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Cushing's Syndrome and Acute Lymphoblastic Leukemia

Cushing's Syndrome and Acute Lymphoblastic Leukemia Abstract • Cushing's disease developed in a 5-year-old girl with acute lymphoblastic leukemia 18 months after her last therapeutic exposure to adrenal glucocorticosteroids. Obesity, hyperpigmentation, striae, osteoporosis, and hirsutism were accompanied by elevated levels of plasma cortisol. These showed no diurnal fluctuation and they were not suppressed by dexamethasone. At autopsy, the adrenal glands were enlarged and the pituitary gland showed increased numbers of basophils of the adrenocorticotropic hormone (ACTH)/melanocyte-stimulating hormone secreting type. Leukemic infiltrates in brain tissue were prominent in the hypothalamus and in the limbic system. It is postulated that the destructive leukemic infiltrate of the limbic system removed a restraining influence on pituitary function, with basophilic hyperplasia, ACTH hypersecretion, adrenocortical hypertrophy, and clinical Cushing's disease the consequences. (Am J Dis Child 132:888-892, 1978) References 1. Eberlein WR, Bongiovanni AM, Rodriquez CS: The complications of steroid treatment . Pediatrics 40:279-282, 1967. 2. Ganong WF: The central nervous system and the synthesis and release of corticotropin hormone , in Nalbandov AV (ed): Advances in Neuroendocrinology . Urbana, Ill, Univ of Ill Press, 1963, p 92. 3. Mangili G, Motta M, Martini L: Control of adrenocorticotropic hormone secretion , in Martini L, Ganong WF (eds): Neuroendocrinology . New York, Academic Press Inc, 1966, p 297. 4. Golden A: Cytology of the human adenohypophysis . Arch Pathol 77:218-219, 1964. 5. Nugent CA, Nichols T, Tyler FH: Diagnosis of Cushing's syndrome: Single dose dexamethasone suppression test . Arch Intern Med 116:172-176, 1965.Crossref 6. Roessle R, Roulet F: Mass und Zahl in der Pathologie , band 5, in Aschoff L, Elias H, Eppinger H, et al (eds): Pathologie und Klinik. Berlin, Verlag von Julius Springer , 1932, p 78. 7. Russfield AB: Adenohypophysis , in Blood-worth JMB (ed): Endocrine Pathology . Baltimore, Williams & Wilkins Co, 1968, pp 75-116. 8. Baker RD: Postmortem Examination . Philadelphia, WB Saunders Co, 1967, p 176. 9. Hayles AB, Hahn HB, Sprague RG, et al: Hormone secreting tumors of the adrenal cortex in children . Pediatrics 37:19-25, 1966. 10. McArthur RG, Cloutier MD, Hayles AB, et al: Cushing's disease in children . Mayo Clin Proc 47:318-326, 1972. 11. Soyka LF: Alternate-day corticosteroid therapy , in Schulman I (ed): Advances in Pediatrics . Chicago, Year Book Medical Publishers Inc, 1972, vol 19, pp 47-70. 12. Liddle GW: Tests of pituitary-adrenal suppressibility in the diagnosis of Cushing's syndrome . J Clin Endocrinol Metab 20:1539-1560, 1960.Crossref 13. Nelson DH, Meakin JW, Dealy JB, et al: ACTH-producing tumor of the pituitary gland . N Engl J Med 259:161-164, 1958.Crossref 14. Plotz CM, Knowlton AI, Ragan C: The natural history of Cushing's syndrome . Am J Med 13:597-614, 1952.Crossref 15. Halmi NS, Moriarty GC: The cells of origin of ACTH in man . Ann NY Acad Sci 297:167-181, 1977.Crossref 16. Feldman JM: Cushing's disease: A hypothalamic flush? N Engl J Med 293:930-931, 1975.Crossref 17. Rubin RT, Madell AJ, Crandall PH: Corticosteroid response to limbic stimulation in man: Localization of stimulus sites . Science 153:767-770, 1966.Crossref 18. Krieger DT: Neurotransmitter regulation of ACTH release . Mt Sinai J Med NY 40:302-314, 1973. 19. DeWied D, de Jong W: Drug effects and hypothalamic-anterior pituitary function , in Elliott HW (ed): Annual Review of Pharmacology . Palo Alto, Calif, Annual Reviews Inc, 1974, vol 14, pp 389-412. 20. Frohman LA, Stachura ME: Neuropharmacologic control of neuroendocrine function in man . Metabolism 24:211-234, 1975.Crossref 21. Ganong WF: Evidence for a central noradrenergic system that inhibits ACTH secretion , in Knigg KM, Scott DE, Weinal A (eds): International Symposium on Brain-Endocrine Interaction . Basel, Switzerland, S Karger, 1972, pp 254-266. 22. Egdahl RH: The paradox of adrenal cortical hypersecretion in dogs with isolated pituitaries , in Martini L, Fraschini F, Molta M (eds): Proceedings of the Second International Congress on Hormonal Steroids . Amsterdam, Excerpta Medica Foundation, 1967, vol 21, pp 990-996. 23. Rasmussen AT, Gardner WJ: Effects of hypophyseal stalk resection on the hypophysis and hypothalamus of man . Endocrinology 27:219-226, 1940.Crossref 24. Russfield AB: Pituitary tumors , in Somers SC (ed): Pathology Annual . New York, Appleton-Century-Crofts, 1967, vol 2, pp 314-350. 25. Legait E: Cytophysiologie du lobe intermediare du l'hypophyse des mammiferes , in Benoit J, DaLage C (eds): Cytologie de l'Adenohypophyse . Paris, Editions du Centre National de la Recherche Scientifique, 1963, p 215. 26. Crispell KR, Parson W: Coexistence of Cushing's syndrome and internal hydrocephalus produced by a cerebellar tumor . Am J Med 13:247-250, 1952.Crossref 27. Heinbecker P, Pfeiffenberger M: Further clinical and experimental studies on the pathogenesis of Cushing's syndrome . Am J Med 9:3-23, 1950.Crossref 28. Thomas LB: Pathology of leukemia in the brain and meninges: Postmortem studies of patients with acute leukemia and of mice given inoculations of L1210 leukemia . Cancer Res 25:1555-1571, 1965. 29. Pierce MI: Neurological complications in acute leukemia in children . Pediatr Clin North Am 9:425-442, 1962. 30. Price RA, Johnson WW: The central nervous system in childhood leukemia: I. The arachnoid . Cancer 31:520-533, 1973.Crossref 31. Williams HM, Diamond MD, Craven LF, et al: Neurological Complications of Lymphomas and Leukemias . Springfield, Ill, Charles C Thomas Publishers, 1959, pp 8-72. 32. Dameshek W, Gunz F: Leukemia . New York, Grune & Stratton Inc, 1964, p 180. 33. Roy S, Johnson WW: Diabetes insipidus in a child with erythromyelocytic leukemia . Am J Dis Child 119:82-85, 1970. 34. Malter IJ, Gross S, Terel T: Diabetes insipidus complicating acute lymphocytic leukemia . Am J Dis Child 117:228-230, 1969. 35. Barak Y, Libon E: Hypothalamic hyperphagia, obesity, and disturbed behavior in acute leukemia . Acta Paediatr Scand 57:153-156, 1968.Crossref 36. Gold RM: Hypothalamic obesity: The myth of the ventromedial nucleus . Science 182:488-490, 1973.Crossref 37. Hyman CB, Bogle JM, Brubaker CA, et al: Central nervous system involvement by leukemia in children: I. Relationship to systemic leukemia and description of clinical and laboratory manifestations . Blood 25:1-12, 1965. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png American Journal of Diseases of Children American Medical Association

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References (44)

Publisher
American Medical Association
Copyright
Copyright © 1978 American Medical Association. All Rights Reserved.
ISSN
0002-922X
DOI
10.1001/archpedi.1978.02120340064012
Publisher site
See Article on Publisher Site

Abstract

Abstract • Cushing's disease developed in a 5-year-old girl with acute lymphoblastic leukemia 18 months after her last therapeutic exposure to adrenal glucocorticosteroids. Obesity, hyperpigmentation, striae, osteoporosis, and hirsutism were accompanied by elevated levels of plasma cortisol. These showed no diurnal fluctuation and they were not suppressed by dexamethasone. At autopsy, the adrenal glands were enlarged and the pituitary gland showed increased numbers of basophils of the adrenocorticotropic hormone (ACTH)/melanocyte-stimulating hormone secreting type. Leukemic infiltrates in brain tissue were prominent in the hypothalamus and in the limbic system. It is postulated that the destructive leukemic infiltrate of the limbic system removed a restraining influence on pituitary function, with basophilic hyperplasia, ACTH hypersecretion, adrenocortical hypertrophy, and clinical Cushing's disease the consequences. (Am J Dis Child 132:888-892, 1978) References 1. Eberlein WR, Bongiovanni AM, Rodriquez CS: The complications of steroid treatment . Pediatrics 40:279-282, 1967. 2. Ganong WF: The central nervous system and the synthesis and release of corticotropin hormone , in Nalbandov AV (ed): Advances in Neuroendocrinology . Urbana, Ill, Univ of Ill Press, 1963, p 92. 3. Mangili G, Motta M, Martini L: Control of adrenocorticotropic hormone secretion , in Martini L, Ganong WF (eds): Neuroendocrinology . New York, Academic Press Inc, 1966, p 297. 4. Golden A: Cytology of the human adenohypophysis . Arch Pathol 77:218-219, 1964. 5. Nugent CA, Nichols T, Tyler FH: Diagnosis of Cushing's syndrome: Single dose dexamethasone suppression test . Arch Intern Med 116:172-176, 1965.Crossref 6. Roessle R, Roulet F: Mass und Zahl in der Pathologie , band 5, in Aschoff L, Elias H, Eppinger H, et al (eds): Pathologie und Klinik. Berlin, Verlag von Julius Springer , 1932, p 78. 7. Russfield AB: Adenohypophysis , in Blood-worth JMB (ed): Endocrine Pathology . Baltimore, Williams & Wilkins Co, 1968, pp 75-116. 8. Baker RD: Postmortem Examination . Philadelphia, WB Saunders Co, 1967, p 176. 9. Hayles AB, Hahn HB, Sprague RG, et al: Hormone secreting tumors of the adrenal cortex in children . Pediatrics 37:19-25, 1966. 10. McArthur RG, Cloutier MD, Hayles AB, et al: Cushing's disease in children . Mayo Clin Proc 47:318-326, 1972. 11. Soyka LF: Alternate-day corticosteroid therapy , in Schulman I (ed): Advances in Pediatrics . Chicago, Year Book Medical Publishers Inc, 1972, vol 19, pp 47-70. 12. Liddle GW: Tests of pituitary-adrenal suppressibility in the diagnosis of Cushing's syndrome . J Clin Endocrinol Metab 20:1539-1560, 1960.Crossref 13. Nelson DH, Meakin JW, Dealy JB, et al: ACTH-producing tumor of the pituitary gland . N Engl J Med 259:161-164, 1958.Crossref 14. Plotz CM, Knowlton AI, Ragan C: The natural history of Cushing's syndrome . Am J Med 13:597-614, 1952.Crossref 15. Halmi NS, Moriarty GC: The cells of origin of ACTH in man . Ann NY Acad Sci 297:167-181, 1977.Crossref 16. Feldman JM: Cushing's disease: A hypothalamic flush? N Engl J Med 293:930-931, 1975.Crossref 17. Rubin RT, Madell AJ, Crandall PH: Corticosteroid response to limbic stimulation in man: Localization of stimulus sites . Science 153:767-770, 1966.Crossref 18. Krieger DT: Neurotransmitter regulation of ACTH release . Mt Sinai J Med NY 40:302-314, 1973. 19. DeWied D, de Jong W: Drug effects and hypothalamic-anterior pituitary function , in Elliott HW (ed): Annual Review of Pharmacology . Palo Alto, Calif, Annual Reviews Inc, 1974, vol 14, pp 389-412. 20. Frohman LA, Stachura ME: Neuropharmacologic control of neuroendocrine function in man . Metabolism 24:211-234, 1975.Crossref 21. Ganong WF: Evidence for a central noradrenergic system that inhibits ACTH secretion , in Knigg KM, Scott DE, Weinal A (eds): International Symposium on Brain-Endocrine Interaction . Basel, Switzerland, S Karger, 1972, pp 254-266. 22. Egdahl RH: The paradox of adrenal cortical hypersecretion in dogs with isolated pituitaries , in Martini L, Fraschini F, Molta M (eds): Proceedings of the Second International Congress on Hormonal Steroids . Amsterdam, Excerpta Medica Foundation, 1967, vol 21, pp 990-996. 23. Rasmussen AT, Gardner WJ: Effects of hypophyseal stalk resection on the hypophysis and hypothalamus of man . Endocrinology 27:219-226, 1940.Crossref 24. Russfield AB: Pituitary tumors , in Somers SC (ed): Pathology Annual . New York, Appleton-Century-Crofts, 1967, vol 2, pp 314-350. 25. Legait E: Cytophysiologie du lobe intermediare du l'hypophyse des mammiferes , in Benoit J, DaLage C (eds): Cytologie de l'Adenohypophyse . Paris, Editions du Centre National de la Recherche Scientifique, 1963, p 215. 26. Crispell KR, Parson W: Coexistence of Cushing's syndrome and internal hydrocephalus produced by a cerebellar tumor . Am J Med 13:247-250, 1952.Crossref 27. Heinbecker P, Pfeiffenberger M: Further clinical and experimental studies on the pathogenesis of Cushing's syndrome . Am J Med 9:3-23, 1950.Crossref 28. Thomas LB: Pathology of leukemia in the brain and meninges: Postmortem studies of patients with acute leukemia and of mice given inoculations of L1210 leukemia . Cancer Res 25:1555-1571, 1965. 29. Pierce MI: Neurological complications in acute leukemia in children . Pediatr Clin North Am 9:425-442, 1962. 30. Price RA, Johnson WW: The central nervous system in childhood leukemia: I. The arachnoid . Cancer 31:520-533, 1973.Crossref 31. Williams HM, Diamond MD, Craven LF, et al: Neurological Complications of Lymphomas and Leukemias . Springfield, Ill, Charles C Thomas Publishers, 1959, pp 8-72. 32. Dameshek W, Gunz F: Leukemia . New York, Grune & Stratton Inc, 1964, p 180. 33. Roy S, Johnson WW: Diabetes insipidus in a child with erythromyelocytic leukemia . Am J Dis Child 119:82-85, 1970. 34. Malter IJ, Gross S, Terel T: Diabetes insipidus complicating acute lymphocytic leukemia . Am J Dis Child 117:228-230, 1969. 35. Barak Y, Libon E: Hypothalamic hyperphagia, obesity, and disturbed behavior in acute leukemia . Acta Paediatr Scand 57:153-156, 1968.Crossref 36. Gold RM: Hypothalamic obesity: The myth of the ventromedial nucleus . Science 182:488-490, 1973.Crossref 37. Hyman CB, Bogle JM, Brubaker CA, et al: Central nervous system involvement by leukemia in children: I. Relationship to systemic leukemia and description of clinical and laboratory manifestations . Blood 25:1-12, 1965.

Journal

American Journal of Diseases of ChildrenAmerican Medical Association

Published: Sep 1, 1978

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