Hypoglycemia, Pulmonary and Peripheral Edema


Question

I am an IM doc in Yuma, AZ. I recently had a patient, 31y/o WF, hospitalized after showing up in the ER semi-comatose, with a glucose of 40 and pulmonary and peripheral edema. Only PMH is depression for which she takes Cymbalta with good results.

Her fasting (12hr) insulin was <2, her pro-insulin <5 and c-peptide was 1.0. Her CMP/CBC/TSH were normal. I thought maybe insulinoma before I drew the labs, and now I'm thoroughly confused. Any ideas? Thank you. RSmythe MD

Response

Since I do not have much clinical information I will answer this based on several different assumptions.

Assumption 1. The glucose was from a venous sample, not a finger stick. If this patient was in cardiac failure and in a degree of cardiovascular collapse, it is possible that there was peripheral vasoconstriction. When this occurs, it has been shown to lead to a false low glucose level on a finger stick test.

Assumption 2 -The Patient Did Not Have Cardiac Failure

In 2000, Ortega et al in Diabetes care (Ortega et al. 23 (7): 1023. (2000) published their observation of the relationship of hypoglycemia and pulmonary edema. This occurred in a diabetic patient who had a hypoglycemic seizure. In a follow-up letter, Matz (Diabetes Care 23 (11): 1715. (2000)), pointed out a long forgotten association of non cardiac pulmonary edema as a consequence of grandmal seizures.

Thus in this case, given that the finding of hypoglycemia was real (see above), then hypoglycemia and seizure could still be underlying this.

Assumption 3. The Patient Did Have Cardiac Failure

In this case, the cardiovascular issues raised above again must be satisfied. If the glucose level was "real," then one can rarely see severe hypoglycemia with severe hepatic congestion and dysfunction. One always would be concerned about the possibility of ethanol with hypoglycemia and cardiac problems.

So given all the above, where does that leave us. At this point, the data you present does not help. Insulin levels, proinsulin and c-peptide will only help if they are drawn at the time of hypoglycemia. In addition, testing for sulfonylureas would need to be done, with specific request that glimepiride and meglitinides be tested as these are not checked for on the routine screening tests of the past.

Proactive testing at this point can be done with a formal 72 hour fast that would require hospitalization. 99% of patients with an insulinoma will reveal themselves during this time. Other tests, such as a 72 hour continuous glucose monitor can be done, but given the history here, it is unclear if that test would be as helpful.

After these tests, if hypoglycemia is found, the concurrent insulin, c-peptide, proinsulin, and cortisol levels should lead to a correct diagnosis.Robert J. Rushakoff, MD

Note added- Cymbalta has been associated with the “inappropriate ADH syndrome” which might be part of this problem but could not explain it all. What was her serum sodium? L DeG