Pediatric Cushing's syndrome: clinical features, diagnosis, and treatment

Abstract

Cushing's syndrome (CS) results from prolonged exposure to supraphysiological levels of circulating glucocorticoids, endogenously or exogenously derived. Although rare in childhood, CS remains a difficult condition to diagnose and treat. A multidisciplinary approach and close collaboration with adult colleagues is adopted at most large centres that manage pediatric CS patients. Although pediatric protocols are derived from adult data, significant differences exist between adult and childhood CS. Furthermore, long term outcome parameters including final height, bone mineral density, reproductive function, body composition and psychological health pose challenges for pediatric care. This article will aim to provide an overall view of pediatric CS highlighting some of the differences between adult and pediatric CS. A síndrome de Cushing (SC) resulta da exposição prolongada a níveis suprafisiológicos de glicocorticóides circulantes, tanto endógenos como de seus derivados exógenos. Embora rara na infância, a SC permanece uma condição difícil de ser diagnosticada e tratada. Uma avaliação multidisciplinar e a colaboração próxima com colegas da área não-pediátrica são adotadas na maioria dos grandes centros que cuidam de pacientes pediátricos com SC. Embora os protocolos pediátricos sejam derivados de dados em adultos, existem diferenças significativas entre a SC no adulto e na infância. Além disso, parâmetros evolutivos finais, incluindo altura final, densidade mineral óssea, função reprodutiva, composição corporal e saúde psicológica trazem desafios no cuidado pediátrico. Este artigo procura oferecer uma visão geral da SC pediátrica, focalizando algumas das diferenças entre a SC adulta e a pediátrica.

An 18-Month-Old Boy with Decreasing Height Velocity

“…In children, these features include a decrease in linear growth velocity, weight gain, obesity, and facial plethora. 3 The growth retardation is explained by two mechanisms. First, for reasons not completely understood, prolonged excess of glucocorticoids causes suppression of growth hormone production, or the glucocorticoid receptor represses activator protein-1, a transcription factor that mediates the effects of IGF-1 and is responsible for the differentiation, proliferation, and apoptosis of cells.…”

“…Patients require intraoperative and postoperative steroid replacement followed by a taper over a period of 6 months. 3,7,9 Additional steroid bursts may be necessary during illness or stress. Patients will need ongoing monitoring of blood pressure, routine blood chemistries and hormone levels, renal and pelvic ultrasounds, and physical examinations to evaluate for reoccurrence of the tumor.…”

Congenital Immature Teratoma Mimicking Cushing’s Disease

“…The causes can be further classified according to the age of onset. For example, CS in infancy is usually associated with McCune-Albright syndrome; adrenocortical tumors most commonly occur in children under 4 years of age [8]. Cushing’s disease is the commonest cause of CS after 5 years of age, though there have been case reports of functioning pituitary macroadenoma in infants [9].…”

“…This contrasts with adults, where EAS accounts for approximately 15% of adult ACTH-dependent CS [8]. The majority of the pediatric cases result from carcinoid tumors of bronchial or thymic origin.…”

Recommendations of the Neuroendocrinology Department of the Brazilian Society of Endocrinology and Metabolism for the diagnosis of Cushing’s disease in Brazil

“…It is noteworthy to mention that the same reference values for adults can be used in children over 45 kg, with a sensitivity of approximately 89% (74,75).…”