Presentation & Diagnosis
Clinical Presentation
Diagnosis
NICTH may present with mild symptoms that can quickly escalate1,2
Initial, autonomic symptoms of hypoglycemia may go undetected and progress into an emergency that leads to the diagnosis of non-islet cell tumor hypoglycemia (NICTH).1,2
Symptoms of hypoglycemia may also overlap with tumor-related symptoms (such as night sweats or orthostasis), making it crucial to monitor patients for warning signs that may otherwise be overlooked.1,3,4
Hypoglycemia-associated symptoms
Tumor-associated symptoms
Autonomic symptoms
Initial warning signs in the body that are not always detectable1:
Diaphoresis
Tremors
Palpitations
Nausea
Intense hunger
Paresthesia
Feeling of anxiety or nervousness
Even subtle signs of hypoglycemia, especially between meals or in the morning, can indicate non-islet cell tumor hypoglycemia (NICTH).5
Neuroglycopenic symptoms
Due to deprivation of glucose in the brain1:
Disorientation
Decreased motor activity
Behavioral changes
Seizure
Loss of consciousness
If a patient with a known tumor is unconscious but lacks signs of a vascular event or brain metastases, NICTH should be considered.5
IGF-2, insulin-like growth factor 2.
NICTH can significantly impact quality of life1,3
Uncontrolled hypoglycemia has serious physical implications, especially long term:
Coma
Seizures
Neurological damage
Interference with tumor-directed therapy
Organ failure
Acute morbidity
Cardiovascular events
Cerebrovascular events
Patients may also experience:
Anxiety and fear of hypoglycemia6,7
Fear of losing consciousness in front of loved ones
Impacted ability to drive, walk distances, or even shower alone
Significant lifestyle disruption1,8
Compounding burden of symptoms from both the tumor and hypoglycemia
Lifestyle disruption from supportive interventions and repeated hospitalizations
Differential diagnosis for NICTH
Collaboration between oncologists and endocrinologists is highly valuable in the diagnosis and management of non-islet cell tumor hypoglycemia (NICTH). Consultation with an endocrinologist is recommended at the earliest suspicion of hypoglycemia.1
NICTH commonly presents in the setting of a known malignancy, but should be considered in any case of unexplained, recurrent hypoglycemia.1,9
The clinical criteria for hypoglycemia should be met before biochemical testing to confirm non-islet cell tumors as the cause.1
Confirm patient meets criteria for hypoglycemia1
72-hour supervised fast to measure serum insulin, C peptide, pro-insulin, β-hydroxybutyrate, and glycemic response to glucagon
Measure IGF-1 and IGF-2 levels,
and big IGF-2 concentrations (if available)
Higher IGF-2:IGF-1 ratio suggestive of NICTH
In patients with no known tumor history, imaging of the chest, abdomen, and pelvis should be done for localization.
10% to 15% of patients do not have a known tumor upon onset of hypoglycemia and typically present with a severe hypoglycemic event10
Unlike insulinomas, in NICTH the neoplasm is usually diagnosed before the onset of hypoglycemia1
Delayed or misdiagnosis of NICTH has clinical consequences1,3,9
It may put patients at risk of emergency medical intervention and worsened prognosis for tumor management.9
Understand current treatment options for NICTH
Current Management
References: 1. Karamanolis N, et al. Paraneoplastic hypoglycemia: an overview for optimal clinical guidance. Metab Open. 2024;23(100305):1-9. doi:10.1016/j.metop.2024.100305 2. Voon K, et al. Three cases of non-islet cell tumor hypoglycemia highlighting efficacy of glucocorticoid treatment. JCEM Case Rep. 2023;1(4):1-4. doi:10.1210/jcemcr/luad045 3. Cleveland Clinic. Hypoglycemia (low blood sugar). Published January 21, 2023. Accessed April 13, 2026. https://my.clevelandclinic.org/health/diseases/11647-hypoglycemia-low-blood-sugar 4. Akavia L, et al. Extreme hypoglycaemia in anaplastic large cell lymphoma. Eur J Case Rep Intern Med. 2016;4(2):1-3. doi:10.12890/2016_000510 5. De Groot J, et al. Non-islet cell tumor-induced hypoglycemia: a review of the literature including two new cases. Endocr Relat Cancer. 2007;14(4):979-993. doi:10.1677/ERC-07-0161 6. Przezak A, et al. Fear of hypoglycemia—an underestimated problem. Brain Behav. 2022;12:e2633 7. Data on file. Rezolute, Inc. 8. Elsdai I, et al. Marked reduction in the hospital admission rate of a man with nonislet cell tumor hypoglycemia after starting steroids: a case report. Ann Med Surg. 2023;85(5):2007-2009. doi:10.1097/MS9.0000000000000537 9. Bodnar T, et al. Management of non-islet cell tumor hypoglycemia: a clinical review. J Clin Endocrinol Metab. 2013;99(3):713-722. doi:10.1210/jc.2013-3382 10. Data on file. Rezolute Scientific Platform. 2025.
