본문 바로가기
KERD
논문KCI 등재

Cushing disease in pediatrics: an update

Concepción-Zavaleta Marcio José|Armas Cristian David|Quiroz-Aldave Juan Eduardo|García-Villasante Eilhart Jorge|Gariza-Solano Ana Cecilia|Durand-Vásquez María del Carmen|Concepción-Urteaga Luis Alberto|Zavaleta-Gutiérrez Francisca Elena
대한소아내분비학회 (Korean Society Of Pediatric Endocrinology)|2023.06|Annals of Pediatric Endocrinology & Metabolism|제28권 제2호|pp. 87-97|DOI 10.6065/apem.2346074.037

2

조회

0

다운로드

0

인용

0

참고문헌

키워드

TreatmentDiagnosisCushing syndromeCushing diseaseNeuroendocrinology
주제분류소아과학

초록

Cushing disease (CD) is the main cause of endogenous Cushing syndrome (CS) and is produced by an adrenocorticotropic hormone (ACTH)-producing pituitary adenoma. Its relevance in pediatrics is due to the retardation of both growth and developmental processes because of hypercortisolism. In childhood, the main features of CS are facial changes, rapid or exaggerated weight gain, hirsutism, virilization, and acne. Endogenous hypercortisolism should be established after exogenous CS has been ruled out based on 24-hour urinary free cortisol, midnight serum or salivary cortisol, and dexamethasone suppression test; after that, ACTH dependence should be established. The diagnosis should be confirmed by pathology. The goal of treatment is to normalize cortisol level and reverse the signs and symptoms. Treatment options include surgery, medication, radiotherapy, or combined therapy. CD represents a challenge for physicians owing to its multiple associated conditions involving growth and pubertal development; thus, it is important to achieve an early diagnosis and treatment in order to control hypercortisolism and improve the prognosis. Its rarity in pediatric patients has led physicians to have limited experience in its management. The objective of this narrative review is to summarize the current knowledge about the pathophysiology, diagnosis, and treatment of CD in the pediatric population.

Abstract

Cushing disease (CD) is the main cause of endogenous Cushing syndrome (CS) and is produced by an adrenocorticotropic hormone (ACTH)-producing pituitary adenoma. Its relevance in pediatrics is due to the retardation of both growth and developmental processes because of hypercortisolism. In childhood, the main features of CS are facial changes, rapid or exaggerated weight gain, hirsutism, virilization, and acne. Endogenous hypercortisolism should be established after exogenous CS has been ruled out based on 24-hour urinary free cortisol, midnight serum or salivary cortisol, and dexamethasone suppression test; after that, ACTH dependence should be established. The diagnosis should be confirmed by pathology. The goal of treatment is to normalize cortisol level and reverse the signs and symptoms. Treatment options include surgery, medication, radiotherapy, or combined therapy. CD represents a challenge for physicians owing to its multiple associated conditions involving growth and pubertal development; thus, it is important to achieve an early diagnosis and treatment in order to control hypercortisolism and improve the prognosis. Its rarity in pediatric patients has led physicians to have limited experience in its management. The objective of this narrative review is to summarize the current knowledge about the pathophysiology, diagnosis, and treatment of CD in the pediatric population.

참고문헌 (96)

  1. Lodish MB, "Cushing’s syndrome in pediatrics : an update", Endocrinol Metab Clin North Am, 47, pp.451~462 (2018)
  2. Dutta K, "Cushing’s syndrome in a child", J Pediatr Surg Case Rep, 65, pp.101749~ (2021)
  3. Ferrigno R, "Paediatric Cushing's disease : epidemiology, pathogenesis, clinical management and outcome", Rev Endocr Metab Disord, 22, pp.817~835 (2021)
  4. Zheng X, "Diagnosis, manifestations, laboratory investigations, and prognosis in pediatric and adult Cushing's disease in a large center in China", Front Endocrinol(Lausanne), 12, pp.749246~ (2021)
  5. Storr HL, "Management of endocrine disease : paediatric Cushing’s disease", Eur J Endocrinol, 173, pp.R35~R45 (2015)
  6. Pasternak-Pietrzak K, "Paediatric Cushing’s disease-a literature review of epidemiology, pathogenesis, clinical symptoms, and diagnostics", Endokrynol Pol, 71, pp.87~95 (2020)
  7. Storr HL, "Comparisons in the epidemiology, diagnostic features and cure rate by transsphenoidal surgery between paediatric and adult-onset Cushing's disease", Eur J Endocrinol, 164, pp.667~674 (2011)
  8. Tabarin A, "Consensus statement by the French Society of Endocrinology(SFE)and French Society of Pediatric Endocrinology & Diabetology(SFEDP)on diagnosis of Cushing's syndrome", Ann Endocrinol(Paris), 83, pp.119~141 (2022)
  9. Ragnarsson O, "The incidence of Cushing's disease : a nationwide Swedish study", Pituitary, 22, pp.179~186 (2019)
  10. Nayak S, "Cushing's disease in children : a review", Neurol India, 68, pp.52~65 (2020)
  11. Baethge C, "SANRA—a scale for the quality assessment of narrative review articles", Res Integr Peer Rev, 4, pp.5~ (2019)
  12. Raff H, "Cushing’s syndrome : from physiological principles to diagnosis and clinical care", J Physiol, 593, pp.493~506 (2015)
  13. Lacroix A, "Cushing’s syndrome", Lancet Lond Engl, 386, pp.913~927 (2015)
  14. Stratakis CA, "Cushing syndrome in pediatrics", Endocrinol Metab Clin North Am, 41, pp.793~803 (2012)
  15. Hernández-Ramírez LC, "Genetics of Cushing's syndrome", Endocrinol Metab Clin North Am, 47, pp.275~297 (2018)
  16. Albani A, "Genetics of Cushing's disease", Clin Endocrinol, 88, pp.3~12 (2018)
  17. Savage MO, "Fundamental principles of clinical and biochemical evaluation underlie the diagnosis and therapy of Cushing's syndrome", J Pediatr Endocrinol Metab, 27, pp.1029~1031 (2014)
  18. Güemes M, "Management of Cushing syndrome in children and adolescents : experience of a single tertiary centre", Eur J Pediatr, 175, pp.967~976 (2016)
  19. Batista DL, "Diagnostic tests for children who are referred for the investigation of Cushing syndrome", Pediatrics, 120, pp.e575~e586 (2007)
  20. Gafni RI, "Nighttime salivary cortisol measurement as a simple, noninvasive, outpatient screening test for Cushing's syndrome in children and adolescents", J Pediatr, 137, pp.30~35 (2000)
  21. Shapiro L, "Investigation for Paediatric Cushing’s Syndrome Using Twenty-Four-Hour Urinary Free Cortisol Determination", Horm Res Paediatr, 86, pp.21~26 (2016)
  22. Guaraldi F, "Paediatric pituitary adenomas : a decade of change", Horm Res Paediatr, 81, pp.145~155 (2014)
  23. Shah NS, "Childhood Cushing disease : a challenge in diagnosis and management", Horm Res Paediatr, 76(Suppl 1), pp.65~70 (2011)
  24. Turan H, "Diagnostic Value of Bilateral Petrosal Sinus Sampling in Children with Cushing Disease : A Multicenter Study", J Clin Res Pediatr Endocrinol, 14, pp.2936~ (2022)
  25. Lonser RR, "Outcome of surgical treatment of 200children with Cushing's disease", J Clin Endocrinol Metab, 98, pp.892~901 (2013)
  26. Nieman LK, "Treatment of Cushing's Syndrome : An Endocrine Society Clinical Practice Guideline", J Clin Endocrinol Metab, 100, pp.2807~2831 (2015)
  27. Tatsi C, "Pediatric Cushing syndrome; an overview", Pediatr Endocrinol Rev, 17, pp.100~109 (2019)
  28. Stratakis CA, "An update on Cushing syndrome in pediatrics", Ann Endocrinol, 79, pp.125~131 (2018)
  29. Buchfelder M, "Pituitary surgery for Cushing's disease", Neuroendocrinology, 92, pp.102~106 (2010)
  30. Marino AC, "Surgery for pediatric pituitary adenomas", Neurosurg Clin N Am, 30, pp.465~471 (2019)
  31. Kanter AS, "Single-center experience with pediatric Cushing's disease", J Neurosurg, 103(5 Suppl), pp.413~420 (2005)
  32. Shirvani M, "Outcome of microscopic transsphenoidal surgery in Cushing disease : a case series of 96 patients", World Neurosurg, 87, pp.170~175 (2016)
  33. Lu L, "Prognostic factors for recurrence in pituitary adenomas : recent progress and future directions", Diagnostics, 12, pp.977~ (2022)
  34. Locatelli D, "Endoscopic endonasal transsphenoidal surgery for sellar tumors in children", Int J Pediatr Otorhinolaryngol, 74, pp.1298~1302 (2010)
  35. Storr HL, "Endonasal endoscopic transsphenoidal pituitary surgery : early experience and outcome in paediatric Cushing's disease", Clin Endocrinol(Oxf), 80, pp.270~276 (2014)
  36. Bora SK, "Management of Cushing's disease : changing trend from microscopic to endoscopic surgery", World Neurosurg, 134, pp.e46~e54 (2020)
  37. Broersen LHA, "microscopic transsphenoidal surgery for Cushing's disease : a systematic review and meta-analysis", Pituitary, 21, pp.524~534 (2018)
  38. Katznelson L, "Bilateral adrenalectomy for Cushing's disease", Pituitary, 18, pp.269~273 (2015)
  39. Guerin C, "Bilateral adrenalectomy in the 21st century: when to use it for hypercortisolism?", Endocr Relat Cancer, 23, pp.R131~R142 (2016)
  40. Thomas CG, "Nelson's syndrome after Cushing’s disease in childhood : a continuing problem", Surgery, 96, pp.1067~1077 (1984)
  41. Hopwood NJ, "Incidence of Nelson's syndrome after adrenalectomy for Cushing's disease in children : results of a nationwide survey", Am J Dis Child, 131, pp.1353~1356 (1977)
  42. Castinetti F, "Gamma knife for Cushing disease-time for a reappraisal?", Nat Rev Endocrinol, 13, pp.628~629 (2017)
  43. Martirossian AN, "The Novel use of stereotactic radiotherapy for remnant adrenal tissue in Nelson syndrome", AACE Clin Case Rep, 6, pp.e33~e36 (2020)
  44. Minniti G, "Modern techniques for pituitary radiotherapy", Rev Endocr Metab Disord, 10, pp.135~ (2008)
  45. Storr HL, "Clinical and endocrine responses to pituitary radiotherapy in pediatric Cushing's disease : an effective second-line treatment", J Clin Endocrinol Metab, 88, pp.34~37 (2003)
  46. Acharya SV, "Radiotherapy in paediatric Cushing’s disease : efficacy and long term follow up of pituitary function", Pituitary, 13, pp.293~297 (2010)
  47. Feelders RA, "Advances in the medical treatment of Cushing’s syndrome", Lancet Diabetes Endocrinol, 7, pp.300~312 (2019)
  48. Tucker WS Jr, "Reversible adrenal insufficiency induced by ketoconazole", JAMA, 253, pp.2413~2414 (1985)
  49. Best TR, "Persistent adrenal insufficiency secondary to low-dose ketoconazole therapy", Am J Med, 82, pp.676~680 (1987)
  50. "Ketoconazole: summary of product characteristics" (2022)[URL]
  51. "Pediamécum" (2022)[URL]
  52. Acquafredda A, "Ketoconazole treatment of two adolescents with Cushing's disease", Pediatr Res, 33, pp.S30~ (1993)
  53. Carral F, "Therapeutic efficacy of ketoconazole in Cushing's syndrome", An Pediatr, 52, pp.381~384 (2000)
  54. Ying YJ, "Ketoconazole associated hepatotoxicity : a systematic review and metaanalysis", Biomed Environ Sci, 26, pp.605~610 (2013)
  55. Daniel E, "Therapy of endocrine disease : steroidogenesis enzyme inhibitors in Cushing’s syndrome", Eur J Endocrinol, 172, pp.R263~R280 (2015)
  56. Wojcik M, "The first description of metyrapone use in severe Cushing Syndrome due to ectopic ACTH secretion in an infant with immature sacrococcygeal teratoma. Case Report", Neuro Endocrinol Lett, 36, pp.653~655 (2015)
  57. Verbeeten K, "Rectal metyrapone for treatment of hypercortisolism in an infant with McCune-Albright syndrome", J Pediatr Pharmacol Ther, 22, pp.233~236 (2017)
  58. "Metopirone® (metyrapone)capsules: US prescribing information"[URL]
  59. Al-Salama ZT, "Metyrapone in Cushing's syndrome : a profile of its use", Drugs Ther Perspect, 37, pp.393~406 (2021)
  60. Oddie PD, "Mitotane in the treatment of childhood adrenocortical carcinoma : a potent endocrine disruptor", Endocrinol Diabetes Metab Case Rep, 2018 (2018)
  61. Kuhlen M, "Key factors for effective mitotane therapy in children with adrenocortical carcinoma", Endocr Relat Cancer, 29, pp.545~555 (2022)
  62. Motte E, "Mitotane(op'DDD)restores growth and puberty in nine children with Cushing's disease", Endocr Connect, 7, pp.1280~1287 (2018)
  63. Morgan FH, "Mifepristone for management of Cushing’s syndrome", Pharmacother J Hum Pharmacol Drug Ther, 33, pp.319~329 (2013)
  64. Pivonello R, "Medical treatment of Cushing's disease : an overview of the current and recent clinical trials", Front Endocrinol(Lausanne), 11, pp.648~ (2020)
  65. Banerjee RR, "Mifepristone treatment of Cushing’s syndrome in a pediatric patient", Pediatrics, 136, pp.e1377~e1381 (2015)
  66. "Osilodrostat (Isturisa®):summary of product characteristics" (2022)[URL]
  67. "FDA approves new treatment for adults with Cushing’s disease" (2022)[URL]
  68. Meredith EL, "Discovery and in vivo evaluation of potent dual CYP11B2(aldosterone synthase)and CYP11B1inhibitors", ACS Med Chem Lett, 4, pp.1203~1207 (2013)
  69. Groselj U, "Osilodrostat for Cushing disease and its role in pediatrics", Horm Res Paediatr (2022)[DOI]
  70. "A phase II, Multicenter, open-label, noncomparative study to evaluate the pharmacokinetics, pharmacodynamics, and tolerability of osilodrostat in children and adolescent patients with Cushing's disease"[URL]
  71. Juszczak A, "The therapy of Cushing’s disease in adults and children : an update", Horm Metab Res, 45, pp.109~117 (2013)
  72. Güven A, "Remission with cabergoline in adolescent boys with Cushing's disease", J Clin Res Pediatr Endocrinol, 5, pp.194~198 (2013)
  73. Yordanova G, "Long-term outcomes of children treated for Cushing's disease : a single center experience", Pituitary, 19, pp.612~624 (2016)
  74. Bertrand A, "Cabergoline therapy of paraneoplastic Cushing syndrome in children", Pediatr Blood Cancer, 55, pp.589~590 (2010)
  75. Pasternak-Pietrzak K, "Treatment challenges in pediatric Cushing’s disease : review of the literature with particular emphasis on predictive factors for the disease recurrence", Endocrine, 66, pp.125~136 (2019)
  76. Biller BM, "Treatment of adrenocorticotropindependent Cushing's syndrome : a consensus statement", J Clin Endocrinol Metab, 93, pp.2454~2462 (2008)
  77. Savage MO, "Pediatric Cushing's disease : management Issues", Indian J Endocrinol Metab, 16(Suppl 2), pp.S171~S175 (2012)
  78. Batista DL, "Postoperative testing to predict recurrent Cushing disease in children", J Clin Endocrinol Metab, 94, pp.2757~2765 (2009)
  79. Lodish M, "Recovery of the hypothalamic-pituitary-adrenal axis in children and adolescents after surgical cure of Cushing’s disease", J Clin Endocrinol Metab, 97, pp.1483~1491 (2012)
  80. Ironside N, "Earlier post-operative hypocortisolemia may predict durable remission from Cushing's disease", Eur J Endocrinol, 178, pp.255~263 (2018)
  81. He X, "Glucocorticoid Withdrawal Syndrome following treatment of endogenous Cushing Syndrome", Pituitary, 25, pp.393~403 (2022)
  82. Hochberg Z, "Endocrine Withdrawal Syndromes", Endocr Rev, 24, pp.523~538 (2003)
  83. Varlamov EV, "Perioperative management of a patient with Cushing disease", J Endocr Soc, 6, pp.bvac010~ (2022)
  84. Acree R, "Patient and provider perspectives on postsurgical recovery of Cushing syndrome", J Endocr Soc, 5, pp.bvab109~ (2021)
  85. Pasternak-Pietrzak K, "Predictive factors for the recurrence of Cushing's disease after surgical treatment in childhood", Endokrynol Pol, 71, pp.313~318 (2020)
  86. Pasternak-Pietrzak K, "Long-term outcome in patients after treatment for Cushing's disease in childhood", PLoS One, 14, pp.e0226033~ (2019)
  87. Keil MF, "Quality of life and other outcomes in children treated for Cushing syndrome", J Clin Endocrinol Metab, 98, pp.2667~2678 (2013)
  88. Sippel RS, "Waiting for change : symptom resolution after adrenalectomy for Cushing’s syndrome", Surgery, 144, pp.1054~1060 (2008)
  89. Leong GM, "Effects of child-and adolescentonset endogenous Cushing syndrome on bone mass, body composition, and growth : a 7-year prospective study into young adulthood", J Bone Miner Res, 22, pp.110~118 (2007)
  90. Lodish MB, "Effects of Cushing disease on bone mineral density in a pediatric population", J Pediatr, 156, pp.1001~1005 (2010)
  91. Keil MF, "Anthropometric measures and fasting insulin levels in children before and after cure of Cushing syndrome", Clin Nutr, 31, pp.359~363 (2012)
  92. Magiakou MA, "Blood pressure in children and adolescents with Cushing’s syndrome before and after Surgical Cure", J Clin Endocrinol Metab, 82, pp.1734~1738 (1997)
  93. Lodish MB, "Blood pressure in pediatric patients with Cushing syndrome", J Clin Endocrinol Metab, 94, pp.2002~2008 (2009)
  94. Merke DP, "Children experience cognitive decline despite reversal of brain atrophy one year after resolution of Cushing syndrome", J Clin Endocrinol Metab, 90, pp.2531~2536 (2005)
  95. Gkourogianni A, "Pediatric Cushing disease : disparities in disease severity and outcomes in the Hispanic and African-American populations", Pediatr Res, 82, pp.272~277 (2017)
  96. Gkourogianni A, "Death in pediatric Cushing syndrome is uncommon but still occurs", Eur J Pediatr, 174, pp.501~507 (2015)

관련 논문AI추천

Long-term follow-up on Cushing disease patient after transsphenoidal surgery김자혜, 오문연, 유한욱, 정인숙, 조자향, 최진호대한소아내분비학회 · Annals of Pediatric Endocrinology & Metabolism2014 · 제19권 제3호A patient with Cushing disease lateralizing a pituitary adenoma by inferior petrosal sinus sampling using desmopressin: a case report권아름, 김호성, 채현욱, Duk-Hee Kim, Joo Hee Lim, Ki Eun Kim, Mo Kyung Jung, Soo Jung Kim대한소아내분비학회 · Annals of Pediatric Endocrinology & Metabolism2016 · 제21권 제1호A rare case of multiple pituitary adenomas in an adolescent Cushing disease presenting as a vertebral compression fracture김수영, 김유미, 김지연, 문수진, 백승국, 성순기, 송지연, 전종근, 황재연대한소아내분비학회 · Annals of Pediatric Endocrinology & Metabolism2017 · 제22권 제3호Cushing syndrome with acute kidney injury due to ureteral stones in a 6-year-old boy권아름, 김호성, 채현욱, Choi Han Saem, Song Kyungchul, Suh Junghwan대한소아내분비학회 · Annals of Pediatric Endocrinology & Metabolism2020 · 제25권 제4호Multiple osteoblastomas in a child with Cushing syndrome due to bilateral adrenal micronodular hyperplasias신충호, 양세원, 윤수미, 정혜림, 조원임, 조환성, 최근희, Hyeoh Won Yu대한소아내분비학회 · Annals of Pediatric Endocrinology & Metabolism2016 · 제21권 제1호Diverse etiologies, diagnostic approach, and management of primary adrenal insufficiency in pediatric ageYoo Han-Wook대한소아내분비학회 · Annals of Pediatric Endocrinology & Metabolism2021 · 제26권 제3호

이 간행물의 다른 논문 (10건)

Molecular basis and genetic testing strategies for diagnosing 21-hydroxylase deficiency, including CAH-X syndromeKim Gu-Hwan, Yoo Han-Wook, Choi Jin-Ho, Kim Ja Hyepp. 77-86Denosumab use in osteogenesis imperfecta: an update on therapeutic approachesFerjani Hanene Lassoued, Nessib Dorra Ben, Kaffel Dhia, Maatallah Kaouther, Hamdi Wafa, Majdoub Fatmapp. 98-106The effect of hypothalamic involvement and growth hormone treatment on cardiovascular risk factors during the transition period in patients with childhood-onset craniopharyngioma이영아, 신충호, 정혜운, 천정은, Lee Yun Jeong, Park Sang Heepp. 107-115Short-term effect of growth hormone treatment in childhood leukemia survivors with growth hormone deficiencyAhn Moon Bae, Kim Seongkoo, Cho Bin, Suh Byung-Kyu, Jung Min Ho, Jang Min Jeong, Shin Chungwoo, 이재욱, Chung Nack-Gyunpp. 116-123Effect of the COVID-19 pandemic lockdown on the physique of school-age children in JapanTakai Yasuyuki, Nakao Masatoshi, Moriguchi Hisako, Higashide Takashi, Tanoue Jitsuo, Sakaguchi Hiromi, Takaya Ryuzo, Higashino Hirohiko, Takaya Junjipp. 124-130
원문 보기