Diagnosis, management and therapeutic outcome in prepubertal Cushing's disease.
OBJECTIVE
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.


METHODS
Retrospective patient case note review.


RESULTS
Between 1985 and 2008, 17 prepubertal children (13M, 4F), aged 5.7-14.1 years 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 and hypertension were seen in 41% of patients. The investigation with highest sensitivity (100%) for CD was excessive increase of serum cortisol to i.v. CRH (mean increase 113%). Pituitary imaging performed in all the patients showed poor concordance with findings at surgery (31%). In contrast bilateral simultaneous inferior petrosal sinus sampling (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%. Of the 16 patients, 9 patients who were not cured by TSS received external pituitary radiotherapy.


CONCLUSIONS
Prepubertal CD had distinctive features with increased frequency in males, abnormal auxology and excessive virilisation. The cortisol response to i.v. 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.
Dias
R P
RP
Department of Endocrinology, Barts and the Royal London School of Medicine and Dentistry, London EC1A 7BE, UK.
Kumaran
A
A
Chan
L F
LF
Martin
L
L
Afshar
F
F
Matson
M
M
Plowman
P N
PN
Monson
J P
JP
Besser
G M
GM
Grossman
A B
AB
Savage
M O
MO
Storr
H L
HL
D000236:Adenoma / Q000150:complications / Q000175:diagnosis / Q000628:therapy*; D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D003346:Corticotropin-Releasing Hormone; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D006973:Hypertension / Q000209:etiology; D007118:Immunoassay; D008279:Magnetic Resonance Imaging; D008297:Male; D050177:Overweight / Q000209:etiology; D047748:Pituitary ACTH Hypersecretion / Q000150:complications / Q000175:diagnosis* / Q000628:therapy*; D010902:Pituitary Gland / Q000503:physiopathology; D010911:Pituitary Neoplasms / Q000150:complications / Q000175:diagnosis / Q000628:therapy*; D012189:Retrospective Studies; D016896:Treatment Outcome; D014770:Virilism / Q000209:etiology
D003346:Corticotropin-Releasing Hormone; D006854:Hydrocortisone