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Discussion Section 13 Outbreak - an Epidemic of Thyrotoxicosis! PART I On the afternoon of June 16, 1985, an endocrinologist at the University of South Dakota, Sioux Falls, was examining a patient with recent-onset thyrotoxicosis (manifestations of excess thyroid hormone) when the patient mentioned that there were four other people in his small town with the same problem. The patient was the postmaster of Valley Springs, South Dakota (population 801). Just a few days earlier, the endocrinologist had read an abstract of a CDC investigation describing an epidemic of painless thyroiditis in York County, Nebraska, in early 1984. Although the cause was never determined, the most likely etiology was believed to be viral infection. By speaking with other local physicians, the endocrinologist identified seven other patients with possible thyrotoxicosis. Six of the patients lived in Valley Springs, and two lived in southwest Minnesota. All exhibited classic symptoms of thyrotoxicosis (anxiety, shortness of breath, palpitations, rapid heartbeat, weight loss), and all had markedly elevated thyroxine (T4) levels. All but one had abnormally low radioiodine thyroid uptakes. The endocrinologist called CDC and provided the EIS Officer with the information summarized in the line listing below. Question 1: Place yourself in the role of the EIS Officer. Based on the information provided above, can you say that an epidemic exists? Question 2: What additional information might you try to collect on the phone call? Additional discussions involved the EIS Officer, the South Dakota State Epidemiologist, the Director of the South Dakota Department of Health Communicable Disease Program, and CDC staff. The South Dakota State Epidemiologist invited CDC to send a team to investigate the cluster in Valley Springs. Accordingly, the EIS Officer and a medical student departed from Atlanta for Sioux Falls, South Dakota, on June 23 to assist the state health department in an investigation. On the airplane, the Officer and medical student reviewed the differential diagnosis for thyrotoxicosis, as summarized in Table 2.
The endocrinologist met the CDC investigators at the airport and gave them additional information about the area. Valley Springs, S.D., is located about 15 miles east of Sioux Falls on Interstate 90. Luverne, Minn. (population 4,568), lies 10 miles to the east of Valley Springs. The economy of the entire area is agricultural and is based on the production of beef cattle. There are no physicians in Valley Springs. Luverne has one medical clinic and a community hospital. Specialty referrals for the entire area are generally made to Sioux Falls. At this point, the investigative team included the endocrinologist, staff from the South Dakota Health Department, the EIS Officer, and the medical student. Question 3: The state health officials want to proceed by conducting additional case finding, to determine the extent of the problem. Your supervisor wants you to conduct a quick case-control study to try and identify possible etiologies. What do you do? The investigators decided to start the investigation by interviewing the eight known case-patients in order to verify the disease process and to look for obvious etiologic clues. They took blood specimens from the case patients as well as from their family members.
Question 4: Was it appropriate to obtain blood specimens from case-patients and family members at this point in this investigation? Why or why not? The eight interviews produced no valuable etiologic clues. The case-patients were geographically clustered but seemed to have no identifiable common exposures. Blood specimens from case-patients and their family members underwent a variety of tests, including tests for virus-specific antibodies, T4, free T4, T3 resin uptake, and T3. While waiting for the blood test results, the team decided that the next step should be to increase case ascertainment. Question 5: What case-finding method(s) might you use? Since radioactive-iodine-uptake scans were performed in only two facilities in the entire area, two hospitals in Sioux Falls, the team decided to begin case ascertainment by reviewing the results of all uptakes done there in the past year. They identified 33 patients with abnormally low uptakes. These patients were clustered around Luverne, Minnesota. Question 6: How might you proceed? PART II Following discussions with the Minnesota State Epidemiologist, the Minnesota Department of Health joined the investigation. The investigators visited the only source of health care in Luverne, a clinic. The medical director of the clinic stated that he had seen an unusual number of elevated T4's lately, but said that he had ascribed the phenomenon to laboratory error. Team members reviewed the charts of all clinic patients with elevated T4's in the past year. They interviewed and obtained blood from all these patients and their families. Laboratory results from the blood taken from the first 15 case-patients were now available. As expected, all had elevated free T4's. The team was startled to find, however, that 75% of asymptomatic family members of case-patients also had elevated T4's. The total number of case-patients with unexplained thyrotoxicosis was now 28. About five to eight new cases per week were being recognized at the Luverne clinic. Patients' symptoms are shown in Table 3.
The investigators agreed to widen case finding to define the extent of the outbreak. They decided to review patients' records from the medical clinics in five communities in southwestern Minnesota around Luverne, in southeastern South Dakota, and in northwestern Iowa for the previous 18 months. The team also planned to contact by telephone all physicians in eight counties in southwestern Minnesota and question them about the occurrence of thyrotoxicosis among their patients in the past 6 months. In addition, the investigators decided to send letters to all physicians in South Dakota and southwestern Minnesota describing the outbreak and requesting them to report suspected cases to their state health departments. In order to do this, team members decided that they needed a more formal case definition. Question 7: Write the case definition that you would now use during widened case surveillance. How might this definition differ from the case definition you might use in a case-control study of the same illness? PART III A case was defined as an illness characterized by the presence of one or more values for T4, free T4, or T3 that were at least 25% higher than the upper limit of normal in the laboratory in which the test was performed, and included two or more of the following symptoms: sleeplessness, nervousness, headache, increased heart rate or palpitations, shortness of breath, fatigue, excessive sweating, tremor, diarrhea, heat intolerance, or weight loss. Patients were excluded if they had Graves' disease or if they had received thyroid hormone replacement therapy during the 2 months before diagnosis. Question 8: What are the advantages and disadvantages of this case definition? Widened surveillance produced additional cases (total N = 121). An age-sex breakdown of cases, an epidemic curve, and an incidence map are shown in Table 4.
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