs during surgery or in the first 18 hours after the procedure. The mortality rate for patients with thyroid storm can be as high as 40 percent (table 3). In a systemic review, the risk varied from 0 to 14 percent after thyroidectomy [23]. The clinical manifestations, diagnosis, and treatment of thyroid storm are discussed in more detail separately. (See "Thyroid storm".)

SUMMARY AND RECOMMENDATIONS

●Preoperative measurement of thyroid-stimulating hormone (TSH) – Despite the relatively high prevalence of thyroid disease in the general population, we believe there is no need to screen for thyroid disease during the preoperative medical consultation. However, if the history and physical examination are suggestive of thyroid disease, it is reasonable to try to make the diagnosis since it can have effects upon perioperative management. (See 'Is preoperative measurement of TSH necessary?' above and "Preoperative medical evaluation of the healthy adult patient".)

●Approach to the patient with hypothyroidism undergoing nonthyroid surgery

•Subclinical hypothyroidism – For patients with subclinical hypothyroidism (elevated serum TSH, normal free thyroxine [T4]), we suggest not postponing surgery (Grade 2C). Such patients can proceed with either urgent or elective surgeries. (See 'Subclinical hypothyroidism' above.)

•Moderate hypothyroidism – For patients with moderate (overt) hypothyroidism who require urgent surgery, we suggest not postponing surgery (Grade 2C), with the knowledge that minor perioperative complications might develop. Such patients should be treated with thyroid hormone as soon as the diagnosis is made. Generally, young patients are started on close to full replacement doses of T4 (1.6 mcg/kg), while older patients or patients with cardiopulmonary disease are started on 25 to 50 mcg daily with an increase in dose every two to six weeks. (See 'Moderate (overt) hypothyroidism' above.)

On the other hand, when moderate hypothyroidism is discovered in a patient being evaluated for elective surgery, we suggest postponing surgery until the euthyroid state is restored (Grade 2C). (See 'Management' above.)

•Severe hypothyroidism – In patients with severe hypothyroidism (myxedema coma; severe clinical symptoms of chronic hypothyroidism such as altered mentation, pericardial effusion, or heart failure; or very low levels of total T4 [eg, less than 1.0 mcg/dL] or free T4 [eg, less than 0.5 ng/dL]), surgery should be delayed until hypothyroidism has been treated. If emergency surgery is required, the severely hypothyroid patient should be treated as soon as the diagnosis is made. If emergency surgery must be performed in a patient with myxedema coma, we suggest treatment with both triiodothyronine (T3) and T4, rather than T4 alone (Grade 2C). (See 'Severe hypothyroidism' above and "Myxedema coma", section on 'Treatment'.)

Patients with autoimmune-mediated primary hypothyroidism may have concomitant primary adrenal insufficiency. In addition, patients with central hypothyroidism may have associated hypopituitarism and secondary adrenal insufficiency. If the status of the pituitary adrenal axis is uncertain and deficiency is considered likely in a patient with severe hypothyroidism requiring emergency surgery, patients should be given stress doses of steroid until the integrity of the axis is ascertained. If the clinical situation permits, a cosyntropin stimulation test should be performed prior to administering steroids. (See 'Severe hypothyroidism' above and "Myxedema coma", section on 'Treatment'.)

●Approach to the hospitalized or critically ill patient with suspected hypothyroidism – If the diagnosis of hypothyroidism is in doubt in a critically ill patient (because of the difficulty assessing thyroid function in this population) and surgery cannot be postponed, we treat with thyroid hormone replacement in the pre- and perioperative periods if there is clinical evidence to suggest a diagnosis of moderate to severe hypothyroidism (eg, bradycardia and hypothermia along with slow mentation, puffy face, a possible personal or strong family history of thyroid disease, or personal history of hypothalamic or pituitary disease or cranial irradiation). In the absence of suspected myxedema coma, repletion should be cautious, beginning with approximately half the expected full replacement dose of T4 (0.8 mcg/kg for young patients and 25 to 50 mcg daily for older patients or patients with cardiopulmonary disease). (See 'Suspected hypothyroidism in hospitalized/seriously ill patients' above.)

●Approach to the patient with hyperthyroidism undergoing nonthyroid surgery

•Subclinical hyperthyroidism – In our experience, patients with subclinical hyperthyroidism (low TSH, normal free T4 and T3) can typically proceed with elective or urgent surgeries. Unless contraindicated, we administer a beta blocker preoperatively to older patients (>50 years), or younger patients with cardiovascular disease, and taper after recovery. (See 'Subclinical hyperthyroidism' above.)

•Overt hyperthyroidism

-Elective surgery – In patients with untreated or poorly controlled overt hyperthyroidism, an acute event such as surgery can precipitate thyroid storm, a potentially life-threatening condition. Thus, we suggest postponing surgery in patients with newly discovered overt hyperthyroidism until the patient has achieved adequate control of their thyroid condition (normal free T4 and T3), which usually takes three to eight weeks (Grade 2C). (See 'Overt hyperthyroidism' above and "Graves' hyperthyroidism in nonpregnant adults: Overview of treatment" and "Treatment of toxic adenoma and toxic multinodular goiter".)

-Urgent surgery – For overtly hyperthyroid patients in whom surgery cannot be postponed, preoperative treatment of hyperthyroidism should be initiated as soon as possible. (See 'Overt hyperthyroidism' above and 'Preoperative preparation for urgent surgery' above.)

●Preoperative preparation for urgent surgery

•Beta blockers – In the absence of contraindications, we recommend administering a beta blocker (Grade 1B), typically atenolol 25 to 50 mg daily with the dose increased as needed to maintain the pulse rate below 80 beats/minute. Beta blockers should be continued until the patient's thyroid disease is under control. Intravenous propranolol (0.5 to 1 mg over 10 minutes followed by 1 to 2 mg over 10 minutes every few hours) can be used to control fever, hypertension, and tachycardia intraoperatively. (See 'Beta blockers' above.)

•Thionamides – In addition, once the diagnosis of hyperthyroidism due to Graves' disease or toxic adenoma/multinodular goiter is established, we suggest starting a thionamide (Grade 2B), with the aim of controlling hyperthyroidism in the postoperative period. Methimazole (10 mg two to three times daily or 20 to 30 mg once daily) is usually preferred to propylthiouracil, except during the first trimester of pregnancy, because of its longer duration of action (allowing for single daily dosing) and a lesser degree of toxicity. (See 'Thionamides' above.)

•Potassium iodide for severe hyperthyroidism – If hyperthyroidism is severe and the need for surgery is urgent, we suggest adding potassium iodide solution (Grade 2B) (SSKI, one to five drops three times daily) one hour after thionamides. Iodide must always be used cautiously. Iodide will not exacerbate hyperthyroidism due to Graves' disease in iodine-replete areas, but iodide may worsen hyperthyroidism in patients with toxic adenoma or toxic multinodular goiter if thionamides are not given continuously and, preferably, in divided doses. For patients who are unable to continue oral thionamides, thionamides can be prepared for rectal administration (table 2). (See 'Iodine' above.)

•Intolerance to thionamides – For patients with Graves' hyperthyroidism who are allergic to or are intolerant of thionamides, the combination of beta blockers and iodine can be used for preoperative preparation; corticosteroids and cholestyramine can be added if the hyperthyroidism is severe. Patients with toxic adenoma/multinodular goiter who are allergic to or are intolerant of thionamides should be treated with beta blockers alone, as iodine may worsen hyperthyroidism. (See 'Intolerance to thionamides' above.)