Summary
We present the case of a 39-year-old man with Klinefelter's syndrome and metastatic Leydig cell carcinoma in whom autonomous cortisol production induced by the interstitial cell tumor was found. Apart from the Cushing's syndrome the endocrine activity of the tumor was demonstrated by the secretion of estradiol, estrone, alkaline phosphatase, and testosterone. This is, to our knowledge, the first description of a Cushing's syndrome not caused via ACTH production but directly induced by ectopic steroid production. While being resistent to chemotherapy and radiation, the tumor responded favorably to treatment with o,p′-DDD. The reduction of tumor size was accompanied by a continuous decrease of serum markers.
The etiology of the tumor is discussed in the light of the hormonal derangement caused by the genetic abnormality of Klinefelter's syndrome.
Zusammenfassung
Wir berichten über einen 39jährigen Patienten mit einem Klinefelter-Syndrom, bei dem sich die autonome Produktion von Cortisol durch einen metastasierenden Leydig-Zell-Tumor nachweisen ließ. Die endokrine Tumoraktivität zeigte sich — neben einem Cushing-Syndrom — in der abnormen Sekretion von Östradiol, Östron, alkalischer Phosphatase und Testosteron. Es handelt sich dabei unseres Wissens um den ersten beschriebenen Fall eines Cushing-Syndroms, das nicht über die Bildung von ACTH, sondern durch ektope Steroidproduktion verursacht wurde.
Bei fehlender Radio- und Chemotherapiesensibilität zeigte sich eine Tumorrückbildung während der Behandlung mit o,p′-DDD, die mit einem dauerhaften Abfall der biologischen Tumormarker verbunden ist. Die Ätiologie des Tumors im Zusammenhang mit dem Klinefelter-Syndrom wird besprochen.
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References
Abelson D, Bulaschenko H, Trommer PR, Valdes-Dapena A (1966) Malignant interstitial-cell tumor of the testis treated with o,p′-DDD. Metabolism 15:242–256
Dodge OG, Jackson AW, Muldal S (1969) Breast cancer and interstitial cell tumor in a patient with Klinefelter's syndrome. Cancer 24:1027–1032
Engel LL, Lanman G, Scully RE, Villee DB (1966) Studies on an interstitial-cell tumor of the testis: formation of cortisol-14C from acetate-1-14C. J Clin Endocrinol Metab 26:381–392
Ferguson-Smith MA, Lennox B, Mack WS, Stewart JS (1957) Klinefelter's syndrome. Frequency and testicular morphology in relation to nuclear sex. Lancet 2:167–169
Fore WW, Bledsoe T, Weber DM, Akers R, Brooks RT (1972) Cortisol production by testicular tumors in adrenogenital syndrome. Arch Intern Med 130:59–63
Geraedts JPM, Mol A, Briet E, Hartgrink-Groeneveld CA, Den Ottolander GJ (1980) Klinefelter's syndrome: predisposition to acute non-lymphocytic leukaemia? Lancet 1:774
Gunn SA, Gould TC, Anderson WAD (1963) Cadmium-induced interstitial-cell tumors in rats and mice and their prevention by zinc. J Natl Cancer Inst 31:745–759
Hamwi GJ, Gwinup G, Mostow JH, Besch PK (1963) Activation of testicular adrenal rest tissue by prolonged excessive ACTH production. J Clin Endocrinol Metab 23:861–869
Hedinger C (1954) Beidseitige Hodentumoren und kongenitales adrenogenitales Syndrom. (Leydig-Zellen oder Nebennierenrindengewebe?) Schweiz Z Allg Pathol 17:743–750
Higi M, Niederle N, Scheulen ME, Richter HJ (1979) Metastasierender Leydig-Zell-Tumor des Hodens mit einem Markerenzym. J Cancer Res Clin Oncol 94:325–331
Jackson AW, Muldal S, Ockey CH, O'Connor PJ (1965) Carcinoma of the male breast in association with the Klinefelter syndrome. Br Med J 1:223–225
Johnstone G (1967) Prepubertal gynaecomastia in association with an interstitial-cell tumor of the testis. Br J Urol 39:211–220
Krieger DT, Samojlik E, Bardin CW, (1978) Cortison and androgens secretion in a case of Nelson's syndrome with paratesticular tumors: response to cyproheptadine therapy. J Clin Endocrinol Metab 47:837–844
Lipsett MB, Sarfaty GA, Wilson H, Bardin CW, Fishman LM (1966) Metabolism of testosterone and related steroids in metastatic interstitial-cell carcinoma of the testis. J Clin Invest 45:1700–1709
Odell WD, Wolfsen AR (1978) Humoral syndromes associated with cancer. Annu Rev Med 29: 379–406
Paulsen CA, Gordon DL, Carpenter RW, et al. (1968) Klinefelter's syndrome and its variants: a hormonal and chromosomal study. Recent Prog Horm Res 24:321–363
Roe FJC, Dukes CE, Cameron KM, Pugh RCB, Mitchley BCV (1964) Cadmium neoplasia: testicular atrophy and Leydig cell hyperplasia and neoplasia in rats and mice following the subcutaneous injection of cadmium salts. Br J Cancer 18:674–681
Savard K, Dorfman RI, Baggett B, Fielding LL, Engel LL, McPherson HT, Johnson DS, Hamblen EC, Engel FL (1959) Clinical, morphological, and biochemical studies of a virilizing tumor in the testis. J Clin Invest 39:534–553
Tamoney HJ Jr, Noriega A (1969) Malignant interstitial-cell tumor of the testis. Cancer 24:547–551
Ward JA, Krantz S, Mendeloff J, Haltiwanger E (1960) Interstitial-cell tumor of the testis. Report of two cases. J Clin Endocrinol Metab 20:1622–1632
Weidmann P, Siegenthaler W, Ziegler WH, Sulser H, Endres P, Werning C (1969) Hypertension associated with tumors adjacent to renal arteries. Am J Med 47:528–533
Weinberger MH, Collins RD, Dowdy AJ (1969) Hypertension induced by oral contraceptives containing estrogen and gestagen. Effects on plasma renin activity and aldosterone excretion. Ann Intern Med 71:891–902
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Knyrim, K., Higi, M., Hossfeld, D.K. et al. Autonomous cortisol secretion by a metastatic Leydig cell carcinoma associated with Klinefelter's syndrome. J Cancer Res Clin Oncol 100, 85–93 (1981). https://doi.org/10.1007/BF00405905
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DOI: https://doi.org/10.1007/BF00405905