Seizures in pediatric thyroid storm: Two cases and a literature review

Abstract

Thyroid storm is a life-threatening disorder caused by thyrotoxicosis. Diagnostic criteria in adults emphasize central nervous system (CNS) symptoms, including seizures, as CNS symptoms are associated with irreversible damage. However, children have a lower seizure threshold than adults, which may lead to overestimation of severity in pediatric cases with seizures. This study reports two pediatric cases of thyroid storm with seizures, fever, and tachycardia. The more severe case remained unconscious and restless, necessitating intubation and intensive care. The other case regained consciousness spontaneously following the initiation of treatment for thyroid storm. A literature review of 84 children and adolescents with thyroid storm revealed 16 cases (19%) that exhibited seizures. The prevalence of seizures was higher in infants (30.0%) and children (30.4%) than in adolescents (7.3%). Almost all 16 cases with seizures had favorable outcomes, suggesting that seizures in pediatric thyroid storm cases may not be associated with poor prognosis. Although seizures appear to be more common in pediatric thyroid storm and may not necessarily predict poor outcomes, the presence of seizures warrants careful evaluation because of the life-threatening nature of the condition.

Highlights

● In thyroid storm, seizures are more frequent in children than in adults.

● Pediatric thyroid storm with seizures may not necessarily lead to poor outcomes.

Introduction

Thyroid storm is a rare but life-threatening disorder characterized by multiple organ failure due to thyrotoxicosis. The fatality rate is approximately 11% (1); therefore, prompt diagnosis is essential to prevent death. Nationwide surveys in Japan estimate that the incidence of thyroid storm is ~0.2 individuals per 100,000 annually, with 0.22% of all thyrotoxic cases developing thyroid storm (1). Since no large cohort studies on pediatric thyroid storm have been conducted, its incidence remains unknown.

Among adult patients, the diagnostic criteria for thyroid storm emphasize the importance of central nervous system (CNS) symptoms, including seizures, because of their prognostic significance (1). The prevalence of seizure among thyroid storm cases is approximately 4% (1). Children generally have a lower seizure threshold than adults, and children with thyroid storm may be more prone to seizures (2, 3). Since febrile seizures are common in children, particularly between the age of six months and six years, pediatric patients with thyroid storm who develop fever and seizures may initially be diagnosed with febrile seizures (3). It remains unclear whether the prognosis of pediatric patients with thyroid storm presenting with CNS symptoms is as poor as that of adults, partly because thyroid storm is rarer in children than in adults. Additionally, owing to its rarity, pediatric-specific diagnostic criteria and treatment guidelines have not yet been established (2). Therefore, accumulation of pediatric thyroid storm cases is needed for prompt diagnosis and treatment.

This study presents two pediatric cases treated for thyroid storm with seizures, fever, and tachycardia, exhibiting different degrees of severity.

Case Presentation

Case 1

An 11-yr-old girl was taken to hospital in an ambulance because of generalized tonic-clonic seizure lasting for 10 min. The patient had fever (highest body temperature of 39.7°C) since the day before the onset of seizure. Over the past several months, she had difficulty concentrating in class and was considered for placement in a special needs class. The patient had exophthalmos for two mo and fatigability for a few weeks. Hypertension (160/75 mmHg) and tachycardia were also observed. Hyperthyroidism was suspected because tachycardia was more severe than her body temperature would suggest. The patient also presented with hyperthyroidism (Table 1). She presented with seizures for three min, followed by restlessness. She was diagnosed with thyroid storm and administered methimazole (MMI) 10 mg/dose and hydrocortisone 100 mg/dose. The patient was transferred to our hospital for treatment of thyroid storm. The Glasgow Coma Scale (GCS) score was 9 at the time of admission. Slight eye proptosis was observed. Thyroid volume was 11.1 mL (+2.0 standard deviation (SD)) on ultrasound. Based on the percentile data reported by Suzuki et al. (4), approximate SD values were estimated using the range between the 2.5th and 97.5th percentiles (SD ≈ [97.5th − 2.5th]/4), assuming a near-normal distribution. Chest X-ray showed mild cardiomegaly without pulmonary edema. Echocardiogram revealed an estimated left ventricular ejection fraction of 72%. The patient did not indicate liver failure or jaundice (Table 1). Rapid antigen tests for influenza, group A streptococcus, and adenovirus yielded negative results. The venous blood culture results were negative. The thyroid-stimulating hormone receptor antibody (TRAb) level was elevated (Table 1). Since consciousness disorder and restlessness persisted, the patient was placed on mechanical ventilation for two days in the intensive care unit. She was administered MMI via a nasogastric tube, hydrocortisone via intravenous injection, and potassium iodine per os (po) (Table 1). Tachycardia was controlled by landiolol hydrochloride. On day 14 of admission, free T₃ and free T₄ were within normal ranges. The patient was discharged on day 17 after admission without after-effects, and did not develop seizures thereafter. She went on to graduate from vocational college. The patient experienced several relapses of Graves’ disease and was still taking MMI at the age of 19 yr.

Table 1. Clinical manifestations of two cases.

Case 2

A 7-yr-old girl experienced poor weight gain for approximately 1 yr. She did not have CNS symptoms such as restlessness or psychiatric disturbances. She was born at 23 wk gestation and weighed 498 g. She also had mild intellectual disability. She developed fever the day before hospitalization. She was rushed to hospital because of generalized tonic seizures lasting 5 min, followed by 5 min of sursumvergence. Although the patient’s consciousness was clear when she arrived at the hospital, her age was atypical for the first onset of febrile seizures; thus, the cause of the seizures was investigated. The patient presented with thyroid swelling, fever, tachycardia, and thyrotoxicosis (Table 1). Rapid antigen tests for influenza, group A streptococcus, and adenovirus yielded negative results. The patient was diagnosed with thyroid storm and transferred to our hospital. Thyroid volume was 17.6 mL (+13.0 SD), estimated according to the percentile data reported by Suzuki et al. (4). Slight eye proptosis was observed. Chest X-ray showed no cardiomegaly or pulmonary edema. Echocardiogram revealed an estimated left ventricular ejection fraction of 81%. Liver enzyme levels were slightly elevated (Table 1). The patient was administered MMI (po), hydrocortisone (intravenous injection), potassium iodine (po), and propranolol (Table 1). Brain MRI was normal on day 11 of admission. On day 12 after admission, the patient was discharged without after-effects. Electroencephalograph (EEG) was normal approximately one month after discharge.

At the age of 8 yr, the patient developed liver damage 1 yr and 3 mo after initiating MMI (AST 64 IU/L, ALT 277 IU/L, LDH 283 IU/L, total bilirubin 0.8 mg/dL). Thyroidectomy was performed because of uncontrolled liver damage at the age of 8 yr. By taking levothyroxine, the patient has mostly maintained euthyroid. After developing frontal lobe epilepsy, treatment with levetiracetam was initiated at the age of 10 yr. The last epileptic seizure occurred at the age of 14 yr.

Literature Review

The PubMed database was searched in March 2025 using the keywords “Thyroid storm,” filtering by age and article language as “Child: birth–18 yr” and “English,” respectively. The PubMed database was also searched using the keywords ((Thyroid storm) AND (child)) OR ((Thyroid storm) AND (pediatric)), filtering by article language as “English.” A total of 84 cases with thyroid storm were identified, aged 0–18 yr, containing clinical information (Supplementary Fig. 1, Supplementary Table 1). Sixteen of 84 cases with thyroid storm (19.0%) had seizures. Infants and children with thyroid storm had a higher frequency of seizures (approximately 30%) than adolescents (Fig. 1, Supplementary Table 2).

Fig. 1.

Seizure frequency in thyroid storm. The black bars show the frequency of cases with seizures in our literature review. ‘Birth–infant’ includes cases aged 0–5 yr. ‘Child’ includes cases aged 6–12 yr. ‘Adolescent’ includes cases aged 13–18 yr. The frequency in each group was 30.0% (6 of 20 cases), 30.4% (7 of 23 cases), and 7.3% (3 of 41 cases), respectively. The white bar indicates frequency in a nationwide Japanese survey, 3.9% (14 of 356 cases), of which include mostly adult cases (reference number 1).

In 16 pediatric cases with seizures during thyroid storm, one case developed stroke leading to persistent neurological defects, whereas 15 of 16 cases recovered from thyroid storm without persistent complications (Table 2, Supplementary Table 3) (3, 5,6,7,8,9,10,11,12,13,14,15,16,17). We retrospectively calculated the Burch-Wartofsky Point Scale (BWPS) scores for pediatric thyroid storm cases with seizures (Table 2, Supplementary Table 3). When the original article did not provide BWPS details, we estimated scores based on reported clinical features, written in italics in Table 2 and Supplementary Table 3. The scores ranged from 50 to 105 (median 75).

Table 2. Two current cases and 16 pediatric cases with seizures from the literature review.

Discussion

In the present study, two pediatric cases with hyperthyroidism exhibited the same three symptoms —seizures, fever, and tachycardia—that met the adult diagnostic criteria for thyroid storm. However, the severity varied in the acute phase. Case 1 presented a more severe form with prolonged unconsciousness and restlessness following seizures, requiring intubation and intensive care. In contrast, while Case 2 met the diagnostic criteria, the clinical course was much milder, regaining consciousness spontaneously soon after seizure; however, tachycardia and high fever persisted at the start of treatment for hyperthyroidism.

Both diagnostic criteria for adult patients with thyroid storm, the Japan Thyroid Association (JTA) diagnostic criteria (1) and the BWPS (18), were applicable to our cases. The JTA criteria do not use a grading system because the mortality rate does not differ significantly between the two graded groups (definite and suspected groups) (1). However, irreversible neurological defects were more frequent in the definite group (1). The BWPS criteria use scoring to identify thyroid storm; however, this may not be directly applicable to pediatric patients because of physiological differences, such as a naturally higher heart rate.

Notably, both our cases had identical BWPS scores despite clearly different severities, suggesting limitations in assessing severity via the BWPS score. In particular, the BWPS allocates 30 points for seizures, which can dramatically increase the total score. In the literature review conducted for this study, one pediatric case with persistent neurological complication (due to stroke) had an estimated BWPS score of 65 (13), whereas several cases with higher scores indicated favorable outcomes (Supplementary Table 3). These findings highlight that the BWPS may overestimate severity in pediatric cases, particularly when seizures develop. Nonetheless, because of the high fatality rate of thyroid storm, seizure should not be neglected when diagnosing thyroid storm in children, just as in adults.

In this study’s review of 84 pediatric thyroid storm cases, 16 (19%) presented with seizures (3, 5,6,7,8,9,10,11,12,13,14,15,16,17). This frequency is substantially higher than the 4% reported in a nationwide Japanese survey which comprised mostly adults (median age 44 yr) (1) (Fig. 1). Furthermore, seizure prevalence was lower among adolescents, and no cases aged 16–18 yr developed seizures (Supplementary Table 3). These results highlight that younger children with thyroid storm are more likely to develop seizures because of their lower seizure thresholds.

All 16 cases with seizures identified in our review survived, and only one case (6.3%) had persistent neurological complication due to stroke (Supplementary Table 3). One of the current patients (Case 2) developed epilepsy three years after the thyroid storm; however, the causal relationship remains unclear. Since the EEG and MRI in Case 2 showed no abnormal findings after thyroid storm (2 wk after admission and 12 d after admission, respectively), thyroid storm would be less likely to cause epilepsy three years after admission. Furthermore, the patient had other risk factors for epilepsy such as premature birth and mild developmental delays. Case 1 did not develop epilepsy or developmental impairment after thyroid storm for at least eight years. These findings suggest that seizures during thyroid storm do not necessarily predict poor prognosis. However, given the life-threatening potential of thyroid storm, the presence of seizures should not be ignored when assessing disease severity.

In the cases presented in this study, viral infection was not fully excluded because viral polymerase chain reaction panels such as FilmArray were not performed. Therefore, the possibility of febrile seizures triggered by infection combined with undiagnosed Graves’ disease cannot be ruled out, rather than a direct CNS complication of thyroid storm. Fever is more commonly caused by viral infection than thyrotoxicosis, particularly in children. Since thyroid hormones lower the seizure threshold (19, 20), children with thyrotoxicosis may easily develop febrile seizures. However, since infection is also a common trigger of thyroid storm, it is difficult to clearly distinguish between seizures as a CNS manifestation of thyroid storm and febrile seizures coinciding with thyrotoxicosis.

In conclusion, while seizures are more common in pediatric thyroid storm and do not necessarily predict poor outcomes, the presence of seizures warrants careful evaluation because of the potentially life-threatening condition.

Conflict of interests

The authors have no conflicts of interest to declare.