Cost-Effectiveness of Follow-Up Imaging for Incidental Adrenal Nodules to Rule Out Adrenocortical Carcinoma
Mark M. Hammer, MDa,b, William W. Mayo-Smith, MDb,c
Abstract
Purpose: Several follow-up recommendations have been developed to assess the risk for malignancy of incidental adrenal nodules, but none has been validated in prospective trials. The purpose of this study was to develop a simulation model that evaluates the cost- effectiveness of follow-up imaging to detect adrenocortical carcinoma in adrenal nodules in patients with no known malignancy.
Methods: Using 1 million simulated adult patients with incidental adrenal nodules measuring 1 to 4 cm detected on contrast-enhanced CT, follow-up strategies were evaluated, including ACR and American Urological Association recommendations. Variants of the ACR recommendations using noncontrast CT only, or noncontrast MRI only, instead of washout CT were also evaluated. Costs and life years (LYs) were calculated for the simulated cohort. A probabilistic sensitivity analysis was performed by varying model parameters.
Results: In the base-case analysis, the only cost-effective strategy under a willingness-to-pay threshold of 241 per patient). The standard ACR recom- mendation with washout CT resulted in fewer LYs at increased cost. The probabilistic sensitivity analysis demonstrated that at the $100,000 per LY threshold, the variant ACR recommendation with noncontrast CT was cost effective in 50% of simulations, the American Urological Association recommendations (washout-disregarded variant) were cost effective in 20%, the variant ACR recommendation with MRI was cost effective in 16%, and no follow-up was cost effective in 10%.
Conclusions: Follow-up imaging with noncontrast CT for incidental adrenal nodules appears to be cost effective to rule out adre- nocortical carcinoma. However, strategies using washout CT are not cost effective.
Key Words: Cost-effectiveness, adrenal nodule, adrenal incidentaloma, adrenal adenoma, adrenal cortical carcinoma, washout CT
J Am Coll Radiol 2025;22:877-886. @ 2025 American College of Radiology
INTRODUCTION
Incidental adrenal nodules, defined as adrenal nodules found in patients who underwent radiologic examinations for other reasons, are a common finding on CT, estimated to occur in 4% to 7% of adults [1,2]. These nodules can represent benign or malignant neoplasms (most commonly a benign nonfunctioning adrenal adenoma). However, the risk of
aProgram Director, Thoracic Imaging Fellowship, Department of Radi- ology, Brigham and Women’s Hospital, Boston, Massachusetts.
“Harvard Medical School, Boston, Massachusetts.
Vice Chair of Education, Department of Radiology, Brigham and Women’s Hospital, Boston, Massachusetts.
Corresponding author and reprints: Mark M. Hammer, MD, Thoracic Division, Department of Radiology, Brigham and Women’s Hospital, 75 Francis Street, Boston, MA 02115; e-mail: mmhammer@bwh.harvard.edu.
Mark M. Hammer, MD, reports a relationship with the National Institutes of Health that includes: funding grants; also reports a relationship with the RSNA that includes: board membership. William W. Mayo-Smith, MD, states that he has no conflict of interest related to the material discussed in this article. Both authors are employees.
primary adrenal malignancy, although very low, has prompted multiple societies to issue guidelines for follow- up imaging of these incidental nodules to detect occult primary neoplasms.
The most common neoplasm of the adrenal gland is a benign adenoma. The most common malignant tumor of the adrenal gland is metastasis from a primary cancer else- where. Thus, whether the patient has a known extra-adrenal malignancy is important to accurately assess the likelihood of malignancy in an adrenal nodule. For purposes of this analysis, we assume that the patients do not have known malignancies and therefore are not at risk for metastasis. The most common primary adrenal malignancy in this setting is adrenocortical carcinoma, which is quite rare. In this study, we focus on incidental nodules measuring 1 to 4 cm. Most guidelines recommend surgical resection for nodules >4 cm in size, as these have a higher incidence of primary malig- nancy [3]. The risk for malignancy (primarily adrenal cortical carcinoma [ACC]) in the 1 to 4 cm size range has
been reported as ranging between 0% and 0.6% [4-6]. However, ACC is a highly mortal cancer, with overall survival for patients with stage IV disease being less than 1 year [7]. Whether follow-up imaging, with its associated costs and potential false positives, is beneficial given such a small risk for malignancy has yet to be proved. In addition, the optimal follow-up modality (CT, CT with washout, or MRI) is controversial.
Of note, incidental adrenal tumors can be functional; that is, they can secrete physiologically active hormones such as catecholamines in pheochromocytomas or cortisol in functioning adenomas or adrenocortical carcinomas. Serum and/or urine laboratory testing are required to determine if an adrenal tumor is functional. If an adrenal incidentalomas is functional, resection is the recommended treatment. Laboratory testing was not the focus of this study.
Several recommendations and guidelines exist regarding follow-up imaging for incidental adrenal nodules measuring 1 to 4 cm, including those of the ACR [3] and the American Urological Association (AUA) and Canadian Urological Association [8]. These recommendations consider nodules measuring ≤10 Hounsfield units (HU) as being definitively benign and requiring no further follow-up. The low density is due to high intracellular lipid content, which is a charac- teristic of benign lipid-rich adenomas. If the adrenal lesion measures >10 HU, adrenal washout CT may be performed. Adrenal washout CT includes unenhanced CT of the adrenal glands, measurement of the density, and if >10 HU two subsequent acquisitions at 90 seconds and 15 min after the administration of intravenous iodinated contrast. The HU values from these three phases of adrenal are used to calculate the rate at which contrast “washes out” of the adrenal gland. Higher washout rates are more common in adenomas compared with malignant adrenal tumors, although there is overlap between benign and malignant nodules [9]. In addition, some radiologists recommend follow-up with ad- renal MRI (without or with intravenous gadolinium contrast agents) rather than CT because of its lack of ionizing radiation and increased sensitivity for intracellular lipid detected on out-of-phase imaging [10]. Because there is no perfect test to differentiate benign from malignant adrenal nodules, recommendations differ as to how to manage these patients. Older, more aggressive follow-up recommendations did not exclude patients with nodules <10 HU and also continued follow-up regardless of the presence of washout [11].
None of these guidelines has been validated in a ran- domized, controlled trial. Simulation modeling can provide evidence to support follow-up recommendations, and compare guidelines, in situations in which randomized trials are impractical to perform. Follow-up strategies can be evaluated for their cost-effectiveness, which is measured by
the cost per life year (LY) gained, also termed the incre- mental cost-effectiveness ratio (ICER). In this study, we evaluated the cost-effectiveness of several recommendations for follow-up imaging of an incidental adrenal nodule detected on contrast-enhanced CT measuring 1 to 4 cm.
METHODS
Model Structure
The simulation model was developed in Java (version 11.0) for computational efficiency. Output was analyzed with several custom Perl scripts (version 5.30) to generate the efficient frontier by implementing strong and weak domi- nance. Data were summarized and graphed in Excel version 16 (Microsoft).
The simulation assumes that a patient starts with an incidental adrenal nodule on contrast-enhanced CT measuring 1 to 4 cm and no known extra-adrenal malig- nancy (we assumed that no prior study was available to evaluate for nodule stability). Patients are assumed to receive recommended endocrine laboratory testing to determine functional status, which is beyond the scope of this analysis. All adrenal malignancies are assumed to be ACC. Charac- teristics of each adrenal nodule are assigned as random variables at the initial time point, including whether an adrenal nodule measures <10 HU on noncontrast CT (only for benign nodules) and the growth rate of the nodule, which depends on whether it is benign or malignant and is assigned from an exponential distribution. Nodule size at baseline was not considered in the simulation.
Various follow-up strategies (recommendations) were tested separately, as shown in Figure 1 and Supplemental Figure 1. Several assumptions were made in the implementation of these strategies given the lack of certain details in the original articles. Specifically, for the ACR recommendations, a growth cutoff of 0.8 cm/year was taken from Pantalone et al [12], which was cited by the ACR recommendations although not explicitly given; this cutoff distinguished nodules that would be considered benign (growth of <0.8 cm/year) versus those sent to surgery (note that other strategies used different growth rate cutoffs, eg, 0.5 or 1 cm).
We created several variants of the ACR recommenda- tions for testing, as potentially better alternatives. Specif- ically, we tested a variant of the ACR recommendations in which postcontrast washout CT was not performed; instead, only noncontrast CT was done at initial detection. If the lesion was ≤10 HU, no further follow-up was done, and otherwise the nodule was followed up at 1 year to assess for growth. We tested an additional variant of the ACR rec- ommendations in which noncontrast MRI was done to
A
No follow-up
Benign
LE by Age
Incidental adrenal mass
No follow-up imaging
Malignant
LE for Early Stage ACC
1 year
LE for Late Stage/ Untreated ACC
B ACR Recommendations
Growth > 0.8 cm
Go to Resection
1 year*
1-2 cm
Follow-up adrenal CT
Incidental adrenal mass
<10 HU Or washout OR no growth
Go to No Follow-up
Washout or No enhancement
Go to No Follow-up
2-4 cm
Follow-up adrenal CT
Growth > 0.8 cm
Go to Resection
No washout
1 year*
Follow-up CT
Stable or Growth < 0.8 cm
Go to No Follow-up
<10 HU
Go to No Follow-up
<10 HU
Go to No Follow-up
*If malignant, account for early stage mortality
C Variant ACR Recommendation, Non-con CT only
Incidental adrenal mass
1-4 cm
Non-con CT
Growth > 0.8 cm
Go to Resection
1 year*
Follow-up CT
Stable or Growth < 0.8 cm
Go to No Follow-up
<10 HU
Go to No Follow-up
<10 HU
Go to No Follow-up
*If malignant, account for early stage mortality
assess for dropout on chemical shift imaging; if there was dropout, then no further follow-up was done, otherwise the nodule was followed up at 1 year with CT to assess for growth.
Two versions of the recommendations from Young [11] in the New England Journal of Medicine (hereafter referred to as the Young recommendations) were tested: one in which nodules that did not wash out were sent for more aggressive follow-up (version 1) and one in which such nodules were sent straight to surgery (version 2). Addi- tionally, two versions of the AUA and Canadian Urological Association recommendations (hereafter referred to as the AUA recommendations) were tested: one in which nodules with washout had no follow-up (version 1) and one in which such nodules had follow-up imaging recommended regard- less (version 2; washout disregarded). Finally, to determine if detection of ACC might be more cost effective in younger
patients (who live longer than older patients), we tested versions of each strategy with an age cutoff of 45 years; that is, patients younger than 45 years were recommended for follow-up per the strategy, and those older than 45 years received no follow-up.
For patients who are sent to surgical resection, the subsequent model is shown in Figure 2. Patient survival was determined as follows: for patients with benign nodules not sent for surgical resection, survival was determined by life expectancy by patient sex and age. For patients with benign nodules sent for surgical resection, survival was determined by a small risk for surgical mortality but otherwise by sex and age. For patients with malignant nodules not sent to surgical resection, survival was determined by survival for early-stage ACC for the first year, then by survival for untreated ACC after the first year. For patients with malignant nodules sent to surgical
Benign
LE by Age
Resection
Malignant
LE for Stage I ACC
Surgical mortality
resection, survival is determined by a small risk for surgical mortality but otherwise by survival for early-stage ACC.
Base-Case Parameter Values
The default values of model settings (parameters), and their sources, are given in Table 1. This includes patient demographics, as well as parameters for benign and malignant nodules (including the sensitivities and specificities for unenhanced CT, washout CT, and unenhanced MR), survival, and costs. Cost of imaging tests was obtained from data published by CMS. The base-case risk for malignancy in adrenal inci- dentalomas was chosen at 0.1% from Kahramangil et al [5], which was the largest series we know of in the literature.
Model Runs
A set of 1 million simulated patients was generated. For each management strategy tested, the simulation was run, and total LYs and costs were tabulated. Costs and LYs were discounted by the commonly used value of 3% per year. After testing all of the strategies, the efficient frontier was calculated using weak and strong dominance. The efficient frontier represents the set of strategies that are cost effective (ie, lead to the greatest number of LYs for a given amount of cost paid). Management strategies on the efficient frontier were compared by calculating the ICER, and those along the efficient frontier were identified to find the cost-effective strategies.
Confidence intervals for the ICERs were generated by bootstrapping, with 500 runs on the base-case analysis. A standard of $100,000 per quality-adjusted LY willingness- to-pay threshold was used, which is standard for US health care [13].
One-Way Sensitivity Analysis
To evaluate the impact of each parameter value by itself, the simulation was run by varying certain parameters separately. In particular, malignancy rate was varied from 0% to 0.6%, fraction of benign lesions with washout was varied from
60% to 90%, fraction of malignant lesions with washout was varied from 0% to 30%, fraction of benign lesions growing by ≥6 mm/y was varied from 0% to 10%, fraction of malignant lesions growing by ≥6 mm/y was varied from 70% to 100%, time delay to metastatic disease for untreated malignant nodules was varied from 1 to 5 years, and surgical mortality was varied from 0.2% to 0.8%. The efficient frontier was calculated, and at each parameter level, we identified the optimal strategy at a willingness-to-pay threshold of $100,000 per quality-adjusted LY.
PROBABILISTIC SENSITIVITY ANALYSIS
In addition to varying each parameter separately in the one- way sensitivity analysis, we also performed probabilistic sensitivity analysis (PSA) varying multiple parameters simultaneously. Five hundred separate runs of each strategy were performed while varying a subset of parameters, as specified in Table 1. For each run, the value of each parameter was sampled from the PSA distribution specified in Table 1. The efficient frontier was then determined for each set of parameter values. The results of the runs were tabulated, and the fraction of runs in which a strategy was optimal at willingness-to-pay thresholds of 100,000 was calculated.
RESULTS
Efficient Frontier
At the base-case parameter values (summarized in Table 1), the following strategies were on the efficient frontier: the variant of ACR recommendations using noncontrast CT portion of the adrenal CT protocol only (ie, no washout), AUA recommendations version 2 (washout CT results disregarded), and Young recommendations version 1 (multiple follow-up CT until 2 years). Table 2 shows the results of the efficient frontier strategies as well as the no follow-up strategy and the standard ACR recommendation. As seen in Table 2, the strategies are separated by small differences in average life expectancy across the 1 million
| Parameter | Value | Sensitivity Analysis | Reference(s) |
|---|---|---|---|
| Mean age (y) | 58 ± 13 | NA | [5,6] |
| Sex, female | 60% | NA | [5,6] |
| Mean size (range), cm | 2 (1-4) | NA | [4,5] |
| Malignancy risk | 0.1% | Exponential distribution, μ = 0.16% | [4-6,16] |
| Age- and sex-specific survival | Social Security actuarial table | NA | [17] |
| Median survival for early-stage ACC, y | 24 years | NA | [7] |
| Median survival for untreated/late-stage ACC, y | 0.75 years | NA | [18] |
| Benign adrenal mass <10 HU on initial CT | 50% | NA | [16] |
| Benign adrenal mass <10 HU on nonenhanced CT | 68% | NA | [16] |
| Malignant adrenal mass <10 HU on noncontrast CT | 4% | NA | [14] |
| Washout in benign nodules | 76% | Normal distribution, μ = 0.8, σ = 0.07 | [5,9] |
| Washout in malignant nodules | 20% | Lognormal distribution, μ = - 1.42, σ = 0.24 | [5,9] |
| Dropout on chemical shift MRI | NA | ||
| Benign, <10 HU on CT | 94% | [10] | |
| Benign, >10 HU on CT | 72% | [19,20] | |
| Malignant | 5% | [10] | |
| Growth of benign nodules by ≥6 mm/y | 2% | Gamma distribution, a = 1.42, 5 = 0.024 | [5,12] |
| Growth of malignant nodules by ≥6 mm/y | 72% | Gamma distribution, a = 3,072, o = 0.00024 | [5,12] |
| Adrenalectomy surgical mortality | 0.5% | Lognormal distribution, μ = - 5.32, σ = 0.2 | [21] |
| Adrenalectomy cost | $12,173 | NA | [21] |
| Yearly cost for advanced-stage ACC | Year 1, $124,000; year 2 and later, $66,000 | NA | [22] |
| Abdominal CT adrenal protocol cost | $278 | NA | CMS |
| Abdominal CT without contrast cost | $144 | NA | CMS |
| Abdominal CT with contrast cost | $248 | NA | CMS |
| Abdominal MRI without contrast | $208 | NA | CMS |
Note: ACC = adrenal cortical carcinoma; HU = Hounsfield units; NA = not applicable.
simulated patients because malignancies are very rare. Note that no follow-up and the standard ACR recommendations were not on the efficient frontier. A cost-effectiveness plot, with the efficient frontier, is shown in Figure 3.
Under the base-case parameter values, the strategy with the highest LYs under a 234 per patient. The AUA recommendations (version 2) were higher than the 503,981 (95% confidence interval, 1,935,252). The standard ACR recommenda- tion (which stopped follow-up for lesions with washout) resulted in lower LYs because of a higher rate of death of
ACCs (456 versus only 345 for the variant ACR recom- mendation using noncontrast CT only). The variant ACR recommendations with noncontrast MRI was not on the efficient frontier under base-case parameter values; it yiel- ded slightly lower LYs (16.94351 versus 16.94355) than the noncontrast CT variant with slightly higher cost (241).
The addition of an age cutoff was not cost effective. No strategy with an age cutoff was on the efficient frontier (data not shown).
One-Way Sensitivity Analysis
The results of the one-way sensitivity analyses, which measured changes in outcome if only a single parameter
| Table 2. Selected strategies | ||||||
|---|---|---|---|---|---|---|
| Strategy | LYs per Patient | Cost per Patient | % Patients Undergoing Follow-up | Deaths From Surgical Mortality | Deaths From Metastatic ACC | ICER (95% CI) |
| Young version 1 | 16.9451 | $1,892 | 100 | 329 | 82 | $1,370,272 ($895,015- $3,054,487) |
| AUA version 2 | 16.9441 | $525 | 50 | 82 | 263 | $503,981 |
| (washout | ($262,273- | |||||
| disregarded) | $1,632,114) | |||||
| Variant ACR | 16.9435 | $241 | 50 | 15 | 375 | NA |
| (noncontrast CT only) | ||||||
| Standard ACR* | 16.9421 | $311 | 49 | 15 | 486 | NA |
| No follow-up* | 16.9353 | $266 | 0 | 0 | 969 | NA |
Note: ACC = adrenal cortical carcinoma; AUA = American Urological Association; CI = confidence interval; ICER = incremental cost- effectiveness ratio; LY = life years; NA = not applicable.
*The strategy was not on the efficient frontier, and therefore ICER was not calculated.
was varied, are shown in Figure 4. Perhaps the most notable parameter is the malignancy rate. At a rate of 0% malignancies in incidental adrenal nodules, as observed in a study of 1,049 patients as described by Song et al [4], no follow-up is the optimal strategy. At a rate of 0.1%, as observed in study of 2,219 patients by Kahramangil et al [5] (and the base-case value), the optimal strategy is the variant ACR recommendation with
noncontrast CT only. At a malignancy rate of 0.2%, the optimal strategy is the variant ACR recommendation with noncontrast MRI. At a malignancy rate between 0.3% and 0.5%, the optimal strategy is the AUA recommendations (version 2). At a malignancy rate of 0.6%, as observed in study of 1,096 patients by Mantero et al [6], and higher, the optimal strategy is the Young recommendations (version 2).
16.946
Var ACR, Non-con only
Young Recommendations v1
AUA Recommendations v2
16.944
Var ACR, MR only
16.942
AUA Recommendations v1
Young Recommendations v2
Life years/patient
16.94
ACR Recommendations
16.938
16.936
No follow-up
16.934
16.932
0
500
1000
1500
2000
2500
Cost/patient (US Dollars)
Malignancy Rate
0.0%
0.2%
0.3%
0.5%
0.6%
0.8%
Fraction of Benign Lesions with Washout
60%
66%
72%
78%
84%
90%
Fraction of Malignant Lesions with Washout
0%
6%
12%
18%
24%
30%
Growth fraction of Benign Lesions
0%
2%
4%
6%
8%
10%
Growth fraction of Malignant Lesions
70%
76%
82%
88%
94%
100%
Delay to Metastatic Disease
1
2
3
3
4
Surgical Mortality
0.2%
0.3%
0.4%
0.6%
0.7%
0.8%
No follow-up
ACR Rec
Young Rec v1
Young Rec v2
AUA Rec v1
AUA Rec v2
2 ACR Var Noncon Only
ACR Var MR Only
100%
90%
80%
70%
Percent of simulations
60%
50%
40%
30%
20%
10%
0%
$1
$10,000
$20,000
$30,000
$40,000
$50,000
$60,000
$70,000
$80,000
$90,000
$100,000
ICER Threshold
No follow-up
Variant ACR, MR
AUA Recommendation v2
Variant ACR Non-con Only
Others
PSA
In addition to varying each parameter separately, we also performed a PSA, varying multiple parameters simulta- neously. The results of the PSA are shown in Figure 5. The figure shows the fraction of simulations (parameter combinations) in which a given follow-up strategy is optimal at a specific willingness-to-pay threshold. No follow-up is the optimal strategy in approximately one-third of simulations up to a threshold of 100,000 per LY. At a willingness-to-pay threshold of $100,000 per LY, the optimal strategies are the variant ACR recommendation with noncontrast CT only in 50% of simulations, the AUA recommendations (version disregarding washout) in 20%, the variant ACR recommendation with noncontrast MRI in 16%, and no follow-up in 10% of simulations; additional strategies made up the remaining 6% of simulations.
DISCUSSION
In summary, we performed a simulation-based cost- effectiveness analysis of imaging follow-up for incidental ad- renal nodules measuring 1 to 4 cm to rule out adrenocortical
carcinoma in patients with no known malignancy. The analysis shows that follow-up imaging is likely cost effective. Under the base-case parameter values, the only cost-effective strategy under a 100,000 per LY threshold, no follow-up was optimal for 10% of parameter values, and the variant ACR recommendations with noncontrast CT only were optimal for 50% of parameter values. A variant ACR recommendation with noncontrast MRI was cost effective for 16% of parameter values. Strategies using results of washout CT were not on the efficient frontier.
It is not surprising that a key factor in determining whether (and which) follow-up is cost effective for adrenal nodules is the rate of malignancy. Large case series have observed varied rates from 0% to 0.6% [4-6]. Given that multiple series have demonstrated a nonzero risk, which in our analysis corresponded to follow-up imaging being cost effective, it is likely that follow-up imaging is cost effective in the real world. However, the risk is clearly quite low, and
therefore follow-up recommendations must balance the benefit of finding adrenal malignancies with the potential costs of unnecessary imaging and surgery. Patient comor- bidities are also important parameters to consider when evaluating the utility of imaging follow-up for an inciden- tally detected adrenal nodule and were not evaluated in our simulation. However, the use of an age cutoff was not found to be beneficial, likely because of the extremely mortality of metastatic ACC, which significantly shortens the lifespans of patients of most ages. Thus, even older patients would gain survival benefit because early detection and high mortality rate from ACC rewards early treatment.
The fact that a variant of the ACR recommendations with noncontrast CT only was cost effective, whereas the standard ACR recommendations were not, suggests that washout CT is not cost effective. The standard ACR rec- ommendations performed poorly because some patients with ACCs had washout but were not followed up and therefore died of metastatic disease. Similarly, the version of the AUA recommendations that was cost effective was the variant that still followed nodules regardless of washout characteristics. Although initially encouraging as a reliable discriminator between lipid-poor adenomas and malignant adrenal masses, the utility of adrenal washout CT has been questioned in more recent studies [5,9,14]. Indeed, the AUA recommendations also question the utility of washout, even though they recommend performing it [8]. On the basis of the results from this simulation study, washout CT appears to be both costly and ineffective, incorrectly categorizing some malignant nodules as benign.
We also explored whether noncontrast MRI (chemical shift imaging) was cost effective by testing a variant of the ACR recommendations in which noncontrast MRI was the initial imaging modality after indeterminate contrast- enhanced CT. This strategy was not cost effective in the base-case parameter values but was cost effective in a mi- nority of simulations with varied parameter values. Although there are fewer data on the diagnostic accuracy of MRI for adrenal lesions, MRI is slightly more sensitive than CT but more expensive and may be slightly less specific [10]. Overall the performance of MRI was very close to that of CT in our simulations, so it could be a reasonable alternative to noncontrast CT.
This study had a number of limitations. Most notably, as the study was a simulation, the results are dependent upon model parameter values. However, by using sensitivity analysis, we were able to explore how results differ depending on these specific values.
Other limitations include the assumption that the only adrenal malignancies were ACC; occasional malignant pheochromocytomas may occur as well (although these are quite rare). We also excluded the situation of an adrenal
nodule in a patient with known extra-adrenal malignancy, in which there is a risk for metastatic disease to the adrenal gland. In addition, the costs and willingness-to-pay threshold used in this analysis are for US health care and may differ for other countries.
Finally, although we did examine several follow-up recommendations, we did not include all guidelines; for example, the European Society of Endocrinology has recently published guidelines [15]. However, these guidelines are very similar to those already tested in this analysis.
TAKE-HOME POINTS
· Through the use of simulation analysis, we have validated that follow-up imaging for incidental adrenal nodules measuring 1 to 4 cm is likely cost effective to detect adrenocortical carcinomas.
Performing an initial noncontrast CT study to prove that a lesion is benign is a low-cost intervention with clear benefit; remaining indeterminate nodules may be followed at 1-year intervals to determine growth rates, again a relatively low-cost intervention.
We found that strategies using washout as a discrim- inator between benign and malignant nodules are not cost effective, leading to lower average LYs because of missed cancers.
Adrenal MRI was not cost effective compared with CT, but the difference was minimal.
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