A Rare Adrenal Cancer That Secreted IGF-2 and Caused Dangerous Low Blood Sugar
A 59-year-old woman's adrenal tumor was found to secrete both IGF-2 (causing severe hypoglycemia) and steroid hormones (causing postmenopausal bleeding), representing two distinct clinical syndromes from one cancer.
Quick Facts
What This Study Found
The patient had an IGF-2:IGF-1 ratio of 60.7 (normal <10) with low insulin and C-peptide levels, confirming non-islet cell tumor hypoglycemia caused by the adrenal mass. Symptomatic hypoglycemia developed within 5 hours of a supervised fast. The tumor also caused biochemical hyperandrogenism with elevated testosterone, estradiol, and adrenal androgens, leading to endometrial hyperplasia and postmenopausal bleeding.
Postoperative pathology confirmed adrenocortical carcinoma with a Ki67 proliferation index of 12% and positive immunostaining for IGF-2, providing direct histological evidence that the tumor was producing this peptide growth factor.
Key Numbers
How They Did This
This was a clinical case report of a single 59-year-old female patient. Doctors used blood tests during a supervised fasting protocol to measure IGF-2, IGF-1, insulin, and C-peptide levels. Cross-sectional imaging identified the adrenal mass, and after surgical removal, pathology and immunostaining confirmed the diagnosis.
Why This Research Matters
This case highlights how a single tumor can produce both peptide factors and steroid hormones simultaneously, creating two distinct clinical syndromes that might seem unrelated. Recognizing IGF-2-mediated hypoglycemia is critical because it requires different management than insulin-driven low blood sugar, and the underlying cause is a malignancy that needs surgical treatment.
The Bigger Picture
Non-islet cell tumor hypoglycemia from IGF-2 secretion is an uncommon but important paraneoplastic syndrome. This case adds to a small body of literature showing that adrenocortical carcinomas can cosecrete peptide growth factors alongside steroid hormones, complicating diagnosis and requiring awareness of IGF-2 as a cause of unexplained hypoglycemia in cancer patients.
What This Study Doesn't Tell Us
As a single case report, these findings cannot be generalized to other patients. There is no long-term follow-up data reported, and the mechanisms behind dual peptide and steroid secretion from one tumor are not fully explored.
Questions This Raises
- ?How commonly do adrenocortical carcinomas cosecrete IGF-2 alongside steroid hormones, and is dual secretion associated with different outcomes?
- ?Could routine IGF-2 screening in patients with adrenal masses help catch tumor-driven hypoglycemia earlier?
- ?What is the long-term prognosis after surgical removal of IGF-2-secreting adrenocortical carcinomas?
Trust & Context
- Key Stat:
- IGF-2:IGF-1 ratio of 60.7 Over 6 times the upper limit of normal, confirming the adrenal tumor as the source of life-threatening hypoglycemia
- Evidence Grade:
- This is a single case report, which provides the lowest level of clinical evidence. It documents a rare presentation but cannot establish prevalence, causation patterns, or treatment efficacy.
- Study Age:
- Published in 2025, this is a current case report reflecting modern diagnostic techniques including IGF-2 immunostaining.
- Original Title:
- Adrenocortical Carcinoma With 2 Distinct Syndromes From Secretion of Insulin-Like Growth Factor 2 and Steroid Hormones.
- Published In:
- JCEM case reports, 3(6), luaf078 (2025)
- Authors:
- Lonergan, Eibhlín Marie, Tan, Lok Yi Joyce, O'Sullivan, Adrian, Kanazaki, Keizo, Morita, Miwa, O'Halloran, Domhnall
- Database ID:
- RPEP-12288
Evidence Hierarchy
Frequently Asked Questions
What is non-islet cell tumor hypoglycemia?
It's a condition where a tumor outside the pancreas produces IGF-2, a growth factor that mimics insulin's blood sugar-lowering effects. Unlike typical hypoglycemia caused by too much insulin, this type shows low insulin levels alongside low blood sugar.
Why did the same tumor cause both low blood sugar and postmenopausal bleeding?
The adrenal tumor was producing two types of substances simultaneously: IGF-2 (a peptide that drives blood sugar down) and steroid hormones like testosterone and estrogen (which stimulated the uterine lining and caused bleeding). This dual secretion from one tumor is exceptionally rare.
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Cite This Study
https://rethinkpeptides.com/research/RPEP-12288APA
Lonergan, Eibhlín Marie; Tan, Lok Yi Joyce; O'Sullivan, Adrian; Kanazaki, Keizo; Morita, Miwa; O'Halloran, Domhnall. (2025). Adrenocortical Carcinoma With 2 Distinct Syndromes From Secretion of Insulin-Like Growth Factor 2 and Steroid Hormones.. JCEM case reports, 3(6), luaf078. https://doi.org/10.1210/jcemcr/luaf078
MLA
Lonergan, Eibhlín Marie, et al. "Adrenocortical Carcinoma With 2 Distinct Syndromes From Secretion of Insulin-Like Growth Factor 2 and Steroid Hormones.." JCEM case reports, 2025. https://doi.org/10.1210/jcemcr/luaf078
RethinkPeptides
RethinkPeptides Research Database. "Adrenocortical Carcinoma With 2 Distinct Syndromes From Secr..." RPEP-12288. Retrieved from https://rethinkpeptides.com/research/lonergan-2025-adrenocortical-carcinoma-with-2
Access the Original Study
Study data sourced from PubMed, a service of the U.S. National Library of Medicine, National Institutes of Health.
This study breakdown was produced by the RethinkPeptides research team. We analyze and report published research findings without making health recommendations. All interpretations are based solely on the published abstract and study data.