Department of Molecular and Clinical Endocrinology and Oncology University "Federico II" in Naples Naples 80131, Italy
To the editor:
In a single center study on incidental adrenal adenoma published recently (1), we reported on unexpectedly high occurrence of cardiovascular risk factors in subclinical Cushings syndrome (CS), among which hypertension (92%), obesity (50%), type 2 diabetes mellitus (DM) (42%), and alteration in serum lipid concentrations (50%). Their frequency was higher than that reported in the Italian multicentric study published just 2 months before ours (2), where hypertension, diabetes and obesity were reported in 41%, 8%, and 38% of subclinical CS patients, respectively. Moreover, frequencies found in our study were higher than those reported in CS (3, 4), and it is well known that patients with CS exhibit frequently glucose intolerance but less commonly overt DM (3, 4). Although the patients with subclinical CS were generally older than those with overt CS (1 2), we hypothesized an overestimation of cardiovascular risk factors in our center, related to the small number of subjects evaluated. However, in 24 subclinical CS patients evaluated until now, the impaired glucose tolerance was found in similar proportion (62.5%) to those previously reported (1).
Fernández-Real et al. (5) had previously found a frequency of impaired glucose tolerance in adrenal incidentalomas similar to ours (58.3%), in both a multicentric (61%) and a single center study (66%). In the study by Fernández-Real et al. (5), the diagnosis of DM was performed according to the National Diabetes Data Group (NDDG) (6) by the oral glucose tolerance test (OGTT). The NDDG criteria considered fasting glucose values above 140 mg/dL (conversion factor to SI units, 0.056) as suggestive of DM. On the other hand, fasting glucose values above 126 mg/dL were diagnostic of DM in our study, according to the new criteria of the American Diabetes Association (7). Some patients who were not affected by DM according to the first criteria (NDDG), should be diabetic on the basis of the new one (American Diabetes Association).
However, 3 of 12 subclinical CS patients (1) were already on treatment for DM, 1 by multiple insulin administration and 2 by glucose-lowering agents; in two patients DM was first diagnosed during the evaluation for incidentaloma, on the basis of more than two fasting glucose values above 126 mg/dL. Their values were between 126 and 140 mg/dL and would, thus, not be considered as diabetic with the NDDG criteria. Nevertheless, the best diagnostic approach to DM is still a matter of debate. The gold standard has been reported to be the OGTT, but this test is not perfectly reproducible and its results are liable to be influenced by a variety of factors, including diet, previous fasting duration, the time of day the test is performed, and physical activity (8, 9, 10). Some authors have found fasting glucose concentration to be more stable (11). However, in the above mentioned study (1), the OGTT was performed in nondiabetic patients and glucose impaired tolerance was detected in two of them. Moreover, four of five patients with DM had a positive family history for type 2 DM, as described previously for CS.
Recent evidence suggests that incidental adrenal adenomas are characterized by variable alteration in cortisol secretion rates, degree of autonomous cortisol production being a continuum from slightly abnormal to completely pathological and biochemically similar to the pattern of overt CS (1, 12). The diagnosis of subclinical CS represents an arbitrary separation of the category of subjects with a greater degree of autonomous cortisol production.
In conclusion, we agree with Fernández-Real et al. (5) that all nondiabetic patients with incidental adrenal tumors should be tested for glucose tolerance, to decide the best therapeutic strategy.
Received October 27, 2000.
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