I thank you in advance for your work in providing endo text.  It is a very valuable resource.

I am writing with an inquiry regarding a challenging patient I am presently caring for with non-islet cell hypoglycemia.  He is a 70 year old male with a ~ 15 year history of metastatic adrenal cortical carcinoma. He has very bulky disease with complete infiltration of the liver.   He recently developed intractable, severe hypoglycemia resulting in loss of consciousness.  His insulin levels are low and his cortisol levels are normal.    He is presently euglycemic on oral hydrocortisone therapy.

I suspected IGF-II as the likely culprit of his problem, but his ratio of IGF-II (167 ng/ml) to IGF-I (53 ng/ml) is ~ 3.  His Growth Hormone level is elevated at 3.78 ng/ml.  My differential diagnosis for this gentleman is “big IGF-II”or tumor consumption.  A less likely diagnosis that I will consider is ectopic production of somatostatin.    I have contacted multiple laboratories and can not find a commercially available “big IGF-II” assay.

Can  you comment on the questions of

1)      Are you aware of a laboratory that runs the “big IGF-II” assay?

2)      Is the “big IGF-II” worth pursuing in this case

3)      Is there a test to confirm the diagnosis of tumor consumption as a cause for NICH?

I thank you in advance for your assistance with this case.Mark Wilson, MD  Santa Barbara, CA

RESPONSE--Dear Dr. Wilson-Thank you for sharing your challenging case, and your current successful management.  I agree that your patient with non-islet cell hypoglycemia could have elevated levels of "big" or immature forms of IFG-II +/- increased glucose utilization by the tumor.  Additional contributing factors could be his extensive liver disease and presumed poor nutritional status.  I am not aware of any commercial laboratories that specifically measure "big" IGF-II, only IGF-II as you have already obtained.

In addition to diet, treatment of this condition with glucocorticoids has been successful as apparently is the case for your patient.  If this later fails, in addition to the other available general medical treatments described, growth hormone could be tried (there are some case reports indicating success with this combination).

When the available biochemical/hormonal tests do not document a specific etiology for hypoglycemia increased glucose utilization is assumed to be a contributing factor. Treating the tumor medically or surgical debulking can be helpful.  Actual measurements of glucose utilization are usually made in research settings.

We have just revised/updated our section in Endotext, including this information.  Thank you for sharing this case with us. Ruth Weinstock,  MD