Insulinoma and Tuberous Sclerosis: A Possible Mechanistic Target of Rapamycin (mTOR) Pathway Abnormality?
Open accessAbstract
A 23-year-old New Zealand Māori male with tuberous sclerosis (TSC) and associated neurocognitive abnormalities presented with altered behavior and increasing seizure frequency. Endogenous hyperinsulinemia from an underlying insulinoma was confirmed and this was managed surgically. This case represents only the sixth description of insulinoma in TSC to date. The role of the hamartin-tuberin complex in regulation of the mechanistic target of rapamycin pathway provides a plausible pathogenetic mechanism between insulinoma and TSC. This rare disease association should be considered in TSC patients who present with otherwise unexplained worsening neurocognitive symptoms.
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The majority of insulinomas are sporadic, but ~5-10% are inherited as part of MEN1 syndrome, and even more as part of NF1 and tuberous sclerosis phenotype.
“The majority of insulinomas are sporadic, but ~5-10% are inherited as part of multiple endocrine neoplasia type 1 (MEN1) syndrome, and even more as part of the neurofibromatosis type 1 and tuberous sclerosis phenotype [83,84].”
From Non-Diabetic Hypoglycemia: Evaluation and Management in Adults (2025) · cites this paper as [84]
The Discussion (page not provided) describes the MEN1–insulinoma association as well established but says insulinoma with tuberous sclerosis has been reported only sporadically, with five prior cases identified. That contradicts the claim that insulinomas occur even more often as part of the tuberous sclerosis phenotype than as part of MEN1. The paper does not provide the claimed 5–10% figure or address the NF1 comparison. (LLM, conf=0.88)
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Cites
The TSC1–TSC2 complex: a molecular switchboard controlling cell growth
Huang, J., & Manning, B. D. (2008) · Biochemical Journal · doi:10.1042/bj20080281 · Cited by 1,237 · cited 1× · see citing works
“Therefore, loss of the hamartin–tuberin complex results in the constitutive activation ofmTOR complex 1 and unregulated cellular growth and proliferation [3].”
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Research works printed but not linked: 11
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Cited by
Sorted by citations
Non-Diabetic Hypoglycemia: Evaluation and Management in Adults
Looi, E., & Lawler, H. M. (2025) · Journal of Clinical Medicine · doi:10.3390/jcm14134393 · Cited by 10 · see citing works
“The majority of insulinomas are sporadic, but ~5–10% are inherited as part of multiple endocrine neoplasia type 1 (MEN1) syndrome, and even more as part of the neurofibromatosis type 1 and tuberous sclerosis phenotype [83,84].”
- Authors
- Kang, M. Y., Yeoh, J., Pondicherry, A., Rahman, H., & Dissanayake, A.
- Affiliations
- Middlemore Hospital (NZ)
- Corresponding author
- Kang, Michael Yoon
- Venue
- Journal of the Endocrine Society
- Publisher
- The Endocrine Society
- Published
- 2017-07-17
- Volume
- 1
- Issue
- 9
- Pages
- 1120-1123
- ISSN
- 2472-1972 (ISSN-L)
- PMC
- PMC5686638
- OpenAlex
- W2750125036
- Cited by
- 11
- References
- 1
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 3 · 2023: 3 · 2022: 1 · 2021: 2
- FWCI
- 0.00
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Journal of the Endocrine Society (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Tuberous Sclerosis Complex Research
- Health Sciences › Medicine › Epidemiology › Neuroendocrine Tumor Research Advances
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Keywords
- insulinoma, tuberous sclerosis complex, mTOR signaling, hamartin, tuberin, hyperinsulinemia, seizures, TSC1/TSC2, surgical resection
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