Brief Report 852 · March 18, 1999 The New England Journal of Medicine I MPAIRED COUNTERREGULATION OF GLUCOSE IN A PATIENT WITH HYPOTHALAMIC S ARCOIDOSIS FRANÇOISE FÉRY, M.D., PH.D., LAURENCE PLAT, M.D., PHILIPPE VAN DE BORNE, M.D., PH.D., ELIE COGAN, M.D., PH.D., AND JEAN MOCKEL, M.D., PH.D. From the Departments of Endocrinology (F.F., L.P., J.M.) and Internal Medicine (E.C.) and the Hypertension Clinic (P.B.), Hôpital Erasme, Uni- versité Libre de Bruxelles, Brussels, Belgium. Address reprint requests to Dr. Féry at the Department of Endocrinology, Hôpital Erasme, 808 route de Lennik, B-1070 Brussels, Belgium, or at ffery@med.ulb.ac.be. ©1999, Massachusetts Medical Society. YPOGLYCEMIA stimulates rapid increases in the secretion of several hormones, in- cluding catecholamines, glucagon, cortisol, and growth hormone, that act in concert to increase the plasma glucose concentration. The chief role of the central nervous system in triggering the release of such counterregulatory hormones during hypo- glycemia is well recognized. The specific region of the hypothalamus responsible for this process is probably the ventromedial region, because bilateral lesions or perfusion of D-glucose into this region re- duces the increases in plasma glucagon and catechol- amines in response to hypoglycemia in rats. 1,2 We describe a patient with a hypothalamic sarcoid infil- trate who had complete loss of the counterregula- tory response to hypoglycemia. CASE REPORT A 31-year-old woman in whom sarcoidosis had been diagnosed at the age of 27 years had an 18-month history of secondary amenorrhea, a 12-month history of weight gain of about 20 kg, and polydipsia and polyuria. Apart from the presence of obesity (weight, 86 kg; height, 171 cm) and a tendency toward hypother- mia, the results of the physical examination were normal. A water- deprivation test confirmed the diagnosis of central diabetes insip- idus. Measurements of plasma and urinary hormones disclosed partial pituitary insufficiency, with low plasma concentrations of free thyroxine and cortisol and hyperprolactinemia. Plasma lute- inizing hormone and follicle-stimulating hormone concentrations were normal, but the responses to gonadotropin-releasing hor- mone were supranormal. Magnetic resonance imaging revealed a normal pituitary gland but multiple infiltrates in the brain, including one in the hypothalamic region. The diagnosis of sar- coidosis was confirmed by the findings of a high plasma an- giotensin-converting enzyme concentration, bilateral hilar lym- phadenopathy with reticular interstitial infiltrates on computed tomography of the chest, and typical findings on transbronchial biopsy. Treatment was initiated with 32 mg of methylpredniso- lone per day, 100 μg of levothyroxine per day, 30 μg of desmo- pressin acetate per day, and a combination of 30 μg of ethinyl es- H tradiol and 75 μg of gestodene given on days 1 to 21 of the menstrual cycle. After one month of methylprednisolone therapy, pituitary magnetic resonance imaging showed complete resolu- tion of all the infiltrates except the one in the hypothalamus, and it remained unchanged thereafter. During the next two years, the dose of methylprednisolone was gradually reduced to 6 mg per day and then replaced by cortisone acetate (37.5 mg per day). Shortly thereafter, the patient began to report episodes of faintness that lasted one to two hours and oc- curred about once a week. These episodes were unrelated to eat- ing or activity and were not accompanied by other symptoms. The patient’s only other symptoms were frequent episodes of hyper- natremia resulting from impaired thirst perception, the develop- ment of cushingoid features, and progressive weight loss of 18 kg. She was hospitalized for assessment of faintness. On admission, her blood pressure and heart rate were normal but she still had hypothermia. Laboratory tests were normal except for a plasma glucose concentration (measured while she was fasting) of 55 mg per deciliter (3.1 mmol per liter), which prompted further evalu- ation of several aspects of glucose homeostasis. During the evalua- tion the patient continued to receive her usual treatment for hy- popituitarism, except that her morning dose of 25 mg of cortisone acetate was delayed until the end of testing on each study day. METHODS The studies were approved by the ethics committee of the Fac- ulty of Medicine of the University of Brussels, and the patient gave oral informed consent. Plasma glucose was measured by a glucose oxidase method (Boehringer Mannheim, Mannheim, Germany), and glycosylated hemoglobin was measured by affinity high-pressure liquid chroma- tography (Bio-Rad Laboratories, Hercules, Calif.); the normal range is 4.0 to 6.5 percent. Plasma insulin, growth hormone, cor- tisol, glucagon, and pancreatic polypeptide were measured by radioimmunoassay. 3-5 Plasma and urinary catecholamines were measured by high-pressure liquid chromatography with electro- chemical detection. 6 RESULTS Base-Line Hormonal Status Plasma growth hormone concentrations were unde- tectable, and plasma cortisol concentrations, measured approximately 14 hours after the evening dose of 12.5 mg of cortisone acetate, averaged 1.5 μg per deciliter (41 nmol per liter), whereas plasma glucagon and catecholamine concentrations and urinary catechol- amine excretion were within the normal range. Glucose Homeostasis Blood glucose was measured at least eight times per day throughout the 33-day hospitalization, and no hypoglycemia was detected. The lowest values oc- curred on waking; the mean (±SD) of these values was 58±8 mg per deciliter (3.2±0.5 mmol per li- ter). The mean blood glucose concentrations two hours and four hours after a meal were 110±45 and 90±35 mg per deciliter (6.1±2.5 and 5.0±1.9 mmol per liter), respectively. The mean value at 3 a.m. was 85±28 mg per deciliter (4.7±1.6 mmol per liter). The glycosylated hemoglobin value was 5.3 percent. During a three-day fast, the patient’s plasma glu- cose concentration fell from 66 mg per deciliter (3.7 mmol per liter) to 50 mg per deciliter (2.8 mmol per liter), and the plasma insulin concentration fell from Copyright © 1999 Massachusetts Medical Society. All rights reserved. Downloaded from www.nejm.org at KU LEUVEN BIOMEDICAL LIBRARY on January 24, 2007 .