Severe Myoclonus Masking Thyroid Storm Following Etomidate Administration: A Case Report

Introduction

Myoclonus is a hyperkinetic movement disorder characterized by sudden, brief, shock-like involuntary movements. Many cases of drug-induced myoclonus are transient [1]. Etomidate is the most commonly reported drug causing myoclonus in the literature [2]. Etomidate is a rapid and short-acting non-barbiturate intravenous anesthetic, and there are numerous studies on the possible mechanisms by which it induces myoclonic jerks. One hypothesis suggests that etomidate inhibits the function of the brainstem reticular formation by affecting gamma-aminobutyric acid type A (GABA-A) receptors, thereby increasing the sensitivity of neural pathways connected to skeletal muscles through its influence on GABA neurons, leading to the occurrence of spontaneous nerve impulses and causing myoclonus [3]. Another hypothesis proposes that the massive intravenous infusion of etomidate results in cortical inhibition preceding subcortical inhibition, leading to disinhibition of subcortical structures. Etomidate-induced myoclonus does not originate from epileptic foci but rather from a transient imbalance in drug effects due to varying drug concentrations in different regions of the central nervous system and differences in cerebral blood flow affinity for the drug, causing disinhibition in subcortical areas [4]. Additionally, some research indicates that etomidate can competitively inhibit endogenous dopamine by competing with dopamine receptors in brain regions such as the substantia nigra and striatum, producing symptoms similar to those caused by reduced endogenous dopamine, thereby triggering myoclonus [5]. Myoclonic jerks can lead to adverse effects such as tachycardia, hypertension, and hyperkalemia, which resemble the symptoms of thyroid storm, making it difficult to diagnose promptly.

The clinical prevalence of hyperthyroidism ranges from 1% to 3%. The missed diagnosis of hyperthyroidism in patients undergoing elective surgery occasionally occurs because not all patients undergo thyroid function tests before surgery, especially when the symptoms of hyperthyroidism are not obvious. This is the primary reason for missed diagnosis. General anesthesia is recognized as a potential trigger for thyroid storm (TS) in patients with hyperthyroidism. However, the precise perioperative risk of TS in this population remains unquantified. A recent systematic review of case reports involving non-optimized or partially optimized thyrotoxic patients undergoing general anesthesia observed that many developed perioperative TS. Nevertheless, meaningful risk stratification remains unfeasible due to the scarcity of robust evidence and significant heterogeneity among existing cohort studies [6]. Severe TS can lead to multiple organ failure and death [7]. Given the lethality and severity of TS complications, optimizing thyroid function prior to surgery – including emergency procedures where feasible – is strongly advised. Historical studies have indicated that mortality rates among patients with thyroid storm range from 8% to 30%. However, more recent literature suggests that these rates have decreased to between 1.2% and 3.6%, likely due to advances in high-quality, aggressive intensive care [8].

Despite this progress, there have been no previously reported cases of thyroid storm occurring in conjunction with severe myoclonus after administration of etomidate. We present a case report of severe myoclonus that obscured the signs of a possible thyroid storm.

Case Report

A 37-year-old man was admitted to the hospital with a primary concern of fever accompanied by cough and sputum production for 4 consecutive days. His condition worsened with the onset of dyspnea 1 day prior to admission.

Medical examination and findings: Upon admission, a series of relevant auxiliary examinations were conducted. The chest computed tomography (CT) scan (Figure 1, Video 1) revealed bilateral pneumonia with no active lesions present. Notably, the NT-proBNP (N-terminal pro-B-type natriuretic peptide) level was significantly elevated at 1130 pg/ml. Despite this, the results of his complete blood count, blood urea nitrogen, serum electrolytes, electrocardiogram (ECG), and echocardiography were all within normal ranges.

Treatment plan: Given the patient’s clinical presentation and chest CT findings, a diagnosis of suspected pulmonary infection was made. Consequently, he was scheduled for an electronic bronchoscopy under general anesthesia to further investigate and confirm the diagnosis.

Prior to initiating the surgical procedure, he underwent comprehensive electrocardiographic monitoring in the operating room. The saturation level of peripheral oxygen (SPO2) was 98%, indicating adequate oxygenation. Blood pressure was stable at 128/68 mmHg, with a heart rate of 78 beats per minute and a normal body temperature of 36.5°C.

Anesthesia Induction Phase: After intravenous administration of 12 mg of etomidate, he had the onset of myoclonus, which progressively worsened. Within a short period, the heart rate surged to 180 beats per minute, accompanied by an elevation in blood pressure to 180/120 mmHg. In response to these changes, the medical team promptly initiated a management protocol that included fluid resuscitation, an increase in the depth of anesthesia, and assisted ventilation. However, despite these interventions, there was no significant improvement in the patient’s clinical condition. The myoclonus persisted, with the heart rate fluctuating between 160 and 180 beats per minute and blood pressure remained elevated at 160–180 mmHg systolic and 100–120 mmHg diastolic. To address the tachycardia and hypertension, intermittent intravenous injections of esmolol were administered immediately, 10 mg per dose, for a total of 40 mg. After 10 minutes, the senior physician arrived and directed an increase in fluid administration. Another dose of 12.5 mg of cyclizine, 20 mg of rocuronium, and 10 mg of dexamethasone were intravenously administered, the myoclonus gradually subsided, and the patient’s circulation stabilized with blood pressure 130–140 mmHg systolic and 85–90 mmHg diastolic. The tachycardia persisted but was reduced to 110–130 beats per minute. The duration of myoclonus was approximately 20 minutes. After 5 minutes, the heart rate fell to 90–110 beats per minute, and the tachycardia lasted about 25 minutes.

A size 4 laryngeal mask was then placed, and mechanical ventilation was initiated to maintain adequate respiratory function. The surgical procedure was uneventful and was completed within approximately 10 minutes. Following the surgery, the patient exhibited signs of stress, including sweating, with a body temperature of 36.9°C. In response, fluid administration was further increased. Approximately 20 minutes later, spontaneous breathing resumed, and the patient was able to open his eyes on command and follow instructions.

The laryngeal mask was removed after 3 minutes, and the patient was safely transferred to the post-anesthesia care unit (PACU) for further monitoring and care.

Upon arrival in PACU, he had spontaneous breathing and stable circulation. The Steward score was 6, indicating stable anesthesia recovery. Twenty minutes later, he suddenly developed altered consciousness and became unresponsive to questions. Bilateral pupils were 5 mm, equal and round, with absent light reflexes. At this point, the vital signs remained stable: SPO2 was 99% (with nasal cannula oxygen delivery at 2 L/min), heart rate was 85 beats per minute, and blood pressure was 125/70 mmHg. All operating room staff were informed and mobilized and laboratory tests were ordered (Table 1). Two minutes later, he had motor responses, spontaneously opened his eyes, and bilateral pupils returned to a normal size of 2.0 mm, equal and round, with restored light reflexes. He responded to questions, regained consciousness, and could follow instructions. The Steward score remained at 6. He reported weakness in both lower limbs, with muscle strength graded at 3 on the Medical Research Council (MRC) scale. The symptoms lasted approximately 30 minutes. The lower-limb muscle strength recovered to normal levels. An urgent cranial CT showed no significant abnormalities. Electromyography was also conducted, revealing no notable abnormalities. After 1 hour of close monitoring in the PACU, the patient reported no significant discomfort and vital signs remained stable; therefore, he was subsequently transferred to the ward for further observation and management. All observations and assessments were conducted by qualified medical staff, and all findings were accurately recorded. The patient’s condition was closely monitored throughout the PACU stay to ensure timely intervention and appropriate care.

This young male patient had no significant past medical history prior to the onset of his symptoms. After experiencing myoclonus, he exhibited marked hypermetabolic symptoms, including transient altered consciousness and weakness in both lower limbs. These symptoms prompted us to suspect thyroid dysfunction or other metabolic disorders. To investigate further, thyroid function tests were performed on the first postoperative day (Table 2). Additionally, thyroid ultrasound (Figure 2) showed diffuse lesions in both lobes of the thyroid gland, further confirming the diagnosis. Upon further questioning of the patient’s family, it was revealed that he had been diagnosed with hyperthyroidism 4 months prior to presentation at our facility. However, he had not taken the diagnosis seriously and had not received any treatment for the condition.

On the first postoperative night following his initial presentation, he had weakness in both lower limbs again, with muscle strength graded at 2 of 5. Urgent electrolyte testing was performed (Table 3). After he returned to the ward, we urgently contacted an endocrinologist for consultation. The recommendation was to administer methimazole tablets orally at 10 mg, 3 times daily. The patient returned to our hospital for a follow-up examination after 20 days, and thyroid function showed some improvement (Table 4). This was the last time he visited our hospital. Subsequent telephone follow-up revealed that he had discontinued the medication on his own after 2 months after discharge and did not seek further medical attention.

Discussion

The association between etomidate and myoclonus was assessed by 2 adverse drug reaction (ADR) assessment methods: the World Health Organization-Uppsala Monitoring Centre (WHO-UMC) Causality Assessment and the Naranjo ADR scale. According to the WHO-UMC scale, the inability to establish a higher-level causality classification (eg, “probable”) in this case stem from the absence of re-exposure evidence and overlapping manifestations between drug-related symptoms and the thyroid storm itself. The Naranjo scale score of 3 (Table 5) [9] indicated a possible adverse drug reaction. Furthermore, intraoperative sympathetic hyperactivity necessitates careful differentiation from critical conditions such malignant hyperthermia and pheochromocytoma crisis. While these conditions similarly present with adrenergic hyperactivity, their therapeutic approaches are distinctly different from that used for thyroid storm.

Myoclonus is one of the major adverse effects of etomidate anesthesia, with an incidence rate exceeding 60%. Although the incidence is high, there is limited systematic description in the literature regarding its specific manifestations and duration. To date, only 1 case report involving 3 patients and 1 prospective study have specifically focused on this phenomenon, reporting that severe myoclonus lasts approximately 2 minutes [10,11]. However, in the present case, myoclonus persisted for about 20 minutes, significantly exceeding the duration described in existing literature. This unusual presentation suggests the possible involvement of additional pathogenic mechanisms. Through subsequent analysis, we believe that the patient concurrently experienced a thyroid crisis, which may have been the key contributing factor to the prolonged myoclonus. Thyroid storm is a stressful event arising from infection, surgery, anesthesia, or trauma. Although etomidate can exacerbate symptoms in hyperthyroid patients through its adverse effects, it is not a typical trigger for thyroid storm. Our patient developed thyroid storm after the administration of etomidate. We primarily considered his history of uncontrolled hyperthyroidism and the presence of other triggering factors such as infection or emotional stress.

Perioperative thyroid storm is a rare but life-threatening emergency, posing significant risks to patients undergoing surgical procedures [12]. The diagnosis of thyroid storm primarily relies on clinical manifestations and laboratory tests, but there is currently no unified diagnostic standard. The present case involved an “undiagnosed” hyperthyroid patient who, after receiving intravenous etomidate, developed severe myoclonus, followed by tachycardia and blood pressure fluctuations. These symptoms are relatively common during anesthesia and lack specificity. Additionally, anesthetic agents (such as ciprofol and rocuronium) can mask the neuromuscular symptoms of thyroid storm (such as muscle weakness), while also suppressing the thermoregulatory center, making the hyperthermia associated with thyroid storm atypical. As a result, it is difficult to promptly recognize the onset of thyroid storm. Long-standing hyperthyroidism leads to a gradual increase in muscle tone due to the persistent influence of thyroid hormones, which could explain the severe and prolonged myoclonus observed in our patient following etomidate induction. However, after anesthesia recovery, he regained consciousness and exhibited significant discomfort (eg, weakness in both lower limbs and severe hypokalemia) due to the strong stressors of anesthesia and surgery.

Hypokalemia in thyrotoxic periodic paralysis (TPP) occurs because of the shift of potassium into cells and not due to total body potassium depletion [13]. Therefore, correction of the underlying hyperthyroid state is the mainstay of therapy. Management of TPP includes active potassium supplementation, beta-blockers, and the use of anti-thyroid drugs. Potassium supplementation should be done gradually and with continuous monitoring of potassium, as systemic potassium remains constant and can cause life-threatening hyperkalemia after reaching a normal thyroid state [14].

Another notable symptom exhibited by our patient was severe tachycardia. Sinus tachycardia or atrial fibrillation, presenting in 10–25% of patients, is a common manifestation of SVT, which, although atypical, is a life-threatening precipitating symptom of thyroid storm [15]. The non-specific nature of these symptoms often complicates the diagnosis of thyroid storm in acute situations, especially when thyroid function test results are still pending [16].

Recognized precipitating factors and triggers for thyroid storm are numerous and include, but are not limited to, long-standing untreated or inadequately treated hyperthyroidism, trauma, infection, surgery, childbirth, drug-induced states or reactions, heart failure, and diabetic ketoacidosis [7]. In surgical patients, the effects of anesthetic agents can mask the typical symptoms of thyroid storm, making diagnosis even more challenging.

In our case, despite deepening anesthesia after the onset of severe myoclonus, the patient’s symptoms did not significantly improve. Furthermore, 20 minutes after emerging from anesthesia, he had transient altered mental status and bilateral lower-limb weakness. Subsequent postoperative laboratory tests and further medical history-taking confirmed our suspicion that he had experienced a thyroid storm during induction of general anesthesia.

The Burch-Wartofsky Point Scale (BWPS), introduced in 1993, is a widely accepted tool for diagnosing thyroid storm [17,18]. The scoring system considers various factors such as body temperature, cardiovascular system, central nervous system, and gastrointestinal symptoms, as well as the presence of identified precipitating factors. A BWPS score of ≥45 suggests thyroid storm, while a score of 25–44 indicates pre-thyroid storm. Based on our patient’s persistent intraoperative symptoms and a BWPS score of 55, which includes 25 points for the cardiovascular system (heart rate ≥140 bpm), 20 points for the central nervous system (postoperative transient consciousness impairment), and 10 points for precipitating factors (surgery and anesthesia), he was diagnosed with thyroid storm. Given his history of untreated hyperthyroidism and the current presentation of myoclonus, hypermetabolic symptoms, transient altered consciousness, weakness in both lower limbs, and hypokalemia, it is clear that his condition was exacerbated by untreated hyperthyroidism.

NT-proBNP is a protein-based hormone produced by the ventricles of the heart. It is released in response to cardiac wall stress during heart failure events as a protection mechanism for reducing the workload on the heart and improving its efficiency [19]. Increased cardiac muscle damage correlates with higher NT-proBNP levels, which are associated with increased cardiovascular mortality rates [20]. However, in the subsequent diagnostic and treatment activities, we did not perform any cardiac-related examinations (eg, myocardial enzymes, NT-proBNP), which was a significant oversight in the management of this case. It is also worth noting that the elevated NT-proBNP level preoperatively, although not immediately, explained by the ECG and echocardiography results, indicated potential cardiac involvement or stress, necessitating further exploration and monitoring.

Finally, throughout the entire diagnostic and treatment process, the patient never mentioned his history of hyperthyroidism. The reasons for patients concealing medical history are complex and multifaceted, involving both psychological and social factors. These factors collectively contribute to patients choosing to withhold critical information during medical consultations. This behavior reflects, to some extent, a lack of trust in the healthcare system, which hinders effective communication and the doctor–patient relationship, ultimately compromising the quality of medical care.

Conclusions

This case highlights the critical need for thorough preoperative evaluation, vigilant patient monitoring, and prompt investigation of abnormal findings in hyperthyroid patients undergoing surgery. The perioperative crisis resulted from uncontrolled hyperthyroidism, lapses in clinical/anesthetic practices, and the patient’s nondisclosure of medical history.

To prevent such events, multidisciplinary collaboration (endocrinology, anesthesiology, and surgery) is essential. Key measures include strict preoperative screening, enhanced patient education, and early recognition and management of thyroid storm. These steps can significantly reduce risks and improve outcomes.