Treatment challenges in pediatric Cushing’s disease: Review of the literature with particular emphasis on predictive factors for the disease recurrence

Abstract

Cushing’s disease (CD) is a rare endocrine condition caused by a corticotroph pituitary tumor that produces adrenocorticotropic hormone. The current state of knowledge of CD treatment is presented in this article including factors that can be helpful in predicting remission and/or recurrence of the disease. The primary goals in CD treatment are quick diagnosis and effective, prompt treatment as the persistent disease is associated with increased morbidity and mortality. Cooperation of a team consisting of experienced pediatrician/adult endocrinologist, neuroradiologist, transsphenoidal neurosurgeon and (if necessary) radiotherapist contribute to the best treatment effects.

Clinical features, diagnosis and treatment outcomes of Cushing's disease in children: A multicenter study

“…25 In case of surgical failure or recurrence, there are options for a second pituitary surgery, radiotherapy, medical treatment or bilateral adrenalectomy, which should be decided on a case-by-case basis. 29 In this series, hemihypophysectomy was performed due to surgical failure in two and due to | 25 recurrence in two patients who had undergone TSA. Due to another recurrence in one of these four patients, one patients underwent a total hypophysectomy, while two were treated with cabergoline due to persistent disease.…”

“…Although 3 patients in this cohort had preoperative use of ketoconazole, it is not approved by the Food and Drug Administration neither in children nor in adults. 29 TSA is the recommended first-line treatment in paediatric CD if the adenoma is easily identified during surgery, or if not, hemi-or total hypophysectomy may be performed. 30 In this cohort, TSA was performed in the majority of the patients (78.1%), while hemihypophysectomy was preferred as the treatment of choice in three patients with MRI-negative disease, which resulted in cure.…”

“…During surgical preparation, ketoconazole is a short‐term medical treatment option to control hypercortisolism; its use as a definitive treatment is not recommended, especially because it is highly hepatotoxic. Although 3 patients in this cohort had preoperative use of ketoconazole, it is not approved by the Food and Drug Administration neither in children nor in adults 29 …”

“…In a large study including 200 patients, this rate in 179 patients with at least 1‐year follow‐up data was found to be 8% 7–11.7 years after surgery 25 . In case of surgical failure or recurrence, there are options for a second pituitary surgery, radiotherapy, medical treatment or bilateral adrenalectomy, which should be decided on a case‐by‐case basis 29 . In this series, hemihypophysectomy was performed due to surgical failure in two and due to recurrence in two patients who had undergone TSA.…”

Cushing disease in pediatrics: an update

“…There is no consensus on CD remission criteria. 75) Postopewww.e-apem.org rative morning serum cortisol is the most important marker in defining remission. Two or more measurements within 2 weeks after surgery (on the 5th and 14th postoperative day) are recommended.…”