Hyperthyroidism in Disguise: A Case of New-Onset Atrial Fibrillation and Acute Reversible Paralysis

Abstract

Thyrotoxic periodic paralysis (TPP) is a rare and potentially life-threatening disorder characterized by transient muscle weakness due to hypokalemia in the setting of hyperthyroidism. We present a case of a 32-year-old male with no prior history of thyroid disease who developed acute, progressive paralysis of all 4 extremities. Laboratory findings revealed profound hypokalemia, hypophosphatemia, and elevated lactate. Electrocardiography showed new-onset atrial fibrillation with a rapid ventricular response. Thyroid function tests confirmed hyperthyroidism, and further evaluation led to the diagnosis of Graves disease. The patient was treated with intravenous potassium and phosphorus replacement, leading to full neurological recovery within 24 hours. He was subsequently started on carbimazole for long-term thyroid hormone suppression. The occurrence of atrial fibrillation in TPP is an uncommon yet significant complication. Additionally, elevated lactate is an extremely rare finding.

Introduction

Thyrotoxic periodic paralysis (TPP) is a rare and potentially life-threatening complication of hyperthyroidism. It is characterized by acute, reversible episodes of muscle weakness or paralysis [1]. We report a rare case of TPP with 2 uncommon findings. These include new-onset atrial fibrillation and elevated serum lactate.

Case Presentation

A 32-year-old male individual presented to the emergency department reporting inability to move. His symptoms began with weakness in his lower extremities upon awakening in the morning, which progressively worsened, ultimately resulting in paralysis of both lower and upper limbs by the time of presentation. He was unable to mobilize independently from his bed.

The patient reported that he had performed his routine activities as usual. He worked until the afternoon. Later in the evening he engaged in a 12-kilometer walk in his neighborhood between 7:00 Pm and 9:00 Pm. This was followed by a dinner with his friends that included rice and potato-based dishes. He denied any significant sun exposure or exposure to unusual substances. He had no history of trauma, back pain, or saddle anesthesia. There were no changes in sensation. He also denied consumption of medications, illicit drugs, or alcohol.

Onset of symptoms was described as abrupt, beginning in the morning and intensifying throughout the day. By the evening, he experienced 2 episodes of vomiting, one of which occurred after his arrival in the emergency department. He denied any associated pain, fever, chills, or other systemic symptoms.

The patient's medical history was unremarkable, with no known prior illnesses. He reported no significant family history of neurological or chronic conditions. He does not consume alcohol or tobacco. He is employed as a driver in a vehicle transportation company and had relocated to the United Arab Emirates from Pakistan, approximately 1 month and 20 days prior to presentation.

Diagnostic Assessment

On examination, the patient was alert and oriented. Vital signs revealed a heart rate of 128 bpm, blood pressure of 134/78 mmHg, and a respiratory rate of 16 breaths per minute, without any fever. Pupils were equal, round, and reactive to light. His Glasgow Coma Scale score was 15/15. Sensory function was intact in all 4 limbs. On the Medical Research Council Scale for Muscle Strength, motor strength was graded as 1/5 on abduction of both shoulders and on flexion and extension of the elbows, wrists, and fingers. Muscle strength was graded 1/5 on knee flexion and extension, hip flexion, ankle dorsiflexion, and plantar flexion. Sensation to light touch and temperature was normal. Patellar reflexes were intact. Respiratory examination revealed unlabored breathing with symmetrical chest wall expansion. Abdominal examination demonstrated normal bowel sounds, with no distention or palpable organomegaly.

Laboratory investigations showed a potassium (K) level of <1.50 mEq/L (SI: <1.50 mmol/L) (reference range, 3.40-5.10 mEq/L [SI: 3.40-5.10 mmol/L]) and phosphate level of 0.78 mg/dL (SI: 0.25 mmol/L) (reference range, 2.5-4.5 mg/dL [SI: 0.81-1.45 mmol/L]) while sodium, calcium, and magnesium levels were within normal limits (Table 1). Arterial blood gas analysis demonstrated a blood pH of 7.37 (reference, 7.35-7.45), a lactate of 26.1 mg/dL (SI: 2.9 mmol/L) (reference range, 4.5-14.4 mg/dL [SI: 0.5-1.6 mmol/L]) and anion gap <14 (reference, 7-16). Serum creatinine was 0.62 mg/dL (SI: 55 µmol/L) (reference range, 0.70-1.20 mg/dL [SI: 62-106 µmol/L]) and an estimated glomerular filtration rate (eGFR) of 131 mL/min (≥60 mL/min). Serum glucose was 167 mg/dL (SI: 9.3 mmol/L) (reference range, 70-140 mg/dL [SI: 3.9-7.8 mmol/L]) and CK was 976 IU/L (reference: 39-308 IU/L).

Table 1.

Laboratory data

Variable	Reference range	On presentation	24 hours	Day 2
Sodium	136-145 mmol/L (136-145 mEq/L)	144 mmol/L (144 mEq/L)	ND	ND
Potassium	3.40-5.10 mmol/L (3.40-5.10 mEq/L)	<1.50 mmol/L < 1.50 mEq/L	5.15 mmol/L 5.15 mEq/L	ND
Chloride	98-107 mmol/L (98-107 mEq/L)	108 mmol/L (108 mEq/L)	ND	ND
Carbon dioxide	22-29 mmol/L (22-29 mEq/L)	23 mmol/L (23 mEq/L)	ND	ND
Urea nitrogen	2.80-8.10 mmol/L (7.84-22.69 mg/dL)	6.69 mmol/L (18.97 mg/dL)	ND	ND
Creatinine	62-106 µmol/L (0.70-1.20 mg/dL)	55 µmol/L (0.62 mg/dL)	ND	ND
Glucose	3.90-7.80 mmol/L (70-140 mg/dL)	9.30 mmol/L (167 mg/dL)	ND	ND
Anion gap	7-16 mmol/L	<14 mmol/L	ND	ND
Calcium	2.15-2.55 mmol/L (8.60-10.20 mg/dL)	2.45 mmol/L (9.80 mg/dL)	ND	ND
Magnesium	0.66-1.07 mmol/L (1.60-2.60 mg/dL)	0.91 mmol/L (2.20 mg/dL)	ND	ND
Alkaline phosphatase	40-129 IU/L	98 IU/L	ND	ND
Alanine aminotransferase	≤ 50 IU/L	ND	44 IU/L	ND
Aspartate aminotransferase	≤ 50 IU/L	ND	28 IU/L	ND
Bilirubin
Total	Total—< 21.00 μmol/L (<1.20 mg/dL)	ND	Total—7.40 μmol/L (0.43 mg/dL)	ND
Direct	Direct— < 5.00 μmol/L (<0.30 mg/dL)		Direct—3.90 μmol/L (0.23 mg/dL)
Albumin	35-52 g/L (3.50-5.20 g/dL)	ND	38 g/L (3.80 g/dL)	ND
Lactate	0.50-1.60 mmol/L (4.50-14.40 mg/dL)	2.90 mmol/L (26.10 mg/dL)	ND	ND
Creatine kinase	39-308 IU/L	976 IU/L	ND	ND
Venous blood gases
pH	7.35-7.45	7.39	ND	ND
Partial pressure of oxygen	25.00-40.00 mmHg	48.40 mmHg	ND	ND
Partial pressure of carbon dioxide	35.00-45.00 mmHg	38.80 mmHg	ND	ND
Urine potassium	12-20 mmol/L (12-20 mEq/L)	ND	25.57 mmol/L (25.57 mEq/L)	ND
Urine osmolality	300-900 mmol/kg (300-900 mOsm/kg)	ND	394.34 mmol/L (394.34 mOsm/kg)	ND
Thyroid-stimulating hormone (TSH)	0.270-4.200 mIU/L (0.270-4.200 µIU/mL)	ND	ND	0.005 mIU/L (0.005 µIU/mL)
Free triiodothyronine (T3)	3.10-6.80 pmol/L (2.02-4.42 pg/mL)	ND	ND	18.30 pmol/L (11.90 pg/mL)
Free thyroxine (T4)	12.00-22.00 pmol/L (9.32-17.09 pg/mL)	ND	ND	53.30 pmol/L (41.42 pg/mL)

Abnormal values are shown in bold font. Values in parenthesis are conventional units.

Abbreviation: ND, no data.

Hematological analysis revealed white blood cell (WBC) count of 13.6 × 10⁹/L (reference: 4-11 × 10⁹/L) and C-reactive protein (CRP) of 4.55 mg/L (reference: ≤5.00 mg/L). Serum toxicology screen was negative for acetaminophen, ethanol, salicylates, and tricyclic antidepressant medication.

Electrocardiography (ECG) demonstrated atrial fibrillation with ventricular rate of 111 bpm (Fig. 1). The patient was promptly admitted to the medical intensive care unit and initiated on intravenous potassium and phosphorus infusions.

Figure 1.

12-lead ECG showed atrial fibrillation with rapid ventricular response, ST deviation, and moderate T-wave abnormality.

The following day, laboratory tests showed a thyroid-stimulating hormone (TSH) level of 0.005 µIU/mL (SI: 0.005 mIU/L) (reference range, 0.270-4.200 µIU/mL [SI: 0.270-4.200 mIU/L]), triiodothyronine (T3) of 11.90 pg/mL (SI: 18.3 pmol/L) (reference range, 2.0-4.3 ng/dL [SI: 3.10-6.80 pmol/L]), and thyroxine (T4) at 4.1 ng/dL (SI: 53.3 pmol/L) (reference range, 0.9-1.7 ng/dL [SI: 12.0-22.0 pmol/L]). Serum K was 5.15 mEq/L (SI: 5.15 mmol/L), phosphate levels were 4.2 mg/dL (SI: 1.35 mmol/L), and urine K was 25.5 mEq/L (SI: 25.5 mmol/L) (reference range, 12-20 mEq/L [SI: 12-20 mmol/L]). The transtubular potassium gradient (TTKG) was calculated at 3.83.

Thyroid autoantibody testing revealed TSH-receptor antibodies (TRAb) 12.8 IU/L (reference: ≤1.75 IU/L) and thyroid peroxidase (TPO) 344 IU/mL (reference: ≤34 IU/mL), consistent with Graves disease.

The endocrinology team assessed the patient; there was no history of weight loss, tremors, palpitations, or heat intolerance. A diffuse goiter without any palpable nodules was noted on physical examination. He demonstrated recovery of full motor function in all extremities and was able to ambulate to the restroom with assistance. Given the elevated thyroid hormone levels, suppressed TSH, and normal inflammatory markers, a diagnosis of Graves disease with thyrotoxic hypokalemic periodic paralysis was established. The Burch-Wartofsky score was calculated to be 30 and using the Japan Thyroid Association criteria, the patient was classified as TS1.

Treatment

The patient was initiated on carbimazole 10 mg daily for thyroid hormone suppression. Beta-blockers were not initiated due to the patient's blood pressure of 99/67 mmHg and heart rate of 69 beats per minute. He was transferred to the ward.

Outcome and Follow-Up

On hospital day 3, the patient's motor strength was graded as 4/5 by the Medical Research Council Scale for Muscle Strength on abduction of both shoulders and on flexion and extension of the elbows, wrists, and fingers. Muscle strength was graded 4/5 on knee flexion and extension, hip flexion, ankle dorsiflexion, and plantar flexion. His vital signs showed a heart rate of 69 bpm, respiratory rate of 17 breaths per minute, and blood pressure of 99/67 mmHg. Given his clinical stability and resolution of significant motor deficits, he was discharged home.

At the follow-up evaluation, the patient reported no active symptoms of hyperthyroidism and was in good overall health. Neurological examination demonstrated full motor strength (5/5) in both upper and lower extremities bilaterally. There were no signs of muscle weakness, hyperhidrosis, palpitations, or visual disturbances on physical examination.

Discussion

We report a rare case of TPP with 2 uncommon findings. These include new-onset atrial fibrillation and elevated serum lactate.

A distinctive finding in our patient is new-onset atrial fibrillation, a finding which had not been previously documented in this patient. Sinus tachycardia and atrial fibrillation are the most frequent cardiac arrhythmias observed in hyperthyroidism patients, occurring in approximately 10% to 20% of cases [2, 3]. However, the concurrent diagnosis of TPP and atrial fibrillation is relatively uncommon [3, 4]. We could not find a report of atrial fibrillation as a presenting finding in TPP in the literature. The incidence of atrial fibrillation in TPP varies across populations but is generally lower than in other patients with hyperthyroidism [3-5]. The reduced incidence is attributed to the demographic profile of TPP patients, who are predominantly younger males with fewer comorbidities commonly associated with atrial fibrillation [4, 5]. In TPP, both hyperthyroidism and hypokalemia contribute to cardiac arrhythmias [3]. During an attack, hypokalemia slows repolarization, prolongs the refractory period, and thereby predisposes to arrhythmias. This is exacerbated as ventricular repolarization is also prolonged in hyperthyroidism [3]. Atrial fibrillation associated with TPP is often reversible. Once thyroid function normalizes and the underlying metabolic derangements are corrected, the arrhythmia typically resolves without the need for long-term antiarrhythmic therapy [6].

The elevated lactate in our patient is a remarkable and rare finding. To our knowledge, only 2 cases of high lactate associated with TPP have been reported [7, 8]. A postulated mechanism for this phenomenon is that it occurs as a result of acute muscle metabolic stress during paralytic episodes [7, 8]. Excess thyroid hormone enhances Na⁺/K⁺-ATPase activity, particularly in skeletal muscle, leading to significant intracellular potassium shifts and increased ATP consumption [1, 7, 8]. This high metabolic demand, along with reduced muscle perfusion and impaired oxidative phosphorylation during paralysis, shifts energy production toward anaerobic glycolysis, resulting in lactate accumulation [7, 8]. Additionally, elevated catecholamines and insulin in hyperthyroid states further amplify glycolytic flux and lactate production [7, 8].

The elevated lactate may also reflect altered carbohydrate metabolism in thyrotoxicosis, where excess thyroid hormone promotes glycolysis and glycogenolysis, favoring lactate production over complete glucose oxidation [9-11]. Patients with TPP are often reported to have hyperinsulinemia, particularly following high-carbohydrate loads, which may further enhance glycolytic activity and contribute to lactate accumulation [10]. However, this association has not been consistently observed across all studies [10]. The resulting shift toward anaerobic metabolism reflects increased substrate flux through glycolysis rather than elevated lactate dehydrogenase (LDH) activity. Although rare cases report abnormal LDH isoenzymes in thyrotoxicosis, this is not typical of TPP [9, 10].

While lactate accumulation may contribute to transient muscle fatigue through intracellular acidosis and impaired calcium handling, it does not directly cause paralysis in TPP [7, 8]. Thus, elevated lactate likely reflects a secondary consequence of metabolic disturbance and acute muscle stress rather than a primary cause of weakness or paralysis.

TPP is generally more frequently reported among individuals of Asian descent [1, 12, 13]. However, a closer review of the literature reveals that the vast majority of reported cases are from East Asian populations [1, 12-14]. The patient described in this case, although residing in the Middle East, was of South Asian origin. While South Asians are often categorized within the broader “Asian” demographic, there is limited literature specifically addressing TPP in this subgroup [1]. This under-representation may be attributable to both underdiagnosis and insufficient reporting. The patient's ethnicity and recent immigration to the Middle East highlight the evolving distribution of TPP, particularly in the context of shifting global migration patterns [3, 15]. As populations become increasingly mobile and diverse, conditions such as TPP, once considered rare outside specific ethnic groups, may emerge in previously unexpected geographic and demographic settings [1, 3, 14].

This evolving demographic distribution also calls attention to the underlying genetic predispositions that may differ across populations. Although our patient was not specifically tested for it, certain haplotypes of KCNJ18 are associated with a higher susceptibility to and therefore also explain ethnic differences in TPP. Mutations in potassium channels, particularly Kir2.6 encoded by KCNJ18, predispose individuals to TPP by altering channel expression, membrane localization, or function, leading to hypokalemic paralysis during thyrotoxic states [1, 16]. For instance, the D252N mutation in the C-terminus of Kir2.6 has been shown to downregulate the channel, supporting its direct role in TPP pathogenesis [13, 17]. Genetic studies reveal population-specific differences in prevalence of KCNJ18 variants, with certain polymorphisms and haplotypes more prevalent in East and Southeast Asians compared to Caucasian or Middle Eastern groups [16, 18]. Our patient, of Pakistani origin, represents a South Asian demographic where TPP is under-reported, although emerging evidence suggests similar Kir2.6 polymorphisms may also exist in this population [18]. These findings highlight that Kir2.6 mutations contribute significantly to TPP development, influenced by genetic background.

Learning Points

• Rare association with new-onset atrial fibrillation: While atrial fibrillation is common in hyperthyroid patients, its occurrence during an acute TPP episode is rare. This case suggests that the combined effects of hypokalemia and thyrotoxicosis can trigger arrhythmias, emphasizing the need for ECG monitoring in all suspected TPP cases.

• Elevated lactate is an unusual finding in TPP: While TPP typically presents with hypokalemic paralysis, elevated lactate is not commonly seen. In this case, it likely reflects acute muscle metabolic stress from thyroid hormone excess, highlighting the need to consider thyrotoxic related metabolic changes when interpreting unexpected lactate elevations.

• Changing epidemiology of TPP with global migration: As populations become more mobile and diverse, TPP, once considered rare outside specific ethnic groups, may present in unusual settings.

Contributors

All authors made individual contributions to authorship. U.S., N.A., and S.D. were involved in the diagnosis and management of the patient and manuscript submission. All authors reviewed and approved the final draft.

Abbreviations

ECG

electrocardiography

K

potassium

TSH

thyroid-stimulating hormone

TTP

thyrotoxic periodic paralysis

Funding

No public or commercial funding.

Disclosures

The authors declare that they have no conflict of interest to disclose.

Informed Patient Consent for Publication

Signed informed consent obtained directly from patient.

Data Availability Statement

Data sharing is not applicable to this article as no datasets were generated or analyzed during the current study.