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: Diabetic ketoacidosis (DKA) and thyroid storm are individually rare but potentially fatal endocrine crises in pregnancy. Each carries significant maternal and fetal morbidity, with mortality risk compounded when they occur concomitantly. Physiological and pharmacokinetic changes of pregnancy, combined with overlapping symptoms, necessitate urgent treatment strategies. Case: A 29-year-old G2P2 female at 29 weeks’ gestation, with poorly controlled type 2 diabetes mellitus (hemoglobin A1c 8.1%) on a basal–bolus insulin regimen and Graves’ disease managed with carbimazole, non-adherent to medications, presented with fever, vomiting, and dyspnea. On examination, she was tachycardic (HR 138 bpm), hypotensive (BP 94/60 mmHg), and hypoxic. Laboratory investigations revealed hyperglycemia (glucose 27.1 mmol/L), severe metabolic acidosis (pH 7.02, bicarbonate 4.9 mmol/L), and elevated serum ketones (4.6 mmol/L), consistent with DKA. Thyroid function tests showed suppressed thyroid-stimulating hormone (<0.005 mIU/L) and elevated free T4 (28.2 pmol/L), with a Burch–Wartofsky score of 70. Unfortunately, intrauterine fetal demise was confirmed upon the patient’s presentation to the emergency department. She was intubated and admitted to the intensive care unit, receiving fluid resuscitation judiciously according to the DKA regimen, with frequent assessment of volume status. Intravenous insulin and potassium supplements were commenced concurrently. Metabolic stabilization was achieved within 24 hours. Carbimazole, propranolol, Lugol’s iodine, and intravenous hydrocortisone were started for treatment of thyroid storm. A breech-assisted vaginal delivery was performed, and her postpartum course was uneventful. Conclusion The case reveals the catastrophic potential of concurrent DKA and thyroid storm in pregnancy, where rapid maternal deterioration and poor fetal outcomes can occur despite timely intervention. High clinical suspicion, early biochemical confirmation, and coordinated multidisciplinary management are vital. Precipitating factors, particularly medication non-adherence, must be addressed through intensive patient education and structured follow-up to prevent recurrence.
Female ; Pregnancy ; Diabetic Ketoacidosis ; Thyroid Crisis

Introduction: Hurthle cell adenoma is a rare benign thyroid neoplasm that can only be diagnosed through histopathological examination. Hurthle cell neoplasm typically presents as nonfunctioning cold nodule on thyroid scintigraphy. We report a rare case of Hurthle cell adenoma presenting with thyroid storm, with unusual findings of “cold” within “hot” thyroid nodule on scintigraphy. Case: A 73-year-old male with hypertension, chronic kidney disease, coronary artery disease, and Parkinson’s disease presented to the emergency department with fever and diarrhea. His temperature was 38.4°C, heart rate 106 bpm, and blood pressure 138/75 mmHg, with atrial fibrillation and signs of heart failure. The Burch-Wartofsky score was 50, consistent with thyroid storm. Laboratory tests revealed free thyroxine 4 37.8 pmol/L (NR 11.5–22.7), free thyroxine 3 5.6 pmol/L (NR 3.5–6.5), and thyroid-stimulating hormone <0.01 mIU/L (NR 0.55– 4.78). Thyroid autoantibodies, including anti-thyroid peroxidase, anti-thyroglobulin, and thyroid-stimulating immunoglobulins, were negative (<0.10 IU/L). The thyroid storm was precipitated by invasive Klebsiella syndrome with endophthalmitis and lung and liver abscess. He was treated with Lugol’s iodine, corticosteroid, antibiotics, and carbimazole. Ultrasound thyroid revealed a mixed cystic-solid nodule in the left thyroid lobe, measuring 2.3 × 3.3 × 4.3 cm (TIRADS category 3). Technetium-99m thyroid scintigraphy demonstrated a hyperfunctioning left thyroid nodule with a focal intranodular cold spot measuring 5.0 × 3.7 cm. Fine needle aspiration cytology of the nodule was benign follicular cells. Following stabilization with anti-thyroid treatment, he underwent left hemithyroidectomy. Histopathology examination revealed a Hurthle cell adenoma without capsular or vascular invasion. Postoperatively, he remained clinically euthyroid. Surveillance ultrasound performed 8 months later showed a normal right thyroid lobe, and lifelong surveillance was planned. Conclusion This case illustrates a rare and unusual presentation of thyroid storm caused by a toxic Hurthle cell adenoma containing an intranodular cold spot on scintigraphy. To our knowledge, only one similar case has been reported in the literature, and our case is the first to present with thyroid storm.
Oxyphil Cells ; Thyroid Crisis ; Adenoma

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: Long-term antithyroid drug (LT-ATD) has emerged as a feasible treatment strategy for patients who decline radioactive iodine (RAI) or thyroidectomy for relapsed or refractory Graves’ disease (GD). Benefits include faster achievement of euthyroidism, lower risk of hypothyroidism, a more favorable cardiovascular profile, and avoidance of surgical risks. Although fluctuations in thyroid status may occur despite good compliance, thyroid storm is exceedingly rare in patients on LT-ATD. While there is no specific data on the incidence of thyroid storm in this cohort, surveys suggest an overall low incidence (0.2–0.76 cases per 100,000 annually). We report a patient with stable GD who developed a thyroid storm despite more than 10 years of LT-ATD. Case: A 40-year-old female was diagnosed with GD 11 years earlier during pregnancy. Treatment was stopped at 25 weeks’ gestation, but she relapsed at 7 months postpartum and was started on carbimazole. She declined RAI or surgery following a relapse and remained on carbimazole 5–10 mg daily, with good compliance. She presented with a 1-day history of fever, cough, rhinorrhea, diarrhea, and palpitations. She was compliant with carbimazole 5 mg daily. On presentation, BP was 132/70 mmHg, HR 140 bpm, temperature 38.5°C, and SpO2 98% on air. She was alert without agitation, had a diffuse goiter, mild proptosis, and conjunctival injection, with otherwise normal findings. Electrocardiogram showed sinus tachycardia. Laboratory investigations demonstrated mild transaminitis, leukocytosis, markedly elevated free T4 (>154 pmol/L), suppressed thyroid-stimulating hormone (<0.008 mIU/L), and elevated thyroid-stimulating immunoglobulin (2.25 IU/L, reference <0.55). Thyroid function tests 1 month ago was normal. Her Burch-Wartofsky score was 60, consistent with thyroid storm, likely precipitated by upper respiratory tract infection. She improved with treatment and was discharged with carbimazole 30 mg daily with planned tapering, subsequently agreeing to RAI as definitive treatment. Conclusion Infection may trigger thyroid storm despite good compliance with LT-ATD. Patients should be counselled regarding this risk and advised to seek early medical attention if thyrotoxic symptoms recur.
Antithyroid Agents ; Thyroid Crisis

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