A systematic review of literature on Insulin-like growth factor-2-mediated hypoglycaemia in non-islet cell tumours

Our plain-English summary of A systematic review of literature on Insulin-like growth factor-2-mediated hypoglycaemia in non-islet cell tumours, by F. Ata, H. Choudry, A.A. Khan, et al (Endocrinology, Diabetes & Metabolism, 2024).

The study

• Authors: F. Ata, H. Choudry, A.A. Khan, Anum, I. Khamees, A. Al-Sadi, A. Mohamed, L. Malkawi, E. Aljaloudi
• Journal: Endocrinology, Diabetes & Metabolism
• Published: 2024;7(2):e00471
• Type of article: Systematic review
• Cited by: 18 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Introduction: Insulin-like growth factor-2 (IGF-2)-mediated hypoglycemia is a rare yet clinically significant entity with considerable morbidity and mortality. Existing literature is limited and fails to offer a comprehensive understanding of its clinical trajectory, management and prognostication.

Methods: Systematic review of English-language articles reporting primary patient data on IMH was searched using electronic databases (PubMed, Scopus and Embase) from any date up to 21 December 2022. Data were analysed in STATA-16.

Results: The systematic review contains 172 studies, including 1 Randomised controlled trial, 1 prospective observational study, 5 retrospective observational studies, 150 case reports, 11 case series and 4 conference abstracts. A total of 233 patients were analysed, averaging 60.6 ± 17.1 years in age, with comparable proportions of males and females. The commonest tumours associated with Insulin-like Growth Factor-2-mediated hypoglycaemia were fibrous tumours (N = 124, 53.2%), followed by non-fibrous tumours originating from the liver (N = 21, 9%), hemangiopericytomas (N = 20, 8.5%) and mesotheliomas (N = 11, 4.7%). Hypoglycaemia was the presenting feature of NICT in 42% of cases. Predominant clinical features included loss of consciousness (26.7%) and confusion (21%). The mean IGF-2 and IGF-1 levels were 882.3 ± 630.6 ng/dL and 41.8 ± 47.8, respectively, with no significant correlation between these levels and patient outcomes. Surgical removal was the most employed treatment modality (47.2%), followed by medication therapy. The recovery rate was 77%, with chronic liver disease (CLD) significantly associated with a poor outcome (OR: 7.23, P: 0.03). Tumours originating from fibrous tissues were significantly associated with recovery (p < .001). In the logistic regression model, CLD remained a significant predictor of poor outcomes.

Conclusion: This systematic review highlights that most non-islet-cell tumour-hypoglycaemia (NICTH) is due to fibrous tumours. NICTs demonstrate a variable prognosis, which is fair if originating from fibrous tissue. Management such as octreotide, corticosteroids, diazoxide, embolization, radiotherapy and surgical resection have disparate success rates.

© 2024 The Authors. Endocrinology, Diabetes & Metabolism published by John Wiley & Sons Ltd.

In plain English

This systematic review covered published reports of low blood sugar (hypoglycaemia) caused by IGF-2, a hormone-like protein made by tumours other than insulin-producing pancreatic tumours. The authors searched three databases to December 2022. They included 172 studies, mostly case reports, covering 233 patients (mean age 60.6 years). Fibrous tumours accounted for 124 patients (53.2%), non-fibrous tumours originating from the liver for 21 (9%), hemangiopericytomas for 20 (8.5%) and tumours of the mesothelium for 11 (4.7%). Asbestos was not discussed, and no separate treatment or outcome results were given for these 11 patients. Low blood sugar was the first sign of the tumour in 42% of patients. Surgery was used in 110 patients (47.2%) and steroids in 91 (39.1%). Of 223 patients with known outcomes, 172 (77%) recovered. Chronic liver disease (six patients) was associated with death (OR 7.23, p 0.03). Fibrous tumours were more common among patients who recovered than among those who died. No statistically significant association was found between IGF levels and outcome. The authors concluded that most cases were due to fibrous tumours, whose outlook was fair.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Systematic review of published studies reporting individual patient data (1 randomised controlled trial, 1 prospective observational study, 5 retrospective observational studies, 150 case reports, 11 case series, 4 conference abstracts)
• Who was studied: 233 patients (125 males, 108 females; mean age 60.6 years) with IGF-2-mediated hypoglycaemia caused by non-islet cell tumours, drawn from English-language literature published up to December 2022
• Exposure: Not applicable. The review did not study asbestos or any fiber exposure. It studied tumours causing IGF-2-mediated hypoglycaemia and their treatments.
• Main results:
  • Fibrous tumours were the most common tumour type: 124 of 233 patients (53.2%)
  • Non-fibrous tumours originating from the liver accounted for 21 patients (9%)
  • Hemangiopericytomas accounted for 20 patients (8.5%) and tumours of the mesothelium for 11 patients (4.7%)
  • Hypoglycaemia was the presenting feature of the tumour in 42% (98) of patients
  • Loss of consciousness (26.7%) and confusion (21%) were the most common features
  • Surgical removal was used in 110 patients (47.2%) and steroids in 91 (39.1%)
  • Outcomes were available for 223 patients, of whom 172 (77%) recovered
  • Chronic liver disease, present in six of the 233 patients, was associated with death rather than recovery (OR 7.23, P 0.03)
  • Fibrous tumours were found in 65.1% of patients who recovered versus 33% of those who died (p less than .001)
  • No statistically significant association was found between IGF levels at presentation, or the IGF-2 to IGF-1 ratio, and outcome
  • In the logistic regression model, tumour category and chronic liver disease remained significant predictors of outcome after adjusting for each other and for the IGF-2 to IGF-1 ratio
  • The IGF-2 to IGF-1 ratio exceeded 10 in 87.6% of the patients
• The authors' conclusion: The authors concluded that most non-islet cell tumour hypoglycaemia is due to fibrous tumours, that prognosis varies and is fair for tumours of fibrous origin, and that treatments (octreotide, corticosteroids, diazoxide, embolization, radiotherapy, surgical resection) had variable success rates.
• Limitations the authors state:
  • Only patients who developed hypoglycaemia were included, so the overall prevalence or burden of these tumours could not be calculated
  • Possible publication bias
  • Some studies were excluded because individual-level data were unavailable, which may affect comprehensiveness and generalizability

Topics

Medical terms in this study, explained in our Lexicon: Systematic Review, Mesothelioma, Prognosis, Surgical Resection.

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