1. A Case of Non-Islet Cell Tumor Hypoglycemia
Sagarika Sinha, MD & Amanda Mika, DO
ACP Resident Members
National Jewish Health | Saint Joseph Hospital
May 14, 2019
ACP Colorado Chapter Resident/Fellow Meeting

2. Case Presentation
Chief Complaint: 64-year-old man with weakness and dizziness x 1 day
HPI:
Initially presented to ED with a glucose of 40
Resolved with oral intake, discharged home
Recurrent symptoms the following day, found to have a glucose of 18
No confusion, diaphoresis, vision changes, palpitations, nausea, vomiting, or seizures

3. Case Presentation
PMHx: Hepatitis B, Hepatocellular carcinoma, Seizure Disorder, Osteoporosis
PSHx: None
Family Hx: Unknown
Medications: Entecivir, Levetiracetam, Lamotrigine, Alendronic acid, Mirtazapine
Social Hx: Born and raised in Vietnam. Former smoker, no alcohol use, no drugs use

4. Case Presentation Vitals: Exam:
T:99.7 F // BP:138/63 // P:93 // RR:18 // SpO2: 97% RA
Exam:
General: No acute distress; alert, well appearing
Mental Status: Alert, answers appropriately
Lungs: Clear without wheezes, rhonchi or rales.
Heart: Regular rate, no murmur
Abdomen: non distended, bowel sounds present, non ttp. No masses palpated.
Neurologic: Cranial nerves grossly intact, strength and sensation intact throughout

5. Case Presentation Labs:
BMP: Na 144 / K 2.8 / Cl 111 / CO2 23 / BUN 6 / Cr 0.45 / Glu 47
LFTs: Ca 7.8 / Tbili 0.7 / AST 128 / ALT 63 / Alk Phos 142 / Alb 3.5
CBC: Wbc 5.77 / Hgb 14.2 / Hct 44.5 / Plt 276
Coags: PT INR 1.13
AM Cortisol: 10.8
TSH: 1.49
C- Peptide: <0.1

8. Differential Diagnosis
Low suspicion for exogenous insulin use or oral hypoglycemic agent
No history of gastric bypass surgery
No evidence of severe liver dysfunction

9. Differential Diagnosis
Insulin
C-peptide
Proinsulin
Beta-Hydroxybutyrate
Insulinoma
Autoimmune
Insulin-like Growth Factor (IGF)
Not insulin mediated

10. Differential Diagnosis
Insulin
C-peptide
Proinsulin
Beta-Hydroxybutyrate
Insulinoma
Autoimmune
Insulin-like Growth Factor (IGF)
Not insulin mediated

11. Diagnosis: Non-Islet Cell Tumor Hypoglycemia (NICTH)
Syndrome of hypoglycemia associated with any neoplasm other than an insulinoma
True incidence unknown
Tumor Type
Epithelial Origin (45%); Most common etiology is HCC
Mesenchymal Origin (42%)
Overproduction of IGF-2
Posttranslational precursor is called “big IGF-2”
Activates insulin receptors resulting in hypoglycemia
de Groot, J. et al (2007). Non-islet cell tumour-induced hypoglycaemia: a review of the literature including two new cases, Endocrine-Related Cancer, 14(4),

12. Insulin-like growth factor-2 (IGF-2)
- Mostly produced in the liver
- Structurally related to proinsulin
Yevgeniya Dynkevich et al; Tumors, IGF-2, and Hypoglycemia: Insights From the Clinic, the Laboratory, and the Historical Archive, Endocrine Reviews, Volume 34, Issue 6, 1 December 2013, Pages 798–826

13. Diagnosis of NICTH Fasting labs
Low insulin, proinsulin, and c-peptide levels
Elevated IGF-2 or Big IGF-2 levels
IGF-2 and IGF-1 can be normal or low
Elevated IGF-2: IGF-1 ratio is suggestive of the diagnosis

14. Treatment of NICTH Hypoglycemia-Directed - Glucocorticoids
- Recombinant Growth Hormone
- Octreotide not effective
- Glucose infusions, glucagon
Tumor-Directed
- Surgical resection
- Debulking
- Embolization

15. Recombinant Growth Hormone
Suspected mechanism
Stimulates liver to produce IGF binding protein which hampers the activity of IGF-2
Administered at supraphysiologic doses
Concerns
May stimulate tumor growth
Cost

16. Case Presentation
Medical Oncology, Radiation Oncology and Interventional Radiology were consulted for potential options to decrease tumor burden
Patient was not a candidate for any intervention due to severe hypoglycemia and extensive tumor burden

17. Case Presentation
Euglycemia was achieved and patient was discharged with the following:
Prednisone
Frequent high carbohydrate meals
Growth hormone at supraphysiologic doses (5mg daily)
Re-presented about 10 days after discharge in respiratory distress thought to be due to metastatic disease and passed away

18. Implications
Important diagnosis to consider in patients unexplained hypoglycemia and malignancy
Correct diagnosis influences medical management

19. Questions? Thank You! Sagarika.Sinha@sclhealth.org