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.
IGF-2:IGF-1 ratio of 60.7Over 6 times the upper limit of normal, confirming the adrenal tumor as the source of life-threatening hypoglycemia
What the researchers 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.
Why it 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.
How the study worked
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.
What this study cannot 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.
How to read the evidence
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.
When this study was published
Published in 2025, this is a current case report reflecting modern diagnostic techniques including IGF-2 immunostaining.
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.
Questions still open
- 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?
Common questions
What is non-islet cell tumor hypoglycemia?
Why did the same tumor cause both low blood sugar and postmenopausal bleeding?
Read the original research
Adrenocortical Carcinoma With 2 Distinct Syndromes From Secretion of Insulin-Like Growth Factor 2 and Steroid Hormones.
JCEM case reports, 3(6), luaf078
Citation
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