Cushing's Disease Associated with an lntrasellar Gangliocytoma Producing Corticotrophin-Releasing Factor
Authors: SYLVIA L. ASA
Journal: Annals of Internal Medicine (1984)

Short Papers1 December 1984Cushing's Disease Associated with an lntrasellar Gangliocytoma Producing Corticotrophin-Releasing FactorSYLVIA L. ASA, M.D., KALMAN KOVACS, M.D., Ph.D., GEORGE T. TINDALL, M.D., DANIEL L. BARROW, M.D., EVA HORVATH, Ph.D., PAUL VECSEI, M.D.SYLVIA L. ASA, M.D., KALMAN KOVACS, M.D., Ph.D., GEORGE T. TINDALL, M.D., DANIEL L. BARROW, M.D., EVA HORVATH, Ph.D., PAUL VECSEI, M.D.Author, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-101-6-789 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptA 58-year-old woman had Cushing's disease with elevated plasma adrenocorticotrophin and an intrasellar tumor. Light microscopy showed that the tumor was a gangliocytoma containing immunoreactive corticotrophinreleasing factor accompanied by pituitary corticotroph hyperplasia. Ultrastructural examination identified an intimate association and desmosomal attachments between interdigitating cell processes of neurons and corticotrophs. It is suggested that Cushing's disease was due to the effect of corticotrophin-releasing factor on corticotrophs; this case represents a syndrome supporting the concept that, in some patients, Cushing's disease may have a hypothalamic origin....References1. CUSHING H. The basophil adenomas of the pituitary body and their clinical manifestations (pituitary basophilism). Bull Johns Hopkins Hosp. 1932;50:137-95. Google Scholar2. ROBERTPELLETIERHARDY FGJ. Pituitary adenomas in Cushing's disease: a histologic, ultrastructural, and immunocytochemical study. Arch Pathol Lab Med. 1978;102:448-55. MedlineGoogle Scholar3. SALASSALAWSCARPENTERNORTHCUTT REPR. Transsphenoidal removal of pituitary microadenoma in Cushing's disease. Mayo Clin Proc. 1978;53:24-8. MedlineGoogle Scholar4. TYRRELLBROOKSFITZGERALDCOFOIDFORSHAMWILSON JRPPPC. Cushing's disease: selective trans-sphenoidal resection of pituitary microadenomas. N Engl J Med. 1978;298:753-8. CrossrefMedlineGoogle Scholar5. BIGOSSOMMARASIO SME. Cushing's disease: management by transsphenoidal pituitary microsurgery. J Clin Endocrinol Metab. 1980;50:348-54. CrossrefMedlineGoogle Scholar6. LAGERQUISTMEIKLEWESTTYLER LACF. Cushing's disease with cure by resection of a pituitary adenoma: evidence against a primary hypothalamic defect. Am J Med. 1974;57:826-30. CrossrefMedlineGoogle Scholar7. SCHNALLBRODKEYKAUFMANPEARSON AJBO. Pituitary function after removal of pituitary microadenomas in Cushing's disease. J Clin Endocrinol Metab. 1978;47:410-7. CrossrefMedlineGoogle Scholar8. FITZGERALDARONFINDLING PDJ. Cushing's disease: transient secondary adrenal insufficiency after selective removal of pituitary microadenomas; evidence for a pituitary origin. J Clin Endocrinol Metab. 1982;54:413-22. CrossrefMedlineGoogle Scholar9. PIETERSHERMUSSMALSBARTELINKBENRAADKLOPPENBORG GAAATP. Responsiveness of the hypophyseal-adrenocortical axis to corticotropin-releasing factor in pituitary-dependent Cushing's disease. J Clin Endocrinol Metab. 1983;57:513-6. CrossrefMedlineGoogle Scholar10. SHIBASAKINAKAHARASHIZUME TMK. Pituitary adenomas that caused Cushing's disease or Nelson's syndrome are not responsive to ovine corticotropin-releasing factor in vitro. J Clin Endocrinol Metab. 1983;56:414-6. CrossrefMedlineGoogle Scholar11. KRIEGER D. Physiopathology of Cushing's disease. Endocr Rev. 1982;4:22-43. CrossrefGoogle Scholar12. KRIEGER D. The central nervous system and Cushing's disease. Med Clin North Am. 1978;62:261-8. CrossrefMedlineGoogle Scholar13. LAMBERTSSTEFANKODE LANGE SSS. Failure of clinical remission after transsphenoidal removal of a microadenoma in a patient with Cushing's disease: multiple hyperplastic and adenomatous cell nests in surrounding pituitary tissue. J Clin Endocrinol Metab. 1980;50:793-5. CrossrefMedlineGoogle Scholar14. KRIEGERAMOROSALINICK DLF. Cyproheptadine-induced remission of Cushing's disease. N Engl J Med. 1975;293:893-6. CrossrefMedlineGoogle Scholar15. LANKFORDTUCKERBLACKARD HHW. A cyproheptadine-reversible defect in ACTH control persisting after removal of the pituitary tumor in Cushing's disease. N Engl J Med. 1981;305:1244-8. CrossrefMedlineGoogle Scholar16. ISHIBASHIYAMAJI MT. Direct effects of thyrotropin-releasing hormone, cyproheptadine, and dopamine on adrenocorticotropin secretion from human corticotroph adenoma cells in vitro. J Clin Invest. 1981;68:1018-27. CrossrefMedlineGoogle Scholar17. PIETERSSMALSGOVERDEPESMANMEYERKLOPPENBORG GAHGEP. Adrenocorticotropin and Cortisol responsiveness to thyrotropin-releasing hormone and luteinizing hormone-releasing hormone discloses two subsets of patients with Cushing's disease. J Clin Endocrinol Metab. 1982;55:1188-97. CrossrefMedlineGoogle Scholar18. SHIBASAKIMASUI TH. Effects of various neuropeptides on the secretion of proopiomelanocortin-derived peptides by a cultured pituitary adenoma causing Nelson's syndrome. J Clin Endocrinol Metab. 1982;55:872-6. CrossrefMedlineGoogle Scholar19. WHITEADAMSLOIZOUMASHITER MEMK. Vasoactive intestinal peptide stimulates adrenocorticotropin release from human corticotropinoma cells in culture: interaction with arginine vasopressin and hydrocortisone. J Clin Endocrinol Metab. 1982;55:967-72. CrossrefMedlineGoogle Scholar20. WHITEADAMSLOIZOUMASHITERFAHLBUSCH MEMKR. Corticotropin releasing factor stimulates ACTH release from human pituitary corticotropic tumour cells in culture [Letter]. Lancet. 1982;1:1251-2. CrossrefMedlineGoogle Scholar21. ORTHDEBOLDDECHERNEY DCG. Pituitary microadenomas causing Cushing's disease respond to corticotropin-releasing factor. J Clin Endocrinol Metab. 1982;55:1017-9. CrossrefMedlineGoogle Scholar22. NAKAHARASHIBASAKISHIZUME MTK. Corticotropin-releasing factor test in normal subjects and patients with hypothalamic-pituitary-adrenal disorders. J Clin Endocrinol Metab. 1983;57:963-8. CrossrefMedlineGoogle Scholar23. MULLERSTALLAVON WERDER OGK. Corticotropin-releasing factor: a new tool for the differential diagnosis of Cushing's syndrome. J Clin Endocrinol Metab. 1983;57:227-9. CrossrefMedlineGoogle Scholar24. MCNICOL A. Patterns of corticotropic cells in the adult human pituitary in Cushing's disease. Diagn Histopathol. 1981;4:335-41. MedlineGoogle Scholar25. TAYLORVELASCOBRODKEY HMJ. Remission of pituitary-dependent Cushing's disease after removal of nonneoplastic pituitary gland. Arch Intern Med. 1980;140:1366-8. CrossrefMedlineGoogle Scholar26. SAEGER W. Die Morphologie der paraadenomatosen Adenohypophyse: Ein Beitrag zur Pathogenese der Hypophysenadenome. Virchows Arch (Pathol Anat). 1977;372:299-314. CrossrefMedlineGoogle Scholar27. SCHNALLKOVACSBRODKEYPEARSON AKJO. Pituitary Cushing's disease without adenoma. Acta Endocrinol. 1980;94:297-303. CrossrefMedlineGoogle Scholar28. SCHEITHAUERKOVACSRANDALL BKR. The pituitary gland in untreated Addison's disease: a histologic and immunocytologic study of 18 adenohypophyses. Arch Pathol Lab Med. 1983;107:484-7. MedlineGoogle Scholar29. KOVACSHORVATHRYAN KEN. Immunocytology of the human pituitary. In: DELELLIS RA, ed. Diagnostic Immunohistochemistry. New York: Masson Publishing USA Inc. ; 1981: 17-35. Google Scholar30. PRICELEEALBRIGHTRONNEKLEIVGUTAI RPAOJ. Treatment of sexual precocity by removal of a luteinizing hormone-releasing hormone secreting hamartoma. JAMA. 1984;251:2247-9. CrossrefMedlineGoogle Scholar31. JAKUMEITZIMMERMANGUIOT HVG. Intrasellar gangliocytomas: report of four cases. J Neurosurg. 1974;40:626-30. CrossrefMedlineGoogle Scholar32. OLIVIERRACADOTVILA-PORCILERACADOT LJEO. Adénomes hypophysaires et ganglioneuromes de la selle turcique [Abstract]. J Microsc Biol Cell. 1975;23:66-7a. Google Scholar33. ASASCHEITHAUERBILBAO SBJ. A case for hypothalamic acromegaly: a clinicopathological study of six patients with hypothalamic gangliocytomas producing growth hormone-releasing factor. J Clin Endocrinol Metab. 1984;58:796-803. CrossrefMedlineGoogle Scholar34. VALESPEISSRIVIERRIVIER WJCJ. Characterization of a 41-residue ovine hypothalamic peptide that stimulates secretion of corticotropin and beta-endorphin. Science. 1981;213:1394-7. CrossrefMedlineGoogle Scholar35. RIVIERSPIESSVALE JJW. Characterization of rat hypothalamic corticotropin-releasing factor. Proc Natl Acad Sci USA. 1983;80:4851-5. CrossrefMedlineGoogle Scholar36. BUGNONFELLMANNGOUGETCARDOT CDAJ. Ontogeny of the corticoliberin neuroglandular system in rat brain. Nature. 1982;298:159-61. CrossrefMedlineGoogle Scholar37. SWANSONSAWCHENKORIVIERVALE LPJW. Organization of ovine corticotropin-releasing factor immunoreactive cells and fibers in the rat brain: an immunohistochemical study. Neuroendocrinology. 1983;36:165-86. CrossrefMedlineGoogle Scholar38. SHIBAHARAMORIMOTOFURUTANI SYY. Isolation and sequence analysis of the human corticotropin-releasing factor precursor gene. EMBO J 1983;2:775-9. CrossrefMedlineGoogle Scholar39. NIEUWENHUIJZEN-KRUSEMANLINTONLOWRYREESBESSER AEPLG. Corticotropin-releasing factor immunoreactivity in human gastrointestinal tract. Lancet. 1982;2:1245-6. CrossrefMedlineGoogle Scholar40. GROSSMAN A, NIEUWENHUIJZEN-KRUSEMAN AC PERRY L et al.. New hypothalamic hormone, corticotropin-releasing factor, specifically stimulates the release of adrenocorticotropic hormone and Cortisol in man. Lancet. 1982;1:921-2. MedlineGoogle Scholar41. DEBOLDDECHERNEYJACKSON CGR. Effect of synthetic ovine corticoptropin-releasing factor: prolonged duration of action and biphasic response of plasma adrenocorticotropin and Cortisol. J Clin Endocrinol Metab. 1983;57:294-8. CrossrefMedlineGoogle Scholar42. ORTHJACKSONDECHERNEY DRS. Effect of synthetic ovine corticotropin-releasing factor: dose response of plasma adrenocorticotropin and Cortisol. J Clin Invest. 1983;71:587-95. CrossrefMedlineGoogle Scholar43. TSUKADANAKAIKOHTSUJIIIMURA TYTSH. Plasma adrenocorticotropin and Cortisol responses to intravenous injection of corticotropin-releasing factor in the morning and evening. J Clin Endocrinol Metab. 1983;57:869-71. CrossrefMedlineGoogle Scholar44. UPTONAMATRUDA GT. Evidence for the presence of tumor peptides and corticotropin-releasing factor-like activity in the ectopic ACTH syndrome. N Engl J Med. 1971;285:419-24. CrossrefMedlineGoogle Scholar45. BIRKENHAGERUPTONSELDENRATHKRIEGERTASHJIAN JGHDA. Medullary thyroid carcinoma: ectopic production of peptides with ACTH-like, corticotrophin releasing factor-like and prolactin production-stimulating activities. Acta Endocrinol. 1976;83:280-92. CrossrefMedlineGoogle Scholar46. SUDADEMURADEMURA THR. Corticotropin-releasing factor-like activity in ACTH producing tumor. J Clin Endocrinol Metab. 1977; 44:440-6. CrossrefMedlineGoogle Scholar47. HASHIMOTOTAKAHARAOGAWA KJN. Adrenocorticotropin, beta-endorphin, and corticotropin-releasing factor-like activity in an adrenocorticotropin-producing nephroblastoma. J Clin Endocrinol Metab. 1980;50:461-5. CrossrefMedlineGoogle Scholar48. CAREYVARMADRAKE RSC. Ectopic secretion of corticotropin-releasing factor as a cause of Cushing's syndrome: a clinical, morphological and biochemical study. N Engl J Med. 1984;311:13-20. CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Toronto, Ontario, Canada Atlanta, Georgia; and Heidelberg, Federal Republic of Germany▸From the Department of Pathology, St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada; the Department of Surgery, Division of Neurosurgery, Emory University, Atlanta, Georgia; and the Department of Pharmacology, University of Heidelberg, Heidelberg, Federal Republic of Germany. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byHypothalamic Neuroendocrine NeoplasmsNeuroendocrine Neoplasms and Lesions of the HypothalamusHypothalamic hormone-producing tumorsPituitary Gangliocytoma Producing TSH and TRH: A Review of "Gangliocytomas of the Sellar Region"Eje hipotálamo hipofisario. Fisiología y patologíaEctopic cushing's syndrome due to corticotropin releasing hormoneHypothalamic Endocrine Tumors: An UpdateHypothalamic Vasopressin-Producing TumorsMixed gangliocytoma-pituitary adenoma in the sellar region: a large-scale single-center experienceTranssphenoidal Surgery for Mixed Pituitary Gangliocytoma-AdenomasTransdifferentiation of Neuroendocrine CellsMixed Gangliocytoma-Pituitary AdenomaThe HypothalamusCushing DiseaseGangliocytomas of the sellar region: A challenging diagnosisGangliocytoma and GangliogliomaHypophyseHypothalamic Syndromes∗NeuroendocrinologyInfrasellar pituitary gangliocytoma causing Cushing's syndromePituitary adenoma with gangliocytic component: report of 5 cases with focus on immunoprofile of gangliocytic componentEndoscopic Approach to a Collision Tumor of Growth Hormone-Secreting Adenoma and Gangliocytoma in the Pituitary GlandConcurrent somatotroph and plurihormonal pituitary adenomas in a catGangliocitoma selar asociado a adenoma hipofisario productor de hormona de crecimiento. Caso clínicoClinicopathological Correlations in Pituitary AdenomasThe HypothalamusCushing's diseaseNeuroendocrinologyHypothalamus and NeurohypophysisFunctioning AdenomasHypothalamic SyndromesCombined Gangliocytoma and Prolactinoma of the Pituitary GlandGanglioglioma of the NeurohypophysisChapter 10 Disorders of the Sella and Parasellar RegionUnusual causes of Cushing's syndromeGanglion cell containing pituitary adenomas: signs of neuronal differentiation in adenoma cellsCushing's Syndrome Due to Ectopic Production of Corticotropin-Releasing Hormone in an Infant with GanglioneuroblastomaMeningioma presenting with Cushing's syndrome: An unusual clinical presentationProduction of Pituitary Hormone by Human Pituitary Adenoma is under Autocrine and Paracrine Regulation of Hypothalamic Hormones Secreted from Adenoma CellsACTH Secreting Pituitary AdenomasEtiology of Pituitary TumoursClonality of Pituitary Tumours: More Complicated than Initially Envisaged?The Role of Hormones, Growth Factors and Their Receptors in Pituitary Tumorigenesis`Gangliocytomas' of the PituitaryExpression of Corticotropin-Releasing Hormone Messenger Ribonucleic Acid in Human Pituitary Corticotroph Adenomas Associated with Proliferative PotentialHypothalamic Involvement in Disorders of Pituitary Hormone SecretionEctopic Corticotroph Adenoma in the Cavernous Sinus: Case ReportAntisense oligonucleotide—induced inhibition of adrenocorticotropic hormone release from cultured human corticotrophsIntrasellar adenoid cystic carcinoma and papillary mucinous adenocarcinoma: Two previously undescribed primary neoplasms at this siteTHE PATHOLOGY OF PITUITARY TUMORSThe Cytogenesis and Pathogenesis of Pituitary Adenomas*Intrasellar Pituitary Gangliocyto- adenoma Presenting with Acromegaly: Case ReportPituitary Tumor Pathogenesis1Salivary Gland-Like Tumors of the Sellar RegionIntrasellar Pituitary Gangliocyto-Adenoma Presenting with Acromegaly: Case ReportDifferentiating neuroblastoma of pituitary gland: neuroblastic transformation of epithelial adenoma cellsIntrasellar neuronal choristoma associated with growth hormone-producing pituitary adenoma containing amyloid depositsMolecular pathogenesis of pituitary tumoursFailure of partial hypophysectomy as definitive treatment in cushing's disease owing to nodular corticotrope hyperpiasia; report of four casesCerebral and cerebellar gangliocytomas: a morphological study of nine casesPathogenesis of Pituitary Cushing's Syndrome: Pituitary Versus HypothalamicEctopic ACTH Syndrome and CRH-Mediated Cushing's SyndromeCushing's Syndrome and PregnancyCorticotropin-releasing hormone production by a small cell carcinoma in a patient with ACTH-dependent Cushing's syndromeProopiomelanocortin mrna expression by small cell bladder carcinoma associated with cushing's syndrome: diagnostic contribution of in situ hybridizationDiseases of the PituitaryPituitary Adenoma with Neuronal Choristoma (PANCH): Composite Lesion or Lineage Infidelity?Cushing's Disease in a Child Caused by a Corticotropin-releasing Hormone-secreting Intrasellar Gangliocytoma Associated with an Adrenocorticotropic Hormone-secreting Pituitary AdenomaCushing's Disease in a Child Caused by a Corticotropin-releasing Hormone-secreting Intrasellar Gangliocytoma Associated with an Adrenocorticotropic Hormone-secreting Pituitary AdenomaHigh prolactin levels in patients with Cushing's disease without pathological evidence of pituitary adenomaEctopic Secretion of Peptides of the Proopiomelanocortin FamilyThe Role of Hypothalamic Hormones in the Pathogenesis of Pituitary AdenomasTransnasal Microsurgery of Cushing's Disease 1990ACTH-Producing Pituitary TumorsThe Cushing SyndromesIntrasellar hamartoma associated with pituitary adenomaContinuous Dexamethasone Infusion for Seven Hours in Patients with the Cushing Syndrome A Superior Differential Diagnostic TestPieter Biemond, MD, Frank H. de Jong, PhD, Steven W. J. Lamberts, MDIntrasellar gangliocytoma with multiple immunoreactivitiesPituitary Gland and HypothalamusMixed gangliocytoma-adenoma: A distinct neuroendocrine tumor of the pituitary fossaCushing's syndrome due to ACTH-production of an ovarian carcinoidINTRASELLAR GANGLIOCYTOMA CONTAINING GASTRIN AND GROWTH HORMONE-RELEASING HORMONE ASSOCIATED WITH A GROWTH HORMONE-SECRETING PITUITARY ADENOMAAn Update on the Cellular and Molecular Biology of Brain TumorsEndocrine and Metabolic Function in Patients with Neoplastic DiseaseHormone Production by Tumors: Ectopia or Gene DerepressionImmunocytochemistry of four mixed pituitary adenomas and intrasellar gangliocytomas associated with different clinical syndromes: Acromegaly, amenorrhea-galactorrhea, Cushing's disease and isolated tumoral syndromeCHARACTERIZATION OF HUMAN CORTICOTROPHIN-RELEASING HORMONE AND PRO-OPIOMELANOCORTIN-RELATED PEPTIDES IN A THYMIC CARCINOID TUMOUR RESPONSIBLE FOR CUSHING'S SYNDROMEGlucocorticoid Excess Syndromes Causing HypertensionSuprasellar craniopharyngioma associated with hyperprolactinemia, pituitary lactotroph hyperplasia, and microprolactinomaCase reportDiagnostic Evaluation of Cushing's SyndromeCorticotropin-Releasing HormoneReversible sellar enlargement due to growth hormone-releasing hormone production by pancreatic endocrine tumors in an acromegalic patient with multiple endocrine neoplasia type I syndromeCushing's Syndrome Due to Primary Multinodular Corticotrope HyperplasiaCushing's SyndromeRegulation of EGF Receptor and Transforming Growth Factor-Alpha ExpressionCase 52-1987Diagnostic Dilemmas in the Management of Hypothalamic-Pituitary-Adrenal DisordersPathogenesis of Pituitary TumorsPathology of Pituitary TumorsCushing's DiseaseEctopic Pituitary and Hypothalamic Hormone SyndromesCerebral gangliocytomaCushing's syndrome and hypertension.A CRF-Producing and -Secreting Tumor of the LungCushing's Syndrome: Update of Diagnosis and ManagementHistopathology of the pituitaryThe CRFs and their control: Chemistry, physiology and clinical implicationsBruising and thin skin in a 54-year-old woman 1 December 1984Volume 101, Issue 6Page: 789-793KeywordsAdrenocorticotropic hormoneGrowth hormoneNeurosurgeryPharmacologyProlactinProteinsRenal diseasesSomatostatinSurgeryVasopressin Issue Published: 1 December 1984 Copyright & Permissions© 1984 American College of PhysiciansPDF downloadLoading ...