Browse
Search for other papers by Jenny S W Yun in
Google Scholar
PubMed
Search for other papers by Chris McCormack in
Google Scholar
PubMed
Search for other papers by Michelle Goh in
Google Scholar
PubMed
University of Melbourne, Parkville, Victoria, Australia
Search for other papers by Cherie Chiang in
Google Scholar
PubMed
Summary
Acanthosis nigricans (AN) is a common dermatosis associated with hyperinsulinemia and insulin resistance. However, AN has been rarely reported in patients with insulinoma, a state of persistent hyperinsulinemia. We present a case of metastatic insulinoma, in whom AN manifested after the first cycle of peptide receptor radionuclide therapy (PRRT). A 40-year-old man was diagnosed with metastatic insulinoma after 5 months of symptomatic hypoglycemia. Within 1 month post PRRT, the patient became euglycemic but developed a pigmented, pruritic rash which was confirmed on biopsy as AN. We discuss the rare manifestation of AN in subjects with insulinoma, the role of insulin in the pathogenesis of AN, malignant AN in non-insulin-secreting malignancies and association with other insulin-resistant endocrinopathies such as acromegaly.
Learning points
-
Acanthosis nigricans (AN) is a common dermatosis which is typically asymptomatic and associated with the hyperinsulinemic state.
-
Malignant AN can rapidly spread, cause pruritus and affect mucosa and the oral cavity.
-
AN is extremely rare in patients with insulinoma despite marked hyperinsulinemia.
-
Peptide receptor radionuclide therapy might have triggered TGF-α secretion in this subject which led to malignant AN.
-
Rapid spread or unusual distribution of pruritic AN warrants further investigation to exclude underlying malignancy.
Eastern Health Clinical School, Monash University, Victoria, Australia
Search for other papers by Ming Li Yee in
Google Scholar
PubMed
Search for other papers by Rosemary Wong in
Google Scholar
PubMed
Medical Imaging, Eastern Health, Box Hill, Victoria, Australia
Search for other papers by Mineesh Datta in
Google Scholar
PubMed
Department of Medicine and Radiology, University of Melbourne, Victoria, Australia
Search for other papers by Timothy Nicholas Fazio in
Google Scholar
PubMed
Search for other papers by Mina Mohammad Ebrahim in
Google Scholar
PubMed
Search for other papers by Elissa Claire Mcnamara in
Google Scholar
PubMed
Search for other papers by Gerard De Jong in
Google Scholar
PubMed
Eastern Health Clinical School, Monash University, Victoria, Australia
Department of Medicine, Eastern Health, Box Hill, Victoria, Australia
Search for other papers by Christopher Gilfillan in
Google Scholar
PubMed
Summary
Mitochondrial diseases are rare, heterogeneous conditions affecting organs dependent on high aerobic metabolism. Presenting symptoms and signs vary depending on the mutation and mutant protein load. Diabetes mellitus is the most common endocrinopathy, and recognition of these patients is important due to its impact on management and screening of family members. In particular, glycemic management differs in these patients: the use of metformin is avoided because of the risk of lactic acidosis. We describe a patient who presented with gradual weight loss and an acute presentation of hyperglycemia complicated by the superior mesenteric artery syndrome. His maternal history of diabetes and deafness and a personal history of hearing impairment led to the diagnosis of a mitochondrial disorder.
Learning points:
-
The constellation of diabetes, multi-organ involvement and maternal inheritance should prompt consideration of a mitochondrial disorder.
-
Mitochondrial encephalomyopathy, lactic acidosis, stroke-like episodes (MELAS) and maternally inherited diabetes and deafness (MIDD) are the most common mitochondrial diabetes disorders caused by a mutation in m.3243A>G in 80% of cases.
-
Metformin should be avoided due to the risk of lactic acidosis.
-
There is more rapid progression to insulin therapy and higher prevalence of diabetic complications compared to type 2 diabetes.
-
Diagnosis of a mitochondrial disorder leads to family screening, education and surveillance for future complications.
-
Superior mesenteric artery syndrome, an uncommon but important cause of intestinal pseudo-obstruction in cases of significant weight loss, has been reported in MELAS patients.
Search for other papers by Senhong Lee in
Google Scholar
PubMed
Search for other papers by Aparna Morgan in
Google Scholar
PubMed
Search for other papers by Sonali Shah in
Google Scholar
PubMed
Department of Medicine, School of Clinical Sciences, Monash University, Clayton, Victoria, Australia
Search for other papers by Peter R Ebeling in
Google Scholar
PubMed
Summary
We report a case of a 67-year-old man with type 2 diabetes presented with diabetic ketoacidosis, two weeks after his first dose of nivolumab therapy for non–small-cell lung carcinoma. He was started on empagliflozin two days prior in the setting of hyperglycaemia after the initiation of nivolumab therapy. Laboratory evaluation revealed an undetectable C-peptide and a positive anti-glutamic acid decarboxylase (GAD) antibody. He was treated with intravenous fluids and insulin infusion and was subsequently transitioned to subcutaneous insulin and discharged home. He subsequently has developed likely autoimmune thyroiditis and autoimmune encephalitis.
Learning points:
-
Glycemic surveillance in patients receiving immune checkpoint inhibitors is recommended.
-
Early glycemic surveillance after commencement of anti-programmed cell death-1 (PD-1) inhibitors may be indicated in selected populations, including patients with underlying type 2 diabetes mellitus and positive anti-glutamic acid decarboxylase (GAD) antibody.
-
Sodium-glucose co transporter-2 (SGLT2) inhibitors should be used with caution in patients on immunotherapy.
Search for other papers by Sarah Y Qian in
Google Scholar
PubMed
Search for other papers by Matthew J L Hare in
Google Scholar
PubMed
Search for other papers by Alan Pham in
Google Scholar
PubMed
Department of Medicine, Monash University, Melbourne, Australia
Search for other papers by Duncan J Topliss in
Google Scholar
PubMed
Summary
Insulinomas are rare neuroendocrine tumours that classically present with fasting hypoglycaemia. This case report discusses an uncommon and challenging case of insulinoma soon after upper gastrointestinal surgery. A 63-year-old man presented with 6 months of post-prandial hypoglycaemia beginning after a laparoscopic revision of Toupet fundoplication. Hyperinsulinaemic hypoglycaemia was confirmed during a spontaneous episode and in a mixed-meal test. Localisation studies including magnetic resonance imaging (MRI), endoscopic ultrasound (EUS) and gallium dotatate positron emission tomography (68Ga Dotatate PET) were consistent with a small insulinoma in the mid-body of the pancreas. The lesion was excised and histopathology was confirmed a localised well-differentiated neuroendocrine pancreatic neoplasm. There have been no significant episodes of hypoglycaemia since. This case highlights several key points. Insulinoma should be sought in proven post-prandial hyperinsulinaemic hypoglycaemia – even in the absence of fasting hypoglycaemia. The use of nuclear imaging targeting somatostatin and GLP1 receptors has improved accuracy of localisation. Despite these advances, accurate surgical resection can remain challenging.
Learning points:
-
Hypoglycaemia is defined by Whipple’s triad and can be provoked by fasting or mixed-meal tests.
-
Although uncommon, insulinomas can present with post-prandial hypoglycaemia.
-
In hypoglycaemia following gastrointestinal surgery (i.e. bariatric surgery or less commonly Nissen fundoplication) dumping syndrome or non-insulinoma pancreatogenous hypoglycaemia syndrome (NIPHS) should be considered.
-
Improved imaging techniques including MRI, endoscopic ultrasound and functional nuclear medicine scans aid localisation of insulinomas.
-
Despite advances in imaging and surgical techniques, accurate resection of insulinomas remains challenging.
