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

Abstract

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, 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.

Paediatric Cushing’s disease — a literature review of epidemiology, pathogenesis, clinical symptoms, and diagnostics

“…The first one [30] showed that BSIPSS correctly predicted the tumour position in all (4) cases; in the second [75] and third [76] research there was concordance between the BSIPSS finding and the position of the microadenoma at surgery in, respectively, 81% (17/21) and 91% (10/11) patients. The last study reported that in 91% of patients BSIPSS showed the correct position of pituitary adenoma [70].…”

“…Bilateral simultaneous inferior petrosal sinus sampling is a highly specialised technique and should be performed by experienced interventional neuroradiologists with a team of trained operators [30,69]. In the majority of cases, general anaesthesia (GA) is not required; however, in young children GA may be necessary [30,70]. In the study by Dias et al children with GA were aged 5.6 and 6.6 years, and BSIPSS, despite GA, gave valid results [70].…”

“…In the majority of cases, general anaesthesia (GA) is not required; however, in young children GA may be necessary [30,70]. In the study by Dias et al children with GA were aged 5.6 and 6.6 years, and BSIPSS, despite GA, gave valid results [70].…”

The Diagnosis of Pediatric Cushing's Syndrome is not always simple

“…The earlier the state of disease the more subtle may be the signs and symptoms. Several reviews and guidelines try to help in diagnosing this disease state [2][3][4] . The accuracy and usefulness of the laboratory tests and procedures for the diagnosis of CS was also evaluated 5 .…”

Cushing’s syndrome in children and adolescents: a Danish nationwide population-based cohort study

“…CS in children and adolescents is estimated to comprise 10% of diagnosed cases, but population-based epidemiological data are lacking (3). As in adults, CD remains the most common cause of endogenous CS in children (85%), with a female predominance (4) (although a male predominance has been reported in prepubertal children (5,6,7). The onset of the disease is insidious, but its hallmark is obesity combined with longitudinal growth retardation (4,5).…”