Diagnosis and Treatment > Signs and Symptoms

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Frank Gao Department of Endocrinology and Diabetes, The Alfred Hospital, Melbourne, Australia

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Stephen Hall Department of Medicine, Monash University and Cabrini Health, Melbourne, Australia

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

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Summary

Sodium/glucose co-transporter 2 (SGLT2) inhibitors are novel oral hypoglycaemic agents that are increasingly used in the management of type 2 diabetes mellitus (T2DM). They are now recommended as second-line pharmacotherapy (in conjunction with metformin) in patients with type 2 diabetes and established atherosclerotic heart disease, heart failure or chronic kidney disease due to their favourable effects on cardiovascular and renal outcomes. We report a case of a 69-year-old man who developed muscle pain, weakness and wasting after commencing the SGLT2 inhibitor empagliflozin. This persisted for 1 year before he underwent resistance testing, which confirmed muscle weakness. His symptoms resolved within weeks of ceasing empagliflozin, with improvement in muscle strength on clinical assessment and resistance testing and reversal of MRI changes. No other cause of myopathy was identified clinically, on biochemical assessment or imaging, suggesting that empagliflozin was the cause of his myopathy.

Learning points:

  • Empagliflozin, a commonly used SGLT2 inhibitor, was associated with myopathy.

  • A high degree of suspicion is required to diagnose drug-induced myopathy, with a temporal relationship between starting the medication and symptom onset being the main indicator.

  • Recognition of drug-induced myopathy is essential, as discontinuation of the offending drug typically improves symptoms.

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Whitney L Stuard Department of Ophthalmology, University of Texas Southwestern Medical Center, Dallas, Texas, USA

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Bryan K Gallerson Department of Ophthalmology, University of Texas Southwestern Medical Center, Dallas, Texas, USA

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Danielle M Robertson Department of Ophthalmology, University of Texas Southwestern Medical Center, Dallas, Texas, USA

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Summary

The use of in vivo confocal microscopy (IVCM) is rapidly emerging as an important clinical tool to evaluate changes in corneal sensory nerves as a surrogate measure for diabetic peripheral neuropathy. Commonly used metrics to document and grade the severity of diabetes and risk for diabetic peripheral neuropathy include nerve fiber length, density, branching and tortuosity. In addition to corneal nerves, thinning of the retinal fiber layer has been shown to correlate with the severity of diabetic disease. Here, we present a case report on a pre-diabetic 60-year-old native American woman with abnormal corneal nerve morphology and retinal nerve fiber layer thinning. Her past medical history was positive for illicit substance abuse. IVCM showed a decrease in nerve fiber density and length, in addition to abnormally high levels of tortuosity. OCT revealed focal areas of reduced retinal nerve fiber layer thickness that were asymmetric between eyes. This is the first report of abnormally high levels of tortuosity in the corneal sub-basal nerve plexus in a patient with a past history of cocaine abuse. It also demonstrates, for the first time, that illicit substance abuse can have long-term adverse effects on ocular nerves for years following discontinued use of the drug. Studies using IVCM to evaluate changes in corneal nerve morphology in patients with diabetes need to consider a past history of illicit drug use as an exclusionary measure.

Learning points:

  • Multiple ocular and systemic factors can impede accurate assessment of the corneal sub-basal nerve plexus by IVCM in diabetes.

  • Although current history was negative for illicit substance abuse, past history can have longstanding effects on corneal nerves and the retinal nerve fiber layer.

  • Illicit drug use must be considered an exclusionary measure when evaluating diabetes-induced changes in corneal nerve morphology and the retinal nerve fiber layer.

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Liudmila Rozhinskaya Departments of Neuroendocrinology and Bone Diseases

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Ekaterina Pigarova Departments of Neuroendocrinology and Bone Diseases

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Ekaterina Sabanova Departments of Neuroendocrinology and Bone Diseases

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Elizaveta Mamedova Departments of Neuroendocrinology and Bone Diseases

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Iya Voronkova Departments of Pathomorphology

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Julia Krupinova Endocrinology Research Centre, Moscow, Russia

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Larisa Dzeranova Endocrinology Research Centre, Moscow, Russia

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Anatoly Tiulpakov Department and Laboratory of Inherited Endocrine Disorders

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Vera Gorbunova Department of Chemotherapy, Cancer Research Center, Moscow, Russia

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Nadezhda Orel Department of Chemotherapy, Cancer Research Center, Moscow, Russia

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Artur Zalian Department of Chemotherapy, Cancer Research Center, Moscow, Russia

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Galina Melnichenko Endocrinology Research Centre, Moscow, Russia

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Ivan Dedov Endocrinology Research Centre, Moscow, Russia

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Summary

Parathyroid carcinoma is an extremely rare disorder with little treatment options. It could be misdiagnosed in medical centers with little experience in management of such cases. Our clinical case shows that the initial misdiagnosis of a parathyroid carcinoma in a young woman has led to the development of multiple lung metastases, thus making its treatment hardly possible. Initiation of treatment with sorafenib – a multi-kinase inhibitor approved for treatment of different types of cancer but not parathyroid carcinoma – has led to a significant decrease in the size of lung metastases and has prevented the progression of hyperparathyroidism, which is usually severe in cases of parathyroid carcinoma. The detection of a germline CDC73 mutation in this patient has raised additional concerns about the necessity of periodic screening for early detection of renal, jaw and uterine lesions.

Learning points:

  • Diagnosis of parathyroid carcinoma may be challenging due to the absence of reliable diagnostic criteria. Thus, thorough histological examination is needed using immunohistochemical staining of resected tissue in suspicious cases.

  • CDC73 genetic testing should be considered in patients with parathyroid carcinoma.

  • Sorafenib may be a promising treatment of patients with parathyroid carcinoma with distant metastases.

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