A Case of Childhood-Onset Basedow–Graves' Disease Diagnosed as a Result of the Fourth Time of General Anesthesia for Oral and Maxillofacial Surgery

A teenage (16 years 3 months) female patient (height 156 cm, weight 45 kg, body mass index 18 kg/m²) with a history of unilateral left cleft lip and palate was scheduled for secondary unilateral cheiloplasty and rhinoplasty under general anesthesia. She had undergone cheiloplasty at 6 months of age, secondary cheiloplasty at 5 years, and alveolar cleft bone grafting from the right iliac crest at 12, all under general anesthesia without any complications. Other than migraines, for which she was taking mefenamic acid, she was healthy and denied any allergies.

Preoperative physical examination performed 1 month before surgery revealed normal vital signs aside from sinus tachycardia at a rate of 106 beats/min (bpm) and no abnormal findings. The patient's heart rate and blood pressure were notably elevated (155 bpm and 160/90 mm Hg, respectively) upon hospital admission prior to surgery, but she denied any discomfort or palpitations. She expressed nervousness; hence, the tachycardia and hypertension were assumed to be temporary and caused by anxiety. General anesthesia was rapidly induced with propofol (90 mg), remifentanil (0.5 μg/kg/min), and rocuronium (30 mg). Anesthesia was maintained with desflurane (4%) and remifentanil (0.15 μg/kg/min). Local anesthesia via infiltration was performed with 1% lidocaine with 1:200,000 epinephrine (8 mL) prior to the start of operation. Heart rate and blood pressure fluctuated within 85–105 bpm and 125–130/48–55 mm Hg during the operation.

Flurbiprofen (50 mg) and droperidol (1.25 mg) were administered 5 minute prior to the end of the operation. When anesthesia was discontinued, sugammadex (90 mg) was administered.

During emergence from anesthesia, her heart rate suddenly increased to 165 bpm, she became diaphoretic, began shivering, and developed delirium and generalized erythema of the entire body. After extubation, the erythema disappeared in 5 minutes, and delirium disappeared in 10 minutes. Her heart rate and blood pressure remained elevated (150 bpm and 147/87 mm Hg, respectively) even after she returned to normal consciousness. However, because these values approximated those at admission, she did not complain of any pain, and she was spontaneously breathing, her postoperative condition was presumed to be temporary, and she was returned to the high-dependency unit.

The patient reported nausea and anxiety that continued for 30 hours. The internal medicine department was consulted 2 days following the operation and diagnosed the patient with gastritis, which was treated with famotidine, rebamipide, and domperidone, resulting in resolution of the nausea. However, her heart rate remained elevated (130–150 bpm). We compared perioperative heart rates from her anesthesia record 4 years earlier and noted that her current heart rate was notably higher (Figure), leading to the suspicion of abnormal thyroid function. The internal medicine department was consulted to assess her thyroid function. The results showed abnormally high free T3 (fT3; 17.2 pg/mL; normal 2.3–4.0 pg/mL) and free T4 (fT4; 5.58 ng/dL; normal 0.9–1.7 ng/dL). Anti–thyroid-stimulating hormone receptor antibodies and stimulating antibodies were positive. Ultrasonography showed mild thickening of the thyroid isthmus (7.3 mm; normal 4 mm) and increased blood flow. The patient was diagnosed with childhood-onset Basedow's (Graves') disease and started on thiamazole (methimazole; 5 mg/day) and bisoprolol (5 mg/day). She was discharged 2 days later after gradual resolution of the thyrotoxicosis symptoms, stabilization of her heart rate, and reduction of her anxiety. Internal medicine continued to follow her, and 25 days after discharge, her fT3 and fT4 levels had decreased, and no other blood test abnormalities were found.

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DISCUSSION

The prevalence of childhood-onset Graves' disease is low (0.02%), although it increases beginning at age 11 and reaches its highest level during puberty.¹ It is more common in females than in males.¹ The most common clinical finding is a goiter, followed by excessive sweating, fatigue, restlessness, and finger tremors. The primary findings found in adults, such as exophthalmos, weight loss, and tachycardia, are rare in children.¹ Approximately 40% of pediatric patients with Graves' disease in Japan have a family history of the disease.¹ This patient had not been previously diagnosed with Graves' disease and lacked a positive family history. Furthermore, her primary symptom was tachycardia rather than a goiter, which is unique to childhood-onset Graves' disease. There were few other subjective symptoms noted in this case because the slow progression of the disease. When the patient was 12, no perioperative tachycardia was noted. Therefore, it was presumed that the onset of her Graves' disease occurred between 12 and 15 years of age.

In the present case, a remifentanil infusion was initiated at induction of anesthesia. The initial observed tachycardia quickly resolved, likely because of the sympatholytic effects of the remifentanil, and her cardiovascular dynamics became stable. This likely masked the underlying thyrotoxicosis and prolonged the time until it was noted and diagnosed.

In patients with uncontrolled hyperthyroidism, the stress from surgery and/or general anesthesia can trigger a thyroid storm or thyrotoxicosis. The delirium, tachycardia, and nausea/vomiting following extubation noted in the present case are findings similar to the diagnostic criteria for a thyroid storm.² However, these symptoms likely did not worsen postoperatively because of the sympatholytic activity of remifentanil, intraoperative administration of flurbiprofen for analgesia that helped to suppress any hyperthermia, and the fact that the surgical procedure was minimally invasive, as the cheiloplasty was limited to the skin and mucus membranes.

Preoperatively, the patient showed very few subjective symptoms that were suggestive of Graves' disease, aside from tachycardia. As such, suspicion was quite low until symptoms began to arise during emergence. Subsequently, as prolonged symptoms consistent with thyrotoxicosis continued to develop, the potential for thyrotoxicosis increased, prompting her to be formally evaluated, diagnosed, and started on appropriate medical management. Therefore, persistent tachycardia with no other apparent cause in pediatric patients may be a sign of undiagnosed childhood-onset Graves' disease, and further evaluation may be indicated.

This research was originally published in the Journal of the Japanese Dental Society of Anesthesiology (2019;47[4]:146–148).