A physiologic approach to diagnosis of the Cushing syndrome.

Abstract

Reviews17 June 2003A Physiologic Approach to Diagnosis of the Cushing SyndromeHershel Raff, PhD and James W. Findling, MDHershel Raff, PhDFrom St. Luke's Medical Center, Medical College of Wisconsin, Milwaukee, Wisconsin. and James W. Findling, MDFrom St. Luke's Medical Center, Medical College of Wisconsin, Milwaukee, Wisconsin.Author, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-138-12-200306170-00010 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Clinical Principles*GeneralObesityHypertensionMetabolicDiabetes mellitus or impaired glucose toleranceHyperlipidemiaNephrolithiasisPolyuriaSkinPlethoraHirsutismStriaeAcneBruisingMusculoskeletalOsteopenia or osteoporosisProximal myopathyNeuropsychiatricDepressionCognitive impairmentEmotional labilityEuphoriaPsychosisGonadal dysfunctionOligomenorrhea or amenorrheaImpotence, decreased libidoImmune suppression (susceptible to opportunistic infection)*Notice that many of the features of the Cushing syndrome resemble those of the metabolic syndrome (e.g., obesity, hypertension, impaired glucose tolerance, hyperlipidemia, hirsutism, acne, and gonadal dysfunction).Pathophysiologic PrinciplesThe hypothalamicpituitaryadrenal axisControl of adrenal function and growthHypothalamic control of pituitary functionGlucocortcoid-negative feedbackCircadian rhythmThe stress responsePosttranslational processing of proopiomelanocortin to adrenocorticotropic hormoneCortisol plasma binding, metabolism, and excretionGlucocorticoid action11-hydroxysteroid dehydrogenase type 1 and 11-hydroxysteroid dehydrogenase type 2The relationship among obesity, impaired glucose tolerance or diabetes, hypertension, and gonadal dysfunction was initially ...References1. Cushing H. The basophil adenomas of the pituitary body and their clinical manifestations (tuitary basophilism). Bulletin of Johns Hopkins Hospital. 1932;50:137-95. Google Scholar2. Archard C, Thiers J. Le virlisme pilaire et son association a l'insuffisance glycolytique (diabte des femmes a barb). Bull Acad Natl Med. 1921;86:51-64. Google Scholar3. Terzolo M, Pia A, Ali A, Osella G, Reimondo G, Bovio S, . Adrenal incidentaloma: a new cause of the metabolic syndrome? J Clin Endocrinol Metab. 2002;87:998-1003. [PMID: 11889151] CrossrefMedlineGoogle Scholar4. Reincke M, Nieke J, Krestin GP, Saeger W, Allolio B, Winkelmann W. Preclinical Cushing's syndrome in adrenal incidentalomas: comparison with adrenal Cushing's syndrome. J Clin Endocrinol Metab. 1992;75:826-32. [PMID: 1517373] MedlineGoogle Scholar5. Leibowitz G, Tsur A, Chayen SD, Salameh M, Raz I, Cerasi E, . Pre-clinical Cushing's syndrome: an unexpected frequent cause of poor glycaemic control in obese diabetic patients. Clin Endocrinol (Oxf). 1996;44:717-22. [PMID: 8759185] CrossrefMedlineGoogle Scholar6. Contreras LN, Cardoso E, Lozano MP, Pozzo J, Pagano P, Claus-Hermbeg H. Deteccin de sndrome de Cushing preclnico en pacientes con sobrepeso y diabetes mellitas tipo 2. Medicina. 2000;60:326-30. MedlineGoogle Scholar7. Richards JS. New signaling pathways for hormones and cyclic adenosine 3,5-monophosphate action in endocrine cells. Mol Endocrinol. 2001;15:209-18. [PMID: 11158328] MedlineGoogle Scholar8. Findling JW, Raff H. Ectopic ACTH.. In: Mazzaferri EL, Samaan NA, eds. Endocrine Tumors. Cambridge, MA: Blackwell Scientific; 1993:554-66. Google Scholar9. Dallman MF, Akana SF, Scribner KA, Bradbury MJ, Walker CD, Strack AM, . Stress, feedback and facilitation in the hypothalamo-pituitary-adrenal axis. J Neuroendocrinol. 1991;4:517-26. CrossrefGoogle Scholar10. Jacobson L, Sapolsky R. The role of the hippocampus in feedback regulation of the hypothalamic-pituitary-adrenocortical axis. Endocr Rev. 1991;12:118-34. [PMID: 2070776] CrossrefMedlineGoogle Scholar11. Dallman MF, Akana SF, Levin N, Walker CD, Bradbury MJ, Suemaru S, . Corticosteroids and the control of function in the hypothalamo-pituitary-adrenal (HPA) axis. Ann N Y Acad Sci. 1994;746:22-31. [PMID: 7825879] CrossrefMedlineGoogle Scholar12. Aguilera G, Rabadan-Diehl C. Vasopressinergic regulation of the hypothalamic-pituitary-adrenal axis: implications for stress adaptation. Regul Pept. 2000;96:23-9. [PMID: 11102648] CrossrefMedlineGoogle Scholar13. Raff H. Interactions between neurohypophyseal hormones and the ACTH-adrenocortical axis.. In: North WG, Moses AM, Share L, eds. The Neurohypophysis: A Window on Brain Function. New York: New York Academy of Sciences; 1993:411-25. Google Scholar14. Born J, Fehm HL. Hypothalamus-pituitary-adrenal activity during human sleep: a coordinating role for the limbic hippocampal system. Exp Clin Endocrinol Diabetes. 1998;106:153-63. [PMID: 9710353] CrossrefMedlineGoogle Scholar15. Bierwolf C, Kern W, Molle M, Born J, Fehm HL. Rhythms of pituitary-adrenal activity during sleep in patients with Cushing's disease. Exp Clin Endocrinol Diabetes. 2000;108:470-9. [PMID: 11083068] Crossref