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THE SHORT SYNACTHEN TEST IN THE EVALUATION OF ADRENAL MASSES IN PATIENTS WITH MALIGNANCIES
H. S. Willenberg, G. Mansmann, R. Fritzen, M. Schott, J. Feldkamp, H. M. Schulte, W. A. Scherbaum & S. R. Bornstein
To cite this article: H. S. Willenberg, G. Mansmann, R. Fritzen, M. Schott, J. Feldkamp, H. M. Schulte, W. A. Scherbaum & S. R. Bornstein (2002) THE SHORT SYNACTHEN TEST IN THE EVALUATION OF ADRENAL MASSES IN PATIENTS WITH MALIGNANCIES, Endocrine Research, 28:4, 793-797, DOI: 10.1081/ERC-120017075
To link to this article: http://dx.doi.org/10.1081/ERC-120017075
Published online: 07 Jul 2009.
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ENDOCRINE RESEARCH Vol. 28, No. 4, pp. 793-797, 2002
THE SHORT SYNACTHEN TEST IN THE EVALUATION OF ADRENAL MASSES IN PATIENTS WITH MALIGNANCIES
H. S. Willenberg,1 G. Mansmann,1 R. Fritzen,1 M. Schott,1 J. Feldkamp,3 H. M. Schulte,2 W. A. Scherbaum,1 and S. R. Bornstein,1,*
1Department of Endocrinology and 2Department of Surgery, University of Duesseldorf, Germany 3Hospital of Bielefeld, Germany
ABSTRACT
Adrenal computed tomography with determination of Hounsfield units has proved to be sensitive and specific in the differential diagnosis of benign vs. malign adrenal lesions. On the other hand, computed tomography may fail in patients with small adrenal masses of less than 1.0 cm. However, especially in patients with diagnosed malignancies and small adrenal masses which were discovered during the diagnostic staging procedure it is important to determine the origin of the adrenal lesion. An augmented increase in 17x-hydroxypro- gesterone (17-OHP) levels following corticotropin (1-24) stimulation has been noted in incidentally discovered adrenal masses by several groups. Therefore, we tested the hypothesis that elevated ACTH-stimulated 17-OHP (4>2.6 ng/ml) can predict primary adrenal lesions. We evaluated the use of the ACTH test in 85 patients with adrenocortical tumors and in 16 patients who underwent abdominal imaging for staging of a carcinoma other than of adrenal origin. We found an augmented 17-OHP response in 70 (>82%) of patients with known adrenocortical tumors and in 10 (>62%) of patients with adrenal masses and diagnosed malignancies. Results in the latter group have been confirmed in histological studies after operation or puncture. In the group of patients who suffered from a solid malignant tumor and had an adrenal
*Corresponding author. Fax: +(49) 277-8777860; E-mail: stefan.bornstein@nmi-duesseldorf.de
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mass, it was thus possible to separate primary from secondary adrenal lesions in 100%. In the group of patients with known adrenocortical tumors, it failed to differentiate between benign and malignant adrenocortical lesion in one case. We therefore think that the ACTH test is a valuable biochemical tool to distinguish primary adrenal tumors from adrenal metastasis derived from other malignancies.
INTRODUCTION
Nowadays, endocrinologists are confronted with adrenal masses in three different ways. First, in the minority of cases, search for adrenal pathology when hormone abnormalities of adrenal origin, including hyperaldosteronism, hyper- cortisolism, or oversecretion of catecholamines, have been diagnosed. Second, most frequently, evaluation of incidentally discovered adrenal tumors. Although most of the tumors of the adrenal gland are benign, there is still a need to exclude possible malignancies. Third, evaluation of adrenal masses which have been discovered intentionally during staging studies in patients with malignancies. Although in this group, metastasis is most common, there is still a need to differentiate between primary and secondary adrenal lesions. This is especially important for patients in whom the dignity of the adrenal mass either determines a T1-stadium or a T4-stadium of a carcinoma.
Adrenal computed tomography with determination of Hounsfield units has proved to be a reliable tool in the differential diagnosis of benign vs. malign adrenal lesions.[1,2] On the other hand, computed tomography is less specific in adrenal tumors the size of less than 1.0 cm and biopsy of these small lesions becomes less successful. Since an augmented increase in 17x-hydroxyprogesterone (17-OHP) levels following ACTH stimulation has been noted in incidentalomas by several groups,[3] we tested the hypothesis that elevated ACTH-stimulated 17-OHP can differentiate between primary and secondary adrenal lesions.
MATERIALS AND METHODS
Patients
Eighty five patients with a known adrenocortical tumor (group 1) and 16 patients (group 2) with known solid carcinomas (four small cell lung carcinomas, one non-small cell lung carcinoma, one bronchial carcinoid, one thymoma, one breast carcinoma, one melanoma, one renal carcinoma, one colon carcinoma, one carcinoma of unknown primarius, and four contralateral pheochromocytomas) and suspected adrenal metastasis as well as controls (n =68) have been included in this study (Table 1). Controls were partners of patients with congenital adrenal hyperplasia and patients who were sent to us for exclusion of steroid 21- hydroxylase deficiency. All of them had no known adrenal pathology and no known malignancy.
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| Patients | Male | Female | Mean Age (Years) |
|---|---|---|---|
| Group 1 (85 patients) | 29 | 56 | 57 (23-80) |
| Group 2 (16 patients) | 6 | 10 | 68 (19-75) |
| Control group (68 probands) | 8 | 60 | 40 (18-76) |
Endocrine Evaluation
The short 250 µg corticotropin (1-24) i.v. test was employed to diagnose an augmented 17-OHP response. An increase in serum 17-OHP greater than 2.6 ng/ml after 60 min was considered to be significant [3]. Other tests included the overnight 2 mg dexamethasone suppression test, 24 hours UFC, plasma metanephrines and urinary catecholamine and metanephrine excretion, renin, plasma renin activity, and aldosterone measurements.
RESULTS
An augmented 17-OHP response was found in 70 (>82%) of patients with known adrenocortical tumors (Table 2, group 1a). Among the patients with an augmented 17-OHP response there was one (male, 72 years; Table 2, group 1b) who developed an adrenocortical carcinoma (histology). Among the 16 patients with suspected adrenal metastasis, there were 10 (>62%) who had an augmented 17-OHP response (Table 2, group 2a). They turned out to be free of metastasis, and biopsy or histology obtained from their adrenal masses revealed a benign primary adrenal lesion. However, one female patient later developed an adrenal metastasis which was located contralateral to the primary suspected adrenal mass. In addition, six patients in this group had an adrenal metastasis. In three of them adrenal masses were proved to be malignant later through biopsy or histology. In the other three patients, the clinical follow up (rapid growth of metastasis and appearance of other secondary tumors) confirmed diagnosis. However, these six patients showed no significant increase of 17-OHP after ACTH administration (Table 2, group 2b).
Endocrine evaluation of the first group resulted in diagnosis of adrenocortical carcinoma in one case (ca. 1%), cortisol-producing adenomas in 15 cases (17.6%), aldosterone producing adenomas in six cases (7%), no pheochromocytoma. Sixty three patients (74%) with incidentally discovered adrenal masses had no overt endocrinopathy. In group 2a there was a female patient who had a cortisol- producing adenoma (ca. 11%). In group 1a, there was one female patient who had genetically proved steroid 21-hydroxylase deficiency (1%).
DISCUSSION
Augmented 17-OHP response was found in patients with known adreno- cortical tumors with a sensitivity of 82%. In patients with suspected adrenal
| Patients | Cortisol (µg/dL) | 17-OHP (ng/ml) | DHEA (ng/ml) | Androstend. (ng/ml) | 11-DOC (ng/ml) | Aldosterone (pg/mL) | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Basal | 60' | Basal | 60' | D | Basal | 60' | Basal | 60' | Basal | 60' | Basal | 60' | |
| Group 1a | 14.8 | 39.1 | 0.98 | 8.23 | 7.25 | 3.68 | 8.44 | 1.01 | 2.11 | 2.40 | 7.74 | 133 | 356 |
| Group 1b | 29.2 | 55.7 | 1.77 | 6.63 | 4.90 | 0.80 | 1.80 | 0.10 | 2.25 | 1.40 | 5.00 | — | — |
| Group 2a | 17.4 | 35.8 | 0.99 | 6.49 | 5.50 | 4.13 | 6.74 | 0.98 | 1.77 | 2.01 | 7.62 | 136 | 309 |
| Group 2b | 15.4 | 30.3 | 1.27 | 3.73 | 2.42 | 3.89 | 4.12 | 0.89 | 1.27 | 2.21 | 6.73 | 129 | 274 |
| Controls | 12.9 | 29.4 | 0.75 | 2.44 | 1.69 | 5.44 | 12.19 | 1.22 | 1.77 | 2.08 | 4.24 | 43 | 139 |
11-DOC= 11-desoxycortisol.
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SHORT SYNACTHEN TEST OF ADRENAL MASSES
metastasis it was possible to distinguish between primary or secondary adrenal lesions in 100% of cases. Therefore, the short ACTH test with measurement of 17- OHP is a powerful tool in the assessment of adrenal lesions when computed tomography or magnetic resonance imaging fail for technical reasons, including small adrenal masses. However, the test had no power to separate between benign and malignant adrenocortical lesions. Nonetheless, adrenocortical carcinomas are rare and, in the majority of cases, do not appear as small lesions at the time of diagnosis.[4]
Interestingly, there was no hint for adrenocortical insufficiency in the patient group with adrenal metastasis. The one case with genetically confirmed steroid 21- hydroxylase deficiency illustrates one diagnostic dilemma in our study. We did not perform genetic testing for 21-hydroxylase deficiency in every case and one of the patients was found to be heterozygous for this defect. On the other hand, a previous study did not find 21-hydroxylase deficiency as a predisposing factor for adrenal tumourigenesis and only 4% of patients in this study had congenital adrenal hyperplasia.[5]
We see other limitations to this study in the number of patients who could be included. On the other hand, to our knowledge, there is no study of this design in the literature. Since the consequences of confirmation or exclusion of adrenal metastasis for patients with malignancies are of significance, screening for 17-OHP hyperresponsiveness may be a valuable endocrine test adjunct to the currently available imaging techniques.
REFERENCES
1. NIH State-of-the-Science Conference. Ann. Intern. Med. 2002, in press. (http://consensus.nih.gov/)
2. Caoili, E.M .; Korobkin, M .; Francis, I.R .; Cohan, R.H .; Platt, J.F .; Dunnick, N.R .; Raghupathi, K.I. Radiology 2002, 222, 629-633.
3. Seppel, T .; Schlaghecke, R. Clin. Endocrinol. 1994, 41, 445-451.
4. Bornstein, S.R .; Stratakis, C.A .; Chrousos, G.P. Ann. Intern. Med. 1999, 130 (9), 759-771.
5. Maser-Gluth, C .; Reincke, M .; Allolio, B .; Schulze, E. Eur. J. Clin. Invest. 2000, Suppl 3, 83-836.