Proinsulin-Secreting Neuroendocrine Tumors of the Pancreas: A Single-Centre Experience

Кригер, А Г; Берелавичус, С. В.; Калдаров, А. Р.; Panteleev, V I; Gorin, David Semjonovich; Dugarova, R. S.; Yukina, Marina Yur'evna

doi:10.1159/000501455

Cited by 3 publications

(3 citation statements)

References 22 publications

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“…Hypoglycemia due to proinsulinoma is infrequently reported [ 3 , 15 ]. A review of 16 proinsulinoma cases reported a 2:1 female preponderance, with a mean age of diagnosis at 56 years [ 4 ].…”

Section: Discussionmentioning

confidence: 99%

“…Dysregulated insulin secretion in hyperinsulinemic hypoglycemia (HH) drives glucose into insulin-sensitive tissues (eg, skeletal muscle, adipose tissue, and liver) and further exacerbates insulin-mediated inhibition of glycogenolysis, lipolysis, gluconeogenesis, and ketogenesis, predisposing the individual to hypoglycemic brain injury [ 2 ]. Clinical diagnosis can be challenging since symptoms of hypoglycemia mimic nonspecific symptomatology such as seizures, syncope, or psychiatric illness, resulting in delayed diagnosis for approximately 4 years (range of 1-30 years) [ 1 , 3 , 4 ]. On the other hand, misdiagnosis can lead to unnecessary pancreatotomy [ 4 ].…”

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confidence: 99%

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A Novel Somatic Mutation Implicates ATP6V0D1 in Proinsulin Processing

Avari

Salem

et al. 2022

Journal of the Endocrine Society

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Background Prohormone convertase 1/3 (PC1/3), encoded by protein convertase subtilisin kexin type 1 (PCSK1), converts inactive prohormones into biologically active peptides. Somatic mutations of insulinomas are associated with genetic defects interfering with control of insulin secretion from pancreatic beta-cells. However, somatic mutations in proinsulinomas have not been described. Here, we report a case of a proinsulinoma, with suppressed insulin and C-peptide levels. Patients and Methods A 70-year-old woman presented with a 20-year history of ‘blackouts’. During a 72-hour fast, blood glucose level dropped to 1.9 mmol/L with suppressed plasma insulin and C-peptide levels, but proinsulin levels were raised at 37 pmol/L (<10 pmol/L). Imaging revealed three distinct DOTATATE-avid pancreatic lesions. Laparoscopic spleen-preserving distal pancreatomy was performed. In view of discordant insulin, C-peptide and proinsulin levels, whole exome sequencing analysis was performed on the tumour. In the somatic exome of the tumour, we found mutations in PCSK expression regulators, as well as a novel truncating somatic mutation in ATP6V0D1, a subunit of the ion pump that acidifies the β-cell compartments where the PCSKs act. Conclusion Appropriately suppressed insulin levels in the context of hypoglycaemia do not always indicate the absence of neuroendocrine islet cell tumour and proinsulin levels may be indicated to solidify the diagnosis. In the context of elevated proinsulin levels, low insulin and C-peptide levels might be explained by somatic mutations that likely implicate proinsulin processing within the tumour. Furthermore, we propose several mechanistic candidates including ATP6V0D1. Experimental validation using cellular approaches may in future confirm pathomechanisms involved in this rare condition.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

A Novel Somatic Mutation Implicates ATP6V0D1 in Proinsulin Processing

Avari

Salem

et al. 2022

Journal of the Endocrine Society

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“…Kringer et al . suggested that a diagnosis of proinsulinoma can be made according to the clinical presentation and an elevated proinsulin level [ 7 ]. In the present case, the patient had hypoglycemic symptoms and a proinsulin level of 408 pmol/l, which is extremely high compared with previous reports of proinsulinoma [ 8 , 9 ].…”

Section: Discussionmentioning

confidence: 99%

Intraoperative selective arterial calcium injection test to confirm complete resection of a proinsulinoma

Sakamoto

Ogawa

Iwata

et al. 2022

Journal of Surgical Case Reports

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Proinsulinoma is a subtype of insulinoma that is surgically curable, but localization can be difficult as these tumors are typically too small to be visualized by imaging. We report the case of a 53-year-old woman referred to our hospital with dizziness and headache. Her blood glucose level was 46 mg/dl and Whipple’s triad was present. Although her immunoreactive insulin level during hypoglycemia was in the normal range (5.0 μU/ml), the proinsulin level was elevated (408 pmol/l). Imaging examinations showed no evidence of pancreatic tumor. A preoperative selective arterial calcium injection (SACI) test showed excessive insulin secretion in the splenic artery region, which localized the proinsulinoma to the body or tail of the pancreas, and laparoscopic spleen-preserving distal pancreatectomy was performed. Intraoperative SACI test performed after tumor removal did not show excessive insulin secretion. The intraoperative SACI test appears to be useful for localization and for confirming complete resection of proinsulinoma.

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