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: Nonfunctioning pituitary adenomas (NFPA) may cause central hypothyroidism due to pituitary compression, often presenting with low thyroid-stimulating hormone (TSH). However, suppressed TSH in this setting should not automatically be attributed to pituitary dysfunction, as primary hyperthyroidism—such as Graves’ disease—may rarely coexist. Distinguishing between these disorders is essential to avoid misdiagnosis and inappropriate management. Case: A 42-year-old female presented with intermittent headache, visual field impairment, palpitations, fine tremors, and weight loss. Physical examination revealed visual field deficits and no goiter. Laboratory evaluation showed cortisol level of 1 µg/dL (normal: 3.7–19.4 µg/dL), luteinizing hormone 1.62 mU/L (normal: 2.4–12.6 mU/L), follicle-stimulating hormone 5.01 mU/L (normal: 3.5–12.5 mU/L), free thyroxine 4 28.32 pmol/L (normal: 12–22 pmol/L), TSH 0.02 µIU/mL (normal: 0.27–4.2 µIU/mL), and prolactin 70.84 ng/mL. Thyrotropin receptor antibody (TRAb) was 3.53 IU/L, confirming Graves’ disease. Contrast-enhanced brain magnetic resonance imaging demonstrated a pituitary macroadenoma (2.13 × 2.28 × 3.05 cm) with optic chiasm compression. The patient was diagnosed with NFPA, Graves’ disease, secondary adrenal insufficiency, possible hypogonadotropic hypogonadism, and hyperprolactinemia likely due to the stalk effect. Preoperative management included hydrocortisone replacement and antithyroid therapy. The patient subsequently underwent transsphenoidal surgery with appropriate perioperative care. Postoperatively, no new pituitary hormone deficiencies were observed. She was maintained on thiamazole 10 mg daily with clinical improvement and remains under regular follow-up. Conclusion This case highlights a rare but clinically important coexistence of NFPA and Graves’ disease. Suppressed TSH in patients with pituitary adenoma should not be assumed to reflect pituitary dysfunction without thorough evaluation. Comprehensive thyroid assessment is crucial to ensure accurate diagnosis and appropriate management.
Pituitary Neoplasms ; Graves Disease

Introduction: Thyroid eye disease (TED) is a heterogeneous condition and the most common extrathyroidal manifestation of Graves’ disease. Although most cases are mild, disease progression may threaten vision and significantly impact quality of life. Methodology: We described four patients with active moderate-to-severe TED, highlighting their clinical characteristics, therapeutic approaches, and clinical outcomes. Results: Three males and one female patient were included in this descriptive study. Most were identified by the endocrine team. Their median age was 52.5 years (range 47–56 years). All patients had long-standing Graves’ disease (range 6–10 years). Two of them were active smokers. Their clinical activity score ranged from 3 to 5. Common presenting features included diplopia (60%), proptosis (60%), and ocular redness (60%). At the onset of active TED, all patients were euthyroid while receiving either antithyroid therapy or were maintained on stable levothyroxine following radioactive iodine treatment and thyroidectomy. Thyroid receptor autoantibodies were assessed in only two patients, with one elevated result. Orbital computed tomography, performed in 3 patients, demonstrated extraocular muscle enlargement consistent with TED, particularly involving the inferior and medial recti. All patients received standard-dose intravenous methylprednisolone (cumulative 3.5–4.5 g). They showed improvement in visual acuity following treatment, with partial improvement in ophthalmoplegia. Conclusion Clinical risk factors observed in this series were consistent with the literature. TED diagnosis relies heavily on recognition by the endocrine team, underscoring the importance of holistic Graves’ disease management. Highdose corticosteroids remain the mainstay of treatment in our setting, with generally favorable outcomes when timely multidisciplinary care is provided.
Graves Ophthalmopathy

Introduction: Autoimmune thyroid disease is frequently associated with other immune-mediated disorders; however, clinically significant pancytopenia is rare. In patients with Graves’ disease receiving antithyroid therapy, leukopenia raises concern for drug-induced agranulocytosis, a rare but potentially life-threatening complication characterized by severe neutropenia requiring immediate drug withdrawal. The coexistence of hemolytic anemia and thrombocytopenia may instead suggest Evans syndrome, defined by autoimmune hemolytic anemia with immune thrombocytopenia, with or without neutropenia. Importantly, uncontrolled thyrotoxicosis itself may cause immunemediated cytopenias, creating a diagnostic challenge. Case: We report a 55-year-old female with thyroid receptor antibody-positive Graves’ disease who presented with jaundice and pancytopenia while receiving carbimazole therapy. Laboratory evaluation demonstrated anemia with reticulocytosis and a positive direct antiglobulin test, thrombocytopenia and leukopenia. Complement testing revealed reduced C3 with normal C4, consistent with immune-mediated hemolysis. Peripheral blood film showed no blast cells or marrow infiltration, and autoimmune screening, including antinuclear antibodies and anti–double stranded DNA, was negative. The coexistence of Coombs-positive hemolysis and thrombocytopenia initially raised suspicion for Evans syndrome, while leukopenia during carbimazole therapy prompted concern for drug-induced agranulocytosis. However, neutropenia was not severe, and the absence of marrow infiltration or systemic autoimmune disease made alternative causes of pancytopenia less likely. Importantly, blood counts progressively improved following the optimization of thyroid control despite continuation of carbimazole at a reduced dose, without the use of immunosuppressive therapy. This clinical course supported the interpretation of thyrotoxicosis-associated immune cytopenia rather than primary Evans syndrome or carbimazole-induced agranulocytosis. Conclusion This case highlights thyrotoxicosis-associated immune cytopenia as an important mimic of Evans syndrome and carbimazole-related hematological toxicity. Recognizing this entity is essential to avoid unnecessary discontinuation of antithyroid therapy or inappropriate immunosuppressive treatment.
Evans Syndrome ; Carbimazole ; Pancytopenia ; Agranulocytosis ; Graves Disease

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: Beta-blockers are frequently used as adjunctive therapy in hyperthyroidism to manage adrenergic symptoms, yet their potential to precipitate secondary Raynaud’s phenomenon remains under-recognized. This adverse effect is attributed to β2-adrenoceptor blockade, which impairs peripheral vasodilation and promotes reflex vasoconstriction. Nonselective agents such as propranolol carry this particular risk. Case: A 22-year-old female presented with a 6-month history of palpitations, 11 kg weight loss, and fine tremors. There was no personal or family history of autoimmune or connective tissue disease. She denied any malar rash, joint swelling, alopecia, myopathy, oral ulcers, or uveitis. She also denied using any supplements or any herbal or traditional remedies. Examination revealed tachycardia, fine tremors, and Graves’ ophthalmopathy, but no acropachy or organomegaly. Investigations confirmed Graves’ disease: Free T4 of 73 pmol/L, thyroid-stimulating hormone <0.05 mIU/L, with elevated anti-thyroid peroxidase and antithyroglobulin antibodies. Full blood count, renal, and liver function were unremarkable. She was commenced on carbimazole 20 mg daily and propranolol 40 mg three times daily. After 8 months of treatment, she developed cold-induced digital color changes and skin tightening consistently, suggestive of Raynaud’s phenomenon. Dose reduction of propranolol to 20 mg BD only yielded partial improvement. Propranolol was subsequently substituted with verapamil, a nondihydropyridine calcium channel blocker, resulting in significant resolution of Raynaud’s phenomenon. Conclusion Propranolol-induced Raynaud’s phenomenon is an underrecognized complication in the management of Graves’ disease, and this case illustrates that it may develop insidiously after months of therapy and can persist despite dose reduction. Substitution with verapamil achieves rate control without β2-adrenergic antagonism. Clinicians should maintain a low threshold for recognizing this adverse effect and consider early substitution with verapamil in affected patients. While verapamil does not confer the same adrenergic blockade as propranolol, its vasodilatory properties make it a rational and effective alternative in this context.
Raynaud Disease ; Graves Disease

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