Introduction: Medullary thyroid carcinoma (MTC) comprises sporadic and hereditary forms, the latter commonly associated with multiple endocrine neoplasia type 2 (MEN2) which is identifiable through genetic screening of germline RET protooncogene. We compared the clinicopathological features and outcomes of hereditary and sporadic MTC in our single centre. Methodology: We conducted a retrospective audit of patients with MTC from 2000 to 2026. Patients were classified as either hereditary or sporadic based on genetic testing and/or family history of MTC/MEN2A syndrome. Variables analyzed included age at diagnosis, mode of presentation, pre-operative calcitonin, tumor size, lymph node (LN) involvement, post-operative biochemical cure, repeat surgery and presence of structural residual/recurrent disease. Results: A total of 57 patients were included (18 hereditary [31.6%], 39 presumed sporadic [68.4%]) with a median follow-up of 7.5 years (IQR 1.5–12.4). Hereditary MTC was diagnosed at a significantly younger age than sporadic MTC (33.0 vs. 44.7 years, p = 0.010) where 33% of the cases were diagnosed via screening detection whereas sporadic MTC more commonly presented with symptomatic neck swelling (84.6% vs. 50.0%, p = 0.008). There were no significant differences in median pre-operative calcitonin (513.5 vs. 1148.0 pg/mL, p = 0.101), tumor size (24.5 vs. 22.5 mm, p = 0.301), or LN involvement (41.7% vs. 61.5%, p = 0.307) between hereditary and sporadic MTC. Long-term outcomes were also comparable, with no differences in biochemical status, need for repeat surgery or residual/recurrent structural disease. Conclusion Hereditary MTC presents earlier and is more frequently detected due to screening, whereas sporadic MTC often presents symptomatically. Long-term outcomes are not primarily determined by hereditary status alone. Early access to RET mutation testing with a view to initiating prophylactic treatments rather than post detection surgery may improve disease burden.
Thyroid Neoplasms ; Cohort Studies

Introduction: Type 2 diabetes mellitus (T2DM) and thyroid disorders are common endocrine conditions with a bidirectional relationship affecting glucose and lipid metabolism. Adiposity, particularly fat mass index (FMI), may influence thyroid function. but its association with thyroid dysfunction and glycemic control remains unclear, especially in Malaysia. This study aimed to determine the prevalence of thyroid dysfunction in T2DM and its association with glycemic control and FMI at Universiti Teknologi MARA (UiTM). Methodology: A cross-sectional study was conducted among patients with T2DM attending the Endocrine Clinic, UiTM, from December 2025 to March 2026. A total of 91 participants aged 18–70 years were recruited using convenience sampling. Demographic, clinical, anthropometric, and laboratory data were collected. Thyroid dysfunction was defined as thyroid-stimulating hormone (TSH) <0.38 or >5.33 mIU/L. Body composition was assessed using the InBody 380 to determine FMI. Data were analyzed using SPSS version 30 with descriptive statistics and Pearson correlation. Results: The prevalence of thyroid dysfunction among patients with T2DM was 7.7% (7/91), predominantly with low TSH levels. Mean hemoglobin A1c (HbA1c) in the overall study population was 7.59 ± 1.49%, and mean TSH was 1.42 ± 0.95 mIU/L, within the euthyroid range. Mean FMI was 11.95 ± 5.23 kg/m², exceeding normal ranges for both men (3–6 kg/m²) and women (5–9 kg/m²). FMI showed a positive correlation with TSH level (r = 0.379, p <0.001), indicating that higher adiposity was associated with higher TSH levels despite remaining within the euthyroid range. Pearson correlation showed a weak, non-significant negative correlation between HbA1c and TSH (r = −0.127, p = 0.229). Conclusion The prevalence of thyroid dysfunction among patients with T2DM in our cohort was relatively low at 7.7%. However, the significant correlation between FMI and TSH level, even within the euthyroid range, suggests that adiposity may exert a clinically relevant influence on thyroid function.
Diabetes Mellitus, Type 2 ; Prevalence ; Thyroid Gland ; Adipose Tissue

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: Parathyroid carcinoma is a rare endocrine malignancy found in 1–5% of patients with primary hyperparathyroidism. It commonly presents with severe hypercalcemia and markedly elevated parathyroid hormone (PTH) levels. We report a challenging case of parathyroid carcinoma presenting with refractory hypercalcemia with incidental papillary thyroid microcarcinoma. Case: A 63-year-old female with hypertension, diabetes mellitus, dyslipidemia, and ischemic heart disease had been followed for primary hyperparathyroidism since 2014 (PTH5.5 pmol/L, calcium range 2.3–4.7 mmol/L). Initial neck ultrasound was suggestive of parathyroid adenoma over left side, but parathyroid scintigraphy failed to localize a lesion. She refused surgical intervention initially until April 2025, then she later agreed. Re-evaluation prior to operation revealed PTH level 76 pmol/L, and repeated parathyroid scintigraphy showed mild sestamibi avid uptake on left thyroid nodule. While awaiting surgery, she was admitted with a hypercalcemic crisis (serum calcium 3.7–5.38 mmol/L), complicated with acute kidney injury. Repeated ultrasound neck revealed extrathyroidal lesion adjacent to inferior pole of left thyroid (1.6 × 1.7 × 1.2 cm). She required aggressive intravenous hydration, intravenous pamidronate, calcitonin, and Denosumab to optimize her calcium level peri-operatively. She underwent left neck exploration with en-bloc left inferior parathyroidectomy, left hemithyroidectomy, and central neck dissection in November 2025. Histopathological examination confirmed parathyroid carcinoma (pT3N1) with nodal metastasis (1/4 lymph nodes positive) and an incidental papillary thyroid microcarcinoma measuring 1 mm (pT1a). Conclusion This case highlights the challenges of perioperative hypercalcemia management in parathyroid carcinoma. Effective preoperative control often requires multiple treatment modalities. Severe refractory hypercalcemia and high PTH level should raise a high index of suspicion for malignancy. Early complete resection is the cornerstone of treatment and is associated with optimal outcomes.
Papillary Thyroid Microcarcinoma ; Calcium ; Parathyroid Neoplasms

Introduction: Medullary thyroid carcinoma (MTC) has the highest familial predisposition syndrome of any hereditary cancer syndrome. The most common subtype of hereditary MTC is multiple endocrine neoplasia type 2A (MEN2A), which is an autosomal dominant syndrome characterized by MTC, pheochromocytoma, and primary hyperparathyroidism (HPP). This study evaluates the genotypic distribution, phenotypic manifestations, and clinical characteristics of MEN2A within a retrospective MTC cohort. Methodology: A retrospective audit of MTC patients was conducted at a tertiary centre. Patients with clinically or genetically confirmed hereditary MTC were identified for further analysis. Electronic medical records were reviewed for demographic data, RET germline mutations, occurrence of pheochromocytoma and HPP, laterality of disease, and documented surgical interventions. Results: In all, 18 patients (31.6%) were classified as hereditary from a cohort of 57 patients with a median age at diagnosis of 29.2 years. Among genetically confirmed cases with available variant data (n = 11), mutations predominantly involved exon 11 codon 634 (90.9%, n = 10), including p.Cys634Arg (n = 4), p.Cys634Tyr, and p.Cys634Ser, with one codon 618 mutation. Extrathyroidal manifestations were common. Pheochromocytoma occurred in 50.0% (n = 9), of which 77.8% (n = 7) were bilateral. Most patients underwent adrenalectomy, including bilateral procedures in those with bilateral disease. HPP was identified in 44.4% (n = 8), managed with selective parathyroidectomy. Both pheochromocytoma and HPP were present in 22.2% (n = 4), while isolated MTC occurred in 27.8% (n = 5). Conclusion Hereditary MTC in our cohort is predominantly associated with high-risk codon 634 RET mutations and demonstrates substantial penetrance of pheochromocytoma and HPP. The high frequency of bilateral adrenal involvement highlights the importance of systematic biochemical surveillance and appropriately timed surgical management in MEN2A. A nationwide registry would be timely.
Humans ; Multiple Endocrine Neoplasia Type 2a ; Thyroid Neoplasms

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: Muscle weakness in thyroid disease is commonly attributed to thyrotoxic myopathy or hypokalemic periodic paralysis. Nevertheless, autoimmune conditions such as idiopathic inflammatory myopathies (IIM) and myasthenia gravis (MG) should be considered, as they may coexist with Graves’ disease. Case: A 54-year-old female with hypertension and Graves’ disease, treated with carbimazole for 2 years, had her therapy discontinued after remission. She was restarted on low-dose carbimazole following symptom recurrence. Three weeks later, she developed progressive proximal weakness, dysphagia, hoarseness, anorexia, and weight loss. On examination, body mass index was 22 kg/m² with mild proptosis, symmetrical proximal weakness (MRC 4/5), and erythematous rashes on thighs and shins. Otorhinolaryngology evaluation confirmed bilateral vocal cord palsy. Investigations revealed markedly elevated creatine kinase (7,950 U/L), aspartate aminotransferase (349 U/L), and alanine aminotransferase (179 U/L), with euthyroid biochemistry (thyroid-stimulating hormone 5.21 mIU/L, free thyroxine 4 16.6 pmol/L). Hypokalemia correction failed to improve symptoms, excluding periodic paralysis. ANA, C3, and C4 were normal. Myositis panel showed strong anti-Cytosolic 5’-nucleotidase 1A positivity with borderline anti-Ro-52. A diagnosis of IIM with bulbar involvement was made. She was treated with intravenous methylprednisolone and intravenous immunoglobulin, with clinical improvement. Conclusion This case highlights the diagnostic challenge of muscle weakness in thyroid disease. While thyrotoxic myopathy is often presumed, markedly elevated creatinine kinase, rash, and bulbar involvement should prompt suspicion of IIM. Early immunosuppressive therapy is essential to achieve favorable outcomes.
Muscle Weakness ; Thyroid Diseases ; Muscular Diseases

Introduction: A common diagnostic error is the tendency to attribute new symptoms directly to the most obvious laboratory abnormality. In pregnancy, a suppressed thyroidstimulating hormone (TSH) with elevated free T4 is frequently presumed to indicate primary hyperthyroidism, overlooking the possibility of benign gestational transient thyrotoxicosis (GTT). We report a case where this pattern led to the misattribution of acute flaccid paralysis to thyrotoxic periodic paralysis, critically delaying the diagnosis of Guillain-Barré syndrome (GBS). Case: A 21-year-old female Malay primigravida at 19 weeks and 5 days presented with a 2-week history of progressive, descending bilateral lower limb weakness culminating in paralysis, associated with vomiting and 5 kg weight loss. On admission, she was febrile (38.0°C) and tachycardic (150 bpm). Neurological examination revealed proximalpredominant flaccid paralysis and hyporeflexia with intact sensation, without thyroid eye signs or goiter. Thyroid function tests showed profound thyrotoxicosis (TSH <0.005 mIU/L, free thyroxine 4 20.16 pmol/L) with hypokalemia (2.9 mmol/L). A neck ultrasound was normal. A provisional diagnosis of thyrotoxic periodic paralysis with impending storm was made, leading to treatment with potassium replacement, propylthiouracil, and hydrocortisone. Despite biochemical improvement, her paralysis persisted. On day 5, she developed acute bulbar palsy and respiratory failure requiring intubation. A subsequent comprehensive workup for infectious, autoimmune (including thyroid antibodies), and nutritional causes was unremarkable. Nerve conduction studies confirmed the acute motor axonal neuropathy (AMAN) variant of GBS. Treatment with a 5-day course of intravenous immunoglobulin resulted in neurological improvement and successful extubation. Conclusion This case highlights the critical pitfall of prematurely attributing acute neurological deficits to abnormal thyroid function tests in pregnancy. Biochemical thyrotoxicosis, including GTT, should not preclude urgent evaluation for life-threatening neurological conditions such as GBS, particularly when weakness is progressive or refractory to metabolic correction.
Female ; Pregnancy ; Thyroid Function Tests

Introduction: Thyroid hormone resistance syndrome (THR) is a disorder characterized by reduced responsiveness of target tissues to thyroid hormones with non-suppressed thyroidstimulating hormone (TSH) despite elevated free thyroxine 4 (FT4). Diagnosing and managing THR in athyreotic patients, however, is challenging; indeed, TSH levels post thyroidectomy for Differentiated Thyroid Carcinoma in patients with THR have been reported to reach levels as high as 112.59 mIU/L despite high-dose thyroxine-suppressive therapy. This case highlights the complexities in diagnosing Resistance to Thyroid Hormone (RTH) post-thyroidectomy. Case: A 63-year-old female with end-stage renal failure (ESRF) on hemodialysis and prior parathyroidectomy for tertiary hyperparathyroidism underwent total thyroidectomy in 1997 for presumed benign goiter. Following surgery, she demonstrated persistently elevated TSH, ranging from 93.2 to 670.4 mIU/L (0.55–4.78 mIU/L), with normal to mildly elevated FT4 levels, ranging from 17 to 35 pmol/L (11.5–22.7 pmol/L), while on thyroxine replacement doses as low as 0.86 ug/kg. Discordant thyroid function tests (TFTs) were consistent across different assay platforms. Polyethylene glycol precipitation excluded macro-TSH interference. Intermittent levothyroxine increments suppressed TSH but led to thyrotoxic symptoms, including weight loss, heat intolerance, insomnia, and fragility fracture. Uncontrasted pituitary magnetic resonance imaging (risk of nephrogenic systemic fibrosis with gadolinium in ESRF) showed a small pituitary gland without adenoma, excluding TSH-oma. T3 suppression test was relatively contraindicated due to her advanced age and co-morbidities. There was no family history of thyroid disorder; the patient’s only child had a normal TFT, and her parents/siblings could not be tested. A working diagnosis of RTHβ was made. She declined genetic testing for RTH. She is currently on levothyroxine 50 mcg OD (1.07 ug/kg) with FT4 16.1 pmol/L and TSH 562 mIU/L with no symptoms/signs of hypo or hyperthyroidism. Conclusion This case highlights the diagnostic challenges in managing possible RTHβ post-total thyroidectomy. Treatment should be guided by clinical status and target of mid-to-normal FT4 rather than TSH to avoid iatrogenic thyrotoxicosis.
Thyroidectomy ; Thyroid Hormones

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