Synthroid Pre-Surgery Hold Window: What Patients and Clinicians Need to Know

Does levothyroxine need to be held before surgery?

The levothyroxine sodium tablet label describes how the drug is taken and what to watch for, and it sets no number of days to skip ahead of an operation [1]. Where it addresses holding, it points at cardiac symptoms rather than at procedures: if cardiac symptoms develop or worsen, reduce the dose or withhold for one week and restart at a lower dose [1].

The label also notes that the peak effect of a given dose may not be attained for 4 to 6 weeks [1].

What the tablet label says that touches on surgery

• In patients with coronary artery disease receiving suppressive levothyroxine therapy, the label says to monitor for cardiac arrhythmias during surgical procedures [1].
• In patients taking levothyroxine together with sympathomimetic agents, the label says to monitor for signs and symptoms of coronary insufficiency [1].
• The label says oral thyroid hormone products are not recommended to treat myxedema coma and directs use of a product formulated for intravenous administration instead [1].
• The label says patients with adrenal insufficiency should be treated with replacement glucocorticoids before levothyroxine is started, and lists uncorrected adrenal insufficiency as a contraindication [1].

The label describes levothyroxine sodium tablets as having a narrow therapeutic index, with negative effects on cardiovascular function, bone metabolism, growth and development, and glucose and lipid metabolism when the dose is too high or too low [1].

Going into surgery with untreated or undertreated hypothyroidism

Two older matched studies looked at hypothyroid patients having surgery, and they did not agree on everything.

A 1983 retrospective study compared 59 hypothyroid patients with 59 paired euthyroid matched controls. It found no differences in duration of surgery or anesthesia, lowest blood pressure and temperature during surgery, need for vasopressors, time to extubation, arrhythmias, myocardial infarction, sepsis, postoperative respiratory assistance, bleeding complications or time to hospital discharge. The authors concluded that among patients with mild or moderate hypothyroidism there was no evidence to justify deferring needed surgery until the hypothyroidism was corrected [3].

A 1984 retrospective study compared 40 hypothyroid surgical patients with 80 controls matched for age, sex and operative procedure. During noncardiac surgery, intraoperative hypotension occurred in 61% of hypothyroid patients versus 30% of controls (P<0.05); in cardiac surgery, heart failure occurred in 29% versus 6%; postoperative gastrointestinal complications in 19% versus 1%; neuropsychiatric complications in 38% versus 18%. Blood loss, duration of hospitalization, arrhythmia, delayed anesthetic recovery, wound healing and death did not differ. Preoperative clinical and chemical features of hypothyroidism did not identify a subgroup at special risk [4].

A 1982 review of anesthesia in hypothyroidism describes reduced myocardial function, decreased hypoxic and hypercapnic ventilatory responses and impaired hepatic drug metabolism, and states that elective procedures should not be undertaken in the presence of untreated hypothyroidism [5]. The review also notes that most reported complications occurred in patients whose hypothyroidism was unrecognized [5].

The empty-stomach instruction

The label says to take levothyroxine sodium tablets as a single daily dose on an empty stomach, one-half to one hour before breakfast, with a full glass of water to avoid choking or gagging. It also says to evaluate the need for dose adjustments when the drug is regularly taken within an hour of foods that affect absorption [1].

Drugs that change levothyroxine absorption

The label's absorption table lists these groups [1]:

• Phosphate binders, including calcium carbonate, ferrous sulfate, sevelamer and lanthanum, may bind levothyroxine; the label says to give the two at least 4 hours apart [1].
• Bile acid sequestrants (colesevelam, cholestyramine, colestipol) and ion exchange resins such as Kayexalate decrease absorption; the label says to give levothyroxine at least 4 hours before them or monitor TSH [1].
• Proton pump inhibitors, sucralfate and aluminum or magnesium hydroxide antacids may reduce absorption through low gastric acidity; the label gives no fixed hour spacing and says to monitor [1].

The calcium and iron effects have been measured. In a 2000 uncontrolled cohort study, 20 adults on stable levothyroxine took 1,200 mg per day of elemental calcium as calcium carbonate together with their dose for three months; mean free T4 fell from 17 to 15 pmol/L and TSH rose from 1.6 to 2.7 mIU/L, with 20% of patients ending above the normal TSH range [6]. In a 1992 uncontrolled trial, 14 patients took ferrous sulfate 300 mg with their thyroxine daily for 12 weeks; mean TSH rose from 1.6 to 5.4 mU/L (P<0.01) and 9 patients had more symptoms of hypothyroidism [7].

Other drugs that shift T4 levels or interact

Phenytoin and carbamazepine reduce serum protein binding of levothyroxine, and total and free T4 may fall by 20% to 40%, though the label notes most patients keep a normal TSH and remain clinically euthyroid [1].

The label says levothyroxine increases the response to oral anticoagulants, so a decrease in the anticoagulant dose may be warranted when hypothyroidism is corrected or the levothyroxine dose is increased [1]. In diabetes, it says to monitor glycemic control when levothyroxine is started, changed or discontinued [1].