Background/Aims: Growth retardation is a recognised complication of paediatric Cushing’s disease (CD), but there are few published data on skeletal maturation at diagnosis. We assessed factors contributing to skeletal maturation in patients with paediatric CD. Patients/Methods: 17 patients, 12 males, 5 females (median age 12.1 years, range 5.8–17.4) were studied. The bone age (BA) of each child was determined by a single observer using the TW3 RUS method. BA delay, i.e. the difference between chronological age (CA) and BA, was compared with clinical and biochemical variables. Results: BA delay was present in 15/17 patients (mean delay 2.0 years, range –0.5 to 4.1 years) and correlated negatively with height SDS (r = –0.70, p < 0.01) and positively with duration of symptoms (r = 0.48, p = 0.05) and CA (r = 0.48, p = 0.05). No relationships were found with midnight cortisol, ACTH, DHEA-S or cortisol suppression during the low-dose dexamethasone suppression test. Conclusions: BA in most children with CD was delayed and related to length of symptoms and height SDS at diagnosis. Early diagnosis will reduce delay in skeletal maturation and thus contribute to optimal catch-up growth.

1.
Magiakou MA, Mastorakos G, Oldfield EH, Gomez MT, Doppman JL, Cutler GB Jr et al: Cushing’s syndrome in children and adolescents. Presentation, diagnosis, and therapy. N Engl J Med 1994;331:629–636.
2.
Weber A, Trainer PJ, Grossman AB, Afshar F, Medbak S, Perry LA et al: Investigation, management and therapeutic outcome in 12 cases of childhood and adolescent Cushing’s syndrome. Clin Endocrinol (Oxf) 1995;43:19–28.
3.
Davies JH, Storr HL, Davies K, Monson JP, Besser GM, Afshar F et al: Final adult height and body mass index after cure of paediatric Cushing’s disease. Clin Endocrinol (Oxf) 2005;62:466–472.
4.
Lebrethon MC, Grossman AB, Afshar F, Plowman PN, Besser GM, Savage MO: Linear growth and final height after treatment for Cushing’s disease in childhood. J Clin Endocrinol Metab 2000;85:3262–3265.
5.
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.
6.
Strickland AL, Underwood LE, Voina SJ, French FS, Van Wyk JJ: Growth retardation in Cushing’s syndrome. Am J Dis Child 1972;123:207–213.
7.
Arnaldi G, Angeli A, Atkinson AB, Bertagna X, Cavagnini F, Chrousos GP et al: Diagnosis and complications of Cushing’s syndrome: a consensus statement. J Clin Endocrinol Metab 2003;88:5593–5602.
8.
Kristo C, Jemtland R, Ueland T, Godang K, Bollerslev J: Restoration of the coupling process and normalization of bone mass following successful treatment of endogenous Cushing’s syndrome: a prospective, long-term study. Eur J Endocrinol 2006;154:109–118.
9.
Mancini T, Doga M, Mazziotti G, Giustina A: Cushing’s syndrome and bone. Pituitary 2004;7:249–252.
10.
Dupuis CC, Storr HL, Perry LA, Ho JTF, Ahmed L, Ong KK et al: Abnormal puberty in paediatric Cushing’s disease; relationships with adrenal androgens, sex hormone binding globulin and gonadotrophin concentrations. Clin Endocrinol (Oxf) 2006.
11.
Baron J, Huang Z, Oerter KE, Bacher JD, Cutler GB Jr: Dexamethasone acts locally to inhibit longitudinal bone growth in rabbits. Am J Physiol 1992;263:E489–E492.
12.
Koedam JA, Smink JJ, Buul-Offers SC: Glucocorticoids inhibit vascular endothelial growth factor expression in growth plate chondrocytes. Mol Cell Endocrinol 2002;197:35–44.
13.
Lindberg MK, Vandenput L, Moverare SS, Vanderschueren D, Boonen S, Bouillon R et al: Androgens and the skeleton: Minerva Endocrinol 2005;30:15–25.
14.
Vanderschueren D, Vandenput L, Boonen S, Lindberg MK, Bouillon R, Ohlsson C: Androgens and bone. Endocr Rev 2004;25:389–425.
15.
Mazziotti G, Angeli A, Bilezikian JP, Canalis E, Giustina A: Glucocorticoid-induced osteoporosis: an update. Trends Endocrinol Metab 2006;17:144–149.
16.
Scommegna S, Greening JP, Storr HL, Davies KM, Shaw NJ, Monson JP et al: Bone mineral density at diagnosis and following successful treatment of pediatric Cushing’s disease. J Endocrinol Invest 2005;28:231–235.
17.
Storr HL, Afshar F, Matson M, Sabin I, Davies KM, Evanson J et al: Factors influencing cure by transsphenoidal selective adenomectomy in paediatric Cushing’s disease. Eur J Endocrinol 2005;152:825–833.
18.
Newell-Price J, Trainer P, Besser M, Grossman A: The diagnosis and differential diagnosis of Cushing’s syndrome and pseudo-Cushing’s states. Endocr Rev 1998;19:647– 672.
19.
Storr HL, Plowman PN, Carroll PV, Francois I, Krassas GE, Afshar F et al: Clinical and endocrine responses to pituitary radiotherapy in pediatric Cushing’s disease: an effective second-line treatment. J Clin Endocrinol Metab 2003;88:34–37.
20.
Cameron N: The Measurement of Human Growth. London, Croom Helm, 1984.
21.
Freeman JV, Cole TJ, Chinn S, Jones PR, White EM, Preece MA: Cross-sectional stature and weight reference curves for the UK, 1990. Arch Dis Child 1995;73:17–24.
22.
Tanner JM: Growth at Adolescence, ed 2. Oxford, Blackwell, 1962.
23.
Tanner JM, Healy MJR, Goldstein H, Cameron N: Assessment of Skeletal Maturity and Prediction of Adult Height (TW3 Method), ed 3. London, Harcourt, 2001.
24.
Jux C, Leiber K, Hugel U, Blum W, Ohlsson C, Klaus G et al: Dexamethasone impairs growth hormone (GH)-stimulated growth by suppression of local insulin-like growth factor (IGF)-I production and expression of GH- and IGF-I-receptor in cultured rat chondrocytes. Endocrinology 1998;139:3296–3305.
25.
Unterman TG, Phillips LS: Glucocorticoid effects on somatomedins and somatomedin inhibitors. J Clin Endocrinol Metab 1985;61:618–626.
26.
Devoe DJ, Miller WL, Conte FA, Kaplan SL, Grumbach MM, Rosenthal SM et al: Long-term outcome in children and adolescents after transsphenoidal surgery for Cushing’s disease. J Clin Endocrinol Metab 1997;82:3196–3202.
27.
Di Somma C, Pivonello R, Loche S, Faggiano A, Klain M, Salvatore M et al: Effect of two years of cortisol normalization on the impaired bone mass and turnover in adolescent and adult patients with Cushing’s disease: a prospective study. Clin Endocrinol (Oxf) 2003;58:302–308.
28.
Manning PJ, Evans MC, Reid IR: Normal bone mineral density following cure of Cushing’s syndrome. Clin Endocrinol (Oxf) 1992;36:229–234.
29.
Salt AT, Savage MO, Grant DB: Growth patterns after surgery for virilising adrenocortical adenoma. Arch Dis Child 1992;67:234–236.
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