The Medical Detectives Volume I

by Berton Roueche

  "I tell you, I was shaken. I was frightened. And when I got home I got to thinking. I don't know how such things happen. Bui I got to thinking about that flower show, about how I'd felt the next day. And the more I thought about it, the more I wondered. I went to the phone and called the Pennsylvania Horticultural Society and talked to a woman who had something to do with the annual show. I asked her about the use of pesticides and insecticides. She said the society had nothing to do with that. That was up to the individual exhibitors—and there were hundreds of them. She thought it was very probable that some of them, maybe all of them, went in for some sort of chemical control. I thought so, too."

  Dr. Page smiled her wide smile and shook her head. The smile faded away. "I'm just beginning to realize that the world is a very dangerous place. It's something nobody really wants to think about. I mean the thousands and thousands of toxic chemicals that have become so much a part of modern living. I mean the people who use them without really knowing what they can do. I mean the where and how and why they use them. It's frightening. I think I'm pretty much recovered now. I haven't had any trouble for over a year. But you never know. The only thing I'm sure of is that I'm going to have to be very careful for the rest of my life."

  [1988]

  CHAPTER 24

  A Lean Cuisine

  One cold march morning in 1985, Dr. J. Michael McMillin, professor of medicine and head of the Division of Endocrinology at the University of South Dakota School of Medicine and associate chief of staff for research and development at the Veterans Administration Medical Center in Sioux Falls, was walking along a corridor in Sioux Valley Hospital there when he was hailed and stopped by a colleague named James Felker. Dr. Felker was a Sioux Falls internist with a practice that extended throughout the surrounding countryside, and Dr. McMillin knew him to be something of a diagnostic perfectionist.

  "Mike," Dr. Felker said. "I've got a little diagnostic problem. What do you know about thyroiditis?"

  "What do you want to know?" Dr. McMillin said.

  That was a reasonable response. Thyroiditis, as its name suggests, is an inflammation of the thyroid gland. The thyroid, which is common to all mammals, shares membership with the parathyroid, the pituitary, the adrenals, the pancreas, and the gonads in the masterly hormonal manufactory known as the endocrine system, and is situated astride the throat, just below the Adam's apple. Thyroid disease, in general, reflects either an inadequate production of the thyroid hormones (two amino acids that contain iodine) or an excessive supply of them. The former condition is called hypothyroidism. The latter is called hyperthyroidism or, more descriptively, thyrotoxicosis. The usual cause of thyrotoxicosis is a derangement of the body's immune system, producing antibodies that stimulate the thyroid to an excessive hormonal output. This is the condition more familiarly known—in commemoration of the Irish clinician Robert James Graves (1796— 1853), who drew a full-length portrait of it—as Graves' disease. There are, however, other avenues by which the body can be oversupplied with the thyroid hormones. One of these is by direct ingestion. Many health stores, for example, offer their credulous clientele a thyroid preparation as a bracing dietary supplement. Another, and more common, cause of thyrotoxicosis is an inflammation of the thyroid gland, which forces a leaking into the bloodstream of a quantity of hormone normally held in storage. Thyrotoxicosis, whatever its origin, is marked by a panoply of discordant signs and symptoms that include restlessness, irritability, weight loss, increased appetite, rapid heartbeat, a pronounced sensitivity to heat, shortness of breath, and, occasionally, pain or tenderness in the area of the thyroid gland.

  Dr. Felker's response to Dr. McMillin's question was also reasonable enough. He said he had a patient over in Valley Springs who clearly was suffering from thyrotoxicosis. Valley Springs is a farming hamlet (pop. 801) ten miles east of Sioux Falls and less than a mile from the Minnesota border. As a matter of fact, the patient was the Valley Springs postmaster, Richard Jacobson. The diagnosis of thyrotoxicosis derived from the presence in his blood of high levels of thyroid hormone. But it was a thyrotoxicosis that confounded Dr. Felker's understanding of the disease. For one thing, the standard evaluation of thyroid function (a test involving a small dose of radioactive iodine and surveillance by Geiger counter) showed that Jacobson's thyroid wasn't overexerting itself—it was, in fact, underactive. The other thing that puzzled him was that Jacobson insisted that he had no pain in the area of his thyroid. It wasn't even tender.

  "I could understand Jim's confusion," Dr. McMillin told me during a talk we had not long ago in his big, cluttered, librarylike office at the Center. He is a tall man, sandy-haired and nearing fifty, with a narrow, searing blue-eyed gaze, a quick and easy smile, and a way of accompanying every remark with an illustrative gesture or grimace. He ducked his head now in an expression of concern. "The thyroid is a very complex organ. But I'm an endocrinologist and I know some of its secrets. The thyroiditis that Jim seemed to have in mind is called subacute. The inflammation is thought to be the result of a viral infection, and the disturbance to the gland is temporary. As the infection clears, the preformed hormone is gradually excreted in the urine, and the condition reverses itself. Then there is an insufficiency of hormone in the blood. This alerts the pituitary, which governs thyroid activity, and the production of hormone is resumed on a normal basis. It was my feeling that Jacobson's lack of pain or tenderness didn't mean a whole lot. Some people have a high threshold of pain. And many men tend to be stoic. They won't admit to pain. But, as I told Jim, there is another type of thyroiditis that we are only beginning to recognize, called silent thyroiditis, in which there really is no pain. And it, too, is self-limiting. I advised Jim to treat Jacobson with an anti-inflammatory, like aspirin, and perhaps a beta blocker to quiet his heart, and let time and nature do the rest. Then I went about my business. Jacobson dropped out of my mind.

  "A couple of months went by. Then, in late May, I happened to run into Jim Felker again. He said something like 'Remember that guy with thyroiditis I told you about? Well, he isn't any better. In fact, he's worse.' He went on to say that he was admitting him to McKennan Hospital, another hospital in our system, and would I go over and see him? Which I did. I went over the next day, May 30. Jacobson looked sick, all right. His face was flushed, he had a very rapid heartbeat and very rapid reflexes, and he had a fine tremor. He said he had lost some weight, and he was diarrheic and just generally felt weak. I felt his thyroid. It wasn't enlarged—if anything, it was rather small—and he still insisted that it wasn't tender. He told me that he had been more or less sick ever since February. His symptoms seemed to come and go. I began to share Jim's puzzlement. I began to think this was one of those health-food cases. But he didn't really seem to be that sort of psychoneurotic type. I couldn't see him eating kelp or any other iodine-rich substance. And he denied that he had—although that meant nothing. I made arrangements for some further laboratory tests, and suggested to Jim that he discharge him pending the test results. We might know better then."

  Dr. McMillin is an active member of the American Diabetes Association, and a few days after his visit with Jacobson he traveled to Baltimore for the Association's annual meeting. It was a ten-day conference, but he cut his stay short to cover for one of his fellow endocrinologists, who wanted to attend the second half of the meeting. He returned home at the end of the first week in June. In the accumulation of messages awaiting him in his office was one from Richard Jacobson, in Valley Springs. Dr. McMillin returned his call. Jacobson thanked him, and reported that he wasn't feeling much better or much worse, but the reason for his call was something else. He had a question. He said, "Doc, can you tell me why there are four other people in this little town who have the same trouble I have?"

  "That was interesting," Dr. McMillin told me, "but I wasn't too impressed. People are always calling to tell about a cluster of some disease or other. It usually turns out that there is a confusion of diagnoses. Besides, I told Jacobson, thy
rotoxicosis isn't a disease that occurs in epidemic form. It isn't a communicable disease, like measles or influenza. The only outbreak of thyrotoxicosis on record in this country that might be called an epidemic occurred back in the twenties, when iodinated salt was first introduced. It brought on a lot of Graves' disease in susceptible people. Jacobson said something like 'Well, maybe so. But one of those four people is my own mother.' I still wasn't much impressed. And then, that night, something strange happened. I had brought back from Baltimore a number of abstracts of papers to be given later in the meeting, and I was leafing through them at home. I had a grand rounds to present the next day, and I thought I might pick up something new and interesting to add to my presentation. And lo and behold! My eye caught a title—'Painless Thyroiditis: A Community Outbreak in Nebraska.' The outbreak occurred between January and March of 1984 in a seven-county area of southeastern Nebraska, and it numbered fifty-four cases, most of them in the county of York. There was no thyroid enlargement or tenderness. There were no deaths, but six patients were hospitalized. The ages ranged from six to eighty-two. The outbreak ended as mysteriously as it had begun, and the cause was never determined. Well, I could hardly believe it. Now I really was impressed. If it could happen in Nebraska, it could happen here. The minute I finished my grand rounds the next morning, I went over to the Nuclear Medicine Department at McKennan Hospital and looked through the logbook of procedures. Sure enough, there had been a recent increase in thyroid studies, with results pointing to thyroiditis. Some of them were even my own patients. They came from various places: Valley Springs, of course, and several towns or villages just across the line in Minnesota—Beaver Creek, Hills, and Lu- verne, a town of around five thousand. I checked with Sioux Valley Hospital, and the logbook there showed much the same picture. Oddly, none of the cases were here in Sioux Falls, and Sioux Falls is the largest city by far in a rather large surrounding area in South Dakota, Minnesota, and Iowa. 1 arranged for a list of all the names and addresses, and drove back to my office and got out that Nebraska abstract. It gave a list of the participating investigators. Most of them were from the Centers for Disease Control, in Atlanta. I called them, one by one, and they were all out of the office. I left my name and telephone number, and waited. I had to think that I was really onto something.

  "You know how it is when you're waiting for a particular call. The phone keeps ringing, but it's never the call you're waiting for. Then—at last. It was a young doctor named Daniel B. Fishbein.

  He had been at C.D.C. for a number of years, and his major work there was in rabies, but, yes, he had been to York and was still very much interested in that unresolved outbreak. I told him what seemed to be happening here. He said the feeling of the team at York was that the cause was probably a viral illness. A good many of the thyroiditis patients reported an earlier upper-respiratory infection. I told him that that was what I had in mind in our problem here. I asked him if he would be interested in giving me a hand. He was—very much so. But C.D.C. is a federal agency, and there is a very strict protocol governing its investigations. It can come into a state only upon invitation from the state. Fishbein said he would sound out C.D.C. and the South Dakota Health Department. We arranged for the invitation, and Fishbein—or Dan, as I came to know him—got permission from his people. I gave him everything I had—names, addresses, and study results. We set a date: June 15.

  "Meanwhile, I got a call from Jim Felker, asking me for a consultation on Jacobson's mother. She was hospitalized at McKennan. I went to see her. She was very definitely thyrotoxic. She had all the symptoms, and very high blood levels of circulating thyroid hormones. But she also confused things. Her thyroid gland was enlarged. That was atypical of this outbreak. And she had a previous history of thyroid disease—she had a goiter and had been on thyroid-hormone therapy for some years. Her thyroid gland should have been anything but enlarged. That enlargement suggested that something was stimulating it. I began to wonder if I was dealing with a genetic problem—a genetic susceptibility. Mrs. Jacobson had her own house. She didn't live with her son. But they both had what looked like the same illness. On the other hand, that hardly explained the other cases.

  "Well, Dan Fishbein arrived. He had with him an enthusiastic assistant—a young woman medical student named Janet Farhie. She was working at C.D.C. as an interne. Dan was originally from California—from Hollywood, no less! She was from upstate New York. Dan and Jan—as they came to be—had with them another helper: a copy of 'The Thyroid,' by Drs. Sidney Ingbar and Lewis Braverman, the standard text in the field. They had been giving themselves a crash course in endocrinology. But they had something valuable that I didn't have. Dan was trained in epidemiology, with years of experience, and she was learning. They moved into the Holiday Inn here, and we got down to work. We agreed, at least for the moment, that what we seemed to be seeing here was the same as the York outbreak. The fact that the York County outbreak ended so abruptly and inconclusively gave us a sense of urgency. We didn't want to be left dangling here. And our outbreak was growing pretty fast. By the time Dan and Jan arrived, the reports I was getting indicated that we had at least a dozen cases. The first step in an investigation of this sort is to set up what is called the case definition. We had to establish the criteria. We set two grounds for inclusion. Cases were defined as patients with two or more symptoms of thyrotoxicosis and with concentrations of thyroid hormone in the blood at least twenty-five per cent greater than the upper limit of normal established at the testing laboratory. Patients with a previous history of thyroid disease, of course, were excluded. Then, because of the cases that were appearing across the line in Minnesota, there was another matter of protocol. That, too, was arranged, and as it soon became clear that most of the new cases were occurring in Minnesota, the administrative leadership of the investigation was taken over by the Minnesota Department of Health, in Minneapolis. Craig W. Hedberg and Michael T. Osterholm were the department people in charge, and some others came in later. But at this stage, at least, much of the real work, the legwork, devolved on Dan and Jan.

  "At about that time, I had to leave town again. I'm on the national board of directors of the American Cancer Society, and there was a meeting scheduled for the third week of June, out in California, in Beverly Hills, and I was committed to attend. I was sorry about that, but Dan and Jan were well set up to manage on their own. Everything was falling into place. We had our case definition. The next step was to visit the identified cases and interview them about the nature and onset of symptoms and take blood and other samples. Dan and Jan were both, in their jargon, experienced vampires. The samples were to be divided—half to be frozen for highly sophisticated viral studies, if necessary, at the C.D.C. laboratories. The lab work on the other half was to be done here in Sioux Falls by Dr. Mary Jo Jaqua, a microbiologist at the medical school and the V.A. Medical Center. Our feeling was that we were dealing with a viral outbreak, and Dr. Jaqua was to culture the specimens for that. Another aspect of the epidemiological study was, of course, to establish the geography of the outbreak.

  "I was gone a full week. But half of my mind never left Sioux Falls. Thyrotoxicosis is only rarely fatal, and there had been no deaths in York, but even so ... I kept in touch with Dan by phone, and he was always reassuring. There were no ugly surprises. As soon as I got back home, I called Dan, and he and Jan and I sat down together in my office. They'd had a busy week. The case total was now twenty-three. Jan reported on the demographic data. The ages of the confirmed patients were much like those in the York outbreak, ranging from the pediatric to the geriatric. There seemed to be an equal number of men and women involved. I found that strange. Endocrine diseases tend to afflict women four times as often as men. We were definitely dealing with something unusual. As might be expected in an agricultural area like this, about half the patients were farm people. The geography was also interesting. There were still no cases in Sioux Falls, and Sioux Falls is the major trade and population center. The outbreak wa
s confined between Valley Springs, on the west, and Worthington, Minnesota, on the east. The major case center seemed to be Lu- verne. About a third of the patients reported symptoms that included muscle aches and pains. That certainly sounded like a viral illness. Unlike a viral illness, however, there was no evidence of person-to-person transmission. There was no evidence of disease among people who worked together, or among friends who saw a lot of each other. The earliest onsets recorded by Dan and Jan were back in January. So this had been going on for quite a while. That was about where the investigation stood at the moment. Except that, because of the concentration of cases in and around Luverne, Dan and Jan had moved out of their rooms at the Sioux Falls Holiday Inn and were at rest in Luverne—at the Cozy Rest Motel."

  The somewhat puzzling geographical picture of the outbreak drawn by Janet Farhie served as an accurate likeness through the last week of June and into the first week of July. Then it was abruptly blurred. On the afternoon of July 3, Dr. McMillin received a telephone call from a woman who identified herself as Rhonda Peskey. She and her husband and their young son lived in Sioux Falls. She had heard that there was an epidemic of thyroid disease going around, and she thought she and her family might have it. She hadn't seen a doctor. She had heard about the epidemic from her parents, who lived in Valley Springs. Dr. McMillin probably knew them. They were Larry and Margaret Long, and they owned the L & M Clover Farm Store there. But what she was really calling about was this: she was working as a waitress here in Sioux Falls, and she wanted to know if her illness was contagious. Should she quit her job, or what?