Diagnosis and Treatment > Medication
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IMED Biotech Unit, Clinical Discovery Unit, AstraZeneca, Cambridge, UK
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Summary
A 67-year-old woman presented with a generalised rash associated with weight loss and resting tachycardia. She had a recent diagnosis of diabetes mellitus. Biochemical evaluation revealed elevated levels of circulating glucagon and chromogranin B. Cross-sectional imaging demonstrated a pancreatic lesion and liver metastases, which were octreotide-avid. Biopsy of the liver lesion confirmed a diagnosis of well-differentiated grade 2 pancreatic neuroendocrine tumour, consistent with metastatic glucagonoma. Serial echocardiography commenced 4 years before this diagnosis demonstrated a progressive left ventricular dilatation and dysfunction in the absence of ischaemia, suggestive of glucagonoma-associated dilated cardiomyopathy. Given the severity of the cardiac impairment, surgical management was considered inappropriate and somatostatin analogue therapy was initiated, affecting clinical and biochemical improvement. Serial cross-sectional imaging demonstrated stable disease 2 years after diagnosis. Left ventricular dysfunction persisted, however, despite somatostatin analogue therapy and optimal medical management of cardiac failure. In contrast to previous reports, the case we describe demonstrates that chronic hyperglucagonaemia may lead to irreversible left ventricular compromise. Management of glucagonoma therefore requires careful and serial evaluation of cardiac status.
Learning points:
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In rare cases, glucagonoma may present with cardiac failure as the dominant feature. Significant cardiac impairment may occur in the absence of other features of glucagonoma syndrome due to subclinical chronic hyperglucagonaemia.
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A diagnosis of glucagonoma should be considered in patients with non-ischaemic cardiomyopathy, particularly those with other features of glucagonoma syndrome.
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Cardiac impairment due to glucagonoma may not respond to somatostatin analogue therapy, even in the context of biochemical improvement.
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All patients with a new diagnosis of glucagonoma should be assessed clinically for evidence of cardiac failure and, if present, a baseline transthoracic echocardiogram should be performed. In the presence of cardiac impairment these patients should be managed by an experienced cardiologist.
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Search for other papers by Michael D Goldberg in
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Summary
Metformin is recommended as the first-line agent for the treatment of type 2 diabetes. Although this drug has a generally good safety profile, rare but potentially serious adverse effects may occur. Metformin-associated lactic acidosis, although very uncommon, carries a significant risk of mortality. The relationship between metformin accumulation and lactic acidosis is complex and is affected by the presence of comorbid conditions such as renal and hepatic disease. Plasma metformin levels do not reliably correlate with the severity of lactic acidosis. We present a case of inadvertent metformin overdose in a patient with both renal failure and hepatic cirrhosis, leading to two episodes of lactic acidosis and hypoglycemia. The patient was successfully treated with hemodialysis both times and did not develop any further lactic acidosis or hypoglycemia, after the identification of metformin tablets accidentally mixed in with his supply of sevelamer tablets. Early initiation of renal replacement therapy is key in decreasing lactic acidosis-associated mortality.
Learning points:
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When a toxic ingestion is suspected, direct visualization of the patient’s pills is advised in order to rule out the possibility of patient- or pharmacist-related medication errors.
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Though sending a specimen for determination of the plasma metformin concentration is important when a metformin-treated patient with diabetes presents with lactic acidosis, complex relationships exist between metformin accumulation, hyperlactatemia and acidosis, and the drug may not always be the precipitating factor.
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Intermittent hemodialysis is recommended as the first-line treatment for metformin-associated lactic acidosis (MALA).
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An investigational delayed-release form of metformin with reduced systemic absorption may carry a lower risk for MALA in patients with renal insufficiency, in whom metformin therapy may presently be contraindicated.
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Summary
Latent autoimmune diabetes in adults (LADA) is a relatively new type of diabetes with a clinical phenotype of type 2 diabetes (T2D) and an immunological milieu characterized by high titers of islet autoantibodies, resembling the immunological profile of type 1 diabetes (T1D). Herein, we report a case of a young male, diagnosed with LADA based on both clinical presentation and positive anti-glutamic acid decarboxylase antibodies (GAD-abs), which were normalized after combined treatment with a dipeptidyl peptidase-4 inhibitor (DPP-4) (sitagliptin) and cholecalciferol.
Learning points
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Anti-glutamic acid decarboxylase antibodies (GAD-abs) titers in young patients being previously diagnosed as type 2 diabetes (T2D) may help establish the diagnosis of latent autoimmune diabetes in adults (LADA).
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Sitagliptin administration in patients with LADA might prolong the insulin-free period.
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Vitamin D administration in patients with LADA might have a protective effect on the progression of the disease.
