Introduction: Accurate diagnosis of thyrotoxicosis, a condition resulting from excessive thyroid hormone activity, is essential for appropriate management. However, access to diagnostic tools such as thyrotropin receptor antibody (TRAb) assays and thyroid ultrasonography remains limited in resource-constrained settings, highlighting the need for cost-effective alternatives. Recent studies suggest that the free triiodothyronine to free thyroxine (FT3/FT4) ratio may serve as a potential biomarker for differentiating the causes of thyrotoxicosis. Methodology: This cross-sectional study evaluated the FT3/FT4 ratio in newly diagnosed thyrotoxicosis patients aged ≥18 years recruited from Hospital Tengku Ampuan Rahimah, Hospital Banting, Klinik Kesihatan Pelabuhan Klang, and Klinik Kesihatan Pandamaran between February and December 2025. All participants underwent thyroid function testing (FT3, FT4, and TSH) and autoantibody assessment (TRAb and anti-thyroid peroxidase [anti-TPO]). Diagnostic performance of the FT3/FT4 ratio for Graves’ disease was assessed using receiver operating characteristic (ROC) curve analysis. Results: Fifty-eight patients were included, of whom 58.6% were diagnosed with Graves’ disease. Patients with Graves’ disease had significantly higher FT3 levels (median 16.8 pmol/L; IQR 10.9–25.7) compared to those with non-Graves’ thyrotoxicosis (median 8.3 pmol/L; IQR 5.3–13.5; p <0.001), with similar trends observed for FT4 levels (p <0.001). However, the FT3/ FT4 ratio did not differ significantly between groups (p >0.05), with an overall ROC AUC of 0.572, indicating poor discriminatory ability. Subgroup analysis based on FT4 levels improved performance; at FT4 <30 pmol/L, the FT3/FT4 ratio demonstrated 75.0% sensitivity, 91.7% specificity, and 87.5% diagnostic accuracy at a cutoff of 0.3445 (AUC = 0.813; 95% CI: 0.570–1.000; p = 0.069). No significant association was observed between the FT3/FT4 ratio and TRAb or anti-TPO. Conclusion The FT3/FT4 ratio has limited overall diagnostic utility but may provide adjunctive value in selected biochemical contexts, particularly in settings with limited access to immunological testing.
Diagnosis, Differential ; Thyroxine ; Triiodothyronine ; Thyrotoxicosis ; Cross-Sectional Studies

Introduction: Thyrotoxicosis typically manifests as a hypermetabolic state characterized by tachyarrhythmias, such as sinus tachycardia or atrial fibrillation. Bradyarrhythmia, specifically atrioventricular block (AVB), is a rare and atypical cardiac manifestation. While Graves’ disease is the leading cause of hyperthyroidism, non-autoimmune etiologies must be considered when thyroid-stimulating antibodies are absent. The exact mechanism for AVB in thyrotoxicosis remains unclear but may involve myocardial inflammation of the conduction system or autonomic dysfunction. Case: A 16-year-old male with no previous medical history presented with a sudden syncopal attack. Clinical evaluation revealed a complete heart block (CHB) in association with biochemical evidence of thyrotoxicosis, requiring a temporary transcutaneous pacemaker insertion. There were no features of Graves’ disease, such as exophthalmos and thyroid acropachy, and further investigation showed a negative thyroid receptor antibody (TRAb) titer with no family history of thyroid disorders. Thyroid ultrasonography showed increased vascularity, while scintigraphy imaging showed diffuse, homogeneous, and increased uptake in both thyroid lobes. The combination of negative serology and the absence of a family history, along with a hyperfunctional state on imaging, likely suggests a rare presentation of sporadic, non-autoimmune, nonfamilial form of thyrotoxicosis. Following the initiation of anti-thyroid therapy, the CHB completely resolved without the need for further cardiological intervention. He achieved a complete clinical remission after a few months and is being planned for radioactive iodine therapy. Conclusion Most of the thyrotoxicosis-associated CHB reported in the literature was due to Graves’ disease or some forms of autoimmune thyrotoxicosis, with auto-antibodies and activated lymphocytes having a role in the pathogenesis of the CHB. CHB in association with a non-autoimmune, non-familial form of thyrotoxicosis is indeed rare, and as this case illustrates, it completely went into spontaneous sinus rhythm upon initiation of conventional anti-thyroid therapy. This rare presentation of CHB is believed to have a benign clinical course.
Thyrotoxicosis ; Heart Block

Introduction: Graves’ disease is associated with various hematological abnormalities, including anemia, leucopenia, and thrombocytopenia. However, pancytopenia involving all three cell lines is a rare and often under-recognized manifestation of thyrotoxicosis. We present a case of newly diagnosed Graves’ disease complicated by pancytopenia, in which cell counts normalized rapidly following carbimazole initiation. Case: A 51-year-old female with underlying type 2 diabetes mellitus, hypertension, and dyslipidemia presented with dysphagia for 3 months, significant weight loss (from 95 to 75 kg over 6 months), and a 1-week history of fever, palpitations, tremors, orthopnea, and bilateral lower limb swelling. On examination, she was febrile (38.2°C) with bibasal crepitations, pitting edema up to the midshins, bilateral hand tremors, and a multinodular neck mass moving with deglutition. Investigations confirmed thyrotoxicosis (thyroid-stimulating hormone [TSH] 0.01 mIU/L, free T4 130.1 pmol/L, T3 >30.8 pmol/L) with positive autoantibodies (thyroid receptor antibody 31.9 IU/L, anti-thyroid peroxidase 195 IU/mL). Full blood count showed pancytopenia: white cell count 2.73 × 10⁹/L, hemoglobin 10.3 g/dL, and platelets 108 × 10⁹/L. Peripheral blood film suggested normocytic normochromic anemia with leucopenia and thrombocytopenia. Chest radiography showed cardiomegaly with fluid overload, and echocardiography revealed an ejection fraction of 77%. She was treated for impending thyroid storm secondary to pneumonia with Lugol’s iodine, hydrocortisone, propylthiouracil, and intravenous antibiotics. She was discharged on day 3 with a transition to carbimazole. At outpatient follow-up approximately 9 days later, thyroid function had improved significantly (free thyroxine 4 reduced from 130.1 to 29.34 pmol/L with suppressed TSH), and repeat full blood count demonstrated complete normalization of all three cell lines. Conclusion This case illustrates that pancytopenia can be a direct consequence of severe thyrotoxicosis and may reverse completely with effective antithyroid therapy. The temporal relationship between biochemical improvement and hematological recovery supports a causal link. Clinicians should be aware of this rare association to avoid misdiagnosis and unnecessary invasive investigations.
Pancytopenia ; Graves Disease ; Thyrotoxicosis

Introduction: Severe thyrotoxicosis is an endocrine emergency that may present with multiorgan dysfunction, particularly when precipitated by systemic infection. Management becomes challenging when hepatic injury limits the use of standard antithyroid therapy. We report a case of severe thyrotoxicosis with acute hepatitis in the setting of dengue IgM positivity. Case: A 44-year-old male with chronic alcohol use presented with epistaxis. On examination, he was deeply jaundiced and had tremors on outstretched hands. Initial investigations showed severe hepatitis with AST 2029 U/L, ALT 698 U/L, total bilirubin 236 µmol/L, alkaline phosphatase 138 U/L, and thrombocytopenia (34 ×10⁹/L). Viral hepatitis HBV, HCV, HIV, and autoimmune hepatitis screen were negative. Dengue IgM was positive. Thyroid function tests demonstrated overt thyrotoxicosis with free thyroxine 4 (FT4) 58.6 pmol/L and suppressed thyroid-stimulating hormone. He was managed as severe thyrotoxicosis with impending thyroid crisis in view of systemic illness and multiorgan involvement. Due to significant hepatic dysfunction, he was treated with propranolol, dexamethasone, and lithium carbonate 300 mg BD. Over 5 days, there was marked clinical improvement with resolution of tachycardia and tremors. FT4 decreased to 44.8 pmol/L. Liver function tests improved significantly (AST 157 U/L, ALT 195 U/L, bilirubin 163 µmol/L), and thrombocytopenia resolved (platelets 323 ×10⁹/L). He remained hemodynamically stable with normal Glasgow Coma Scale throughout admission. Conclusion This case highlights severe thyrotoxicosis with acute hepatitis and dengue infection, where management was complicated by contraindication to conventional antithyroid therapy. Lithium and corticosteroids provided effective biochemical and clinical improvement. Early recognition and individualized therapy are crucial in complex multisystem thyrotoxic presentations.
Hepatitis A ; Thyrotoxicosis ; Dengue

Introduction: Carbimazole is a first-line therapy for thyrotoxicosis and is generally well tolerated. Drug-induced liver injury is rare (<1%) and typically presents as cholestatic hepatotoxicity, in contrast to propylthiouracil, which more commonly causes hepatocellular injury. Clinical presentation may mimic obstructive jaundice, and delayed recognition can lead to unnecessary investigations and interruption of definitive thyroid management. : A 70-year-old female with toxic multinodular goiter developed painless jaundice 4 weeks after starting carbimazole 20 mg daily for thyrotoxicosis precipitated by urinary tract infection. She had no prior liver disease or alcohol exposure. Examination revealed isolated icterus without features of chronic liver disease. Initial thyroid function tests showed suppressed thyroidstimulating hormone (<0.01 mIU/L) with markedly elevated free T4 (>100 pmol/L), improving after 4 weeks (free T4 29.1 pmol/L). She subsequently developed progressive jaundice without abdominal pain, fever, pruritus, or encephalopathy. Liver biochemistry demonstrated a cholestatic pattern (R factor 1.1) with conjugated hyperbilirubinemia (peak bilirubin 227 µmol/L), mild transaminitis, and elevated alkaline phosphatase. Imaging, including hepatobiliary ultrasonography, contrast computed tomography, and endoscopic ultrasound, excluded biliary obstruction. Viral, autoimmune, and structural causes were negative. Carbimazole-induced cholestatic jaundice was diagnosed based on temporal association and exclusion of alternatives. Carbimazole was discontinued, ursodeoxycholic acid was initiated, and radioactive iodine therapy was performed, followed by gradual recovery. Conclusion Carbimazole-induced hepatotoxicity (0.1–0.2%) is likely idiosyncratic and not dose dependent. Differentiating drug-induced liver injury from thyrotoxicosis-related liver dysfunction is critical, as restoration of euthyroidism alone may normalize liver enzymes. Diagnosis relies on the exclusion of obstruction and recognition of drug chronology. Early drug withdrawal and multidisciplinary management are essential to prevent progression while ensuring timely definitive therapy.
Thyrotoxicosis ; Cholestasis

Introduction: Thyrotoxicosis following neck surgery is typically attributed to transient destructive thyroiditis from follicular disruption. In end-stage renal failure (ESRF), however, altered thyroid hormone kinetics, including reduced protein binding, impaired peripheral metabolism, and decreased clearance, can distort biochemical interpretation. This creates a high-risk scenario where laboratory values overestimate tissue thyrotoxicity, predisposing to inappropriate antithyroid therapy. We present a case demonstrating marked clinical–biochemical dissociation, reframing postoperative thyrotoxicosis in ESRF as a disorder of hormone handling rather than hormone overproduction. Case: A 45-year-old female with ESRF on maintenance hemodialysis and tertiary hyperparathyroidism underwent total parathyroidectomy. Preoperative thyroid function was consistently euthyroid. Within 48 hours postoperatively, she developed severe biochemical thyrotoxicosis (thyroidstimulating hormone 0.28 mIU/L, free thyroxine 4 [FT4] 68 pmol/L). Despite this, she remained clinically euthyroid, with stable hemodynamics, absence of adrenergic or neuropsychiatric features, and no evidence of thyroid eye disease. The temporal relationship strongly suggested destructive thyroiditis secondary to surgical manipulation, with passive release of preformed thyroid hormone. In the context of ESRF, impaired hormone clearance and altered binding likely amplified circulating free hormone levels without proportional end-organ effect, resulting in striking clinical–biochemical dissociation. A conservative strategy was adopted. Antithyroid drugs were withheld, given the non-synthetic mechanism of hormone excess, and the patient was managed with close monitoring and symptom-guided beta-blockade. Serial thyroid function demonstrated spontaneous improvement without complications. Conclusion Post-parathyroidectomy thyrotoxicosis in ESRF represents exaggerated biochemical derangement without true tissue toxicity. Management must prioritize physiology over laboratory values, as misclassification risks iatrogenic harm. This case demonstrates that in ESRF, elevated FT4 may not reflect true tissue thyrotoxicity, and reliance on biochemical severity alone can lead to inappropriate antithyroid therapy and iatrogenic harm.
Parathyroidectomy ; Hyperthyroidism ; Thyrotoxicosis

Introduction: The coexistence of thyroid storm and Guillain–Barré syndrome (GBS) is rare, with few reported cases. A shared autoimmune mechanism has been suggested, although the exact pathophysiology remains unclear. In severe thyrotoxicosis, new neurological symptoms may be overlooked or attributed to metabolic causes, delaying diagnosis and posing a diagnostic and therapeutic challenge. We report a case of a 43-year-old female with Graves’ disease complicated by thyroid storm and Acute Motor Axonal Neuropathy (AMAN), a variant of GBS, highlighting the importance of early recognition and multidisciplinary management. Case: A 43-year-old female with no prior medical illness presented with fever, generalized weakness, fine tremors, and 10 kg weight loss over 5 months. On arrival, she was lethargic, febrile (40.2°C), and tachycardic (148 bpm), consistent with thyroid storm by Burch–Wartofsky criteria. She denied preceding diarrheal illness or upper respiratory tract symptoms. The thyroid function test showed markedly elevated free thyroxine 4 (>64.35 pmol/L) and suppressed thyroid-stimulating hormone (TSH) (<0.008 mIU/L). Subsequent testing revealed elevated TSH receptor antibodies (>40 IU/L), confirming Graves’ disease. Her course was complicated by anaphylactic shock with transient cardiac arrest, followed by acute kidney injury and respiratory failure requiring intensive care unit admission and mechanical ventilation. Following extubation, symmetrical limb weakness with generalized areflexia and bilateral foot drop was observed. Nerve conduction studies demonstrated a symmetrical axonal motor-predominant polyneuropathy consistent with AMAN. She received five sessions of plasma exchange and showed marked neurological improvement, while thyroid and renal function normalized at discharge. Conclusion This case highlights a rare and potentially life-threatening association of thyroid storm and AMAN. Severe thyrotoxicosis can precipitate atypical autoimmune complications, underscoring the need for vigilance. Clinicians should consider neurological evaluation in patients with severe thyrotoxicosis presenting with newonset motor weakness.
Thyrotoxicosis

Introduction: Autoimmune thyroid disease can follow a triphasic course: thyrotoxicosis, a transient euthyroid period, and eventual hypothyroidism, and may coexist with myelodysplastic syndrome (MDS) in the context of immune dysregulation. Case: We describe a 35-year-old male with MDS (multilineage dysplasia) receiving cyclosporine who initially presented with painless thyrotoxicosis, with suppressed thyroidstimulating hormone (TSH) and elevated free thyroxine (FT4). During this hyperthyroid phase, thyrotropin receptor antibody (TRAb) was positive. Over time, his thyroid status fluctuated, progressing to overt hypothyroidism, and he had poor adherence to thyroid medications. On admission, he had prominent hypothyroid features (fatigue, cold intolerance, slowed movement, periorbital puffiness) with severe biochemical hypothyroidism (TSH 49.5 µIU/mL; FT4 0.419 ng/dL). Anti-thyroid peroxidase (anti-TPO) antibodies 12.62 IU/mL (negative <5.61 IU/mL; positive ≥5.61 IU/mL) showed an autoimmune response to the thyroid. Thyroid ultrasound showed heterogeneous, hyperechoic with some hypoechoic parts, and no significant increase in thyroid vascularity was observed, supporting autoimmune thyroiditis representation. His hematologic profile remained consistent with MDS, with chronic macrocytic anemia and thrombocytopenia. Conclusion This case highlights a dynamic autoimmune thyroiditis phenotype progressing from a hyperthyroid phase with TRAb positivity to higher anti-TPO overt hypothyroidism in a patient with MDS. In individuals with MDS and changing thyroid function tests, clinicians should keep autoimmune thyroiditis variants in mind and use thyroid antibodies together with ultrasound to secure the diagnosis when the clinical pattern is typical.
Myelodysplastic Syndromes ; Thyroiditis, Autoimmune ; Hypothyroidism ; Thyrotoxicosis

Humans ; Thyrotoxicosis/chemically induced* ; Amiodarone

Thyroid storm is a life-threatening condition with mortality rates reaching up to 20 to 30%. First-line treatment includes inhibition of thyroid hormone synthesis, prevention of release of preformed hormones, blocking of peripheral FT4 to FT3 conversion, enhancing hormone clearance, and definitive radioactive iodine ablation. However, in the presence of life-threatening adverse effects (e.g., agranulocytosis) and contraindications (e.g., fulminant hepatic failure), therapeutic plasma exchange (TPE) can be used to rapidly remove circulating thyroid hormones, antibodies, and cytokines in plasma; this is recommended by the American Society of Apheresis (ASFA) and the American Thyroid Association (ATA) as second-line treatment for thyroid storm. Here, we report a 49-year-old female with Graves' disease admitted in our emergency room for a 6-week history of fever, weight loss, jaundice, exertional dyspnea, palpitations, and diarrhea. Her initial thyroid hormone levels were: FT4 64.35 (NV 9.01-19.05 pmol/L), FT3 23.91 (NV: 2.89-4.88 pmol/L), and TSH 0.00000 (NV: 0.35-4.94 mIU/L) and we managed her as a case of thyroid storm (Burch-Wartofsky score 70) by initiating high dose propylthiouracil. However, her sensorium deteriorated and serum bilirubin continued to rise from 307.2 on admission to 561.6 umol/L on the 5th hospital day (NV: 3 - 22 umol/L). TPE was performed after consultation with the Division of Hematology. Over the treatment course, her thyroid hormones normalized: FT4 13.18 pmol/L, FT3 2.30 pmol/L. However, despite TPE, her symptoms worsened and she became comatose, had hypotension despite vasopressors and developed new-onset atrial fibrillation. She expired on her 7th hospital day from multiorgan failure. TPE is effective in decreasing circulating thyroid hormone levels. However, it had no effect on clinically important outcomes as our patient still deteriorated and eventually succumbed. We still wrote and submitted this case report since if only successful cases were reported, the true effectiveness rate of TPE could not be determined.Thyroid storm is a life-threatening condition with mortality rates reaching up to 20 to 30%. First-line treatment includes inhibition of thyroid hormone synthesis, prevention of release of preformed hormones, blocking of peripheral FT4 to FT3 conversion, enhancing hormone clearance, and definitive radioactive iodine ablation. However, in the presence of life-threatening adverse effects (e.g., agranulocytosis) and contraindications (e.g., fulminant hepatic failure), therapeutic plasma exchange (TPE) can be used to rapidly remove circulating thyroid hormones, antibodies, and cytokines in plasma; this is recommended by the American Society of Apheresis (ASFA) and the American Thyroid Association (ATA) as second-line treatment for thyroid storm. Here, we report a 49-year-old female with Graves' disease admitted in our emergency room for a 6-week history of fever, weight loss, jaundice, exertional dyspnea, palpitations, and diarrhea. Her initial thyroid hormone levels were: FT4 64.35 (NV 9.01-19.05 pmol/L), FT3 23.91 (NV: 2.89-4.88 pmol/L), and TSH 0.00000 (NV: 0.35-4.94 mIU/L) and we managed her as a case of thyroid storm (Burch-Wartofsky score 70) by initiating high dose propylthiouracil. However, her sensorium deteriorated and serum bilirubin continued to rise from 307.2 on admission to 561.6 umol/L on the 5th hospital day (NV: 3 - 22 umol/L). TPE was performed after consultation with the Division of Hematology. Over the treatment course, her thyroid hormones normalized: FT4 13.18 pmol/L, FT3 2.30 pmol/L. However, despite TPE, her symptoms worsened and she became comatose, had hypotension despite vasopressors and developed new-onset atrial fibrillation. She expired on her 7th hospital day from multiorgan failure. TPE is effective in decreasing circulating thyroid hormone levels. However, it had no effect on clinically important outcomes as our patient still deteriorated and eventually succumbed. We still wrote and submitted this case report since if only successful cases were reported, the true effectiveness rate of TPE could not be determined.