Neurosurgical treatment of Cushing disease in pediatric patients: case series and review of literature
Pituitary adenomas are rare in childhood in contrast with adults. Adrenocorticotropic hormone (ACTH)-secreting adenomas account for Cushing’s disease (CD) which is the most common form of ACTH-dependent Cushing’s syndrome (CS). Treatment strategies are generally based on data of adult CD patients, although some difficulties and differences exist in pediatric patients. The aim of this study is to share our experience of 10 children and adolescents with CD.
Patients and method
Medical records, images, and operative notes of 10 consecutive children and adolescents who underwent transsphenoidal surgery for CD between 1999 and 2014 in Cerrahpasa Faculty of Medicine were retrospectively reviewed. Mean age at operation was 14.8 ± 4.2 years (range 5–18). The mean length of symptoms was 24.2 months. The mean follow-up period was 11 years (range 4 to 19 years).
Mean preoperative cortisol level was 23.435 μg/dl (range 8.81–59.8 μg/dl). Mean preoperative ACTH level was 57.358 μg/dl (range 28.9–139.9 μg/dl). MR images localized microadenoma in three patients (30%), macroadenoma in four patients (40%) in our series. Transsphenoidal microsurgery and endoscopic transsphenoidal surgery were performed in 8 and 2 patients respectively. Remission was provided in 8 patients (80%). Five patients (50%) met remission criteria after initial operations. Three patients (30%) underwent additional operations to meet remission criteria.
Transsphenoidal surgery remains the mainstay therapy for CD in pediatric patients as well as adults. It is an effective treatment option with low rate of complications. Both endoscopic and microscopic approaches provide safe access to sella and satisfactory surgical results.
KeywordsCushing’s disease Endoscopic pituitary surgery Pediatric Transsphenoidal microsurgery
Compliance with ethical standards
Conflict of interest
There are no conflicts of interest.
- 3.Yordanova G, Martin L, Afshar F, Sabin I, Alusi G, Plowman NP, Riddoch F, Evanson J, Matson M, Grossman AB, Akker SA, Monson JP, Drake WM, Savage MO, Storr HL (2016) Long-term outcomes of children treated for Cushing’s disease: a single center experience. Pituitary 19(6):612–624. https://doi.org/10.1007/s11102-016-0756-8 CrossRefPubMedPubMedCentralGoogle Scholar
- 6.Zhan R, Xu G, Wiebe TM, Li X (2015) Surgical outcomes of the endoscopic transsphenoidal route to pituitary tumours in paediatric patients >10 years of age: 5 years of experience at a single institute. Arch Dis Child 100(8):774–778. https://doi.org/10.1136/archdischild-2015-308365 CrossRefPubMedPubMedCentralGoogle Scholar
- 7.Storr HL, Drake WM, Evanson J, Matson M, Berney DM, Grossman AB, Akker SA, Monson JP, Alusi G, Savage MO, Sabin I (2014) Endonasal endoscopic transsphenoidal pituitary surgery: early experience and outcome in paediatric Cushing’s disease. Clin Endocrinol 80(2):270–276. https://doi.org/10.1111/cen.12275 CrossRefGoogle Scholar
- 8.Pledger CL, Elzoghby MA, Oldfield EH, Payne SC, Jane JA Jr (2016) Prospective comparison of sinonasal outcomes after microscopic sublabial or endoscopic endonasal transsphenoidal surgery for nonfunctioning pituitary adenomas. J Neurosurg 125(2):323–333. https://doi.org/10.3171/2015.6.JNS142695 CrossRefPubMedGoogle Scholar
- 12.Valassi E, Feelders R, Maiter D, Chanson P, Yaneva M, Reincke M, Krsek M, Toth M, Webb SM, Santos A, Paiva I, Komerdus I, Droste M, Tabarin A, Strasburger CJ, Franz H, Trainer PJ, Newell-Price J, Wass JA, Papakokkinou E, Ragnarsson O, Group ES (2018) Worse health-related quality of life at long-term follow-up in patients with Cushing’s disease than patients with cortisol producing adenoma. Data from the ERCUSYN. Clin Endocrinol 88(6):787–798. https://doi.org/10.1111/cen.13600 CrossRefGoogle Scholar
- 13.Evang JA, Carlsen SM, Svartberg J, Aanderud S, Johannesen O, Schreiner T, Ramm-Pettersen J, Bakke SJ, Lund-Johansen M, Bollerslev J (2006) Endogenous Cushing’s syndrome. Tidsskrift for den Norske laegeforening : tidsskrift for praktisk medicin, ny raekke 126(5):599–602Google Scholar
- 15.Kuo CH, Yen YS, Wu JC, Chen YC, Huang WC, Cheng H (2015) Primary endoscopic transnasal transsphenoidal surgery for magnetic resonance image-positive Cushing disease: outcomes of a series over 14 years. World Neurosurg 84(3):772–779. https://doi.org/10.1016/j.wneu.2015.04.059 CrossRefPubMedGoogle Scholar
- 16.Osswald A, Plomer E, Dimopoulou C, Milian M, Blaser R, Ritzel K, Mickisch A, Knerr F, Stanojevic M, Hallfeldt K, Schopohl J, Kuhn KA, Stalla G, Beuschlein F, Reincke M (2014) Favorable long-term outcomes of bilateral adrenalectomy in Cushing’s disease. Eur J Endocrinol 171(2):209–215. https://doi.org/10.1530/EJE-14-0214 CrossRefPubMedGoogle Scholar
- 17.Kakade HR, Kasaliwal R, Khadilkar KS, Jadhav S, Bukan A, Khare S, Budyal SR, Goel A, Lila AR, Bandgar T, Shah NS (2014) Clinical, biochemical and imaging characteristics of Cushing’s macroadenomas and their long-term treatment outcome. Clin Endocrinol 81(3):336–342. https://doi.org/10.1111/cen.12442 CrossRefGoogle Scholar
- 18.Clayton RN, Jones PW, Reulen RC, Stewart PM, Hassan-Smith ZK, Ntali G, Karavitaki N, Dekkers OM, Pereira AM, Bolland M, Holdaway I, Lindholm J (2016) Mortality in patients with Cushing’s disease more than 10 years after remission: a multicentre, multinational, retrospective cohort study. Lancet Diabetes Endocrinol 4(7):569–576. https://doi.org/10.1016/S2213-8587(16)30005-5 CrossRefPubMedGoogle Scholar
- 19.Graham KE, Samuels MH, Nesbit GM, Cook DM, O'Neill OR, Barnwell SL, Loriaux DL (1999) Cavernous sinus sampling is highly accurate in distinguishing Cushing’s disease from the ectopic adrenocorticotropin syndrome and in predicting intrapituitary tumor location. J Clin Endocrinol Metab 84(5):1602–1610. https://doi.org/10.1210/jcem.84.5.5654 CrossRefPubMedGoogle Scholar
- 24.Teramoto A, Yoshida Y, Sanno N, Nemoto S (1998) Cavernous sinus sampling in patients with adrenocorticotrophic hormone-dependent Cushing’s syndrome with emphasis on inter- and intracavernous adrenocorticotrophic hormone gradients. J Neurosurg 89(5):762–768. https://doi.org/10.3171/jns.1998.89.5.0762 CrossRefPubMedGoogle Scholar
- 30.Biller BM, Grossman AB, Stewart PM, Melmed S, Bertagna X, Bertherat J, Buchfelder M, Colao A, Hermus AR, Hofland LJ, Klibanski A, Lacroix A, Lindsay JR, Newell-Price J, Nieman LK, Petersenn S, Sonino N, Stalla GK, Swearingen B, Vance ML, Wass JA, Boscaro M (2008) Treatment of adrenocorticotropin-dependent Cushing’s syndrome: a consensus statement. J Clin Endocrinol Metab 93(7):2454–2462. https://doi.org/10.1210/jc.2007-2734 CrossRefPubMedPubMedCentralGoogle Scholar