Food-dependent Cushing's syndrome mediated by aberrant adrenal sensitivity to gastric inhibitory polypeptide

• Published in: The New England journal of medicine Vol. 327; no. 14; pp. 981 - 986
• Main Authors: Reznik, Y. (Centre Hospitalo-Universitaire, Caen, France), Allali-Zerah, V, Chayvialle, J.A, Leroyer, R, Leymarie, P, Travert, G, Lebrethon, M.C, Budi, I, Balliere, A.M, Mahoudeau, J
• Format: Journal Article Web Resource
• Language: English
• Published: Boston, MA Massachusetts Medical Society 01.10.1992
• Subjects: Adrenal glands; Adrenal Glands - drug effects; Adrenal Glands - pathology; Adrenal Glands - physiopathology; Adrenal Glands/drug effects/pathology/physiopathology; Adrenocorticotropic Hormone; Adrenocorticotropic Hormone - blood; Adult; Biological and medical sciences; blood; blood plasma; Carbohydrates; case studies; CORTICOTROPHINE; corticotropin; CORTICOTROPINA; cortisol; Cushing syndrome; Cushing Syndrome - etiology; Dexamethasone; Dexamethasone/diagnostic use; diagnostic use; diet-related diseases; drug effects; drug therapy; Eating; Eating - physiology; Endocrinologie, métabolisme & nutrition; Endocrinology, metabolism & nutrition; Endocrinopathies; ENFERMEDADES GLANDULAS ENDOCRINAS; ESTEROIDES; etiology; Excretion; Fasting; Female; FEMME; Food; Gastric Inhibitory Polypeptide; Gastric Inhibitory Polypeptide - pharmacology; Gastric Inhibitory Polypeptide - physiology; Gastric Inhibitory Polypeptide/pharmacology/physiology; GLANDULAS SUPRARRENALES; Glucose; Hormones; Human health sciences; Humans; Hydrocortisone; Hydrocortisone - blood; Hydrocortisone - urine; Hydrocortisone/blood/urine; Hyperplasia; In Vitro Techniques; Insulin; Meals; Medical sciences; Middle Aged; MUJERES; Nervous system diseases; Octreotide; Octreotide - pharmacology; Octreotide - therapeutic use; Octreotide/pharmacology/therapeutic use; ORINA; pathology; PEPTIDE; PEPTIDOS; pharmacology; physiology; physiopathology; Pituitary; Pituitary gland; Plasma; PLASMA SANGUIN; PLASMA SANGUINEO; Polypeptides; Proteins; Sciences de la santé humaine; Secretion; Somatostatin; Standard deviation; STEROIDE; Stress; SURRENALE; TERAPEUTICA MEDICAMENTOSA; therapeutic use; THERAPEUTIQUE MEDICAMENTEUSE; Tomography; TRASTORNOS METABOLICOS; Triglycerides; TROUBLE DU METABOLISME; TROUBLE ENDOCRINIEN; Tumors; URINE; women; Endocrinopathy; Case study; Human; Diagnosis; Cushing syndrome; Etiopathogenesis
• ISSN: 0028-4793; 1533-4406; 1533-4406
• DOI: 10.1056/NEJM199210013271403

Background. Some patients with Cushing's syndrome have nodular adrenal hyperplasia. In most the disease is corticotropin-dependent, but in others it is corticotropin-independent. The cause of the adrenal hyperplasia in the latter patients is not known. Methods. We studied a 49-year-old woman with Cushing's syndrome and nodular adrenal hyperplasia in whom food stimulated cortisol secretion. Plasma cortisol concentrations were measured in response to the ingestion of mixed meals, glucose, protein, and fat and after the administration of various gastrointestinal and other types of hormones. We also studied the ability of the long-acting somatostatin analogue octreotide to prevent the food-induced increase in plasma cortisol concentrations and to ameliorate the clinical manifestations of Cushing's syndrome in this patient. Results. The patient's fasting plasma cortisol concentrations were subnormal, ranging from 3.0 to 7.5 micrograms per deciliter (83 to 207 nmol per liter), and they increased to as high as 16.5 micrograms per deciliter (455 nmol per liter) after a mixed meal. Her urinary cortisol excretion ranged from 164 to 250 micrograms per day (453 to 690 nmol per day) and could not be suppressed by a large dose of dexamethasone. Plasma corticotropin concentrations were virtually undetectable at all times. The ingestion of glucose, protein, and fat increased plasma cortisol concentrations to 3.6, 2.2, and 4 times the base-line value, respectively; the meal-induced and glucose-induced increases were inhibited by octreotide. The infusion of gastric inhibitory polypeptide (GIP) increased the patient's plasma cortisol concentration to 3.7 times the base-line value, but had no effect in normal subjects. The patient's fasting plasma GIP concentrations were normal both before and after a meal, and there was a close correlation between her plasma cortisol and GIP concentrations. Treatment with octreotide decreased urinary cortisol excretion and ameliorated the clinical manifestations of Cushing's syndrome. Conclusions. The development of aberrant adrenal sensitivity to GIP can result in food-dependent adrenal hyperplasia and therefore in Cushing's syndrome