Atypical Thyroid Storm Manifesting as Refractory Hypoglycemia and Fulminant Liver Failure in an Older Woman: A Case Report

Introduction

Thyroid storm (TS) is a rare, acute, and life-threatening manifestation of thyrotoxicosis that requires immediate medical intervention [1]. It constitutes approximately 1% to 2% of hyperthyroidism-related hospital admissions, with an incidence of 0.57 to 0.76 cases per 100 000 in the general population and 4.8 to 5.6 cases per 100 000 among hospitalized patients [2]. The Japanese National Survey revealed a lower annual incidence of 0.2 per 100 000 people, representing 0.22% of all patients with thyrotoxicosis [3]. Most often associated with Graves’ disease, TS is typically triggered by acute stressors, including infection (the most common precipitant), surgery, trauma, or discontinuation of antithyroid medication [4,5]. The classic clinical presentation includes tachycardia, fever, heart failure, atrial fibrillation, gastrointestinal disturbances (eg, vomiting and diarrhea), hepatic dysfunction, and central nervous system abnormalities [6]. Multiorgan dysfunction, a hallmark of advanced TS, represents the most common cause of mortality in these patients; the overall mortality rate is 8% to 25%, despite modern therapeutic and supportive measures [7]. Although hepatic involvement can occur in thyrotoxicosis, progression to fulminant liver failure remains a rare but catastrophic complication [8,9]. This report describes a 73-year-old woman with an atypical presentation of life-threatening TS, highlighting the diagnostic challenges and poor outcomes associated with delayed diagnosis.

Case Report

A 73-year-old woman with no clinically significant medical history (eg, thyroid disease) presented to our emergency department reporting abdominal distension and palpitations for the preceding month. She denied prior symptoms suggestive of hyperthyroidism, such as weight loss, heat intolerance, tremor, or goiter. One day before admission, she visited a local hospital, where an electrocardiogram revealed paroxysmal atrial fibrillation, and rate-control therapy was initiated. Due to a lack of symptomatic improvement, she was transferred to our center.

On arrival, her vital signs were as follows: heart rate 111 beats/min, respiratory rate 29 breaths/min, blood pressure 175/105 mmHg, and body temperature 36.7°C. She appeared agitated. Physical examination revealed abdominal distension without tenderness or palpable masses. No goiter or thyroid tenderness was noted. Initial laboratory tests showed leukocytosis (white blood cell count 13 290/μL [reference range: 3500–9500/μL]), thrombocytopenia (platelet count 83 000/μL [reference range: 125 000–350 000/μL]), coagulopathy (prothrombin time 25.7 seconds [reference range: 11–15 seconds], INR 2.4 [reference range: 0.85–1.5]), elevated D-dimer (12.19 mg/L [reference range: <0.5 mg/L]), and mild hyperbilirubinemia (total bilirubin 3.0 mg/dL [reference range: ≤1.35 mg/dL]). Arterial blood gas analysis revealed metabolic acidosis with severe lactic acidosis (pH 7.275, lactate 12.4 mmol/L) and, most critically, profound hypoglycemia (glucose 0.6 mmol/L; capillary glucose 0.24 mmol/L).

Given the life-threatening hypoglycemia, intravenous glucose supplementation was immediately initiated. Abdominal ultrasound suggested cholecystitis; however, contrast-enhanced computed tomography showed only gallbladder distension without wall thickening, pericholecystic fluid, or signs of acute cholecystitis. The patient was administered intravenous fluids, metoprolol for rate control, and empirical antibiotics. Concurrently, an endocrinology consultation was obtained to evaluate the persistent hypoglycemia and metabolic derangements. Additional laboratory tests, including thyroid and islet function studies, were performed.

On the second hospital day, the patient developed episodes of agitation. Laboratory tests revealed severe thyrotoxicosis: free triiodothyronine 10.30 pg/mL (reference range: 2.0–4.4 pg/mL), free thyroxine 6.11 ng/dL (reference range: 0.92–1.68 ng/dL), and thyroid-stimulating hormone below 0.008 μIU/mL (reference range: 0.27–4.20 μIU/mL). Anti-thyroid-stimulating hormone receptor antibodies were greatly elevated at 25.2 IU/L (reference range: <1.75 IU/L), and anti-thyroid peroxidase antibodies were very high (111.00 IU/mL [reference range: <34 IU/mL]). To assess adrenal reserve under severe stress, morning plasma adrenocorticotropic hormone and cortisol levels were measured (17.73 pg/mL [reference range: 7.2–63.4 pg/mL] and 46.72 μg/dL [reference range: 4.26–24.85 μg/dL], respectively); these findings indicated an appropriate stress response and ruled out adrenal insufficiency. Concurrently, liver function dramatically deteriorated, such that the aspartate aminotransferase level was 3767 U/L (reference range: 0–40 U/L) and alanine aminotransferase level was 791 U/L (reference range: 9–50 U/L); cardiac enzyme levels also were elevated. Echocardiography showed an increased left ventricular end-diastolic diameter, reduced ejection fraction (43%), and diastolic dysfunction. Heart rate fluctuated between 103 and 158 beats/min, with a maximum temperature of 37.3°C. The Burch-Wartofsky Point Scale score was 70 (≥45 indicates TS), confirming the diagnosis of TS complicated by acute liver failure, disseminated intravascular coagulation, and heart failure.

Therapeutic interventions included hepatic protection, ventricular rate control, low-molecular-weight heparin anticoagulation, and antibiotic prophylaxis. Due to severe hepatic dysfunction, conventional antithyroid drugs were contraindicated. After discussion with the family, stress-dose corticosteroids (intravenous hydrocortisone 100 mg and dexamethasone 5 mg daily) were administered for 2 days in an attempt to mitigate shock and inhibit peripheral T4-to-T3 conversion; however, no clinically or biochemically significant responses were observed. The multidisciplinary team recommended emergent hemodialysis or plasma exchange to reduce circulating thyroid hormone levels as a life-saving measure; however, these invasive procedures were precluded by a prohibitive bleeding risk due to profound coagulopathy secondary to liver failure. After detailed risk-benefit counseling, the family chose palliative discharge with comfort care. The patient died 3 days after discharge (Figure 1).

Discussion

This case highlights several important lessons for clinicians: TS can present with atypical, nonspecific symptoms in patients lacking known hyperthyroidism, and delayed recognition can lead to irreversible multiorgan failure with limited therapeutic options. TS is a rare, life-threatening exacerbation of hyperthyroidism characterized by extreme metabolic disturbances and multiorgan dysfunction, requiring immediate intervention. It typically occurs in individuals with preexisting hyperthyroidism and is precipitated by factors such as infection (the most common trigger), surgery, trauma, or discontinuation of antithyroid medications [1,10]. The clinical presentation reflects a hypermetabolic state with multisystem involvement, including persistent tachycardia, fever, heart failure, atrial fibrillation, gastrointestinal disturbances (eg, vomiting and diarrhea), hepatic dysfunction, and central nervous system abnormalities such as agitation [11]. Diagnosis is primarily clinical and integrates laboratory confirmation of thyrotoxicosis (elevated free T4/T3, suppressed thyroid-stimulating hormone) with scoring systems; the Burch-Wartofsky Point Scale, with a score of 45 or greater, is the most widely used diagnostic tool [6,12]. Although a history of hyperthyroidism increases clinical suspicion, diagnosing TS in patients without a known thyroid disorder – as in the present case – poses a substantial challenge that often leads to delayed thyroid function testing and postponement of critical, life-saving therapies [13]. This difficulty is compounded by the nonspecific, multisystem manifestations of TS, which can mimic sepsis, sympathomimetic toxicity, or other critical illnesses. Similar diagnostic challenges have been reported: Muneem et al described a patient without prior thyroid disease whose TS was initially indicated only by increased ileostomy output [14], whereas Vidanapathirana et al reported a fatal case of TS complicated by acute liver failure and disseminated intravascular coagulation in a patient who initially presented with palpitations and heat intolerance – symptoms more typical of hyperthyroidism than those observed in our patient [15].

Our patient, with no history of hyperthyroidism, experienced more than 1 month of palpitations and abdominal distension. Initial evaluation at a primary care facility identified atrial fibrillation but did not include investigation of underlying etiologies such as TS. Comprehensive testing at our tertiary center, prompted by profound hypoglycemia, confirmed thyrotoxicosis. By that time, progressive hepatic and cardiac failure had already developed. This delay underscores the diagnostic difficulty posed by the nonspecific, multisystem manifestations of TS, which can mimic sepsis, sympathomimetic toxicity, or other critical illnesses [4,13].

In severe thyrotoxicosis, assessment of adrenal reserve is crucial because physiologic stress increases cortisol demand [16]. In the present case, adrenal function testing demonstrated a robust stress response, effectively excluding primary adrenal insufficiency. This finding indicates that the patient’s hemodynamic instability and metabolic derangements were primarily driven by TS. Despite normal adrenal function, stress-dose corticosteroids were administered as adjunctive therapy because standard antithyroid drugs were contraindicated due to severe hepatic injury. The goals were to provide glucocorticoid support and potentially inhibit peripheral T4-to-T3 conversion. However, no clinically or biochemically significant improvement was observed, highlighting the refractory nature of TS in the context of fulminant multiorgan failure, where the overwhelming metabolic crisis may exceed the modulating capacity of steroid therapy.

Conventional management of TS involves a multifaceted approach: control of adrenergic tone with beta-blockers, inhibition of thyroid hormone synthesis with thionamides, blockade of peripheral T4-to-T3 conversion with glucocorticoids, and reduction of circulating thyroid hormone levels with iodine solutions [17]. In the present case, however, profound hepatic dysfunction contraindicated conventional antithyroid drugs; despite administration of stress-dose corticosteroids, the patient’s clinical course continued to deteriorate. For patients with refractory multiorgan failure, salvage therapies such as plasmapheresis and extracorporeal membrane oxygenation (ECMO) have emerged as potential options. Plasmapheresis facilitates rapid reduction of circulating thyroid hormone levels and has demonstrated value in TS complicated by heart or liver failure [18], whereas ECMO provides circulatory support to patients with refractory cardiogenic shock. Eltahir et al reported a case series in which venoarterial ECMO was successfully used to manage TS with multiorgan failure [19]. Li et al described 14 ICU patients with TS who received ECMO; the overall survival rate was approximately 70% [20]. Nagakawa et al described a case of TS with acute liver failure, which required venoarterial ECMO followed by successful living donor liver transplantation [21]. In our patient, the prohibitive bleeding risk from coagulopathy precluded plasmapheresis; the severity of coagulopathy – along with the family’s selection of palliative care – precluded ECMO or other invasive interventions, reflecting the narrow therapeutic window available once multiorgan failure occurs.

For patients with TS-induced refractory multiorgan failure who are not candidates for conventional therapies or plasmapheresis, venoarterial ECMO has emerged as a salvage option. As briefly noted above, Eltahir et al published a case series in which venoarterial ECMO was successfully used to provide circulatory support for patients with TS complicated by cardiogenic shock and multiorgan failure, allowing time for medical therapy to take effect [19]. Although this approach was not feasible for our patient due to the severity of coagulopathy and the family’s selection of palliative care, it represents a potential option in selected refractory cases.

Our patient’s initial presentation, with systemic inflammation and organ dysfunction, strongly suggested septic shock. However, subsequent evaluation – including cross-sectional imaging, normal procalcitonin levels, and surgical consultation – did not identify an acute infectious source or biliary pathology. Empirical antibiotics were administered given that sepsis remains the most common trigger for TS, but the clinical course was predominantly consistent with severe thyrotoxic crisis. This case illustrates the difficulty of distinguishing the systemic inflammatory response of TS from true sepsis.

The etiology of refractory hypoglycemia in our patient was multifactorial. Although sepsis and shock are classic causes, the absence of a confirmed infectious focus made severe infection an unlikely sole explanation. Adrenal insufficiency was also excluded. In this context, hypoglycemia is best understood as the result of converging metabolic disturbances: (1) the hypermetabolic state of thyrotoxicosis substantially increased glucose consumption; (2) poor oral intake before admission led to depleted glycogen stores [22]; (3) most critically, fulminant hepatic failure severely impaired gluconeogenesis and glycogenolysis, the liver’s primary mechanisms of glucose regulation [15]; and (4) under extreme physiologic stress, a state of relative adrenal insufficiency – where normal cortisol levels are inadequate for increased demand – may have impaired counterregulatory responses [23]. Vidanapathirana et al similarly reported hypoglycemia and refractory lactic acidosis in a patient with TS experiencing acute liver failure, underscoring that these metabolic derangements are markers of end-stage hepatic dysfunction rather than isolated events [15]. Thus, our patient’s hypoglycemia served as an early marker of systemic metabolic failure, driven by hypermetabolic substrate depletion compounded by acute loss of hepatic glucoregulatory function. This hypoglycemia may have exacerbated hepatic ischemic-hypoxic injury, thereby accelerating liver failure.

At the time of diagnosis, the patient had already progressed to end-stage multiorgan failure. Conventional first-line therapies were deemed inappropriate due to profound hepatic dysfunction and the lack of short-term benefit. In such scenarios, prompt reduction of circulating thyroid hormone levels is essential. Plasmapheresis serves as a rescue therapy for this purpose and has established value in TS accompanied by heart or liver failure [18,24]. In the present case, however, a prohibitive bleeding risk due to liver-failure-induced coagulopathy precluded this invasive procedure.

Conclusions

This case highlights the critical need to maintain a high index of clinical suspicion for thyroid dysfunction in patients who present with nonspecific multisystem symptoms, even those lacking a prior history of thyroid disease. Delayed diagnosis of atypical TS can lead to irreversible multiorgan failure, underscoring the importance of prompt thyroid function testing to enable timely intervention and potentially improve clinical outcomes. Failure to recognize an atypical presentation of this life-threatening condition carries grave prognostic consequences and emphasizes the need to include TS in the differential diagnosis of patients with unexplained metabolic derangements, hepatic dysfunction, and cardiovascular abnormalities.