Paediatric Cushing’s disease: Epidemiology, pathogenesis, clinical management and outcome

Abstract

Cushing’s disease (CD) is rare in paediatric practice but requires prompt investigation, diagnosis and therapy to prevent long-term complications. Key presenting features are a change in facial appearance, weight gain, growth failure, virilization, disturbed puberty and psychological disturbance. Close consultation with an adult endocrinology department is recommended regarding diagnosis and therapy. The incidence of CD, a form of ACTH-dependent Cushing’s syndrome (CS), is equal to approximately 5% of that seen in adults. The majority of ACTH-secreting adenomas are monoclonal and sporadic, although recent studies of pituitary tumours have shown links to several deubiquitination gene defects. Diagnosis requires confirmation of hypercortisolism followed by demonstration of ACTH-dependence. Identification of the corticotroph adenoma by pituitary MRI and/or bilateral inferior petrosal sampling for ACTH may contribute to localisation before pituitary surgery. Transsphenoidal surgery (TSS) with selective microadenomectomy is first-line therapy, followed by external pituitary irradiation if surgery is not curative. Medical therapy to suppress adrenal steroid synthesis is effective in the short-term and bilateral adrenalectomy should be considered in cases unfit for TSS or radiotherapy or when urgent remission is needed after unsuccessful surgery. TSS induces remission of hypercortisolism and improvement of symptoms in 70–100% of cases, particularly when performed by a surgeon with experience in children. Post-TSS complications include pituitary hormone deficiencies, sub-optimal catch-up growth, and persisting excess of BMI. Recurrence of hypercortisolism following remission is recognised but infrequent, being less common than in adult CD patients. With experienced specialist medical and surgical care, the overall prognosis is good. Early referral to an experienced endocrine centre is advised.

Diagnosis, Manifestations, Laboratory Investigations, and Prognosis in Pediatric and Adult Cushing’s Disease in a Large Center in China

“…As previously reported (3,4,7), there is a significant difference between gender distribution of pediatric and adult-onset CD (P < 0.001). Females dominated the adult CD group (83%), while an equal gender distribution was observed among 30 pediatric patients (50 vs. 50%).…”

“…Gender distribution in pediatric CD patients was analyzed in many studies, some of which reported male predominance. Same as a large series of 102 patients from the NIH, our study showed an equal gender distribution (7). So far, the reason for the higher male proportion in pediatric patients compared with adults is not clear.…”

“…Furthermore, hypertension, osteopenia, glucose intolerance, fatigue, bruising, striae, mood change, and hypokalemia were also prevalent for pediatric patients and would probably further progress and develop into lifelong complications. Therefore, accurate diagnosis and early treatment are crucial to pediatric patients' normalization of metabolism and development both physically and mentally (7,25,26).…”

Consensus on diagnosis and management of Cushing's disease: a guideline update

“…The diagnostic approach and test performances are slightly different from adults, as recently extensively reviewed. 268 The Dex-CRH test is not useful in children. In children over age 6, CD is the most common cause of CS, while adrenal causes are more common in younger children.…”

“…If an underlying genetic syndrome is present, genetic counseling for the child and family members as well as investigations into other disorders associated with the syndrome are necessary. 268,272,273 MF has received grants to the institution from Novartis, Strongbridge, Novo Nordisk, Crinetics, Millendo, Ascendis, and Pfizer, and personal honoraria for consulting and advisory boards from Crinetics, HRA Pharma, Novartis, Recordati, Strongbridge, Sparrow, Ascendis, Novo Nordisk, and Pfizer, and has served on the Board for Pituitary Society.…”