HomeHealth articleshypoglycemiaWhat Is Non-Islet Cell Tumor Hypoglycemia?

Non-Islet Cell Tumor Hypoglycemia - Symptoms, Diagnosis, and Treatment

Verified dataVerified data

3 min read


Hypoglycemia brought on by a tumor is known as non-islet cell tumor hypoglycemia (NICTH). Read the article to know more.

Medically reviewed by

Dr. Rajesh Gulati

Published At August 2, 2023
Reviewed AtFebruary 27, 2024

What Is Non-Islet Cell Tumor Hypoglycemia?

NICTH, a rare paraneoplastic syndrome, can manifest in the presence of both benign and malignant tumors, affecting glucose levels. NICTH is also called Doege-Potter syndrome when it is situated in the thorax. This syndrome has been known for decades and was initially thought to be caused by increased glucose utilization by large tumors. Although complete tumor resection is curative, it is frequently delayed or impossible. No universally accepted treatment protocol has been established for patients with this condition. NICT suggests either no gender preference or a slight male predominance. The reported ages spanned from 2 to 87 years, with a minimum of four cases observed in the pediatric age group.

What Is the Mechanism of Non-Islet Cell Tumor Hypoglycemia?

IGF-II (insulin-like growth factors-II), in particular, encourages continued glucose uptake, primarily by skeletal muscle, and inhibits adipocyte release of free fatty acids. Additionally, this stops the liver's ability to produce glucose and inhibits glycogenolysis, gluconeogenesis, and ketogenesis. IGF-II also inhibits the release of glucagon and growth hormone, two hormones that work as counter-regulators, which increases the NICTH's susceptibility to hypoglycemia.

What Are the Tumor Characteristics?

Tumors of mesenchymal or hepatic origin are most frequently described with NICTH. Thyroid cancer, as well as adrenal cortical carcinoma, have both been linked to NICTH. Most reported cases of NICTH involve primary tumor origin from the chest, abdomen, or pelvis because pleural tumors and tumors with hepatic and gastric origin are more common.

What Are the Symptoms of Non-islet Cell Tumor Hypoglycemia?

Hypoglycemia is the first sign of a tumor, with 52 % having known tumors before the onset of hypoglycemia. Indeed, it is well-described that the tumor mass can present with symptoms before the onset of hypoglycemia. Hypokalemia is also commonly associated with NICTH and is attributed to big IGF-insulin-like activity. The subclinical Cushing syndrome has even been linked to NICTH. Acromegaloid characteristics have also been mentioned in NICTH, and they are known to disappear following tumor removal. Due to recurrent hypoglycemic events and the sneaky nature of NICTH, neuroglycopenic symptoms are more frequently observed than autonomic symptoms.

What Is the Diagnosis of Non-islet Cell Tumor Hypoglycemia?

NICTH should be considered in any patient who has hypoglycemia without an apparent cause. The initial assessment of hypoglycemia should follow standard procedure. This includes assessing and investigating the possibility of medication-induced hypoglycemia, critical illness, organ failure, and or hormone deficiencies (for example - liver failure, kidney failure, adrenal insufficiency, and growth hormone deficiency) as well as endogenous hyperinsulinism (with differential diagnosis of insulinoma, post-gastric bypass hypoglycemia, autoimmune insulin hypoglycemia, and accidental or surreptitious insulin secretagogue ingestion).

Low insulin, proinsulin, C-peptide, and hydroxybutyrate levels and a lack of positive results on an oral hypoglycemic agent screen are all characteristics of NICTH. Low glucose (serum glucose 55 mg/dL) is also a characteristic pattern.

IGF-II with a high molecular weight can be measured to confirm the diagnosis further. Performing imaging scans of the chest, abdomen, and pelvis is highly likely to yield valuable results, especially in cases where a tumor is not previously identified or easily detectable.

What Is the Treatment for Non-islet Cell Tumor Hypoglycemia?

It is essential to simultaneously measure insulin, proinsulin, C-peptide, hydroxybutyrate, and an oral hypoglycemic agent screen by withdrawing a serum glucose level when conducting laboratory investigations of hypoglycemia to confirm hypoglycemia. The standard hypoglycemia assessment also includes a cosyntropin stimulation test, liver and kidney function testing, and other tests. Measuring IGF-I, IGF-II, and GH levels is a further investigation when NICTH is suspected. A low level of hydroxybutyrate suggests an agent mimicking insulin in a hypoglycemic patient with low insulin and C-peptide, which is a reason to measure IGF-I and IGF-II.

  1. Depending on the situation, oral glucose and intravenous glucose or dextrose-containing fluids may be used to treat hypoglycemia as an initial treatment. This is often sufficient to prevent further hypoglycemia. Once NICTH is recognized and a primary tumor is located, surgical resection is done entirely, and it is the mainstay of treatment and curative for hypoglycemia. There have also been instances of subtotal resection where hypoglycemia has resolved. Occasionally in a complete resection, tumor recurrence results in hypoglycemia. Total resection is often postponed or impossible in these situations. Non-resectability can arise due to significant tumor size, extensive metastatic disease, impaired local structures requiring partial resection, unique physical attributes of the tumor, and its proximity to surrounding structures necessitating discontinuation of resection, as well as patient-related considerations.

  2. The most in-depth research on medical treatment for NICTH has focused on glucocorticoids, which include Dexamethasone, Hydrocortisone, Prednisolone, and Prednisone and are typically administered in doses equivalent to Prednisone 30 to 60 mg/dl. In contrast to other therapeutic regimens, high-dose glucocorticoid therapy has an immediate positive impact on symptomatic hypoglycemia, and avoiding long-term side effects can effectively treat the underlying biochemical dysfunction. In cases of NICTH, Glucagon injections may reduce hypoglycemia, but the result is transient.

  3. Successful local antitumor treatments include the resolution of NICTH caused by HCC (hepatocellular carcinoma) after two courses of intrahepatic Adriamycin, the resolution of NICTH caused by GIST (gastrointestinal stromal tumors) after selective use of a GIST before subtotal resection, the stabilization of preoperative glucose using a combination of selective embolization, chemotherapy, and radiation therapy, and the resolution of NICTH with radiation therapy of a large leiomyosarcoma (despite untreated pulmonary metastases, although the patient later died due to tumor bleeding). There have been very few reports of systemic antitumor therapy being successful.


Although prompt and or total resection is curative for NICTH, they are not always possible. There is no distinct "standard of care" in this circumstance. Although they frequently fall short, nutritional approaches can help with hypoglycemia. Some patients may be candidates for and benefit from local or systemic targeted antitumor therapy. Continuous glucagon infusion is a reasonable substitute, given the drawbacks of continuous intravenous treatment. Diazoxide and octreotide play no part in NICTH. To determine if there is a critical mass above which NICH is likely to occur or why only a small percentage of patients develop NICH, more research is required. The effectiveness of newer antibodies also needs to be studied.

Source Article IclonSourcesSource Article Arrow
Dr. Rajesh Gulati
Dr. Rajesh Gulati

Family Physician


non-islet cell tumor hypoglycemiahypoglycemia
Community Banner Mobile
By subscribing, I agree to iCliniq's Terms & Privacy Policy.

Source Article ArrowMost popular articles

Do you have a question on


Ask a doctor online

*guaranteed answer within 4 hours

Disclaimer: No content published on this website is intended to be a substitute for professional medical diagnosis, advice or treatment by a trained physician. Seek advice from your physician or other qualified healthcare providers with questions you may have regarding your symptoms and medical condition for a complete medical diagnosis. Do not delay or disregard seeking professional medical advice because of something you have read on this website. Read our Editorial Process to know how we create content for health articles and queries.

This website uses cookies to ensure you get the best experience on our website. iCliniq privacy policy