Abstract
Cushing's disease (CD), the chronic endogenous hypercortisolism derived from an ACTH-secreting pituitary adenoma, and multiple osteochondromatosis (MO), a congenital mesoderm dyschondroplasia, represent two distinct rare neoplastic diseases. Clinical appearance of MO usually occurs during the first-second decade of life. In fact, the growth of osteochondromas parallels the patient's growth, then becoming quiescent after the closure of the epiphyses and the achievement of final stature. Here we describe an uncommon case of a patient with a long-term history of childhood-onset CD, who surprisingly developed MO during the third decade of life, after the remission of CD. Indeed, a female patient had been followed for CD from the age of 12 to the age of 24 years, when CD definitively remitted. At the age of 26 the patient complained progressively worsening backache and pain at level of hips and feet. Standard radiography of skeleton showed multiple bone dysmorphisms at level of the four limbs, spine and pelvis consistent with multiple osteochondromas and exostoses. A diagnosis of MO was performed. Total body bone scintigraphy with 99mTc-MDP revealed an increased uptake of the radioligand, suggesting an increased metabolic turnover in correspondence of the majority of the osteochondromas. However, the negativity of the majority of the lesions at 99mTc-DMSA scintigraphy and the histological diagnosis of benign osteochondroma of the only positive lesion at 99mTc-DMSA evidenced that the high metabolic activity of the osteochondromas was not due to malignant transformation. However, the activity of the lesions was highly surprising considering that they usually become quiescent after the achievement of the final stature. In last analysis, the uncommon characteristics of MO and, particularly, its occurrence after stable remission of hypercortisolism, suggests a possible role of glucocorticoids in influencing the clinical course of the skeletal disease. The inhibitory effect of hypercortisolism on bone growth and maturation could explain the block in the proliferation of skeletal lesions during the developmental age, where CD was in the active phase, and the opposite effect of stimulation of the ostochondromas growth during stable normalization of cortisol secretion, after CD remission.
REFERENCES
Aron DC, Findling JW, Tyrrell JB. Cushing's disease. Endocrinol Metab Clin North Am 1987;16:705–730.
Harsha WN. The natural history of osteocartilaginous exostoses (osteochondroma). Am Surg 1954;20:65–72.
Farrett WD Jr, Stone PA, McGarry JJ. Rare presentation of hereditary multiple exostoses: A case report. J Am Podiatr Med Assoc 1998;88:135–139.
Etxabe J, Vazquez JA. Morbidity and mortality in Cushing's disease: An epidemiological approach. Clin Endocrinol 1994;40:479–484.
Colao A, Pivonello R, Faggiano A, Spiezia S, Marzullo P, Cerbone G, Ferone D, Filippella M, Siciliani M, Lombardi G. Persistence of increased cardiovascular risk in patients with Cushing's disease after 5 years of successful cure. J Clin Endocrinol Metab 1999;84:2664–2672.
Maldague B, Malghem J, de Deuxchaisnes C. Radiological aspects of glucocorticoid-induced bone disease. Adv Exp Med Biol 1984;171:155–190.
Lukert BP, Raisz LG. Glucocorticoid-induced osteoporosis: Pathogenesis and management.Ann Intern Med1990;112:352–364.
Hermus AR, Smals AG, Swinkels LM, Huysmans DA, Pieters GF, Sweep CF, Corstens FH, Kloppenborg PW. Bone mineral density and bone turnover before and after surgical cure of Cushing's syndrome. J Clin Endocrinol Metab 1995;80:2859–2865.
Canalis E. Mechanisms of glucocorticoid action in bone: Implications to glucocorticoid-induced osteoporosis. J Clin Endocrinol Metab 1996;81:3441–3447.
Allen DB, Goldberg BD. Stimulation of collagen synthesis and linear growth in glucocorticoid-treated children. Pediatrics 1992;89:416–421.
Magiakou MA, Mastorakos G, Chrousos GP. Final stature in patients with endogenous Cushing's syndrome. J Clin Endocrinol Metab 1994;79:1082–1085.
Colao A, Cerbone G, Pivonello R, Aimaretti G, Loche S, Di Somma C, Faggiano A, Corneli G, Ghigo E, Lombardi G. The growth hormone (GH) response to the arginine plus GHreleasing hormone test is correlated to the severity of lipid profile abnormalities in adult patients with GH deficiency. J Clin Endocrinol Metab 1999;84:1277–1282.
Anderson IF. Maffucci's syndrome. South Afric Med J 1965;39:1066.
Little C. Ollier disease: An interdisciplinary approach. Orthop Nurs 1994;13:50–55.
Jingu K, Katayama J, Takahashi M, Chin C. Case of Maffucci's syndrome. Rinsho Hoshasen 1973;18:281–288.
Schnall AM, Genuth SM. Multiple endocrine adenomas in a patient with the Maffucci syndrome. Am J Med 1976;61:952–956.
Marymont JV, Fisher RF, Emde GE, Limbird TJ. Maffucci's syndrome complicated by carcinoma of the breast, pituitary adenoma and mediastinal hemangioma. South Med J 1987;80:1429–1431.
Miki K, Kawamoto K, Kawamura Y, Matsmura H, Asada Y, Hamada A. A rare case of Maffucci's syndrome combined with tuberculum sellae enchondroma pituitary adenoma and thyroid adenoma. Acta Neurochir 1987;87:79–85.
James K, McIntire HD. Maffucci's syndrome in association with adrenal Cushing's syndrome. Aus N Z J Med 1995;25:544.
Turner RT, Riggs BL, Spelsberg TC. Skeletal effects of estrogen. Endocr Rev 1994;15:275–300.
Magiakou MA, Mastorakos G, Gomez MT, Rose SR, Chrousos GP. Suppressed spontaneous and stimulated growth hormone secretion in patients with Cushing's disease before and after surgical cure. J Clin Endocrinol Metab 1994;78:131–137.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Faggiano, A., Pivonello, R., Ruosi, C. et al. Uncommon Clinical Course of Multiple Osteochondromatosis in a Patient with a Long-Term History of Cushing's Disease. Pituitary 4, 187–193 (2001). https://doi.org/10.1023/A:1015371024719
Issue Date:
DOI: https://doi.org/10.1023/A:1015371024719