Tuesday, December 15, 2009

Diagnosis, management and therapeutic outcome in prepubertal Cushing’s disease

European Journal of Endocrinology (2009) In press
DOI: 10.1530/EJE-09-0509
Copyright © 2009 by European Society of Endocrinology

Renuka Dias, Anitha Kumaran, Li Chan, Lee Martin, Fary Afshar, Michael Matson, P N Plowman, John Monson, Michael Besser, Ashley Grossman, Martin Savage and H L Storr

R Dias, Endocrinology, Barts and the London School of Medicine and Dentistry, London, United Kingdom
A Kumaran, Endocrinology, Barts and the London School of Medicine and Dentistry, London, United Kingdom
L Chan, Endocrinology, Barts and the London School of Medicine and Dentistry, London, United Kingdom
L Martin, Endocrinology, Barts and the London School of Medicine and Dentistry, London, United Kingdom
F Afshar, Neurosurgery, Barts and the London School of Medicine and Dentistry, London, United Kingdom
M Matson, Radiology, Barts and the London School of Medicine and Dentistry, London, United Kingdom
P Plowman, Radiotherapy, Barts and the London School of Medicine and Dentistry, London, United Kingdom
J Monson, Endocrinology, Barts and the London School of Medicine and Dentistry, London, United Kingdom
M Besser, Endocrinology, Barts and the London School of Medicine and Dentistry, London, United Kingdom
A Grossman, Endocrinology, Barts and the London School of Medicine and Dentistry, London, United Kingdom
M Savage, Paediatric Endocrinology, Barts and the London School of Medicine and Dentistry, London, United Kingdom
H Storr, Endocrinology, Barts and the London School of Medicine and Dentistry, London, United Kingdom

Correspondence: Renuka Dias, Email: r.dias@qmul.ac.uk

Objectives: Cushing’s disease (CD) in prepubertal children is very rare and presents important diagnostic and therapeutic challenges. We report experience of the management of this subpopulation of CD patients.

Study Design/ Methods: Retrospective patient case note review

Results: Between 1985 and 2008, seventeen prepubertal children (13M, 4F), aged 5.7 to 14.1 yr presented to our centre for diagnosis and management of CD. All children had subnormal linear growth and excessive weight gain at presentation. A high proportion (85% of males, 75% of females) had evidence of excessive virilisation. Striae or hypertension were seen in 41% of patients. The investigation with highest sensitivity (100%) for CD was excessive increase of serum cortisol to IV CRH (mean increase 113%). Pituitary imaging performed in all patients showed poor concordance with findings at surgery (31%). In contrast BSIPSS, performed in 11/16 subjects showed a high correlation with surgical findings (91%). In 16 patients, transsphenoidal selective adenomectomy (TSS) achieved a cure rate of 44%. However, in the 11 patients who had pre-operative BSIPSS the cure rate was 64%. 9/16 patients who were not cured by TSS received external pituitary radiotherapy (RT).

Conclusions: Prepubertal CD had distinctive features with increased frequency in males, abnormal auxology and excessive virilisation. The cortisol response to IV CRH administration was particularly exuberant and contributed to diagnosis. BSIPSS was much more helpful than pituitary imaging in localisation of the microadenoma and was associated with improved cure rate by TSS.

From http://www.eje.org/cgi/content/abstract/EJE-09-0509v1