Episode #344: Man Has A Seizure While Lifting (Mystery Case)

Summary

In this episode of the Barbell Medicine podcast, Dr. Jordan Feigenbaum and Dr. Austin Baraki delve into a medical mystery case involving a 41-year-old male who experienced a seizure while lifting weights. The discussion covers the patient’s presentation, the physiological mechanisms at play, diagnostic workup, and his subsequent course. . The conversation emphasizes the importance of understanding the interplay between exercise, nutrition, and metabolic health.

🎧 Listen on Apple Podcasts: https://podcasts.apple.com/us/podcast/episode-344-man-has-a-seizure-while-lifting-mystery-case/id1199780143?i=1000703991792

Key Takeaways

Episode Timestamps

Clinical Pearls

References

Transcript

Presentation

• 41 yo male was brought into the emergency room after suffering an apparent seizure in the gym while he was lifting weights. He did not suffer any injuries during the episode and was transported to the hospital by ambulance.
• In the ED the patient’s blood sugar was found to be 38mg/dL (Austin?). He was started on fluids with dextrose and able to give a history.
• The patient reports that he has been working out for a long time, typically 4-5 times a week and was doing his usual workout. He says he has no medical issues and does not take any medications. He also says he has never had an episode like this. He denies smoking, use of anabolic steroids, or recreational drug use
• He also says that his mom had “low blood sugar” periodically throughout her life, once so bad, she lost consciousness, fell, and broke her femur. 
• He denies any recent weight loss and his ROS is negative. 
• Thots/play along at home?

Exam + initial workup

• VS normal
• Patient is alert and oriented sitting upright in bed. He appears well groomed and well nourished, his BMI 24
• Physical exam is unremarkable. Specifically, the patient is moving all extremities well with normal strength and reflexes, cardiopulmonary exam normal, and so on
• Repeat labs after dextrose and fluids:
  • Blood glucose normal
  • A1C 4.2%
  • electrolytes normal – kidney function 
  • LFT’s normal
  • Special labs
    • IGF-1 normal
      • Looking for tumors in the pancreas that release IGF-1 and can cause hypoglycemia 
    • Random cortisol level normal
    • Sulfonylurea screen normal
      • Sulfonylureas are medications that stimulate beta cells of pancreas to make insulin
    • Insulin antibodies negative
      • Antibodies to insulin or insulin receptor 
      • Insulin receptor = overactivation
      • Antibodies to insulin, first get hyperglycemia, then insulin dissociates from antibody in uncoordinated fashion hyperinsulinemia and hypo glycemia 
    • Creatine kinase normal
    • Lactate
    • Ammonia normal 
• EKG normal 
• Brain MRI normal 
• CT abdomen looking at pancreas was unremarkable
• Thots/play along at home?

Imaging + further work up

• Patient was admitted for further testing. He underwent a 72 hour fast to check for hyperinsulinemia
  • Blood sugar 41 mg/dL with no symptoms 
  • Insulin level 5.2 mU/L (high) (with appropriate pro-insulin and c-peptide)
  • No symptoms 
• 2nd fast, overnight + exercise on stationary bike
  • Blood glucose dropped to 25mg/dL 
  • Insulin was even higher than the previous fast (high) (with appropriate pro-insulin and c-peptide)
  • Had few symptoms of hypoglycemia despite having frank hypoglycemia 
  • Did this twice more with octreotide
    • Octreotide Inhibits insulin release
    • No hypoglycemia 
• Final diagnosis/play along at home?

Diagnosis and course

• Exercise induced hyperinsulinism causing hypoglycemia and subsequent seizure
•  The patient was found to have a genetic mutation in a gene encoding for monocarboxylate transporter 1. This is a transporter expressed all over the body, but usually silenced in the beta cells of the pancreas which make insulin. The mutation characterized here resulted in a lack of silencing in the beta cells, so they had more of this transporter. This transporter normally shuttles things like lactate and pyruvate, both increased with exercise, into the cell. In beta cells, this can increase insulin release.  His mom had the same gene mutation
• The patient was treated with diazoxide, which inhibits insulin release by opening ATP-dependent potassium channels on pancreatic beta cells, which make insulin. This results in hyperpolarization of the cells and inhibition of insulin release..

Pearls

• Hypoglycemia
  • The potential for low blood sugar (known as “hypoglycemia”) during exercise also increases with reduced carbohydrate availability. The International Hypoglycemia Study Group considers a blood sugar below 54 mg/dL to be low for individuals without diabetes. 
  •  It is possible for individuals to reach this level during periods of prolonged high-intensity exercise. This reduces glucose delivery to the brain, which then reduces the signalling from the brain to the muscles (known as “central drive”), ultimately decreasing force production. 
  • In people without diabetes, hypoglycemia is defined based on symptoms of “neuroglycopenia” which typically occurs as glucose levels fall below 55 mg/dL
    • neuroglycopenic symptoms of insulinoma include confusion, visual changes, irritability, and other strange behavior 
    • Can be preceded by autonomic symptoms like palpitations, tremulousness, and sweating
      • final defense against hypoglycemia aimed to trigger eating behaviors. Sym neural activity associated with these symptoms
• Exercise induced hyperinsulinemia
  • Exercise-induced hyperinsulinism is a hypoglycaemic disorder characterised by inappropriate insulin secretion following anaerobic exercise
  • This pathology in this patient is likely from a mutation in the monocarboxylate transporter 1 protein (MCT-1)
  • The monocarboxylate transporter is widespread in human tissues, allowing transport of things like lactate, pyruvate, and ketone bodies. Normally, this receptor expression is low in pancreatic beta cells, which make and release insulin
  • With this mutation, there is an overexpression of MCT-1, allowing for increased transport of lactate and pyruvate into the beta cell, which can stimulates insulin release from beta cells 
  • So, really, a gain of function mutation causing inappropriate insulin release in response to exogenous catabolic metabolites such as lactate and pyruvate
    • Normally lactate and pyruvate from exercise do not stimulate insulin release 
  • Maybe he just got used to it?
    • Of note, the patient was minimally symptomatic prior to presenting with seizure and had marked hypoglycaemic unawareness. Given this, it is likely he had experienced recurrent hypoglycaemia for some years.
    • In any case, Angus Barbieri He was 27 at the time and worked in a fish and chips shop his father owned. 
    • He was 456 pounds when he was admitted and that’s when the fast started. He got a multivitamin daily, but otherwise didn’t eat at all per the case report write-up
    • Over the 382 days of the fast, he lost 276lbs, going from 456 to 180 pounds. 
    • During the fast, they did a number of tests on Angus to see how things were going.
      • His blood sugar was very, very low, about 30mg/dL after a month until the very end, when it was 20mg/dL!
  • A few other case reports like this
  • Treated with diazoxide like this patient or octreotide 
• V Insulinoma
  • Insulinomas are characterized by their autonomous and unregulated secretion of insulin. 
  • normal beta cells modulate insulin secretion based on serum blood sugar levels
  • the neoplastic cells of insulinomas exhibit a loss of feedback inhibition, so insulin is secreted inappropriately, even during hypoglycemic states, leading to persistent hyperinsulinemia and recurrent episodes of hypoglycemia.
  • Insulinomas are rare tumors, 4 cases per million individuals per year
  • Usually in the pancreas  suggests that insulinomas arise from cells of the ductular/acinar system of the pancreas rather than from neoplastic proliferation of islet cells
  • Whereas most insulinomas are solitary tumors, approximately 10% of patients have multiple intrapancreatic tumors 
  • The majority (≥90%) of insulinomas remain localized to the pancreas
  • Nothing on CT in this patient
    • sensitivity of 70% to 80%. Insulinomas typically appear as small, well-circumscribed, solid masses that enhance with contrast.
    • Could’ve done MRI with contrast 
  • Usually surgery for treatment