This Article Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Osella, G. Articles by Reimondo, G. Search for Related Content PubMed Articles by Osella, G. Articles by Reimondo, G.

Bone and Collagen Turnover in Patients with Active and Preclinical Cushing’s Syndrome and in Subjects with Adrenal Incidentaloma—Authors’ Response

Dipartimento di Scienze Cliniche e Biologiche Cattedra di Medicina Interna, Azienda Ospedaliera S. Luigi Orbassano Torino 10043, Italy

In reply to the letter of Sartorio et al., we would like to comment as follows: the discrepancies between our study (1) and that of Sartorio et al. (2) highlight a number of caveats in the interpretation of serum markers of bone and collagen turnover in patients with adrenal incidentalomas.

First, the term adrenal incidentaloma is an "umbrella" definition that covers very different clinical conditions and hormonal patterns as well. Different series of adrenal incidentalomas are not easily comparable, and indeed, we restricted our evaluation to patients with an adrenocortical adenoma, while Sartorio et al. (2) did not clearly state their inclusion criteria. In this respect, our series is actually more homogeneous than that of Sartorio et al., who also included some patients with a pheochromocytoma. Sartorio et al. focused on patients with "preclinical or subclinical" Cushing’s syndrome, but it seems questionable to look for statistical differences when dealing with only six patients. Such a small group can be hardly considered as representative of the subclinical hypercortisolemic state, which is a very heterogeneous condition, as the authors state in their letter, because different degrees of silent hypercortisolism are likely to exist and because the diagnostic criteria of this subset of patients remain unclear (3). In our opinion, there are presently too many uncertainties surrounding this condition to draw definitive conclusions. The authors also report an association between suppressed bone-GLA protein (BGP) levels and heterozygous 21-hydroxylase deficiency even if the very high rate of patients with partial enzyme deficiency in that series (71%) seems to limit the significance of this finding. In our experience, only one of the four patients with BGP levels below the third percentile of control subjects showed partial 21-hydroxylase deficiency, but we employed more stringent criteria to define 17-hydroxyprogesterone response as excessive.

Second, serum levels of markers of bone and collagen turnover are particularly influenced by age, gender, and menstrual status of the subjects. As Sartorio et al. pointed out in their letter, the differences in the demographic characteristics of the two series could well explain some discrepancies in the results obtained. Pertinently, we employed two separate control groups for an adequate age-matching of patients with Cushing’s syndrome and patients with adrenal incidentalomas, while Sartorio et al. compared both groups of patients, although distinctly different for age distribution, to the same group of control subjects.

Third, the duration of the exposure to (silent) cortisol excess is likely to play a key role in determining variations of serum levels of bone markers (4). Regretfully, if the estimate of the disease duration is quite imprecise in Cushing’s syndrome it is practically impossible in patients with no clear signs or symptoms of hypercortisolism.

For these reasons we believe that it is premature to consider the markers of bone and collagen turnover as a hallmark of abnormal steroid secretion and to propose their use to select patients who require more accurate follow-up. This consideration is also supported by the limited clinical utility of bone markers in the follow-up of patients with osteoporosis (5, 6, 7). More research is needed to confirm that the slight cortisol excess found in some patients with adrenal incidentalomas is associated with alterations in bone markers. At present, BGP seems to be the best candidate indicator of the impact of glucocorticoid excess, either silent or overt, on bone turnover.

Footnotes

Address correspondence to: Giangiacomo Osella, Dipartimento di Scienze Cliniche e Biologiche, Cattedra di Medicina Interna, Azienda Ospedaliera S. Luigi, Orbassano, Torino 10043, Italy.

Received April 9, 1998.

References

1. Osella G, Terzolo M, Reimondo G, et al. 1997 Serum markers of bone and collagen turnover in patients with Cushing’s syndrome and in subjects with adrenal incidentalomas. J Clin Endocrinol Metab. 82:3303–3307.[Abstract/Free Full Text]
2. Sartorio A, Conti A, Ferrero S, et al. 1998 Evaluation of markers of bone and collagen turnover in patients with active and preclinical Cushing’s syndrome and in patients with adrenal incidentaloma. Eur J Endocrinol. 138:146–152.[Abstract]
3. Terzolo M, Osella G, Ali A, et al. 1998 Subclinical Cushing’s syndrome in adrenal incidentaloma. Clin Endocrinol (Oxf). 48:89–97.[CrossRef][Medline]
4. Gronowicz G, McCarthy MB, Raisz LG. 1990 Glucocorticoids stimulate resorption in fetal rat parietal bones in vitro. J Bone Miner Res. 5:1223–1230.[Medline]
5. Woitge HW, Scheidt-Nave C, Kissling C, et al. 1998 Seasonal variation of biochemical indexes of bone turnover: results of a population-based study. J Clin Endocrinol Metab. 83:68–75.[Abstract/Free Full Text]
6. Blumsohn A, Hannon RA, Eastell R. 1995 Long-term retest reliability of biochemical markers of bone turnover in healthy postmenopausal women. J Bone Miner Res. 10(Suppl 1):S182.
7. Kushida K, Takahashi M, Kawana K, Inoue T. 1995 Comparison of markers for bone formation and resorption in premenopausal and postmenopausal subjects, and osteoporosis patients. J Clin Endocrinol Metab. 80:2447–2450.[Abstract]

This Article Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Osella, G. Articles by Reimondo, G. Search for Related Content PubMed Articles by Osella, G. Articles by Reimondo, G.