Diagnosis and Treatment > Investigation > Thyroid function

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Dinesh Giri Department of Paediatric Endocrinology, Alder Hey Children’s NHS Foundation Trust, Liverpool, UK

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Federico Roncaroli Department of Histopathology, Alder Hey Children’s Hospital, Liverpool, UK
Division of Neuroscience, University of Manchester, Manchester, UK

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Ajay Sinha Department of Paediatric Neurosurgery, Alder Hey Children’s Hospital, Liverpool, UK

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Mohammed Didi Department of Paediatric Endocrinology, Alder Hey Children’s NHS Foundation Trust, Liverpool, UK

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Senthil Senniappan Department of Paediatric Endocrinology, Alder Hey Children’s NHS Foundation Trust, Liverpool, UK

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Summary

Corticotroph adenomas are extremely rare in children and adolescents. We present a 15-year-old boy who was investigated for delayed puberty (A1P2G1, bilateral testicular volumes of 3 mL each). There was no clinical or laboratory evidence suggestive of chronic illness, and the initial clinical impression was constitutional delay in puberty. Subsequently, MRI scan of the brain revealed the presence of a mixed cystic and solid pituitary lesion slightly displacing the optic chiasma. The lesion was removed by transphenoidal surgery and the biopsy confirmed the lesion to be pituitary adenoma. Furthermore, the adenoma cells also had Crooke’s hyaline changes and were intensely positive for ACTH. However there was no clinical/biochemical evidence of ACTH excess. There was a spontaneous pubertal progression twelve months after the surgery (A2P4G4, with bilateral testicular volume of 8 mL). Crooke’s cell adenoma is an extremely rare and aggressive variant of corticotroph adenoma that can uncommonly present as a silent corticotroph adenoma in adults. We report for the first time Crooke’s cell adenoma in an adolescent boy presenting with delayed puberty.

Learning points:

  • Constitutional delay of growth and puberty (CDGP) is a diagnosis of exclusion; hence a systematic and careful review should be undertaken while assessing boys with delayed puberty.

  • Crooke’s cell adenomas are a group of corticotroph adenomas that can rarely present in childhood and adolescence with delayed puberty.

  • Crooke’s cell adenomas can be clinically silent but are potentially aggressive tumours that require careful monitoring.

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Han Soo Park Department of Internal Medicine, Division of Endocrinology and Metabolism

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Su Kyoung Kwon Department of Internal Medicine, Division of Endocrinology and Metabolism

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Ye Na Kim Division of Nephrology, Kosin University College of Medicine, Busan, Republic of Korea

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Summary

Thyroid storm is a rare and potentially life-threatening medical emergency. We experienced a case of thyroid storm associated with sepsis caused by pneumonia, which had a catastrophic course including recurrent cardiac arrest and subsequent multiple organ failure (MOF). A 22-year-old female patient with a 10-year history of Graves’ disease was transferred to our emergency department (ED). She had a cardiac arrest at her home and a second cardiac arrest at the ED. Her heart recovered after 20 min of cardiac resuscitation. She was diagnosed with thyroid storm associated with hyperthyroidism complicated by pneumonia and sepsis. Although full conventional medical treatment was given, she had progressive MOF and hemodynamic instability consisting of hyperthermia, tachycardia and hypotension. Because of hepatic and renal failure with refractory hypotension, we reduced the patient’s dose of beta-blocker and antithyroid drug, and she was started on continuous veno-venous renal replacement therapy (CRRT) with intravenous albumin and plasma supplementation. Subsequently, her body temperature and pulse rate began to stabilize within 1 h, and her blood pressure reached 120/60 mmHg after 6 h. We discontinued antithyroid drug 3 days after admission because of aggravated hyperbilirubinemia. The patient exhibited progressive improvement in thyroid function even after cessation of antithyroid drug, and she successfully recovered from thyroid storm and MOF. This is the first case of thyroid storm successfully treated by CRRT in a patient considered unfit for antithyroid drug treatment.

Learning points:

  • The presenting manifestations of thyroid storm vary and can include cardiac arrest with multiorgan failure in rare cases.

  • In some patients with thyroid storm, especially those with severe complications, conventional medical treatment may be ineffective or inappropriate.

  • During thyroid storm, the initiation of CRRT can immediately lower body temperature and subsequently stabilize vital signs.

  • Early initiation of CRRT can be life-saving in patients with thyroid storm complicated by MOF, even when used in combination with suboptimal medical treatment.

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Julian Choi Departments of Internal Medicine

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Perin Suthakar Neurology, Arrowhead Regional Medical Center, Colton, California, USA

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Farbod Farmand Departments of Internal Medicine

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Summary

We describe the case of a young Hispanic female who presented with thyrotoxicosis with seizures and ischemic stroke. She was diagnosed with a rare vasculopathy – moyamoya syndrome. After starting antithyroid therapy, her neurologic symptoms did not improve. Acute neurosurgical intervention had relieved her symptoms in the immediate post-operative period after re-anastomosis surgery. However, 2 post-operative days later, she was found to be in status epilepticus and in hyperthyroid state. She quickly deteriorated clinically and had expired a few days afterward. This is the second case in literature of a fatality in a patient with moyamoya syndrome and Graves’ disease. However, unlike the other case report, our patient had undergone successful revascularization surgery. We believe her underlying non-euthyroid state had potentiated her clinical deterioration. Case studies have shown positive correlation between uncontrolled hyperthyroidism and stroke-like symptoms in moyamoya syndrome. Mostly all patients with these two disease processes become symptomatic in marked hyperthyroid states. Thus, it may be either fluctuations in baseline thyroid function or thyrotoxicosis that potentiate otherwise asymptomatic moyamoya vasculopathy.

Learning points:

  • Awareness of the association between Graves’ disease and moyamoya syndrome in younger patients presenting with stroke-like symptoms.

  • Obtaining euthyroid states before undergoing revascularization surgery may protect the patient from perioperative mortality and morbidity.

  • Although moyamoya disease is usually thought to be genetically associated, there are reports that thyroid antibodies may play a role in its pathogenesis and have an autoimmune link.

  • Fluctuations in baseline thyroid function for patients with known Graves’ disease may be a potentiating factor in exacerbating moyamoya vasculopathy.

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Elizabeth M Madill Department of Endocrinology and Diabetes, The Alfred Hospital, Melbourne, Victoria, Australia

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Shamil D Cooray Department of Endocrinology and Diabetes, The Alfred Hospital, Melbourne, Victoria, Australia

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Leon A Bach Department of Endocrinology and Diabetes, The Alfred Hospital, Melbourne, Victoria, Australia
Department of Medicine (Alfred), Monash University, Melbourne, Victoria, Australia

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Summary

Thyrotoxicosis is an under-recognised but clinically important complication of parathyroidectomy. We report a case of a 37-year-old man with tertiary hyperparathyroidism who initially developed unexplained anxiety, diaphoresis, tachycardia, tremor and hyperreflexia one day after subtotal parathyroidectomy. Thyroid biochemistry revealed suppressed thyroid stimulating hormone and elevated serum free T4 and free T3 levels. Technetium-99m scintigraphy scan confirmed diffusely decreased radiotracer uptake consistent with thyroiditis. The patient was diagnosed with thyrotoxicosis resulting from palpation thyroiditis. Administration of oral beta-adrenergic antagonists alleviated his symptoms and there was biochemical evidence of resolution fourteen days later. This case illustrates the need to counsel patients about thyroiditis as one of the potential risks of parathyroid surgery. It also emphasises the need for biochemical surveillance in patients with unexplained symptoms in the post-operative period and may help to minimise further invasive investigations for diagnostic clarification.

Learning points

  • Thyroiditis as a complication of parathyroidectomy surgery is uncommon but represents an under-recognised phenomenon.

  • It is thought to occur due to mechanical damage of thyroid follicles by vigorous palpation.

  • Palpation of the thyroid gland may impair the physical integrity of the follicular basement membrane, with consequent development of an inflammatory response.

  • The majority of patients are asymptomatic, however clinically significant thyrotoxicosis occurs in a minority.

  • Patients should be advised of thyroiditis/thyrotoxicosis as a potential complication of the procedure.

  • Testing of thyroid function should be performed if clinically indicated, particularly if adrenergic symptoms occur post-operatively with no other cause identified.

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Ling Zhu Department of Endocrinology, Singapore General Hospital, Singapore

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Sueziani Binte Zainudin Department of Endocrinology, Singapore General Hospital, Singapore

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Manish Kaushik Department of Renal Medicine, Singapore General Hospital, Singapore

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Li Yan Khor Department of Pathology, Singapore General Hospital, Singapore

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Chiaw Ling Chng Department of Endocrinology, Singapore General Hospital, Singapore

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Summary

Type II amiodarone-induced thyrotoxicosis (AIT) is an uncommon cause of thyroid storm. Due to the rarity of the condition, little is known about the role of plasma exchange in the treatment of severe AIT. A 56-year-old male presented with thyroid storm 2months following cessation of amiodarone. Despite conventional treatment, his condition deteriorated. He underwent two cycles of plasma exchange, which successfully controlled the severe hyperthyroidism. The thyroid hormone levels continued to fall up to 10h following plasma exchange. He subsequently underwent emergency total thyroidectomy and the histology of thyroid gland confirmed type II AIT. Management of thyroid storm secondary to type II AIT can be challenging as patients may not respond to conventional treatments, and thyroid storm may be more harmful in AIT patients owing to the underlying cardiac disease. If used appropriately, plasma exchange can effectively reduce circulating hormones, to allow stabilisation of patients in preparation for emergency thyroidectomy.

Learning points

  • Type II AIT is an uncommon cause of thyroid storm and may not respond well to conventional thyroid storm treatment.

  • Prompt diagnosis and therapy are important, as patients may deteriorate rapidly.

  • Plasma exchange can be used as an effective bridging therapy to emergency thyroidectomy.

  • This case shows that in type II AIT, each cycle of plasma exchange can potentially lower free triiodothyronine levels for 10h.

  • Important factors to consider when planning plasma exchange as a treatment for thyroid storm include timing of each session, type of exchange fluid to be used and timing of surgery.

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Luísa Correia Martins Department of Pediatric Endocrinology, Diabetes and Growth, Pediatric Unit, Coimbra Hospital and Universitary Center, Coimbra, 3030, Portugal

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Ana Rita Coutinho Department of Pediatric Endocrinology, Diabetes and Growth, Pediatric Unit, Coimbra Hospital and Universitary Center, Coimbra, 3030, Portugal

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Mónica Jerónimo Department of Pediatric Endocrinology, Diabetes and Growth, Pediatric Unit, Coimbra Hospital and Universitary Center, Coimbra, 3030, Portugal

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Joana Serra Caetano Department of Pediatric Endocrinology, Diabetes and Growth, Pediatric Unit, Coimbra Hospital and Universitary Center, Coimbra, 3030, Portugal

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Rita Cardoso Department of Pediatric Endocrinology, Diabetes and Growth, Pediatric Unit, Coimbra Hospital and Universitary Center, Coimbra, 3030, Portugal

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Isabel Dinis Department of Pediatric Endocrinology, Diabetes and Growth, Pediatric Unit, Coimbra Hospital and Universitary Center, Coimbra, 3030, Portugal

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Alice Mirante Department of Pediatric Endocrinology, Diabetes and Growth, Pediatric Unit, Coimbra Hospital and Universitary Center, Coimbra, 3030, Portugal

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Summary

Alternating between hyper- and hypo-thyroidism may be explained by the simultaneous presence of both types of TSH receptor autoantibodies (TRAbs) – thyroid stimulating autoantibodies (TSAbs) and TSH blocking autoantibodies (TBAbs). It is a very rare condition, particulary in the pediatric age. The clinical state of these patients is determined by the balance between TSAbs and TBAbs and can change over time. Many mechanisms may be involved in fluctuating thyroid function: hormonal supplementation, antithyroid drugs and levels of TSAbs and TBAbs. Frequent dose adjustments are needed in order to achieve euthyroidism. A definitive therapy may be necessary to avoid switches in thyroid function and frequent need of therapeutic changes. We describe an immune-mediated case of oscillating thyroid function in a 13-year-old adolescent. After a short period of levothyroxine treatment, the patient switched to a hyperthyroid state that was only controlled by adding an antithyroid drug.

Learning points

  • Autoimmune alternating hypo- and hyper-thyroidism is a highly uncommon condition in the pediatric age.

  • It may be due to the simultaneous presence of both TSAbs and TBAbs, whose activity may be estimated in vitro through bioassays.

  • The clinical state of these patients is determined by the balance between TSAbs and TBAbs and can change over time.

  • The management of this condition is challenging, and three therapeutic options could be considered: I-131 ablation, thyroidectomy or pharmacological treatment (single or double therapy).

  • Therapeutic decisions should be taken according to clinical manifestations and thyroid function tests, independent of the bioassays results.

  • A definitive treatment might be considered due to the frequent switches in thyroid function and the need for close monitoring of pharmacological treatment. A definitive treatment might be considered due to the frequent switches in thyroid function and the need for close monitoring of pharmacological treatment.

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Nicole Maison Endocrine Research Unit, Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, Munich, Germany

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Esther Korpershoek Department of Pathology, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, The Netherlands

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Graeme Eisenhofer Department of Medicine III, Institute of Clinical Chemistry and Laboratory Medicine, Technische Universität Dresden, Dresden, Germany

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Mercedes Robledo Hereditary Endocrine Cancer Group, Human Cancer Genetics Programme, Spanish National Cancer Research Centre (CNIO) and ISCIII Center for Biomedical Research on Rare Diseases (CIBERER), Madrid, Spain

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Ronald de Krijger Department of Pathology, Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, The Netherlands
Department of Pathology, Reinier de Graaf Hospital, Delft, The Netherlands

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Felix Beuschlein Endocrine Research Unit, Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, Munich, Germany

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Summary

Pheochromocytomas (PCC) and paraganglioma (PGL) are rare neuroendocrine tumors arising from chromaffin cells of the neural crest. Mutations in the RET-proto-oncogene are associated with sporadic pheochromocytoma, familial or sporadic medullary thyroid carcinoma (MTC) and multiple endocrine neoplasia type 2. In the past, only few cases of pigmented PCCs, PGLs, and one case of pigmented MTC have been reported in the literature. Herein, we present the case of a 77-year old woman with a history of Tako-tsubo-cardiomyopathy and laboratory, as well as radiological, high suspicion of pheochromocytoma, who underwent left-sided adrenalectomy. The 3 cm tumor, which was located on the upper pole of the left adrenal, appeared highly pigmented with dark red to black color. Histologic examinations revealed highly pleomorphic cells with bizarre, huge hyperchromatic nuclei, that immunohistochemically were positive for chromogranin A and synaptophysin, focally positive for HMB45 and negative for melan A. These clinical and pathological features led to the diagnosis of the rare variant of a melanotic ‘black’ pheochromocytoma. In our case a somatic RET mutation in exon 16 (RET c.2753T>C, p.Met918Thy) was detected by targeted next generation sequencing. In summary, this case represents a rare variant of catecholamine-producing tumor with distinct histological features. A potential relationship between the phenotype, the cellular origin and the genetic alterations is discussed.

Learning points

  • Pheochromocytoma is a rare neuroendocrine tumor.

  • Pigmentation is seen in several types of tumors arising from the neural crest. The macroscopic black aspect can mislead to the diagnosis of a metastasis deriving from a malignant melanoma.

  • RET mutation are seen in catecholamine and non-catecholamine producing tumors of the same cellular origin.

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Niki Margari Department of Endocrinology and Diabetes, Royal London Hospital, Barts Health NHS Trust, London, UK

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Jonathan Pollock Department of Neurosurgery, Queens Hospital, Barking Havering and Redbridge University Hospitals NHS Trust, Romford, Essex, UK

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Nemanja Stojanovic Department of Endocrinology and Diabetes, Queens Hospital, Barking Havering and Redbridge University Hospitals NHS Trust, Romford, Essex, UK

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Summary

Prolactinomas constitute the largest subsection of all secretory pituitary adenomas. Most are microprolactinomas and are satisfactorily treated by medical management alone. Giant prolactinomas, measuring more than 4 cm in diameter, are rare and usually occur more commonly in men. Macroprolatinomas tend to present with symptoms of mass effect rather than those of hyperprolactinaemia. Dopamine agonists (DA) are the treatment of choice for all prolactinomas. Surgery is usually reserved for DA resistance or if vision is threatened by the mass effects of the tumour. We describe the case of a 52 year-old woman with a giant invasive prolactinoma who required multiple surgical procedures as well as medical management with DA. One of the surgical interventions required a posterior approach via the trans cranial sub occipital transtentorial approach, a surgical technique that has not been previously described in the medical literature for this indication. The giant prolactinoma was reduced significantly with the above approach and patient symptoms from the compressing effects of the tumour were resolved. This case highlights the importance of a multidisciplinary approach to the management of such patients who present with florid neurological sequelae secondary to pressure effects. Although this presentation is uncommon, surgery via a sub occipital transtentorial approach may be considered the treatment of choice in suitable patients with giant invasive prolactinomas compressing the brainstem.

Learning points

  • Giant prolactinomas present with symptoms of mass effect or those of hyperprolactinaemia.

  • Interpretation of the pituitary profile is crucial to guide further investigations and management.

  • Treatment of giant invasive prolactinomas may involve a combination of medical management and multiple surgical interventions.

  • Treatment with DA may cause pituitary haemorrhage or infarction in patients with these tumours.

  • A sub occipital transtetorial approach may be considered the treatment of choice in invasive prolactinomas compressing the brainstem.

  • Multidisciplinary approach of such patients is fundamental for a better outcome.

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Milena S Pandrc Department of Internal Medicine, Militar Medical Academy, Crnotravska 1711000, Belgrade, Serbia

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Stanko Petrović Department of Gastroenterology, Militar Medical Academy, Crnotravska 1711000, Belgrade, Serbia

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Vanja Kostovski Clinic for Thoracic Surgery, Militar Medical Academy, Crnotravska 1711000, Belgrade, Serbia

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Marijana Petrović Department of Nephrology, Militar Medical Academy, Crnotravska 1711000, Belgrade, Serbia

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Miloš Zarić Department of Pathology, Militar Medical Academy, Crnotravska 1711000, Belgrade, Serbia

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Summary

Immunoglobulin (Ig)G4-related sclerosing disease (IgG4-RSD) is a new disease entity first proposed with regard to autoimmune pancreatitis. A 67-year-old male patient was examined because of weight loss and an abdominal pain. Based on the clinical characteristics, laboratory parameters and ultrasound features, we identified the diagnosis of the IgG4-related systemic disease (IgG4-RSD), that was confirmed by the histopathological analysis after the biopsy of the head of pancreas. After confirmation, we started with the corticosteroid therapy with a good clinical, biochemical and morphological response. During the previous therapy, the disturbance of glucoregulation appeared, so we had to change the modality of treatment. We decided to add Azathioprine to the therapy in a dose of 150 mg/day. We achieved a stable phase of the disease with IgG 4.37 g/l and IgG4 0.179 g/l, and with no side effects from the therapy.

Learning points

  • There are potential clinical applications of identifying subsets of patients with IgG4 thyroiditis (FVHT and Riedel thyroiditis).

  • A trial of immunosuppressive therapy should be included if a resection is deemed inadvisable.

  • In particular, cases of FVHT that mimic malignancy, tissue and serum IgG4 may provide supportive diagnostic information.

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W C Candy Sze Department of Endocrinology, St Bartholomew's Hospital, London, EC1A 7BE, UK

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Joe McQuillan Department of Ophthalmology, St Bartholomew's Hospital, London, EC1A 7BE, UK

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P Nicholas Plowman Department of Clinical Oncology, St Bartholomew's Hospital, London, EC1A 7BE, UK

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Niall MacDougall Department of Clinical Oncology, St Bartholomew's Hospital, London, EC1A 7BE, UK

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Philip Blackburn Gamma Knife Unit, St Bartholomew's Hospital, London, EC1A 7BE, UK

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H Ian Sabin Gamma Knife Unit, St Bartholomew's Hospital, London, EC1A 7BE, UK

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Nadeem Ali Department of Ophthalmology, St Bartholomew's Hospital, London, EC1A 7BE, UK

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William M Drake Department of Endocrinology, St Bartholomew's Hospital, London, EC1A 7BE, UK

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Summary

We report three patients who developed symptoms and signs of ocular neuromyotonia (ONM) 3–6 months after receiving gamma knife radiosurgery (GKS) for functioning pituitary tumours. All three patients were complex, requiring multi-modality therapy and all had received prior external irradiation to the sellar region. Although direct causality cannot be attributed, the timing of the development of the symptoms would suggest that the GKS played a contributory role in the development of this rare problem, which we suggest clinicians should be aware of as a potential complication.

Learning points

  • GKS can cause ONM, presenting as intermittent diplopia.

  • ONM can occur quite rapidly after treatment with GKS.

  • Treatment with carbamazepine is effective and improve patient's quality of life.

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