Response to Letter to the Editor: “CT Characteristics of Pheochromocytoma: Relevance for the Evaluation of Adrenal Incidentaloma”
Bibliographic record
Abstract
We gladly respond to the interesting letter by Sweeney and Blake (1) regarding our recent paper on the Computed Tomography (CT) characteristics of pheochromocytoma, with relevance for the evaluation of adrenal incidentaloma (2). Our findings suggest that a low unenhanced attenuation of an adrenal lesion (≤ 10 Hounsfield Unit [HU]) has a high negative predictive value (> 99%) for pheochromocytoma (3). On the other hand, we found that a high absolute or relative washout of an adrenal lesion with an unenhanced attenuation of > 10 HU by no means rules out this disease, since the latter was the case in as many as 29% of evaluable pheochromocytomas. This is in line with a previous meta-analysis of 10 studies, which indicated a rate of pheochromocytomas with a high washout pattern of 35% (4). In their letter, the authors point out that rather than washout, portal venous phase (PVP) CT attenuation, that is, the maximum attenuation at 60–75 seconds after the injection of contrast, could be used to facilitate the distinction between pheochromocytoma and adrenocortical adenoma. Based on 2 publications (5, 6), they emphasize that pheochromocytomas have a higher PVP attenuation than adenomas. In the first study, comparing 43 histologically proven adrenal adenomas with 34 pheochromocytomas, applying a cut-off of > 85 HU to diagnose pheochromocytoma yielded a sensitivity of 88% (5). However, in the setting of the evaluation of adrenal incidentalomas, it is of the utmost importance to rule out pheochromocytoma with a high level of certainty, since, obviously, missing this diagnosis potentially has deleterious consequences for the patient. When using the suggested approach to apply contrast-enhanced attenuation for lesions with an unenhanced attenuation of > 10 HU, 12% of pheochromocytomas would, in fact, be missed. The sensitivity of PVP attenuation is therefore clearly inferior to that of plasma-free metanephrines, established at 98% (7). In the second study, again in pheochromocytomas versus adenomas, applying a PVP threshold of > 130 HU resulted in a specificity of 100%, but this was at the cost of a sensitivity of only 38% (6). To find out whether this parameter is truly specific for pheochromocytomas as suggested, adrenocortical carcinomas and other malignant adrenal lesions should also be investigated. Prompted by the authors’ interesting suggestions, we re-analyzed our data regarding PVP values. Among 76 pheochromocytomas with unenhanced HU > 10 and available washout data, PVP was available from the radiology reports in only 6 cases, and among those lesions, only 2 exhibited a PVP of > 85 HU. This could be related to differences in contrast protocols among different centers. Taking into account these considerations, it is our strong opinion that until PVP attenuation is systematically evaluated in a larger population of patients with a mix of different adrenal tumor types, any adrenal lesion with an unattenuated HU > 10 should prompt biochemical evaluation to rule out pheochromocytoma by the measurement of catecholamine metabolites. Disclosure Summary: The authors have nothing to disclose.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.020 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.002 | 0.001 |
| Scholarly communication | 0.002 | 0.003 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.029 | 0.020 |
| Insufficient payload (model declined to judge) | 0.007 | 0.005 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".