Hepatocellular Carcinoma with Chronic Hepatitis B and Non-Islet Cell Tumor Hypoglycemia: A Case Report
NICTH in HCC: A Case Report
Downloads
Non-islet cell tumor hypoglycemia (NICTH) is a rare paraneoplastic syndrome manifestation associated with hepatocellular carcinoma (HCC). This report details a case of a 20-year-old woman with HCC linked to untreated chronic hepatitis B. The patient presented with refractory hypoglycemia that was suspected to be NICTH. She also exhibited decreased consciousness with an initial blood glucose reading of 31 mg/dL. After the administration of intravenous dextrose solution, the patient's consciousness improved, yet intermittent hypoglycemic episodes persisted due to insufficient oral intake. The laboratory findings revealed low levels of insulin and C-peptide. The management of the patient included a continuous infusion of 5% dextrose solution, administration of corticosteroids, and adherence to a high-calorie complex carbohydrate diet. Despite presenting with significant right upper abdominal discomfort and weight loss, the patient was diagnosed with HCC at stage B, according to the Barcelona Clinic Liver Cancer (BCLC) Staging System. The stage was determined based on the presence of extensive multifocal lesions, which rendered surgical resection and transarterial chemoembolization (TACE) non-viable. Consequently, palliative treatment using lenvatinib and antiviral therapy with tenofovir were initiated. NICTH involves an increased insulin-like growth factor 2 (IGF-2) precursor processing by tumor cells, leading to heightened peripheral glucose utilization and persistent hypoglycemia. Although tumor resection is the most effective treatment for NICTH, it was not feasible in this case. This report emphasizes the importance of considering NICTH in the differential diagnosis of refractory hypoglycemia for non-diabetic patients. It also underscores the need for parenteral nutrition and corticosteroid therapy to maintain euglycemia.
Highlights:
- This case report details a rare clinical presentation of non-islet cell tumor hypoglycemia (NICTH) associated with hepatocellular carcinoma (HCC) and chronic hepatitis B in a young patient, adding to the limited documented cases of this paraneoplastic syndrome.
- The report provides a thorough clinical description, extensive diagnostic workup, and comprehensive management strategies, offering valuable insights into the complexities and challenges in diagnosing and treating NICTH in HCC patients.
- This case emphasizes the critical need for early detection and intervention in HCC, particularly in non-cirrhotic patients with chronic hepatitis B, and highlights the importance of considering paraneoplastic syndromes in the differential diagnosis of refractory hypoglycemia in non-diabetic patients.
Albayrak B, Duman MB, Ayvaz E (2022). A case of hepatocellular carcinoma diagnosed with resistant hypoglycemia. Open Journal of Gastroenterology 12(08): 179–185. doi: 10.4236/ojgas.2022.128018.
Alharbi MS (2014). A 94-year-old man with recurrent hypoglycemia caused by non-islet cell tumor hypoglycemia (NICTH). International Journal of Health Sciences 8(4): 430–433. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/25780362.
Alwi I, Salim S, Hidayat R, Kurniawan J, Tahapary D (2019). Penatalaksanaan di bidang ilmu penyakit dalam panduan praktik klinis. PIP Interna, Jakarta, 4th ed. Retrieved from https://library.stikesmus.ac.id/index.php?p=show_detail&id=356&keywords=.
Ariana AM, Permadi GA, Susanto H (2024). Approach to refractory hypoglycaemia in a patient with hepatocellular carcinoma: A case study and literature review. Journal of Agromedicine and Medical Sciences 10(1): 5–11. doi: 10.19184/ams.v10i1.45924.
Azzahra S, Kholili U, Setiawati R, Maimunah U (2023). Profile of patients of hepatocellular carcinoma in the Internal Medicine Inpatient Room at Dr. Soetomo General Academic Hospital. Current Internal Medicine Research and Practice Surabaya Journal 4(1): 1–5. doi: 10.20473/cimrj.v4i1.42287.
Behringer-Massera S, Brutsaert EF, Epstein EJ (2017). Refractory hypoglycemia from paraneoplastic insulin-like growth factor 2 secretion in a patient with hepatocellular carcinoma. AACE Clinical Case Reports 3(4): 364–366. doi: 10.4158/EP171744.CR.
Bodnar TW, Acevedo MJ, Pietropaolo M (2014). Management of non-islet-cell tumor hypoglycemia: A clinical review. The Journal of Clinical Endocrinology & Metabolism 99(3): 713–722. doi: 10.1210/jc.2013-3382.
Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, et al. (2018). Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer Journal for Clinicians 68(6): 394–424. doi: 10.3322/caac.21492.
Garla V, Sonani H, Palabindala V, Gomez-Sanchez C, Subauste J, et al. (2019). Non-islet cell hypoglycemia: Case series and review of the literature. Frontiers in Endocrinology 10. doi: 10.3389/fendo.2019.00316.
Haeri NS, Mahmud H, Korytkowski MT (2021). Paraneoplastic hypoglycemia leading to insulin independence in a patient with type 1 diabetes. AACE Clinical Case Reports 7(6): 376–378. doi: 10.1016/j.aace.2021.05.006.
Huang JS, Chang PH (2016). Refractory hypoglycemia controlled by systemic chemotherapy with advanced hepatocellular carcinoma: A case report. Oncology Letters 11(1): 898–900. doi: 10.3892/ol.2015.3915.
Jannin A, Espiard S, Benomar K, do Cao C, Mycinski B, et al. (2019). Non-islet-cell tumour hypoglycaemia (NICTH): About a series of 6 cases. Annales d’Endocrinologie 80(1): 21–25. doi: 10.1016/j.ando.2018.01.005.
Kew M (2014). Hepatocellular carcinoma: Epidemiology and risk factors. Journal of Hepatocellular Carcinoma 115. doi: 10.2147/JHC.S44381.
Kitada M, Yasuda S, Takahashi N, Okazaki S, Ishibashi K, et al. (2016). Non-islet cell tumor hypoglycemia caused by intrathoracic solitary fibrous tumor: A case report. Journal of Cardiothoracic Surgery 11(1): 49. doi: 10.1186/s13019-016-0463-6.
Maharani I, Koesmarsono N, Laraswati B (2020). Relation between the increase of alpha fetoprotein serum level and the size of hepatocellular carcinoma in multi slice computed tomography examination. Indian Journal of Forensic Medicine & Toxicology 14(2): 2353–2357. doi: 10.37506/ijfmt.v14i2.3380.
Martens P, Tits J (2014). Approach to the patient with spontaneous hypoglycemia. European Journal of Internal Medicine 25(5): 415–421. doi: 10.1016/j.ejim.2014.02.011.
McGlynn KA, Petrick JL, El‐Serag HB (2021). Epidemiology of hepatocellular carcinoma. Hepatology 73(S1): 4–13. doi: 10.1002/hep.31288.
Melmed S, Koenig R, Rosen CJ, Auchus RJ, Goldfine AB (2019). Williams textbook of endocrinology. Elsevier, Philadelphia, 14th ed. Retrieved from https://books.google.co.id/books/about/Williams_Textbook_of_Endocrinology_E_Boo.html?id=j-u9DwAAQBAJ&redir_esc=y.
Muljono DH (2017). Epidemiology of hepatitis B and C in Republic of Indonesia. Euroasian Journal of Hepato-Gastroenterology 7(1): 55–59. doi: 10.5005/jp-journals-l0018-1212.
Putri DRI, Maimunah U, Retnowati E (2022). Serum AFP (alpha fetoprotein) levels profile of hepatocellular ccrcinoma patients in Dr. Soetomo General Academic Hospital, Surabaya, Indonesia. Majalah Biomorfologi 32(1): 6. doi: 10.20473/mbiom.v32i1.2022.6-12.
Regino CA, López-Montoya V, López-Urbano F, Alvarez JC, Roman-Gonzalez A (2020). Paraneoplastic hypoglycemia in hepatocarcinoma: Case report and literature review. Cureus 12(12): e12013. doi: 10.7759/cureus.12013.
Rojbi I, Ben Elhaj W, Mchirgui N, Jrad M, Ben Nacef I, et al. (2021). Non‐islet‐cell tumor hypoglycemia as first manifestation of an advanced hepatocellular carcinoma. Clinical Case Reports 9(10): e05012. doi: 10.1002/ccr3.5012.
Sabatine MS (Ed.) (2020). Pocket medicine: The Massachusetts General Hospital handbook of internal medicine. Wolters Kluwer, 7th ed. Retrieved from https://internalmedicine.lwwhealthlibrary.com/book.aspx?bookid=2726.
Samuel S, Nguyen T, Choi HA (2017). Pharmacologic characteristics of corticosteroids. Journal of Neurocritical Care 10(2): 53–59. doi: 10.18700/jnc.170035.
Sandooja R, Moorman JM, Kumar MP, Detoya K (2020). Critical low catastrophe: A case report of treatment-refractory hypoglycemia following overdose of long-acting insulin. Case Reports in Endocrinology 2020: 1–5. doi: 10.1155/2020/8856022.
Sharma M, Reddy DN, Kiat TC (2015). Refractory hypoglycemia presenting as first manifestation of advanced hepatocellular carcinoma. ACG Case Reports Journal 2(1): 50–52. doi: 10.14309/crj.2014.82.
Thiruchelvam N, Kistangari G, Listinsky C, Daw H, Kumar V (2015). Life-threatening hypoglycemia resulting from a nonislet cell tumor. The Journal of Community and Supportive Oncology 13(8): 296–297. doi: 10.12788/jcso.0163.
Wong WK (2015). Non-islet cell tumour hypoglycaemia (NICTH) in malignant mesothelioma: Case report. The Malaysian Journal of Medical Sciences : MJMS 22(4): 81–5. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/26715913.
World Health Organization (2020). Cancer Indonesia 2020 country profile. Retrieved from https://www.who.int/publications/m/item/cancer-idn-2020.
Copyright (c) 2024 Angela Kimberly Tjahjadi, Ummi Maimunah, Imelda Maria Loho
This work is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License.
Copyright (c) Author
1. The journal allows the author to hold the copyright of the article without restrictions.
2. The journal allows the author(s) to retain publishing rights without restrictions.
3. The formal legal aspect of journal publication accessibility refers to Creative Commons Atribution-Share Alike 4.0 (CC BY-SA).