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The thyroid mystery.

The storekeeper in Valley Springs offered customers a special kind of beef; he called it his lean cuisine.

One cold March morning in 1985, Dr. J. Michael McMillin, a professor of medicine and the head of the Division of Endocrinology at the University of South Dakota School of Medicine and the 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 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 it 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 clienteles thyroid preparations as bracing dietary supplements. 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 weight loss, restlessness, irritability, 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 (population 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, library-like office at the Center, He is a tall man, sandy haired and nearing 50, 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 (ace 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, thyrotoxicosis 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 '20s, 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 54 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 6 to 82. 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 Luverne, a town of around 5,000. I checked with Sioux Valley Hospital, and the logbook there showed much the same picture. Oddly, none of the cases was 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. I 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 CDC 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 CDC 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 CDC 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 she had been on thyroidhormone 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 CDC as an intern. 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 and had 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 that 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."

(continued next issue)
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Author:Roueche, Berton
Publication:Saturday Evening Post
Date:Dec 1, 1988
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