689677

research-article2016
HIS0010.1177/1178632916689677Health Services InsightsPalace

Perioperative Management of Thyroid Dysfunction Health Services Insights

1–5
© The Author(s) 2017
Marcia Rashelle Palace1,2 Reprints and permissions:
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1Division
of Endocrinology, Bronx-Lebanon Hospital Center, Bronx, NY, USA. 2Department of DOI: 10.1177/1178632916689677
https://doi.org/10.1177/1178632916689677
Medicine, Mount Sinai School of Medicine, New York, NY, USA.

ABSTRACT: Due to the manifold effects of thyroid hormone across virtually all organ systems, the complications associated with thyroid
dysfunction are numerous and diverse. The stresses encountered during the perioperative period may exacerbate underlying thyroid disorders,
potentially precipitating decompensation and even death. Thus, it is of the utmost importance for the clinician to comprehend the mechanisms
by which thyroid disease may complicate surgery and postoperative recovery and to be cognizant of the most effective means of optimizing the
status of thyrotoxic and hypothyroid patients perioperatively. This article describes the adverse effects of thyroid dysfunction as they relate to the
patient undergoing both thyroid and nonthyroid surgery and recommends treatment approaches aimed at decreasing perioperative risk.

Keywords: perioperative management, hypothyroid, hyperthyroid, thyrotoxicosis

RECEIVED: August 29, 2016. ACCEPTED: December 19, 2016. Declaration of conflicting interests: The author(s) declared no potential
conflicts of interest with respect to the research, authorship, and/or publication of this
Peer Review: Five peer reviewers contributed to the peer review report. Reviewers’ article.
reports totaled 827 words, excluding any confidential comments to the academic editor.
CORRESPONDING AUTHOR: Marcia Rashelle Palace, Division of Endocrinology,
Type: Review Bronx-Lebanon Hospital Center, 1650 Grand Concourse, Bronx, NY 10457, USA.
Email: [email protected]
Funding: The author(s) received no financial support for the research, authorship, and/or
publication of this article.

Introduction
Patients with thyroid dysfunction are well represented in the adequacy of treatment and to ensure that thyroid therapy is
general population. Studies report the prevalence of abnormal optimized before surgery.
thyrotropin values to be as high as 21% in women and 3% in
men.1 Due to the myriad effects of thyroid hormone through- Complications of Hypothyroidism
out the body, the effects of thyroid dysfunction are manifold Thyroid hormones play a crucial role in homeostasis due to
and may complicate surgical procedures and postoperative their effects on the cardiovascular, respiratory, renal, gastroin-
recovery. Thus, although routine screening to detect thyroid testinal, hematologic, and central nervous systems. The cardio-
disease is not indicated in patients where there is no index of vascular concerns are among the most relevant in perioperative
suspicion for the same, the recognition, diagnosis, and optimi- situations. Patients with hypothyroidism are at increased risk of
zation of preexisting thyroid conditions in patients undergoing coronary events2 possibly due to increased cholesterol levels,3
surgery are important perioperative considerations. This article prolonged half-life of multiple coagulation factors,4 and ane-
will address the issues concerning the perioperative manage- mia.5 Nonspecific ST changes and low voltage on electrocar-
ment of thyroid disease in patients with hypothyroidism and diogram are observed and, less commonly, “torsade de pointes”
hyperthyroidism who are undergoing nonthyroid surgery, as ventricular tachycardia has been described.6
well as specific concerns related to the management of patients Hypothyroidism has been associated with a diminished car-
undergoing thyroid surgery for thyrotoxicosis. diac output of 30% to 50%, with both slowing of the pulse and
decreased contractility.7 Furthermore, deficiency of thyroid
Preoperative Screening hormones causes an increase in peripheral vascular resistance
Routine preoperative thyroid function testing is not recom- resulting in increased cardiac afterload, leading to a decreased
mended for patients with no history of thyroid dysfunction. In pulse pressure via an increase in diastolic pressure and a decrease
such patients, it would be appropriate to check the thyrotropin in systolic blood pressure.8 Even though catecholamine levels
(TSH) level if there is a reason to suspect thyroid disease based are increased in these patients, hypothyroid patients have a pre-
on symptoms such as unexplained weight changes, palpitations, disposition to develop hypotension under anesthesia, likely due
tremor or changes in bowel habits, skin, hair, or eyes that sug- to downregulation of β-adrenergic receptors.9
gest thyroid dysfunction. Furthermore, when the physical In addition to the cardiovascular concerns, hypothyroid
examination or other investigation confirms the presence of patients face additional challenges due to the ventilatory dys-
exophthalmos, goiter, abnormal reflexes, hair or skin abnor- function and renal manifestations associated with this condi-
malities, or tachycardia or bradycardia, a TSH test would be tion. Pleural effusions and respiratory muscle weakness, along
appropriately included in a preoperative evaluation. with impaired hypoxic and hypercapnic respiratory drive and
In patients with known hypothyroidism or hypothyroid- increased prevalence of obstructive sleep apnea, may compli-
ism who have been undergoing treatment, a TSH test should cate their perioperative management, as may a predisposition
be included in the preoperative assessment to determine the to pneumonia and atelectasis.8 Increased antidiuretic hormone

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2 Health Services Insights 

leads to hyponatremia.10 Increased capillary permeability and comparing surgical outcomes in hypothyroid versus euthyroid
resultant shifts of fluid into the extravascular space decrease patients.
intravascular volume and renal perfusion leading to decreased In a prospective study comparing postoperative outcomes in
clearance of medications.11 These pulmonary and renal factors patients with subclinical hypothyroidism, defined as elevated
contribute to the increased susceptibility of hypothyroid thyroid-stimulating hormone with normal free thyroxine, to
patients to anesthetics, tranquilizers, and narcotics.12,13 euthyroid patients undergoing coronary artery bypass grafting,
Decreased gastrointestinal motility, which is most com- no increase in major adverse cardiovascular events, wound
monly manifested as constipation in hypothyroid patients, problems, mediastinitis, leg infection, respiratory complica-
increases the tendency for postoperative ileus.14 This is of tions, delirium, or reoperation during the same hospitalization
increased concern considering that postoperative pain manage- was noted. However, there was an increase in the rate of post-
ment regimens commonly use opioids which independently operative atrial fibrillation in the subclinical hypothyroidism
promote constipation. group.18
Hypothyroidism is associated with several hematologic One retrospective study analyzed the outcome of anesthesia
effects. Most commonly described is a normochromic, normo- and surgery in 59 hypothyroid patients compared with 50
cytic anemia. However, because of the increased prevalence of euthyroid patients. There were no differences in duration of
pernicious anemia among patients with hypothyroidism, con- surgery or anesthesia, lowest temperature and blood pressure
comitant autoimmune-mediated vitamin B12 deficiency may recorded during surgery, need for vasopressors, time to extuba-
cause macrocytosis. Furthermore, in premenopausal women, tion, fluid and electrolyte imbalances, incidence of arrhythmias,
menorrhagia secondary to hypothyroidism results in micro- pulmonary or myocardial infarction, sepsis, need for postopera-
cytic anemia secondary to iron deficiency.8 Other hematologic tive respiratory assistance, bleeding complications, or time to
manifestations of hypothyroidism include a decrease in factor hospital discharge. Analysis of subsets of patients divided based
VIII activity, prolonged partial thromboplastin time,15 and on their thyroxine levels (thyroxine level < 1.0 µg/dL, 1.0 to
acquired von Willebrand disease.16 <3.0 µg/dL, and ⩾3.0 µg/dL) revealed no differences in out-
A rare, yet most dreaded complication of surgery in hypo- comes. Because there were only 7 patients in the group with the
thyroid patients is myxedema coma, a condition that has been lowest T4 concentration, the authors concluded that in mild to
associated with mortality as high as 80%.17 Myxedema coma is moderate hypothyroidism, there is no evidence to justify post-
characterized by altered mental status, which may manifest as poning surgery that is needed, but in severe hypothyroidism,
coma or seizure, and hypothermia, bradycardia, hyponatremia, there is insufficient evidence to make a recommendation.19
heart failure, and hypopnea. It is commonly associated with a In another retrospective study, 40 hypothyroid surgical
precipitant such as surgery, infection, cold exposure, and patients, most of whom had mild to moderate severe hypothy-
administration of sedatives. roidism, were compared with 80 euthyroid surgical patients
who served as controls. Among those undergoing noncardiac
Preoperative Considerations in the Hypothyroid surgery, intraoperative hypotension occurred at a higher rate in
Patient the hypothyroid group. For those undergoing cardiac surgery,
The pathophysiologic changes associated with hypothyroidism the development of heart failure was more prevalent in the
are generally reversible with replacement of thyroid hormone. hypothyroid group. In addition, the hypothyroid group had a
Thus, rather than face the risk of acute decompensation, it is higher rate of gastrointestinal and neuropsychiatric complica-
preferable to postpone elective surgery until adequate treat- tions. Furthermore, even though there was a similar rate of
ment with thyroid hormone has achieved euthyroidism. A full postoperative infection in both groups, the hypothyroid
replacement dose of levothyroxine is usually 1.6 µg/kg/day. patients were less likely to be febrile. No differences were noted
However, in the elderly or those with known coronary artery in perioperative blood loss, duration of hospitalization, rates of
disease, the initial dose is usually 25 µg daily, with a planned arrhythmia, hypothermia, hyponatremia, delayed recovery from
increase every 2 to 6 weeks until a euthyroid state is attained. anesthesia, tissue integrity, wound healing, pulmonary compli-
Once TSH values normalize, surgery can be performed. If the cations, or death. Of note, applicability of conclusions drawn
patient is to fast on the day of surgery, the patient may miss the from these data may be limited as only 2 of the patients studied
dose of levothyroxine that day, as it has a long half-life of were categorized as having severe hypothyroidism.20
approximately 7 days. If oral medications cannot be given post-
operatively, the dose may be missed for several days. However, Recommendations for Hypothyroid Patients
if there is still no ability to administer the drug enterally after 5 Although the definitions of mild, moderate, and severe hypo-
days, intravenous (IV) levothyroxine should be administered at thyroidism are somewhat subject to interpretation and vary
a dose between 60% and 80% of the oral dose.8 between studies, and the number of studies is quite limited, the
In cases where surgery is not elective, the risk of proceed- following conclusions are reasonable based on the literature.
ing with surgery must be weighed against the risks detailed Although elective surgery is best postponed until a euthyroid
above. Unfortunately, there are no large randomized studies state is achieved, patients requiring urgent or emergent surgery
Palace 3

may proceed with surgery if they have mild or moderate hypo- scenario characterized by tachycardia, confusion, fever, gastro-
thyroidism. Levothyroxine should be started preoperatively intestinal complaints, and potentially leading to cardiovascular
and there should be increased awareness of the possibility of collapse, elective surgeries should always be postponed in
minor postoperative complications such as those mentioned patients with overt hyperthyroidism. In those with mild or sub-
above. clinical disease, preoperative β-blockade is considered suffi-
In general, the classification of “severely hypothyroid” includes cient. This is supported by a prospective randomized trial
those patients with myxedema coma or severe complications showing that in hyperthyroid patients undergoing thyroidec-
such as altered mentation, pericardial effusions or heart failure, tomy who were treated with just 5 weeks of metoprolol
or very low levels of thyroxine (<1 µg/dL). Based on the lack of preoperatively, there were no serious intra- or postoperative
outcomes data and an understanding of the risks outlined above, complications, compared with patients who were pretreated for
nonemergent surgery should be postponed until the hypothy- 12 weeks with a combination of methimazole and levothyrox-
roidism has been treated. If emergent surgery is required, thyroid ine to render them euthyroid.27
hormone levels should be normalized as rapidly as possible, For patients with overt hyperthyroidism requiring urgent
using IV levothyroxine in a loading dose of 200 to 500 µg fol- or emergent surgery, cardiac status must be closely monitored.
lowed by 50 to 100 µg IV daily.21 Simultaneous administration Perioperative placement of an arterial line or central venous
of IV liothyronine should be considered if there is suspicion for pressure monitor is appropriate if there is evidence of cardio-
myxedema coma. If there is any suspicion for concurrent adrenal pulmonary disease or the patient is not hemodynamically sta-
insufficiency, glucocorticoids should be administered in stress ble. Cardiac status should be optimized and β-blockers are
doses prior to or together with thyroid hormone. most commonly used for this purpose. Although no particular
Patients who require cardiac revascularization comprise the β-blocker has established superiority over others, atenolol
only subset of patients who may not benefit from preoperative may be preferred in some cases. Like metoprolol, it is a beta-
replacement of thyroid hormone. Although one may intuit 1-selective agent which may be tolerated better in patients
from the above discussion that preoperative optimization of with reactive airway disease. In addition, its long half-life
thyroid hormone status would benefit all patients, in cardiac facilitates once-daily dosing. However, because its metabo-
patients with angina, there is a real possibility of worsening lism is accelerated in thyrotoxicosis, the total daily dose may
cardiac ischemia by replacing thyroid hormone and conse- still need to be divided into 2 doses.28 Although an initial
quently increasing myocardial oxygen demand. In fact, as retro- dose of 25 mg daily may be used, often higher doses, such as
spective and prospective studies of cardiac patients undergoing 50 mg up to more than 200 mg daily, may be required.
cardiac surgery or catheterization found no increase in the rate Although propranolol is a nonselective beta-1 and beta-2-
of adverse events in those patients whose hypothyroidism had blocker with a shorter half-life necessitating the administra-
not been treated,22,23 it is reasonable to proceed with the revas- tion of multiple daily doses, it may have additional benefit
cularization procedure before repleting thyroid hormone. because it inhibits the monodeiodinase type I enzyme which
converts T4 to the more biologically active T3 hormone.29 It
Complications of Hyperthyroidism can be used intravenously to control pulse and blood pressure
As in hypothyroidism, the manifestations of abnormally ele- and even decrease fever intraoperatively.30
vated thyroid hormone levels seen in thyrotoxicosis are numer- Calcium channel blockers should be used in patients who
ous and pervade multiple organ systems. The most salient cannot tolerate β-blockers. These drugs should be titrated to
features are the cardiovascular ones, namely, the positive iono- achieve a heart rate under 80 beats per minute. Because they
tropic and chronotropic effects of thyroid hormone on the decrease sympathetic activity, both reserpine and guanethidine
heart, the vasodilation and decrease in systemic vascular resist- may be considered for those in whom β-blockers and calcium
ance, and the consequent increase in sodium and water reten- channel blockers are contraindicated.31
tion mediated by the renin-angiotensin-aldosterone system, all
of which culminate in an increase in cardiac output by 50% to Recommendations for Treatment of Thyrotoxicosis
300%.24 Atrial fibrillation occurs in 10% to 15% of patients In cases where thyrotoxicosis is due to the increased synthesis
with overt hyperthyroidism and in a similar percentage of those of thyroid hormone, ie, in the Graves disease and toxic nodular
with subclinical hyperthyroidism, ie, decreased TSH with nor- disease, but not in cases of exogenous thyroid hormone intoxi-
mal thyroxine and triiodothyronine.25 The prevalence of atrial cation or thyroiditis, antithyroid drugs (ATDs) should be used
fibrillation increases with age.26 as soon as possible to decrease thyroid hormone levels.
Thionamides, including propylthiouracil (PTU) and methi-
Optimization of Cardiovascular Status Before mazole, which are available in the United States, and carbima-
Surgery in Hyperthyroid Patients zole, which is available elsewhere, inhibit de novo production
There are no published studies evaluating the perioperative of thyroid hormone but do not actually affect the release of
outcomes of hyperthyroid patients compared with euthyroid preformed hormone. Thus, their effects may not be apparent
patients. Because of the risk of precipitating thyroid storm, a for several days. Methimazole may achieve a euthyroid state
4 Health Services Insights 

faster than PTU but is still expected to take between 3 and 8 after approximately 10 days, treatment with iodine should not
weeks. It is preferred because of its decreased potential for be started more than 10 days preoperatively.
hepatotoxicity and its longer half-life which facilitates dosing Iodine may be administered orally, rectally, or intrave-
once or twice daily. Propylthiouracil, in contrast, is adminis- nously.34 Commonly administered doses and formulations
tered every 6 to 8 hours.32 Furthermore, methimazole may be include 1 drop 3 times daily of saturated solution of potassium
started in doses of 20 to 30 mg daily and is available in 5, 10, iodide or a dose of 3 to 5 drops of Lugol’s solution thrice daily.35
and 20 mg tablets, whereas PTU would generally be adminis- In addition, iopadate, an oral cholecystographic agent which
tered in doses of 100 to 150 mg every 6 to 8 hours and is only contains a large iodine load, was used in the past to decrease
available in 50 mg tablets. For patients who are unable to take hormone production and reduce the peripheral conversion of
oral medications, both drugs can be administered rectally. thyroxine to triiodothyronine. However, this agent is no longer
Propylthiouracil offers the additional benefit of reducing available and another iodine-containing product known as
conversion of thyroxine to the more biologically potent triio- iopanoic acid, when administered in a dose of 500 mg twice
dothyronine. In addition, it is generally preferred in the first daily, reduces triiodothyronine levels even faster than the other
trimester of pregnancy because of its decreased teratogenicity iodine preparations mentioned above.28
relative to methimazole. However, both drugs have similar tox- Glucocorticoids decrease the conversion of thyroxine to trii-
icities. Urticaria, rash, arthralgia, and fever occur in 1% to 5% of odothyronine within a matter of hours, so they may be added
patients. Both agents may cause agranulocytosis at a rate preoperatively and tapered over 3 days postoperatively. Suggested
between 1 in 200 and 1 in 5 patients. This effect is dose related regimens include hydrocortisone 100 mg orally or IV every 8
in methimazole and rarely occurs at doses below 40 mg daily.28 hours, dexamethasone 2 mg orally or IV every 6 hours, or beta-
In contrast, regarding PTU, these toxicities are idiosyncratic methasone 0.5 mg orally, intramuscular, or IV every 6 hours.28
and not dose related. It is prudent to avoid both drugs in a Cholestyramine is an additional modality that may be used
patient who has experienced an adverse effect secondary to one to rapidly lower thyroid hormone levels in thyrotoxic patients.
of them because cross-sensitivity can occur. Studied in a dose of 4 g four times daily, cholestyramine
Concomitant use of β-blockers and thionamides should decreases circulating hormone levels by binding thyroid hor-
adequately prepare most patients for surgery within a few mone in the intestine and decreasing its reabsorption.36 As the
weeks. These agents should be continued throughout the enterohepatic circulation of thyroid hormone is increased in
postoperative period to prevent thyroid storm and possibly thyrotoxic individuals, this binding resin is quite effective.36
longer unless the patient is treated with thyroid resection or In fact, the American Thyroid Association, in its recently
I131 ablation and is no longer hyperthyroid. Obviously, in published Guidelines for Diagnosis and Management of
patients undergoing thyroidectomy, thionamides should be Hyperthyroidism and Other Causes of Thyrotoxicosis, specifi-
stopped postoperatively. However, because the half-life of cally recommended that those undergoing thyroidectomy for
levothyroxine is so long, it may still be necessary to continue the Graves should be rendered euthyroid prior to the procedure
β-blockers for about a week, possibly longer, after thyroidec- with ATD pretreatment, with or without β-adrenergic block-
tomy. In patients who have undergone thyroidectomy, thyroid ade, and potassium iodide should be given in the immediate
hormone therapy will be necessary once hormone levels have preoperative period. When it is not possible to render the
declined below normal. patient euthyroid prior to thyroidectomy or when the patient is
Another medication which decreases thyroid hormone allergic to ATDs, the patient should be treated with β-blockade,
release but it is generally avoided due to its other unfavorable potassium iodide, glucocorticoids, and “potentially cholesty-
systemic effects is Lithium.31 ramine” in the immediate preoperative period.37
When there is an urgent need to stabilize the thyrotoxicosis In cases of thyrotoxicosis, due to exogenous thyroid hormone
rapidly, inorganic iodide should be given as an adjunct to intoxication, no specific targeted therapy is indicated other than
thionamides because its administration blocks the organifica- β-blockade or calcium channel blockade, as needed, to stabilize
tion of iodine, decreasing the synthesis of thyroid hormones by cardiovascular status, as the passage of time will permit metabo-
the gland. This transient phenomenon, known as the Wolff- lism of excess hormone within a matter of days to weeks. In
Chaikoff effect,33 is apparent within 24 hours. However, in cases where the etiology of the thyrotoxicosis is thyroiditis, and
patients with toxic thyroid nodules, it is imperative that admin- elevated thyroid hormone levels are attributable to increased
istration of a thionamide precedes that of iodide because of the release of thyroid hormone rather than overproduction, there is,
potential for precipitating an iodine-induced increase in thy- similarly, no role for ATDs. Nonsteroidal anti-inflammatory
roid hormone production via the Jod-Basedow effect. The Jod- medications are advised for those patients. For all patients with
Basedow effect is not relevant in patients with the Graves thyrotoxicosis, regardless of cause, corticosteroids, iopanoic acid,
disease, and those patients, if unable to take thionamides, may and cholestyramine may be considered, as their functionality is
even be treated with just iodine and β-blockade. However, as independent of thyroid hormone production. Steroids and
escape from the Wolff-Chaikoff effect is anticipated to occur iopanoic acid will decrease T4 to T3 conversion regardless of
Palace 5

the source of T4, and cholestyramine will decrease thyroid hor- 6. Fredlund BO, Olsson SB. Long QT interval and ventricular tachycardia of a
“torsade de pointe” type in hypothyroidism. Acta Med Scand. 1983;213:231–235.
mone absorption from the intestines regardless of whether it 7. Anthonisen P, Holst E, Thomsen AA. Determination of cardiac output and
was endogenously produced or exogenously administered. other hemodynamic data in patients with hyper- and hypothyroidism, using dye
dilution technique. Scand J Clin Lab Invest. 1960;12:472–480.
There is another strong recommendation made by the 8. Stahatos N, Wartofsky L. Perioperative management of patients with hypothy-
American Thyroid Association in its recently published guide- roidism. Endocrinol Metab Clin North Am. 2003;32:503–518.
9. Bilezikian JP, Loeb JN. The influence of hyperthyroidism and hypothyroidism
lines which relates specifically to those undergoing thyroidec- on α and β-adrenergic receptor systems and adrenergic responsiveness. Endocr
tomy. The guidelines suggest the supplementation of oral Rev. 1983;4:378–388.
calcium, vitamin D, or both preoperatively to reduce the risk of 10. DeRubertis FR Jr, Michelis MF, Bloom ME, et al. Impaired water excretion in
myxedema. Am J Med. 1971;51:41–53.
postoperative hypocalcemia due to parathyroid injury or 11. Park CW, Shin SY, Ahn JS, et al. Thyroxine treatment induces upregulation of ren-
increased bone turnover.37 The authors reference a meta-anal- nin-angiotensin-aldosterone system due to decreasing effective plasma volume in
patients with primary myxedema. Nephrol Dial Transplant. 2001;16:1799–1806.
ysis of risk factors for postoperative hypocalcemia which deter- 12. Kim JM, Hackman L. Anesthesia for untreated hypothyroidism: report of three
mined that both preoperative vitamin D deficiency and the cases. Anesth Analg. 1977;56:299–302.
13. Abbot TR. Anaesthesia in untreated myxedema. Br J Anaesth. 1967;39:510–514.
Graves disease increased the likelihood of this complication.38 14. Bastenie PA. Paralytic ileus in severe hypothyroidism. Lancet. 1946;1:413–416.
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Conclusions tion. N Engl J Med. 1965;273:1057–1061.
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Although hypothyroidism and hyperthyroidism represent oppo- quired von Willebrand’s disease. Lancet. 1987;1:1007–1009.
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2 0. Ladenson PW, Levin AA, Ridgeway EC, Daniels GH. Complications of sur-
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Author Contributions
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MRP reviewed and approved the final manuscript. Endocrinol Metab Clin North Am. 1993;22:263–277.
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Cooper DS, ed. Medical management of thyroid disease. New York: Marcel Dekker,
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