I had a recent experience in the medical care of an elite cyclist that,for me, became something of a baptism-by-fire education in sports physiology.Reviewing the results of an extensive set of blood tests on an elitecyclist who had recently fallen ill, I found myself at a complete lossto explain a mysterious abnormality that appeared on the charts.Was this a benign variation found in some elite cyclists or the firstdiagnosis of a serious or life-threatening illness? My God, could it alsobe doping? I felt I owed it to the athlete to figure it out. The investigationthat followed was a Pandora’s box of nuanced intrigue that included schoolingby several of the world’s top cycling doctors on the health care of procyclists. I would especially like to thank Dr. MassimoTesta, Dr. Harald Zotter, of the Swiss national doping laboratoryin Lausanne, and Dr.Prentice Steffen for their guidance. It’s nice to know how manyare willing to help a relatively new kid on the block.Background
Red blood cells are partially made up of hemoglobin, which is whatcarries oxygen from the heart and lungs to the muscles. Those red bloodcells live about four months in the bloodstream, and then they die. Sometimesred blood cells die prematurely and burst. This is called hemolysis. Thereare dangerous diseases like sickle cell anemia and immune diseases thatcan cause hemolysis. Vigorous exercise such as marathon running and endurancecycling can also cause red blood cell hemolysis, which is why it is quitereasonable to expect a cyclist competing in something like a three-weektour to have a significantly lower hematocrit at the end of the race thanat the beginning.When the red blood cells die, the hemoglobin inside them breaks freeinto the bloodstream and is collected and broken down in the spleen intobilirubin.The spleen breaks down this no-good hemoglobin into fat-soluble or unconjugatedbilirubin. This is also known as “free” or indirect bilirubin. The unconjugatedbilirubin is then shipped back in the blood to the liver. The liver hasan enzyme called glucuronyl transferase. Glucoronyl transferase convertsthe unconjugated bilurubin from fat-soluble to water-soluble. Water-solublebilirubin is also known as direct or conjugated biliribin.The way it’s supposed to work next is the glucuronyl transferase makesit so you can pass water-soluble bilirubin into the intestines. Bacteriain the intestines convert conjugated bilirubin to urobilinogen and it isexcreted in the stool. The pigmentation of urobilinogen is why a healthybowel movement has that lovely brown color. Normally, all the crud is eliminatedand you stay healthy and pink. Got it?My unusual case
Here is where the athlete had his surprise problem. His blood testsfor total bilirubin were markedly elevated, especially the unconjugatedbilirubin, but there was nothing else wrong with his liver that I coulddetect.He was turning yellow from the jaundice/high bilirubin and I couldn’tfigure out why. He had a situation just like Lucy and the Chocolate Factory.The excess bilirubin from his sudden – and unrelated - illness and thestress of elite bicycle racing was causing too much unconjugated bilirubinto come down the conveyor belt to his liver and overwhelming the liver’sability to process the bilirubin.

Just like Lucy couldn’t put the chocolates in the boxes fast enough,his glucuronyl transferase wasn’t working properly and the chocolates werebacking up on the conveyor belt. Lucy could shove the extra chocolatesin her mouth but the athlete was getting sicker by the hour. The bilirubinwas backing up in his blood. Why? What was wrong with his glucuronyl transferase?We had a long international discussion of the many possible causes ofthe elevated bilirubin. It could have been hepatitis, which made perfectsense with his acute symptoms. But hepatitis causes changes in severalother liver tests such as the transaminases.The other liver tests were completely normal so it wasn’t that. Antibiotics?He says no. Could it be birth control pills? Yeah right, dumbass, nevermind.Also on the long list of possible causes: anabolic steroids. This is theultimate nightmare of sports medicine and the doctor-athlete relationship.So I found myself forced to ask the horrible question.He was adamant that he had never used steroids and other liver and kidneytests that show signs of steroid abuse confirmed that. So what was I leftwith? After consulting with a host of other physicians, the only otherexplanation left was a inherited disorder known as Gilbert’ssyndrome.Gilbert’s syndrome is a genetic disorder that affects about five percentof the population. It is no more or less common among cyclists. Gilbert’ssyndrome leads to a deficiency of the normal level and function of bilirubinUDP-glucuronyl transferase and the liver doesn’t process bilirubin likeit should.At baseline health there is almost always at least a high normal levelof bilirubin in the blood among those with Gilbert’s syndrome. Gilbert’ssyndrome is almost completely harmless and those who are afflicted havea completely normal life expectancy.Dr. Testa has cared for 10-15 elite cyclists with Gilbert’s syndromeover the course of a 20-year career, including one top grand tour pro thathad a severe case that required frequent monitoring and medication availableonly in Europe.Most of those who have it have no idea, are completely unaffected andaren’t diagnosed unless there is a sudden illness. Repeated vomiting, skippingmeals, fever and vigorous exercise are kryptonite for someone with Gilbert’ssyndrome because this worsens the high bilirubin. The weakness and fatigueof simple food poisoning can become compounded exponentially. My athletehad all of these problems at the same time in a perfect storm and thisis why he became so sick and turned yellow.Dr. Testa also described to me some research he had done on Tour deFrance athletes in the middle of the Tour. Many had very high levels ofbilirubin from exertion-induced red blood cell hemolysis. Bilirubin levelswere even higher (total bilirubin 3.5 mg/dl and up) than in my sick athleteand most of them don’t have Gilbert’s syndrome. So the next time you seethe grand tour riders looking a little yellow in the later stages, don’tadjust the color on your TV. They really are yellow.There is a take home message for competitive cyclists. Next time youare getting a complete physical exam ask for liver function tests. It’sgood to know whether you have Gilbert’s syndrome or not as 1 in 20 of youhave it and don’t know it. If you combine Gilbert’s syndrome with foodpoisoning and/or fever, your jaundice symptoms can suddenly become muchmore severe than otherwise expected.If you have Gilbert’s syndrome and are an elite athlete, printout this sheet and present it whenever you get sick with feveror vomiting and need medical care. It will save you and your doctor a lotof worry and testing over why you have turned yellow.I hope you found this as fascinating as I did. Take care, thanks forreading and happy trails.

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Dr. Dawn M Richardson is a Board Certified Emergency Medicine specialistat Roger Williams Medical Center in Providence RI where she serves as sitequality director, and a clinical instructor of emergency medicine at BrownUniversity Medical School. She retired from cycling as a Cat. 2 ridingfor Verizon Wireless Women’s Cycling after 13 racing seasons. She welcomesmedical questions and has just found out that she has the qualificationsnecessary to be medical director of a division 3 UCI team.