Hypothalamic Astrocytoma: Hyperphagia Syndrome & Accompanying Issues

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<ul><li><p>8/2/2019 Hypothalamic Astrocytoma: Hyperphagia Syndrome &amp; Accompanying Issues</p><p> 1/4</p><p>Hypothalamic AstrocytomaSyndrome of Hyperphagia, Obesity, and Disturbances of Behaviorand Endocrine and Autonomic Function</p><p>Robert M. Haugh, MD, William R. Markesbery, MD</p><p>\s=b\A 26-year-old woman had hyperpha-gia, obesity, aggressive behavior, visualhallucinations, reversal of wake-sleeppatterns, hypothermia, hypothyroidism,and amenorrhea. She died of pancreatitis,probably secondary to hypothermia.Autopsy revealed a low-grade astrocyto-ma in the third ventricle and medial ante-rior and mid hypothalamus, primarily onthe right. Although she exhibited thyroidand ovarian hypofunction, the patient hadintact median eminence and pituitaryfunction, suggesting end-organ failure,possibly of an autoimmune nature.</p><p>(Arch Neurol 1983;40:560-563)</p><p>"Uypothalamic tumors are of specialinterest since they offer confir</p><p>mation in humans of the various</p><p>hypothalamic functions described experimentally in others species. Only afew reports of the clinical correlatesof discrete hypothalamic lesions inhumans have been published (review15). It is well known that a variety</p><p>of clinical syndromes can occur withlesions of the hypothalamus, such asdiabetes insipidus; alterations of temperature regulation, food intake,sleep, and behavior; disturbances ofautonomie nervous system function;</p><p>and others.4-5 It is also believed thattumors and other lesions of the hypothalamus can cause changes in themedian eminence and/or tuber cinere-</p><p>um, which are thought to lead todiminution of releasing factors,resulting in decreased pituitary andendocrine function.</p><p>Our purpose is to describe a patientwith a hypothalamic neoplasm thatresulted in behavioral changes, reversal of</p><p>day-night rhythms, hyperpha-gia, obesity, hypogonadism, and hypo-thyroidism. However, this patientalso had documented maintenance ofadequate median eminence-pituitaryaxis function.</p><p>REPORT OF A CASE</p><p>A 26-year-old woman was admitted tothe University of Kentucky Medical Center, Lexington, because of increasing somnolence and lethargy. She had been inexcellent health until two years prior toadmission, when she had been admitted toanother hospital because of an intracerebral hemorrhage. A computed tomograph</p><p>ic (CT) scan of the head was reported toshow blood in the thalamic area and thirdventricle. Four-vessel cerebral angiography demonstrated no aneurysm or tumor.After she recovered from the hemorrhage,the patient had episodes of combative,aggressive behavior and visual hallucinations. She had reversal of her day-nightrhythms, sleeping during the day and staying awake through the night. With thearrival of spring, her behavior and disturbed sleep cycle improved and remainedstable until winter weather returned, atwhich time the hallucinations, combativebehavior, and reversal of day-nightrhythms returned. During this two-year</p><p>period amenorrhea developed, and herweight increased from 68 to 135 kg. Threeweeks prior to admission progressive lethargy and weakness and decline in mentalfunction occurred. The patient had no history of occupational or environmentalexposure to toxins, and she did not usedrugs or alcohol.</p><p>Physical examination showed a somnolent woman weighing 135 kg, with a rectaltemperature of 34.4 C, pulse of 40 beatsper minute, BP of 110/60 mm Hg, andCheyne-Stokes respiration. Remarkable</p><p>findings on physical examination includedmarked obesity, pendulous breasts withoutgalactorrhea, diffuse abdominal tenderness, and decreased bowel sounds. Neurologic examination revealed the patient tobe difficult to arouse. Funduscopic examination showed bilateral optic atrophy. Noother cranial nerve abnormalities werefound. Sensory, motor, and cerebellar functions and muscle stretch reflex were normal. The patient could not cooperate formental status or visual field testing.</p><p>Laboratory Data</p><p>Laboratory findings were as follows: leukocyte count, normal; hematocrit reading,</p><p>33%; platelet count, 78,000/cu mm; bloodchemistry study using an automated multiple analysis system, normal; calcium level, 2.8 mEq/L; amylase level, 328 IU/L; andlipase level, 2.2 Sigma-Tietz units/mL. Liver and renal function test results wereunremarkable. Tests of arterial blood gases showed a pH of 7.40; Pco2, 26 mm Hg;Po2, 79 mm Hg; and 02 saturation, 96%.Thyroxine level was 3.6 Mg/dL (normal, 5 to12 Mg/dL). Triiodothyronine resin uptakewas 24% (normal, 24% to 34%). Thyroid-stimulating hormone (TSH) level onadmission was 43.4 /mL (normal, 2 to 8 /mL). Thyroid antibodies were positiveat a titer of 1:1,600. A protirelin (thyrotro-</p><p>Accepted for publication Dec 16, 1982.From the Departments of Pathology (Drs</p><p>Haugh and Markesbery) and Neurology (DrMarkesbery) and the Sanders-Brown ResearchCenter on Aging (Dr Markesbery), University ofKentucky Medical Center, Lexington.</p><p>Reprint requests to Department of Pathology,University of Kentucky Medical Center, Lexing-ton, KY 40536-0230.</p><p>at Washington State University, on November 14, 2011www.archneurol.comDownloaded from</p>http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/</li><li><p>8/2/2019 Hypothalamic Astrocytoma: Hyperphagia Syndrome &amp; Accompanying Issues</p><p> 2/4</p><p>Fig 1.Coronal section of brain showing tumor (arrows) in thirdventricle ust above optic chiasm, with thinning of anterior commissure.</p><p>Fig 2.</p><p>Moderately cellular astrocytoma composed of cells with roundto oval nuclei and abundant fibrillary processes (hematoxylin-eosin,original magnification X395).</p><p>pin-releasing hormone) stimulation testrevealed the following:</p><p>TSH, Prolactin, /mL ng/mL</p><p>Baseline 53 4530 min 85 8660 min 105 8490 min 68 77</p><p>Luteinizing hormone (LH) level was 120ImU/mL, and follicle-stimuating hormone(FSH) level was 9 ImU/mL. Serum cortisollevel was 14.3 Mg/dL. A cortrysyn stimulation test showed normal results. The CSFcontained no cells, a protein level of 159mg/dL, and a glucose level of 93 mg/dL. AnECG revealed nonspecific T-wave changesand</p><p>prolonged Q-Tc, suggestive of hypothy-roidism. A CT scan and ultrasonogram ofthe abdomen were consistent with acutepancreatitis.</p><p>Hospital Course</p><p>The patient's temperature remained inthe range of 33.9 C to 34.4 C during thefirst three days of hospitalization but onthe fourth day rose to 38.3 C. Serumamylase level continued to rise, calciumlevel declined, and abdominal tendernessworsened. Treatment for pancreatitis wasstarted, and antibiotics were given forpresumed sepsis. The results of the TSHand prolactin response were thought to beconsistent with a hypothalamic diseaseprocess. Intravenous (IV) thyroxine wasadministered, and serum TSH level eventually returned to normal. The initial bradycardia resolved after institution of dopamine hydrochloride and aminophyllinetherapy; however, the patient remainedhypotensive. Flank hematomas developed,and hypocalcemia persisted in spite ofhigh-dose IV calcium gluconate replacement. Despite vigorous supportive efforts,the patient died on the 15th hospital day.</p><p>Autopsy Findings</p><p>The autopsy showed an edematous pancreas discolored by hemorrhage, with fat</p><p>necrosis and saponification of the sur</p><p>rounding retroperitoneal fat. A fibrinopu-rulent exdate covered most intraperitone-al surfaces. The ovaries were markedlyatrophie, and each weighed 3.5 g (normalpremenopausal weight, 8 to 12 g). Microscopic examination revealed rare ovarianfollicles, a few corpora albicantia, and noevidence of corpus luteum formation.Parenchymal fibrosis was present. Therewere no inflammatory infiltrates in theovaries. These histologie findings are consistent with features of an autoimmuneovarian failure. The thyroid was grosslynormal (weight, 17.5 g), but microscopically, lymphocytic and plasma cell infiltrationwas seen in the gland, consistent with</p><p>chronic thyroiditis. Therewere no</p><p>inflammatory infiltrates in other endocrineorgans.</p><p>The brain weighed 1,340 g. There was noevidence of herniation or abnormalities ofthe cortical surfaces. No gross abnormalities of the tuber cinereum, infundibulum,or pituitary were noted. Coronal sectionsrevealed a soft, gray-brown, well-circumscribed tumor arising in the right anteriorhypothalamus (Fig 1). The neoplasm filledmuch of the anterior and mid third ventricle. The lateral ventricles were notenlarged. No other gross lesions werefound in the cerebral hemispheres, brainstem, or cerebellum.</p><p>Histologie examination demonstrated amoderately cellular neoplasm with cellscontaining slightly pleomorphic oval- tospindle-shaped nuclei (Fig 2). Eosinophiliccellular processes gave rise to a fibrillarybackground, and Rosenthal fibers wereabundant. Vascular channels were prominent in the tumor; however, endothelialproliferation was not present. No tumornecrosis was seen. Hemosiderin pigmentwas prominent in many macrophages andlying free within the medial and inferiormargin of the tumor. There was a rim ofreactive gliosis lateral to the tumor. On theright, the astrocytoma and its gliotic rimreplaced the suprachiasmatic, paraventric-</p><p>ular, and anterior hypothalamic nuclei, aswell as a great portion of the medial hypothalamic nucleus (Figs 3 and 4). The tumorbreached the lamina terminalis, and itsmost superior extension bisected the anterior commissure. In its anterior and middle portions the tumor exerted a compressive effect on the optic chiasm (Fig 4). Itessentially replaced the entire right ventromedial and dorsomedial nuclei. Therewas minimal involvement of the right posterior hypothalamic nucleus. The right for-nix was interrupted. It had extended intothe left anterior hypothalamus, with obliteration of the preoptic and suprachiasmat-ic nuclei, a small portion of the anteriorhypothalamic nucleus, and the inferior</p><p>portion of the paraventricular nucleus(Figs 3 and 4). Tumor and gliosis involvedonly a small part of the inferior left ventromedial nucleus. Other hypothalamicnuclei were not involved on the left. Thetumor did not involve the tuber cinereum,pituitary gland, or mammillary bodies.The median eminence was slightlyinvolved by the gliosis delimiting the edgeof the tumor. In the anterior pituitary,acidophils were prominent and had a normal pattern of granulation. Some baso-phils showed mild degranulation. Therewas no evidence of compression or ischemia in the anterior pituitary. The posteriorpituitary was unremarkable.</p><p>COMMENT</p><p>This patient had a low-grade astrocytoma involving the right anteriorand mid hypothalamus and a smallportion of the left anterior hypothalamus. The presence of many hemosid-erin-laden macrophages in the tumorand on its surface indicated that thepatient's initial symptoms werecaused by hemorrhage into the tumor.She subsequently had hyperphagia,obesity, periods of unprovoked aggressive behavior, visual hallucinations,</p><p>at Washington State University, on November 14, 2011www.archneurol.comDownloaded from</p>http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http://www.archneurol.com/http:...</li></ul>