BACKGROUND

Lithium has been known as a second-line treatment for hyperthyroidism. However, it has a narrow therapeutic range especially in patients with impaired renal function. Toxicity can cause neurological, gastrointestinal, cardiovascular, and renal symptoms, including rare cases of renal failure needing renal replacement therapy. This case report highlights a rare instance of acute lithium toxicity in a patient with multinodular goiter and chronic kidney disease, following methimazole-induced agranulocytosis.

A 55-year-old Filipino woman with chronic kidney disease and multinodular toxic goiter who developed methimazole-induced agranulocytosis presented with altered mental status after pre-treatment with lithium. Laboratory tests confirmed elevated lithium levels, consistent with acute lithium toxicity. She developed acute kidney injury, necessitating urgent hemodialysis with hemoperfusion. After two sessions, her neurological status and renal function improved. The patient resumed pre-treatment with carbimazole and subsequently underwent successful RAI then maintained on levothyroxine for long-term thyroid management

Lithium toxicity is rare but can cause life-threatening complications, particularly in patients with pre-existing kidney disease. Hemodialysis remains the treatment of choice for severe toxicity, significantly improving patient outcomes. Lithium toxicity can occur even within therapeutic levels, emphasizing the need for careful monitoring. This case highlights the importance of clinical vigilance when using lithium.

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: 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: Cystic fibrosis (CF) is an autosomal recessive disorder caused by mutations in the CFTR gene. Complications such as cystic fibrosis–related diabetes (CFRD) are well recognized. The association between CF and autoimmune thyroid disease, however, is rare and poorly understood. We report a case of CFRD complicated by Graves’ disease. Case: A 22-year-old male was diagnosed with CF at age 5, confirmed by a positive sweat chloride test. Following the diagnosis, lifelong pancreatic enzyme replacement therapy (Creon) was initiated to treat exocrine pancreatic insufficiency. In 2021, he developed type 3c diabetes, attributed to endocrine pancreatic insufficiency, and required regular basal insulin therapy. In early 2024, he developed hypokalemic periodic paralysis with proximal myopathy, despite potassium correction, and was admitted to the hospital. On admission, examination revealed a fine tremor and diffuse bilateral neck swelling. Biochemical evaluation showed thyrotoxicosis with Free T4 of 37 pmol/L and thyroid-stimulating hormone (TSH) <0.01 mIU/L. He started a tapering dose of carbimazole and propranolol. An urgent neck ultrasound showed a heterogeneous thyroid parenchyma with increased vascularity and no nodules. Elevated anti-thyroid peroxidase (anti-thyroid peroxidase, >600 IU/mL) and TSH receptor antibodies (thyrotropin receptor antibody, 2.57 IU/L) confirmed a diagnosis of Graves’ disease. During follow-ups, he had issues with compliance with the antithyroid therapy. However, the latest thyroid function test in February 2026 showed Free T4 of 20.5 pmol/L with suppressed TSH of <0.01 mIU/L. He remains clinically euthyroid throughout the follow-up. Conclusion This case highlights a rare but clinically relevant coexistence. Clinicians managing symptomatic CF patients should vigilantly screen for thyroid dysfunction to ensure early diagnosis and timely intervention. Early recognition and treatment may improve patient outcomes. Further research is needed to clarify the immunological link between CF and autoimmunity.
Cystic Fibrosis ; Graves Disease

Introduction: Graves’ disease is typically managed with antithyroid drugs (ATDs) and beta-blockers like propranolol. While allergic reactions to ATDs are common, beta-blockers are rarely identified as allergens. Case: A 42-year-old female with Graves’ disease was started on carbimazole 5 mg daily and propranolol 40 mg daily. She developed mild itchiness, which was tolerable. One month later, liver enzyme derangement led to the discontinuation of carbimazole. Propylthiouracil (PTU) 300 mg daily was initiated while continuing propranolol, but caused generalized urticaria, necessitating its cessation. Prednisolone was started, but her thyroid function worsened. Alternative therapies were proposed but declined by the patient. Upon resolution of urticaria, PTU was reintroduced at 50 mg daily without adverse effects, and propranolol was discontinued. Her cutaneous symptoms did not recur, implicating propranolol as the allergen. Conclusion In hyperthyroidism, increased hepatic clearance reduces plasma propranolol levels, minimizing the risk of adverse effects. However, as thyroid function normalizes, propranolol clearance slows, leading to drug accumulation and increased susceptibility to side effects. Clinicians should consider all medications as potential allergens and understand how thyroid states affect drug metabolism to optimize treatment.
Graves Disease ; Allergens

Introduction: Neuropsychiatric manifestations of thyrotoxicosis range from mild anxiety to severe psychosis. While the BurchWartofsky Point Scale (BWPS) reliably identifies systemic thyroid storms, an isolated “cerebral storm”—where profound thyrotoxic encephalopathy presents without peripheral autonomic signs—remains a diagnostic challenge. This case highlights the neuromodulatory pathogenesis of thyrotoxic psychosis and the critical role of biochemical control for psychiatric resolution. Case: A 31-year-old male with Graves’ disease and poor medication adherence presented with a 2-week history of aggressive behavior and auditory hallucinations. Initial investigations revealed overt thyrotoxicosis (thyroidstimulating hormone <0.01 mIU/L; free thyroxine 4 (FT4) 59.53 pmol/L) and an unremarkable computed tomography brain. Despite his severe neuropsychiatric decompensation, a BWPS of 20 precluded a clinical diagnosis of systemic thyroid storm. His symptoms remained refractory to aggressive psychotropic polypharmacy, including haloperidol, olanzapine, lithium, and diazepam. Management was therefore focused on the underlying thyrotoxicosis with an optimized antithyroid regimen of carbimazole and propranolol. Clinical resolution of psychotic symptoms was achieved only after FT4 declined significantly to 20.46 pmol/L, allowing the successful tapering of all psychiatric medications. He was discharged in a stable, clinically euthyroid state with integrated medical and psychiatric follow-up. Conclusion The failure of standard antipsychotics suggests that thyrotoxic psychosis is driven by distinct neuromodulatory mechanisms rather than primary dopaminergic dysfunction. The chronic thyrotoxic state secondary to prolonged treatment non-adherence likely upregulates and sensitizes dopamine receptors while simultaneously suppressing inhibitory GABAergic pathways. This neurochemical imbalance lowers the neurological threshold, precipitating an isolated cerebral storm. This case illustrates the limitations of the BWPS in purely neuropsychiatric presentations and reinforces that restoring euthyroidism is the definitive treatment for thyrotoxic psychosis.
Graves Disease ; Psychotic Disorders

Introduction: Graves orbitopathy (GO) is an autoimmune disease affecting the orbits and the periorbital tissues with an annual incidence of 16 per 100,000 population in women and 2.9 in men. While GO occurs in the spectrum of hyperthyroidism or Graves disease, 7.9% of these patients have a normal thyroid function and only a few are negative for thyroid antibodies. When left untreated, GO may become debilitating and threaten vision. Case Description: A 64-year-old male presented with gross bilateral proptosis and chemosis, which developed over a period of 10 years. Palpitations, hand tremors, heat intolerance, weight loss, and insomnia were notably absent, and the thyroid gland was normal. The bilateral proptosis was left unattended for 10 years until extreme lagophthalmos and chemosis with corneal and mucosal exposure leading to dryness, foreign body sensation, excruciating eye pain, and blurred vision resulted. Thyroid-stimulating hormone (TSH), T3, and T4, were normal. TSH-receptor antibody (TRAb) and thyroid peroxidase antibody were negative. The computed tomography scan with contrast of the orbits showed bilateral proptosis and extraocular muscle enlargement typical for thyroid eye disease. The patient was diagnosed with TRAb- negative euthyroid GO with a European Group on Graves’ Orbitopathy (EUGOGO) clinical score of 7/7, indicating a severe, active disease. Screening prior to administration of GO immunosuppressive therapy revealed chronic hepatitis B infection. The patient was started with tenofovir for 2 weeks before treatment for GO. The patient was given intravenous methylprednisolone with cumulative dose of 4.5 g for 12 weeks, with daily mycophenolate sodium 0.72 g for 12 weeks. Upon completing the 12-week treatment regimen and undergoing an adjunctive lateral canthotomy and partial tarsorrhaphy, the GO signs and symptoms dramatically resolved, and visual acuity markedly improved. Conclusion This case report presents an unusual condition of a euthyroid, TRAb-negative Graves orbitopathy. It provides insights on the diagnosis and treatment of patients with such atypical presentation. Despite the chronicity and severity of this patient’s GO, excellent results were achieved with appropriate and guideline-directed treatment.
Human ; Male ; Middle Aged: 45-64 Yrs Old ; Graves Ophthalmopathy ; Exophthalmos ; Mycophenolic Acid