Think Like a Doctor
Solve a medical mystery with Dr. Lisa Sanders.
On Wednesday, we challenged Well readers to solve the case of a middle-aged woman who suddenly began to have episodes of confusion caused by low blood sugars. Her endocrinologist thought she might have an insulinoma, an insulin-producing tumor of the pancreas, but the testing he did seemed to rule out that diagnosis. Nearly 200 of you took on the challenge of trying to figure out what was causing her life-threatening drops in blood sugar level.
The correct diagnosis is…
Insulinoma
The first respondent to make the diagnosis was Karen Unkel of Kinder, La. She is not a doctor but has a longstanding interest in hypoglycemia that allowed her to recognize the disease even in the face of an apparently negative work-up. Well done, Ms. Unkel.
The Diagnosis
An insulinoma is a rare tumor of pancreatic tissue that makes and secretes insulin independently of blood glucose levels. This results in episodes of hypoglycemia that can be quite severe, even life-threatening. The diagnosis is suspected when a patient fulfills what is known as Whipple's triad: 1) symptoms of hypoglycemia 2) associated with low measured blood sugar and 3) which improve when blood sugar is raised to the normal range.
The diagnosis is made when doctors show that the patient is making too much insulin given his or her blood sugar level. Measuring insulin levels is not always accurate because insulin is processed rapidly in the body and because it is difficult to distinguish between insulin made naturally in the pancreas and any insulin that the patient might be injecting.
What is measured instead is something known as C-peptide. Insulin is first made as a larger molecule known as proinsulin. When blood sugar rises, an extra bit is shaved off the molecule; that extra bit is C-peptide, and both the resulting insulin and C-peptide are released into the bloodstream.
Surgical excision of the tumor is the usual treatment.
How the Diagnosis Was Made
When the endocrinologist heard about the second episode of life-threatening hypoglycemia, after the patient's hip replacement surgery, his understanding and his approach to the problem changed.
He hadn't been sure that the first low sugar measured by the emergency medical technicians had been right. No one is walking and talking with a sugar level that low, or at least not usually. And in his office the patient's sugar was always fine. But her second severely low sugar level was measured in the hospital. So he immediately began to consider a much more unusual cause of hypoglycemia – an insulinoma.
He sent off a blood test to look for high levels of C-peptide, evidence of high insulin levels. He expected the C-peptide to be as high as the patient's sugars were low. But it was normal.
Insulin was also measured. Also normal. When C-peptide was normal a second, then a third time, and a CT scan did not show the suspected tumor in her pancreas, both doctor and patient were puzzled and frustrated. That's when they decided to seek a second opinion.
He referred the patient to Dr. Ronald Tamler, the clinical director of the Mount Sinai Diabetes Center in New York.
A Second Opinion
Dr. Tamler had seen many patients who complained of postprandial hypoglycemia, or low blood sugar after meals. Like this patient, they appeared quite healthy. And like this patient, they reported a need to eat something sweet an hour or two after a meal.
But this patient had something that few of those patients had: a documented Whipple's triad. In the hospital she'd felt dizzy and was found to have an extremely low blood glucose, and she improved once she was given intravenous glucose and her blood sugar normalized.
Dr. Tamler knew that very few things will cause a sugar level to go this low. Patients who have been on steroids like prednisone can have low sugars for months afterward. This patient had once been on steroids for a diagnosis of lupus, but the disease had been quiet for decades and was unlikely to cause hypoglycemia this far out.
Occasionally alcohol can cause low blood sugars. Was she drinking more than she admitted to? Or could she be secretly using a diabetic medication to cause her own episodes of hypoglycemia? Again, it seemed unlikely, yet factitious disorders (like Münchausen syndrome) often seemed unlikely until proven to be true.
These diagnoses were possible and yet, even before performing the first test, Dr. Tamler suspected that the first endocrinologist had been right, that the patient had an insulin-producing tumor. Years of dealing with diseases of the pancreas had taught him that "normal" wasn't always normal.
Still, Dr. Tamler wanted to test the patient for all the possibilities. So, two weeks later she visited the lab.
Lab Testing
As instructed, the patient had eaten nothing that morning. Blood was drawn when she arrived, and then she was given a sugary drink. Her blood would be drawn at regular intervals for the next three hours, revealing how her body responded to sugar.
The results of the very first blood draw told Dr. Tamler what he needed to know. Her fasting blood glucose was 31 — extremely low. With a sugar that low, her C-peptide level should be zero. But it wasn't; it was 2.5. That is in the normal range, but definitely not normal in someone with such a low sugar. A normal pancreas would never do that.
The patient must have an insulin-secreting tumor, he thought. Now all they had to do was find it.
She'd already had a CT scan that didn't show anything. These tumors are often quite small. The doctor ordered an endoscopic ultrasound of the pancreas, which can pick up very small growths. A tiny ultrasound probe is inserted into the patient's mouth, through the stomach and into the small intestine where it can "see" the pancreas. They found a one-centimeter tumor, and it was removed a couple of weeks later.
Back to Normal
The first week after her surgery, the patient carried her juice boxes and candies with her, ready to dose herself if she started to feel odd. She never needed to. She felt great.
But she knew she was really cured a couple of weeks later when she heard her stomach growl, a sound which, because of her hourly snacks, she hadn't heard for years.
Her first endocrinologist learned from the experience. Not long after his patient was cured of her tumor, he made the diagnosis of the same rare tumor in a man with persistent dangerously low sugars. One in a million, twice in one year.
An earlier version of this post misstated the patient's C-peptide level. It was 2.5, not 10.
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