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Forty-Eight-Hour Fast: The Diagnostic Test for Insulinoma
Abstract
Insulinoma causes fasting hypoglycemia due to inappropriate insulin secretion. Its diagnosis is based on demonstrating Whipple's triad during a supervised 72-h fast. For 75 yr, the 72-h fast has been the cornerstone for the diagnosis; however, it has never been critically assessed using newer assays for insulin, C peptide, and proinsulin. Thus, the aim of the current study is to assess the need for a full 72-h fast for the diagnosis of insulinoma. Patients with suspected hypoglycemia with documented glucose concentrations below 45 mg/dL were admitted to the NIH. Data obtained during the supervised fast of patients with pathologically proven insulinoma over a 30-yr period (1970-2000) were reviewed. We identified 127 patients with insulinoma. The average age of patients was 42.7 +/- 15.9 yr, with a predominance of females (62%). 107 patients had a benign tumor, 20 had malignant insulinoma, and 15 patients had multiple endocrine neoplasia type 1. The fast was terminated due to hypoglycemia in 44 patients (42.5%) by 12 h, 85 patients (66.9%) by 24 h, and 120 (94.5%) by 48 h. Seven patients fasted beyond 48 h despite subtle neuroglycopenic symptoms and glucose and insulin concentrations diagnostic of insulinoma. Immunoreactive proinsulin was elevated at the beginning of the fast in 90% of 42 patients. Proinsulin in noninsulinoma, in contrast to insulinoma, patients is usually suppressible; therefore, samples taken in the suppressed state have the greatest diagnostic value. We conclude that with the current available insulin and proinsulin assays, the diagnosis of insulinoma can be made within 48 h. Thus, the 48-h fast should replace the 72-h fast in textbooks and hospital protocols as the new diagnostic standard.
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“Of note, it is helpful to know that 95% of patients with insulinoma meet end-of-fast criteria by 48 h, but the fast may be extended to 72 h as 7% of patients with proven insulinomas developed hypoglycemia after 48 h [87,88].”
From Non-Diabetic Hypoglycemia: Evaluation and Management in Adults (2025) · cites this paper as [87]
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References 31 · Cited by 256
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Metadata
- Authors
- Hirshberg, B., Livi, A., Bartlett, D. L., Libutti, S. K., Alexander, H. R., Doppman, J. L., Skarulis, M. C., & Gorden, P.
- Affiliations
- National Institutes of Health (US)
- National Institute of Diabetes and Digestive and Kidney Diseases (US)
- National Cancer Institute (US)
- Division of Intramural Research, National Institute of Diabetes, Digestive and Kidney Diseases (B.H., A.L., M.C.S.), Bethesda, Maryland 20892
- Corresponding author
- Hirshberg, Boaz
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2000-09-01
- Volume
- 85
- Issue
- 9
- Pages
- 3222-3226
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W1981178839
- Cited by
- 256
- References
- 31
- Citations by year
- 2026: 4 · 2025: 12 · 2024: 12 · 2023: 19 · 2022: 10 · 2021: 7 · 2020: 4 · 2019: 8 · 2018: 13 · 2017: 12 · 2016: 14 · 2015: 11 · 2014: 6 · 2013: 14 · 2012: 9
- FWCI
- 5.10
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Oncology › Neuroendocrine Tumor Research Advances
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pancreatic function and diabetes
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Keywords
- insulinoma, fasting hypoglycemia, proinsulin, C-peptide, insulin secretion, Whipple's triad, neuroglycopenic symptoms, multiple endocrine neoplasia type 1, malignant insulinoma
- MeSH terms
- Adolescent, Adult, Aged, Aged, 80 and over, Child, Fasting, Female, Humans, Insulin, Insulinoma, Male, Middle Aged, Pancreatic Neoplasms, Proinsulin
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- Hirshberg, B., Livi, A., Bartlett, D. L., Libutti, S. K., Alexander, H. R., Doppman, J. L., Skarulis, M. C., & Gorden, P. (2000). Forty-Eight-Hour Fast: The Diagnostic Test for Insulinoma. The Journal of Clinical Endocrinology & Metabolism. https://doi.org/10.1210/jcem.85.9.6807
