Routine evaluation of thyroid nodules using calcitonin determination

TOPIC: Calcitonin measurement for thyroid nodules: is it cost-effective?

Title: Calcitonin measurement in the evaluation of thyroid nodules in the United States: A cost-effectiveness and decision analysis.

Authors: Cheung K, Roman SA, Wang TS, Walker HD, & Sosa JA.

Reference: Journal of Clinical Endocrinology & Metabolism 93: 2173-2180, 2008



European studies have shown that the routine use of calcitonin (CT) screening for medullary thyroid cancer (MTC) in patients with thyroid nodules increases the detection of occult MTC and may also improve patients' outcome. CT screening for MTC has not been recommended in recent U.S. practice guidelines.


The objective was to determine the cost-effectiveness (C/E) of routine CT screening in adult patients with thyroid nodules in the United States.


A decision model was developed for a hypothetical group of adult patients presenting for evaluation of thyroid nodules in the United States. Patients were screened using current American Thyroid Association guidelines only, or American Thyroid Association guidelines with routine serum CT screening. Input data were obtained from the literature, the Surveillance Epidemiology and End Results and Healthcare Cost and Utilization Project's nationwide Inpatient Sample databases, and the Medicare Reimbursement Schedule. Sensitivity analyses were performed for a number of input variables.


Addition of CT screening to current American Thyroid Association guidelines for the evaluation of thyroid nodules would cost $11,793 per LYS ($10,941-$12,646). When extrapolated to the national level, CT screening for MTC in the United States would yield an additional 113,000 life years at a cost increase of 5.3%. CT screening C/E is sensitive to patient age and gender, and to changes in disease prevalence, specificity of fine needle aspiration and CT testing, CT screening level, costs of testing, and length of follow-up.


Routine serum CT screening in patients undergoing evaluation for thyroid nodules appears to be cost effective in the United States, with C/E comparable to the measurement of serum TSH, colonoscopy, and mammography screening.


Medullary thyroid carcinoma (MTC) accounts for 5-8% of all thyroid cancers. Sporadic MTC is the most common type accounting for 70-75% of cases; the rest is caused by familial MTC syndromes. Calcitonin (CT), secreted by thyroid 'C' cells, is a sensitive and specific marker that is used for diagnosis and follow-up of MTC. Multiple European studies have suggested that routine serum CT measurement in patients with thyroid nodules is effective in the detection of unsuspected, occult MTC

leading to curative surgery. Pacini et al. ( JCEM , 1994) were the first to demonstrate this finding. In their study, FNA and thyroid cytology was of limited use in diagnosing small MTC. Since then, several reports, mostly from Europe, have confirmed and expanded on the utility of routine CT measurement in patients with nodular thyroid disease.

The efficacy and the cost effectiveness of routine CT measurement in patients presenting with thyroid nodules is a matter of continued debate. Borget et al. ( JCEM , 2004) from Europe stated their strong support in favor of routine testing. On the other hand, Hodak & Burman ( JCEM , 2004) from the United States expressed concern that CT testing may not always be helpful, that borderline values have only a 13% chance of malignancy, and that for those practicing in the U.S., the unavailability of pentagastrin severely limits the potential value of this test. Current European recommendations suggest that when baseline serum CT is >10 pg/ml, a pentagastrin test should follow to stimulate CT, and thyroidectomy be performed if peak CT levels are >100 pg/ml. In this setting, thyroidectomy will reveal MTC in most patients. In 2006, the European Thyroid Association guidelines endorsed this practice ( Eur J Endocrinol , 2006), whereas the AACE-AME guidelines ( Endocrine Practice , 2006) did not favor routine CT testing. The recent ATA guidelines ( Thyroid , 2006) voted neither for nor against routine CT measurement.

The present report by Cheung et al. demonstrates that the addition of CT screening to current ATA guidelines for the evaluation of thyroid nodules would cost $11,793 per LYS (Life Years Saved) ($10,941-$12,646). Further, when these data were extrapolated to the national level, CT screening for MTC would yield an additional 113,000 life years at a cost increase of 5.3%. The authors illustrate that CT testing has a C/E similar to screening programs for breast and colon cancers.

Limitations of this study are inherent to any cost effective analysis. It studies a hypothetical group of patients and circumstances. Health outcomes were measured in LYS without consideration to quality of life. The study did not address the natural history and biologic importance of microscopic MTC. Finally, cost analysis that includes tests and procedures may not adequately reflect cost estimates in different parts of the U.S., and does not provide compelling evidence that CT screening is useful in the general population of patients with nodular thyroid disease. It seems that this controversy will continue for the time being, pending on more reports and new data.

Summary and commentary prepared by Mahmood Gharib & Hossein Gharib (Related to Chapters 6[d] & 18 of TDM)

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