Long-term outcomes of children treated for Cushing's disease: a single center experience.

Galina Yordanova,Matthew Matson,Jane Evanson,Martin O Savage,Ghassan Alusi,John P Monson,Lee Martin,Ashley B Grossman,Nicholas P Plowman,Fiona Riddoch,Ian Sabin,Farhad Afshar,William M Drake,Helen L Storr,Scott A Akker

doi:10.1007/s11102-016-0756-8

Abstract

PurposePediatric Cushing’s disease (CD) is rare and there are limited data on the long-term outcomes. We assessed CD recurrence, body composition, pituitary function and psychiatric comorbidity in a cohort of pediatric CD patients.MethodsRetrospective review of 21 CD patients, mean age at diagnosis 12.1 years (5.7–17.8), managed in our center between 1986 and 2010. Mean follow-up from definitive treatment was 10.6 years (2.9–27.2).ResultsFifteen patients were in remission following transsphenoidal surgery (TSS) and 5 were in remission following TSS + external pituitary radiotherapy (RT). One patient underwent bilateral adrenalectomy (BA). CD recurrence occurred in 3 (14.3 %) patients: 2 at 2 and 6 years after TSS and 1 7.6 years post-RT. The BA patient developed Nelson’s syndrome requiring pituitary RT 0.6 years post-surgery. Short-term growth hormone deficiency (GHD) was present in 14 patients (81 % patients tested) (11 following TSS and 3 after RT) and 4 (44 % of tested) had long-term GHD. Gonadotropin deficiency caused impaired pubertal development in 9 patients (43 %), 4 requiring sex steroid replacement post-puberty. Four patients (19 %) had more than one pituitary hormone deficiency, 3 after TSS and 1 post-RT. Five patients (24 %) had long-term psychiatric co-morbidities (cognitive dysfunction or mood disturbance). There were significant long-term improvements in growth, weight and bone density but not complete reversal to normal in all patients.ConclusionsThe long-term consequences of the diagnosis and treatment of CD in children is broadly similar to that seen in adults, with recurrence of CD after successful treatment uncommon but still seen. Pituitary hormone deficiencies occurred in the majority of patients after remission, and assessment and appropriate treatment of GHD is essential. However, while many parameters improve, some children may still have mild but persistent defects.

Highlights

Cushing’s disease (CD) is defined as hypercortisolism due to excess pituitary ACTH secretion by a corticotroph adenoma accounting for *75 % of cases of pediatric Cushing’s syndrome [1]
The CRH test was performed in all patients and induced a mean cortisol increase of 90.5 %: in 19/21 (90 %), the cortisol rise during the CRH test was [20 %
CD is rare in childhood and a limited number of centers have the capacity to manage this condition comprehensively

Summary

Introduction

Cushing’s disease (CD) is defined as hypercortisolism due to excess pituitary ACTH secretion by a corticotroph adenoma accounting for *75 % of cases of pediatric Cushing’s syndrome [1]. Long-term consequences of adult CD are well documented, including morbidity, recurrence and its sequelae [3], but limited data exist for pediatric patients after transsphenoidal surgery (TSS) and external pituitary radiotherapy (RT). Growth and body composition are frequently compromised in pediatric CD at diagnosis, and following successful therapy, height and weight may not normalize [4, 5]. Growth hormone treatment following remission of hypercortisolemia may improve catch-up growth and adult height [4]. Defects in pituitary function following remission of CD after TSS or RT are well described [7,8,9]. Hypercortisolemia affects mood and may precipitate psychiatric disturbances, with uncertain long-term sequelae [3]

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Results

Conclusion