An Algorithmic Approach to Thyroid Function Testing in a Managed Care Setting 3-Year Experience

Transcription

1 CLINICAL CHEMISTRY An Algorithmic Approach to Thyroid Function Testing in a Managed Care Setting 3-Year Experience CAROLYN S. FELDKAMP, PHD, AND JOHN L. CAREY, MD Assays of thyroid gland function comprise the highest volume of endocrine tests performed in a variety of settings. These include endocrinology practices, reference laboratories, as well as in general clinics and hospitals. We observed an increasing test volume and a range of test combinations that suggested there was a variable approach to the evaluation or monitoring of thyroid patients and an opportunity for improved delivery of laboratory services. Our objective was to offer needed service and reduce unnecessary testing, thus improving cost efficiency, average turnaround time, and convenience to both patients and physicians. The strength and utility of sensitive thyrotropin (TSH) assays to diagnose thyroid gland dysfunction has been chronicled in recent literature. 12 The availability of TSH assays, which can distinguish both hypothyroidism and hyperthyroidism from the euthyroid population, has transformed the approach to the evaluation of patients suspected of dysfunction of the hypothalamic-pituitarythyroid axis. Thyrotropin has been suggested as afirst,or even only, laboratory test for most diagnostic or monitoring situations. 3 ' 4 It has replaced the thyrotropin releasing hormone (TRH) stimulation test for many cases, 5 ' 6 and is thought to be useful to distinguish residual thyro- From the Immunopathology Division, Department of Pathology. Henry Ford Hospital. Detroit. Michigan. Manuscript received April 11, 1995; revision accepted August 11, Address reprint requests to Dr. Feldkamp: Immunopathology Division, Henry Ford Hospital, Detroit, MI An algorithm (directed thyrotropin [TSH, directed thyroid testing algorithm DRTSH ) for the initial evaluation and monitoring of thyroid function was established in our institution in The algorithm begins with measurement of TSH by a sensitive immunoassay. If TSH is either <0.4 mu/l or >5.5 mu/l, a free thyroid index (T4 X Resin Uptake Ratio (RU)) is automatically performed on the same sample on the same day. In the setting of a large, predominately outpatient, prepaid health care population, the algorithm reduces unnecessary testing and focuses resources on the patients who need it. Three years after its introduction, physician acceptance of this approach is high (>90%), test utilization is reduced, test turnaround time is reduced, and significant cost-savings can be demonstrated. (Key words: TSH; Test algorithms; Reflex testing; Hyperthyroidism; Hypothyroidism) Am J Clin Pathol 1996; 105: troph function in patients with hyperthyroidism. 7 ' 8 However, analytical limitations and the documentation of a variety of physiologic and therapeutic influences on TSH concentrations has led to the conclusion by some authors that there is no single test sufficient for all situations. 9 " 1 ' An estimate of free thyroid hormone(s) and possibly subsequent use of stimulation tests, measurement of thyroid antibodies, or thyroid scans are often useful to confirm a diagnosis or establish the etiology of disease. In 1989, we undertook a review of thyroid test ordering patterns and test results. Based on thesefindings,we designed a simple algorithm (a sequence of tests based on a previous test result) for the initial evaluation of a patient with suspected thyroid disease. 12 " 14 This algorithm begins with a sensitive TSH measurement and directs follow-up free thyroxine index (FTI) as necessary. The reflex test orders are initiated by the laboratory mainframe computer. In this paper, we report our 3-year experience with the implementation and use of this algorithm in a large metropolitan health care setting. MATERIALS AND METHODS Directed Thyroid Testing Algorithm The directed thyroid testing algorithm (DRTSH)(Fig. 1) starts with a sensitive TSH. If the TSH value is <0.4 mu/l or >5.5 mu/l, then thyroxine (T4) and RU are performed, and FTI calculated in the next analytical run (usually the same day) on the same sample. The TSH 11

2 12 CLINICAL CHEMISTRY DRTSH: A THYROID TESTING ALGORITHM T 4l RU FTI TSH <0.4 Normal Range other test ordered >5.5 T»,RU FTI Hyperthyroid NTI Subclinical Hypothyroid hypothyroid FIG. 1. Thyroid testing algorithm (DRTSH). Testing is initiated with TSH. If TSH is in the normal range ( mu/l), testing stops. For samples with TSH <0.4 mu/l or >5.5 mu/l, T 4 and RU are performed and FTI calculated on the same specimen. thresholds for follow-up testing were selected after both consultation with endocrinology staff and a pilot study Initially, a more conservative lower cut-off of 0.5 mu/l was used, but review of patient results indicated that no patients >0.4 mu/l had elevated FTI. The cut-off was subsequently decreased to 0.4 mu/l. The upper cut-off is also selected conservatively because we observed that very few patients with mild elevations of TSH have decreased FTI. However, mild (subclinical) hypothyroidism may have adverse health consequences, although treatment is somewhat controversial. 16 Physicians may select the algorithm on the laboratory request form or may order individual tests. Patients are charged only for the tests actually performed. Patient Population Inpatients from a 750-bed metropolitan hospital and outpatients from 22 satellite clinics serving the suburban area are included (2 million outpatient visits/year). Approximately 92% of thyroid function test requests are from outpatients. The latter group includes patients on thyroid hormone replacement therapy. The current total test volume is 56,000 TSH/year. Preliminary Survey Sequential requests (n = 1,000) for thyroid function tests were reviewed and the frequency of various test combinations tabulated In the population studied, 78% of all TSH results were normal and 84% of T4 results were normal. Pre-algorithm test patterns were then expressed as percent to allow comparison of the effect of changing ordering patterns, independent of the total workload. Total direct costs are adjusted to 1993 prices for comparison of the effect of the algorithm on laboratory cost. Post-algorithm Survey Sequential test requests 1 year (n = 463) and 3 years (n = 625) after implementation were reviewed for test frequency and test combinations ordered. For patients with TSH values meeting the threshold criteria, the frequencies of elevated or decreased FTI were tabulated. Laboratory Tests TSH. Magic Lite T4 chemiluminescent immunometric assay (CibaCorning, Walpole, MA) was used for years 1 and 2. The functional sensitivity was 0.01 mu/l. The normal range was mu/l. In the third year, we used ACS-180 TSH automated chemiluminescent immunometric assay (Ciba-Corning). The normal range is mu/l. The functional sensitivity is 0.04 mu/ L. Functional sensitivity is defined as the concentration above which imprecision is 20% coefficient of variation (CV) or less based on a precision profile. 17 T4. Magic Lite T4 (Ciba-Corning); normal range is Ug/dL. Resin Uptake Ratio (RU). Magic Lite T3 Uptake (Ciba-Corning); normal range is Free Thyroid Index (FTI). FTI is calculated as T4 X RU Mg/dL. Normal range is Mg/dL. RESULTS Implementation and Recommendations The algorithm was introduced to the medical staff through a variety of educational meetings and publications. Education emphasized the function and objectives of the algorithmic approach as well as the characteristics and limitations of the individual tests. The use of the algorithm was recommended for the initial evaluation of a patient with suspected thyroid disease. Other test combinations were recommended for other clinical circumstances based on literature reports and the experience of our endocrinologists (Table 1). TABLE 1. RECOMMENDATIONS FOR THYROID FUNCTION TESTS Diagnose/rule out hyperthyroidism and hypothyroidism Monitor thyroid hormone replacement Monitor therapy for hyperthyroidism Monitor therapy for thyroid cancer DRTSH TSH or DRTSH FTI TSH DRTSH = directed thyroid testing algorithm: TSH - thyrotropini FTI = free thyroid index. A.J.C.P.-January 1996

3 FELDKAMP AND CAREY 13 Thyroid Testing Algorithm TABLE 2. EFFECT OF ALGORITHM ON PHYSICIAN ORDERING PATTERNS Test TSH only DRTSH (algorithm) TSH + T 4 TSH + T 4 + RU T 4 only T 4 + RU Other (includes T 3 ) Prealgorithm (<*>) After 1 year ( fo) After 3 years (%) TSH thyrotropin: DRTSH = directed thyroid testing algorithm; T«= thyroxine: RU! resin uptake ratio. Ordering Patterns We compared test combinations and frequencies of thyroid tests ordered before, and 1 and 3 years after the introduction of an algorithm for initial evaluation of a patient for suspected dysfunction of the hypothalamicpituitary-thyroid axis. Table 2 shows the distribution (%) of the most frequently used combinations of thyroid function tests ordered in our facility. At the time of the pre-algorithm survey (late 1989), reports on the advantages and the availability of a sensitive TSH assay had already influenced physician ordering in our hospital such that one-third of all requests were for TSH alone. Thyrotropin was used as a screen for hypothyroidism or hyperthyroidism or to monitor the effectiveness of therapy for hypothyroidism. Some combinations ordered included TSH and T4 without resin uptake (RU). Others did not use TSH. Only a small fraction used the combination T4 + RU. The latter combination, or another estimate of free T4, was often used as a screen for thyroid dysfunction before the availability of a sensitive TSH assay. In some institutions, this screening panel is still used. Our experience after 1 and 3 years shows significant increase in use in the algorithm (DRTSH) and a concomitant drop in the frequency of other test combinations (Table 2). The use of the "TSH alone" remained relatively constant, the primary application being the monitoring adequacy of thyroxine replacement therapy. Ninety-two percent of all thyroid function tests ordered were for DRTSH or TSH. Cost Savings Projected cost savings were based on initial observations that, overall, 78% of TSH and 84% of T4 were normal in our patient population We anticipated that by reducing follow-up testing on patients who were demonstrated to have normal thyroid function, there would be a reduction in total tests performed, without significant reduction in medical effectiveness. Table 3 compares observed reduction in total test volume with prealgorithm test frequency. There was a decrease of 329 tests performed per 1,000 patients for whom the algorithm was ordered (column 3). The overall post-algorithm test frequencies shown (column 2) include the requests for TSH alone and the approximately 8% of tests still ordered in miscellaneous combinations. Cost-savings reported here are total incremental direct costs (reagents and labor). This method of cost assessment was selected as appropriate to evaluate the impact on laboratory costs in the setting of predominantly prepaid health care. The average total direct cost of each assay is approximately the same ($3.50 per test). There is a total reduction of 329 tests per 1,000 DRTSH used compared to the average pre-algorithm pattern (Table 3). Thus, for each DRTSH, there is an average saving of $ 1.15 (0.33 tests saved per patient X $3.50). The overall tests ordered in 1993 (Table 3, column 2) shows a decrease of 374 tests done per 1,000 patients, reflecting a general reduction of tests ordered and continued use of TSH alone for monitoring purposes. At an annual volume of approximately 56,000 TSH ordered that includes 43,000 as part of the algorithm, there is an annual savings of $74,000 compared to the pre-algorithm average ordering pattern. Clinical Utility of DRTSH in Target Populations Threshold selection. The thresholds that initiate follow-up testing were selected conservatively to assure appropriate follow-up testing on individuals who may exhibit thyroid dysfunction and, at the same time reduce as much as possible unnecessary testing. The appropriateness of the thresholds used (essentially the normal range for TSH) can be seen in Figure 2, which shows the frequency of elevated FTI (> 10 Mg/dL) observed at various concentrations of TSH which qualified for followup testing according to the algorithm (n = 136). A high TABLE 3. EFFECT OF ALGORITHM ON TESTING VOLUME TSH T 4 RU Total Difference Thyroid Function Patients, Prealgorithm (1989) Tests/1,000 Patients, Postalgorithm (1993) , Tests/1,000 DRTSH Ordered 1, , TSH = thyrotropin; T 4 = Ihyroxine; RU = resin uptake ratio; DRTSH = directed thyroid testing algorithm. Vol. 105-No. 1

4 14 CLINICAL CHEMISTRY O TSH plu/ml FIG. 2. FTI in patients with low TSH. Percent of patients with low TSH whose FTI is > 10 Mg/dL (ACS/MagicLite). proportion of patients with TSH <0.04 mu/l had high FTI, consistent with hyperthyroidism. No patients with TSH >0.4 mu/l had elevated FTI. Thus, the algorithm functions as expected to correctly identify biochemically euthyroid individuals. Individuals with TSH between 0.1 mu/l and 0.4 mu/l frequently were receiving thyroid hormone replacement therapy or had other nonthyroidal conditions or therapy that decrease TSH. Severely ill hospitalized patients. Although a small percentage of the total testing volume in our setting (7%), the hospitalized patient offers a unique challenge in evaluating possible thyroid disease. The "sick euthyroid" syndrome has been described as a euthyroid patient with low T4 and low FTI in the context of severe illness. 18 Thyrotropin is often recommended to distinguish between the euthyroid state and true hypothyroidism. We anticipated that our algorithm beginning with TSH would be useful because when TSH is outside the normal limits, it would generate appropriate follow-up. That TSH may be decreased due to the severe illness itself or on treatment with glucocorticoids or dopamine treatment is a problem in interpretation of test values, but not in the function of the algorithm. The effectiveness of the algorithm in severe nonthyroidal illness was evaluated in a series of 71 patients from our intensive care units Thyrotropin was normal in 69% and, thus, would not have qualified for FTI. Of these, one patient had an elevation of both FTI and free T4 and two had low FTI and free T4, but with an elevated RU consistent with the sick euthyroid syndrome. We concluded that if hypopituitarism is not suspected, the algorithm is still effective in confirming euthyroidism in severe illness. In the 31% of patients with TSH >5.5 mu/l and 10% with TSH <0.4 mu/l, FTI or free T4 may or may not clarify the thyroid status. In this group, results of followup tests generated by the algorithm were consistent with the sick euthyroid syndrome. One patient identified was probably hyperthyroid and two were probably hypothyroid. These cases would have been appropriately classified. However, because of the complexity of the clinical situations in the severely ill and the known effects of severe illness and treatments on TSH values, we do not specifically recommend the algorithm over individual tests. Monitoring thyroxine replacement. Thyrotropin alone is appropriate and cost-effective to monitor thyroid hormone replacement. Because testing stops when TSH is normal, choice of the algorithm should not generate significant excess testing. Physician ordering patterns suggests that TSH alone is commonly used in our setting for this purpose (Table 2). Treatment of hyperthyroidism. Because TSH remains suppressed for a period after therapy, DRTSH algorithm was not recommended to follow these patients. The appropriate tests are FTI or free T4. DISCUSSION Review of the results of thyroid function tests revealed that for these high volume tests (both TSH and T4), a high proportion were normal. 15 This finding reflects the patient population studied 93% of patients were outpatients of a large urban and suburban health-care system. The remaining 7% were hospitalized. Other studies had reported that a normal TSH was consistent with a clinically euthyroid state, with rare exceptions. 321 These findings are consistent with current understanding of thyroid physiology and the log-linear relationship between TSH and FTI. 217 Thus, it was concluded that for our population, significant numbers of laboratory tests were redundant and that reduction of follow-up testing should result in cost-savings without reduction of medical effectiveness. The most frequently ordered test combinations before the introduction of the algorithm (Table 2) were screening panels used in the past, but which were no longer optimal. Thyrotropin alone was commonly used to monitor hormone replacement therapy or in some cases to diagnose suspected hypothyroidism or hyperthyroidism. The TSH + T4 combination, without RU, may be ineffective for initial diagnosis because of the influence of thyroxine binding proteins on total T4. However, the combination may be used as follow-up in cases in which the diagnosis had been made. TSH + T4 + RU is excessive unless TSH is outside the normal range. Finally, T4 + RU (or FTI), the screening panel most frequently used before the availability of sensitive TSH assays, had already been largely abandoned in favor of some test com- A.J.C.P.-January 1996

5 FELDKAMP AND CAREY 15 Thyroid Testing Algorithm bination that includes sensitive TSH. However, the FTI remains a useful combination for follow-up after treatment of hyperthyroidism. In the latter circumstances, TSH may remain undetectable for a long time, while T4 levels decrease in response to ablative therapy. The directed thyroid algorithm (Fig. 1) was designed for use in the initial evaluation of an individual clinically suspected of thyroid dysfunction. Screening of asymptomatic individuals is not recommended, with the possible exception of certain high-risk groups such as the elderly, individuals with a strong family history, and the newborn. 21 In addition, it is ordered in other situations in which the algorithm results in the preferred series of tests such as for monitoring therapy for hypothyroidism. The preferred tests to follow therapy for hyperthyroidism was the combination, T4 + RU, and for thyroid cancer, TSH alone. The most important potential for the algorithm to fail to be useful or appropriate is the case of hypopituitary-hypothalamic hypothyroidism (low TSH, low T4) in which condition the TSH concentration may not fall below the cut-off and thus, FTI would not be done. The combination of tests in the algorithm is often useful in the assessment of the hospitalized patient, but test results are subject to the limitations reported elsewhere and the interpretation may be complex The thyroid testing algorithm was developed with the cooperation and consultation of members of our Division of Endocrinology and Metabolism who supported the concept and concurred with the thresholds selected. After a pilot project, 14 it was introduced to the medical staff as an option at educational meetings of the departments of medicine at the hospital and satellite clinics. The laboratory request form includes the algorithm as well as individual tests. After 3 years, 92% of all thyroid test requests are either for TSH or the algorithm, attesting to the remarkable acceptance among the medical staff. The algorithm takes advantage of the excellent sensitivity and precision of contemporary TSH assays. However, it does not require the ultimate in sensitivity to function well. The cut-offs are not near the least detectable concentration so any assay that is second-generation (functional sensitivity = 0.1 mu/l) or better could be used. The objective was to reduce unnecessary testing of individuals who could be reliably determined to be euthyroid. Thyrotropin assays of superior sensitivity are reserved for special cases. 6 ' 7 ' 24 " 26 Successful implementation of the algorithm also used the capabilities of the laboratory computer to automatically order follow-up tests based on results of the first test. Thus, measurements are made on the same sample without additional sample collection or aliquotting. The algorithm directs a series of tests that were generally agreed to be appropriate. In addition to the overall reduction of tests done, endocrinologists who frequently receive requests for consultation are assured that sufficient tests are done before referrals or thyroid scans. Additional tests (eg, triiodothyronine or thyroid antibodies) may be ordered subsequently to understand more complex cases and establish etiology. Cost savings. Cost savings are based on the reduction of T4 and RU tests done. Also, the education process regarding the interpretation of TSH results had the effect of increasing the use of TSH alone for monitoring patients after diagnosis and after the initiation of certain therapies. The frequency of other combinations is very low. Estimates of cost savings based on incremental direct costs is appropriate in the era of managed health care in which a large proportion of patients are covered by HMOs and other pre-paid programs. With automation and changing technologies, reagent and labor costs have changed such that the cost of TSH, T4, and RU are now approximately equal. Thus, we found that the use of an algorithm starting with TSH was cost effective in contrast to earlier projections based on laboratory charges Alternative strategies. Several reports suggest the use of TSH alone, free T4 alone, or the two in combination as approaches to assessing thyroid function. Clearly, TSH assays with sufficient sensitivity are useful in many cases. However, analytical limitations as well as several clinical circumstances which affect TSH and free T4 measurements argue against use of a single test as a screen. In cases of the severely ill patient or one treated with glucocorticoids or dopamine, neither a single test nor the algorithm may be adequate. In the case of severe illness, both TSH and FTI are useful to assess the patient's thyroid status. Other authors have also suggested an algorithmic approach to thyroid testing, but to our knowledge, long-term experience in a managed health-care setting has not been reported. Other more complex algorithms have been suggested that include additional tests directed at defining the etiology of disease or clarifying ambiguous situations. 29 The substitution of free T4 for FTI might further decrease costs without changing the function of the algorithm reported here. Interpretation of free T4 results would, of course, have to take into account any limitations specific to that test. 25 ' 31 " 34 CONCLUSIONS An algorithmic approach to efficient delivery of thyroid testing proved to be well-accepted, clinically useful, Vol. 105-No. I

6 16 CLINICAL CHEMISTRY and cost effective in the context of a large health-care system. The algorithm described functions well in the clinical setting in which most patients are normal (outpatient clinic or reference laboratory). By simply reducing the number of tests done on euthyroid individuals, annual savings in total direct costs were substantial. Flexibility for physicians was maintained by allowing individual tests to be ordered or additional tests to be added later. Educational efforts at the time of implementation improved physician understanding of thyroid function tests and their interpretation and enhanced the acceptance of this approach. In the managed care environment of health care in the future, there will be increased emphasis of control of the use of resources, hopefully without significant loss of medical utility nor quality of services. The DRTSH thyroid testing algorithm is a step in the right direction. REFERENCES 1. Ehrmann DA, Weinberg M, Same DH. 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