Thyroid storm in a patient with unknown hyperthyroidism during nonthyroidal surgery—a case report and literature review

Abstract

Background

Thyroid storm (TS) is a critical manifestation of hyperthyroidism. In recent years, the risk of perioperative TS is significantly decreased in patients with hyperthyroidism undergoing thyroid surgeries with adequate preoperative preparations. However, those who undergo non-thyroidal operations have higher risk of TS due to easily ignoring the evaluation of thyroid function. The purpose of this case report is to present a patient with TS during nonthyroidal surgery and review similar cases in the literature.

Case presentation

A middle-aged female who received unilateral total knee arthroplasty under general anesthesia developed refractory tachycardia during the operation and was diagnosed with hyperthyroidism via laboratory tests after surgery. She was suggestive of TS based on the Burch and Wartofsky scoring system and relieved after etiological treatments. She was discharged 10 days after surgery and continued to take antithyroid medication.

Conclusion

We recommend that a comprehensive history collection is warranted. The clinical manifestations of TS during operation could be versatile and atypical. Any abnormalities during an operation like abnormal heart rate, blood pressure, body temperature, or even the unusual anesthetics needed, should not be ignored. In surgeries with general anesthesia, it is necessary to be cautious about TS with an atypical manifestation of tachycardia. Once suspected, supportive and resuscitative treatment along with antithyroid medication should be promptly initiated.

Background

Thyroid storm (TS) is a rare albeit critical manifestation in patients with hyperthyroidism. The incidence of TS was reported 0.20–0.76/100, 000 persons per year, with 4.8–5.6/100,000 hospitalized patients per year. The mortality rate is 8–25% and rapid diagnosis and treatment are necessary [1]. With adequate preoperative preparations, the risk of perioperative TS is significantly decreased in patients with hyperthyroidism undergoing thyroid surgeries. In comparison, for the reason that almost one quarter to half hyperthyroidism is subclinical, those who undergo non-thyroid operations have higher risk of TS [2]. Under general anesthesia, the clinical manifestations of TS could be more atypical. We report a middle-aged female without an established history of underlying thyroid disease developed TS during the unilateral total knee arthroplasty. We also review and summarize the reported cases of perioperative TS in non-thyroid surgeries.

Case presentation

We obtained written informed patient consent for this report. A 52-year-old female (164 cm, 74 kg) with ASA grade II was scheduled for unilateral knee arthroplasty due to knee arthritis. She had a 2-year history of hypertension which was controlled well with oral reserpine. The patient also complained about a 2-year untreated stomach discomfort and a lumbar disc hernia combined with sciatica. Electrocardiograph (ECG) obtained eight days before surgery showed “sinus rhythm with a heart rate (HR) of 82 beats/min”. After hospitalization, the cardiologist substituted reserpine with nifedipine to avoid depletion of neurotransmitters. In view of a dwelling stomach discomfort, a gastroenterologist was consulted and an endoscopy or a CT scanning was suggested, which however was refused by the patient. After withdrawing from reserpine for 8 days, she received surgery.

Upon entering the operating room, the vital signs revealed a blood pressure (BP) of 145/85 mmHg, a HR of 103 beats/min, and a pulse saturation of oxygen (SpO₂) of 98%. The anesthesia strategy was total intravenous general anesthesia combined with continuous femoral nerve block. Anesthesia was induced with midazolam 2 mg, sufentanil 15 µg, and bispectral index (BIS)-guided (45–55) closed-loop target controlled infusion (TCI) of propofol. When she lost consciousness, rocuronium 50 mg was administered and the target concentration of propofol was 3.5 µg/ml. A laryngeal mask airway was then introduced for mechanical ventilation. Using the in-plane method, a continuous femoral nerve block catheter was placed under the guidance of ultrasound (SonoSite M-Turbo, USA) through which 0.3% ropivacaine 100 mg was administered. Anesthesia was maintained with BIS-guided (45–55) closed-loop TCI of propofol and TCI of remifentanil (3 ng/mL before incision and 5 ng/mL after incision); intermittent rocuronium was given as needed. Before incision, the BP was 120/70 mmHg, the HR was 70 beats/min, and the target concentration of propofol was 3.0 ∼ 3.5 µg/ml. The surgery began after a tourniquet was placed. The BP was 130/70 mmHg, and the HR was 70 beats/min. Afterwards, the patient’s HR gradually increased to 85 beats/min; the target concentration of remifentanil was increased to 8 ng/ml correspondingly. Approximately 45 min after the surgery, the HR suddenly increased to 120 beats/min. An inadequate depth of anesthesia was excluded with a normal BP and a “controlled” BIS value. A hypovolemia was ruled out for an infusion volume of 1200 ml with a urine output of 400 ml and minimal bleeding. A normal blood gas (pH 7.41; pCO₂ 38 mmHg; pO₂ 495 mmHg; Na⁺ 143 mmol/L; K⁺ 3.7 mmol/l; Glucose 5.5 mmol/L; Lac 0.6 mmol/L; Hct 36%; and HGB 12.6 g/dl) excluded electrolyte disturbance, acid-base imbalance, hypercarbia, and hypoglycemia that may cause tachycardia. The patient was free of any history of cardiac disease. Allergic reaction could not be totally excluded, so dexamethasone 10 mg was administered. Intermittent esmolol (20–30 mg) was given to control HR. Nevertheless, the HR can only be temporally controlled to 110 beats/min with a BP of 140/90 mmHg. The surgery lasted for 85 min. The patient was awake immediately after the surgery was completed. The laryngeal mask airway was removed when spontaneous breath and muscle strength were regained. At this time, her HR was 140 beats/min, BP was 130/70 mmHg, and SpO₂ was 98%. The patient had no apparent pain or chills but complained of palpitations as well as slight chest tightness. Additional esmolol (total 0.2 g) and neostigmine (2 mg) were given, but the HR was still between 120 and 130 beats/min. A 12-lead ECG showed a “sinus tachycardia with a HR of 124 beats/min”. The tachycardia sustained even after 0.2 mg cedilanid was administered. Finally, the patient was transferred to the ward and continued with esmolol treatment.

Postoperative blood gas, biochemical tests, myocardial enzymes, D-Dimer, lower limb ultrasound, or echocardiography revealed no apparent abnormalities. Bedside chest radiograph revealed “pulmonary congestion and minor right pleural effusion”. Esmolol infusion was continued, but the HR could only be controlled to 120 beats/min, which made the functional exercise impossible. The patient also had a hyperthermia (38.0 °C ∼ 38.5 °C) lasted for five days after surgery, as well as palpitation, abdominal pain, and anxiety. A thyroid function test was then proposed five days after the surgery and showed “FT3 8.85 pg/ml, FT4 2.52 ng/dl, and thyroid stimulating hormone (TSH) 0.000 µIU/ml” (Table 1). Radioactive iodine uptake test (RAIU) and scan were recommended by the endocrinologist and the high uptake in a diffuse pattern suggested Grave’s disease (GD, Table 2). TS (tachycardia, precipitating factor, hyperpyrexia, gastrointestinal dysfunction, agitation, and congestive x-ray) was thus considered based on the Burch and Wartofsky scoring system. A further inquiry into the patient’s history revealed that she had experienced weight loss (7 kg), diarrhea (3–5 times/day), sweating, insomnia, and palpitations for two months before surgery. She had no apparent neck mass or neck swelling. After the diagnosis of Graves’s disease was confirmed, antithyroid therapy with methimazole, oral β-blockers, and iodine-free diet was initiated. The patient’s HR gradually decreased to 90 beats/min, body temperature lowered to 36.5℃, with other symptoms alleviated. She was discharged ten days after the operation and continued with antithyroid medications.

Table 1 Results of thyroid function tests

Table 2 Results of iodine absorption rate

Discussion and conclusions

We used “thyroid crisis” or “thyroid storm” and “perioperative period” or “surgery” as the key words to search PubMed for case reports on TS developed in patients undergoing non-thyroid surgeries, which were published after year 2000. Finally, 18 reports were retrieved (Table 3) [3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21]. The surgical type involved abdominal, orthopedic, thoracic, gynecological, cardiac, neurosurgical, and otolaryngological operations. These TS mostly occurred in the postoperative (12 cases) and intraoperative stage (3 cases), with the main causes being no diagnosis (12 cases), insufficient preoperative preparation (2 cases), emotional stress, surgical trauma or infection. The patients generally presented as high fever, tachycardia, palpitation, and agitation. The preliminary diagnosis relied on clinical manifestations, but thyroid hormone tests and the Burch-Wartofsky scoring system help the definitive conclusions for most cases. Almost all patients relieved after supportive management, antithyroid medications, and steroids, except for one patient dying of infection.

Table 3 Summary of cases with thyroid storm in the perioperative period of nonthyroidal surgery

The exact pathophysiological mechanisms underlying the development of TS remains poorly understood. The rapid increase of free hormone levels (mean dialyzable fraction of T4 and mean free T4 concentrations) is considered to be more important than the absolute levels in determining clinical presentation. In addition, the enhanced binding to thyroid hormone receptors along with an over-responsiveness to thyroid hormone is often incriminated [22]. Adrenergic activation also plays an important role in TS. However, it is probably not because of an elevated plasma concentrations or increased secretion rates of epinephrine or norepinephrine, but an enhanced responsiveness to endogenous catecholamines.

Thyroid crisis often occurs in patients with untreated or inadequately treated hyperthyroidism. There are many well-described risk factors that can induce TS such as irregular use or discontinuation of antithyroid drugs, thyroidal or nonthyroidal surgery, major trauma, infection, emotional stress, parturition, cerebrovascular accident, pulmonary thromboembolism, etc. Still, about one third patients don’t have a clearly identifiable precipitating factor [22].

The preliminary diagnosis of TS should be made entirely on the basis of nonspecific clinical findings, namely dysfunction of the cardiovascular system, thermoregulatory system, gastrointestinal-hepatic system, and central nervous system. Thyroid hormone plays an important role in regulating the HR, cardiac contractility, myocardial oxygen consumption, and systemic vascular resistance. Patients with hyperthyroidism can presented as palpitations, tachycardia, atrial fibrillation, or even heart failure if progress into TS. The central nervous system manifestations can range from agitation, delirium, and confusion to coma. Hyperthyroidism or TS related gastrointestinal symptoms such as nausea, severe diarrhea, or abdominal pain might be attributed to various pathogenetic mechanisms, including visceral nociception triggered by thyrotoxicosis-induced hypermotility with mechanical stretch, and “mesenteric ischemia from sympathetic hypersensitivity with resultant release of pro-inflammatory pain-mediating cytokines acting on gut mucosal receptors” [23].  Studies revealed that 30% of hyperthyroidism patients may develop liver dysfunction. The underlying mechanism may be due to hepatic congestion, hypoperfusion, or toxic effect from thyroxine to liver cells causing apoptosis of liver cells. TS developing into jaundice probably indicates a poor prognosis [24]. Given the nonspecific nature, TS has been misdiagnosed as acute abdomen, status epilepticus, rhabdomyolysis, lactic acidosis, or other emergent situations in some case reports.

Only few reports have described the TS during the nonthyroidal surgeries [4, 6, 14]. Under general anesthesia, the gastrointestinal -hepatic and central nervous system manifestations will be masked. In anesthetized patients, the primary physical finding of TS is cardiac tachyarrhythmias. All reported cases experienced tachycardia. Thus, Tamada et al. suggested that in surgeries with general anesthesia, it is necessary to be cautious about TS with an atypical manifestation of tachycardia [7]. Although fever has been described, severe hyperpyrexia is more likely to be absent or imperceptible due to the suppression of hypothalamic thermoregulatory center from general anesthetics. There are also other signs indicating the patient may have developed TS under general anesthesia. Our patient received a BIS-guided closed-loop TCI of propofol and a significantly higher concentration was fed back, which at least indicated a high metabolism state. Patients suspected as TS during the operation should be differentiated with other emergencies, like malignant hyperthermia, pheochromocytoma, sepsis, hypoglycemia, heart failure, or blood transfusion reaction.

The most commonly used diagnostic criteria for TS is the Burch-Wartofsky scoring system. A score below 25 excludes thyroid storm, 25–45 suggests impending storm, and above 45 is suggestive of thyroid storm. Although the heart rate and the precipitating factor suggested an “impending TS” during surgery, considering the gastrointestinal and central nervous system manifestations would be masked under general anesthesia and the concurrent hyperpyrexia, diarrhea, abdominal pain, agitation, and suspected congestive manifestation on chest x-ray, the patient should be highly suggestive of TS postoperatively. In our case, predisposing factors for the development of TS might be no treatment before surgery, supplemental narcotics and ephedrine, emotional stress, and surgical trauma. Japanese scholars developed new diagnostic criteria for “definite” and “suspected” TS cases by combining the central nervous system manifestations, fever, tachycardia, congestive heart failure, and gastrointestinal/hepatic disturbances. They hope they will contribute to prompt and precise clinical decisions and the treatment of this disorder, and ultimately achieve a better prognosis of TS [12].

Our case indicates that a comprehensive preoperative history collection is extremely crucial for underdiagnosed patients, especially for elective surgery. Thyroid diseases can be discovered with a more careful preoperative assessment and TS probably prevented. In reported cases listed in Tables 3, 61% (11/18) patients experienced TS due to unrecognized underlying hyperthyroidism preoperatively. The signs and symptoms of hyperthyroidism can be very subtle to clinically overt. Patients with hyperthyroidism commonly experience palpitations, fatigue, tremor, anxiety, disturbed sleep, weight loss, heat intolerance, sweating, tachycardia, and fever. Thyroid nodules or a diffusely enlarged thyroid gland, sometimes with a bruit, may be palpable. Up to 25% of patients with Graves’ disease present with signs of ophthalmopathy. Other rare extrathyroidal Graves’ disease manifestations include pretibial myxedema and acropachy. When patients present with multiple symptoms and signs as mentioned above, hyperthyroidism should be considered as a potential diagnosis. Symptoms that are often overlooked include abdominal discomfort, weight changes, and fatigue. Of note, some non-thyroid diseases and drugs can influence thyroid hormone levels, including gestational trophoblastic disease, McCune-Albright syndrome, teratoma (struma ovarii), TSH-producing pituitary adenomas, and amiodarone [16, 19, 24]. Patients with these diseases have an increased likelihood to develop hyperthyroidism and TS.

When considering the possibility of hyperthyroidism, thyroid hormone level is the best to detect thyroid dysfunction. Once hyperthyroidism is confirmed, the etiology should be explored. The Graves’s disease (GD) is the most common cause of hyperthyroidism, followed by toxic multinodular goiter (TMNG) and single toxic adenoma (TA). Current guidelines recommend measuring TSH-receptor antibody (TRAb) as the initial step in differentiating GD from other causes of thyrotoxicosis [25]. In our case, the endocrinologist recommended TRAb test, unfortunately, it was not available in our center at that time. If the etiology is unclear after TRAb testing, RAIU can be used. RAIU and thyroid scan are usually done together to measure overall thyroid function in hyperthyroidism and help differentiate among different causes. High uptake with a diffused homogeneous pattern usually suggests GD. TMNG will have high or normal uptake in a patch pattern and TA will have a solitary area of high uptake with low uptake in the remainder [26]. High uptake with a diffused pattern and no nodule palpated in the thyroid together suggested GD for our patient. Thyroid uptake (lasting 24 h) takes a relatively long time and can be chosen for preoperative assessment. However, in an emergency, thyroid ultrasound with color flow Doppler is recommended. Gland vascularity is generally increased in GD, indicating increased gland activity [27]. For our patient, we failed to use ultrasound to promptly ascertain the etiology due to inexperience, resulting in a delay in initiating etiological treatment.

For elective surgical patients diagnosed with hyperthyroidism, adequate preoperative preparation is key to ensure an uneventful operation. The question is “do patients with hyperthyroidism need to be euthyroid prior to surgery?” The American Thyroid Association guidelines recommend rendering the patient euthyroid to decrease the risk of a potentially lethal TS in preparation for thyroid surgery [25]. The same practice should be applied in hyperthyroid patients undergoing a non-thyroid surgery. Numerous reported cases of patients experiencing TS due to inadequately managed hyperthyroidism [15, 18,19,20]. However, this goal cannot be always achieved at the time of operation for some patients, especially in emergent situation. TS should be considered before surgery and countermeasures should be prepared. For patients with emotional stress, proper premedication like midazolam is necessary. As for the choice of anesthetic method, where possible, regional anesthesia and peripheral nerve blocks are preferable to general anesthesia. If the surgical procedure does not allow for a regional anesthetic technique or the patient is extremely stressed, general anesthesia is proposed. Analgesia and depth of anesthesia should be adequate to suppress intubation response and stress. Empirical administration of hypnotic or narcotics may lead to an insufficient depth of anesthesia, which places a patient in a stressful state. Adopting appropriate monitoring methods like BIS can help more rationally use of anesthetics. Besides, any medication or disorder that will induce adrenergic activation during the surgery should be avoided, such as ketamine, ephedrine, atropine, hypoxia, or hypercapnia.

It is vital to initiate the treatment of TS as soon as the diagnosis is suspected. The first-line therapy is administration of antithyroid medications to reduce the synthesis and release of thyroid hormone. Adrenergic blockade with β-blockers to block the peripheral effects of circulating thyroid hormone is paramount in the case of surgery, because severe tachycardia can cause myocardial ischemia or heart failure. Nonselective β-adrenergic antagonism propranolol is the most commonly used β-blocker in TS due to its ability to decrease the peripheral conversion of T4 to T3. A shorter acting β -blocker such as esmolol can also be chosen for a more rapid effect. Neostigmine, an acetylcholinesterase inhibitor, may be another choice in patients with TS-induced severe sinus tachycardia which warrant further investigation [14]. High-dose steroid treatment was recommended, but caution is warranted because of a higher infection risk. It is thus not a reasonable choice in an arthroplasty surgery like our case. In refractory cases of TS when conventional treatments are not successful or appropriate, therapeutic plasma exchange might be effective in rapidly reducing thyroid hormone levels with clinical improvement. Besides, some supportive and resuscitative measures such as eliminating predisposing factors, correcting fluid losses, and relieving hyperthermia should be promptly initiated. Salicylates like aspirin should be avoided due to its binding to T4-binding globulin. Resultant increased free hormone levels will exacerbate TS. The diagnosis of TS was not initially considered due to insufficient knowledge of thyroid disease of the patient preoperatively. However, our patient did not progress into a critical condition, which might be attributed to a moderate-high basal metabolic rate upon hospitalization (103 + 60–111 = 52), noninfectious surgery, no severe comorbidity, a guaranteed depth of anesthesia from a closed-loop system for propofol administration, and prompt treatment.

Non-thyroid surgery could be an independent predisposing factor for thyroid storm in patients with hyperthyroidism. The importance of careful preoperative history taking cannot be overestimated. Any abnormalities during an operation like abnormal heart rate, blood pressure, body temperature, or even the unusual anesthetics used, should not be ignored. In surgeries with general anesthesia, it is necessary to be cautious about TS with an atypical manifestation of tachycardia. Once suspected, supportive and antithyroid medication should be promptly initiated.