The case of a 14-year-old female who suffered from hyperosmolar diabetic coma (HODC) after resection of craniopharyngioma and during treatment for hypopituitarism
and diabetes insipidus is presented. In Aug. 1989, craniopharyngioma was diagnosed and she underwent resection surgery and radiotherapy. Since then, she had been on
supplemental therapy with hydrocortisone and thyroxin and desmopressin (DDAVP). On Jan. 17, 1992, she fell into HODC upon ingesting a large amount of soft drink to supplement
water due to persistent polyuria. She improved quickly when supplementary fluids and insulin were administered. She had demonstrated no abnormality in glucose tolerance prior to this manifestation. Insulin therapy was deemed unnecessary after her recovery from HODC. Because of a disorder in the central nervous thirst mechaninm, she lacked the sense of thirst and concomitantly the thirst-mediated water intake in spite of elevated plasma osmolarity due to dehydration and hyperglycemia. This seemed to be the cause of her accelerating dehydration. The resulting insulin resistance then brought about her HODC. Thus, it is difficult to consider such a case of HODC as symptomatic of diabetes when no abnormality in glucose tolerance either before manifestation or after restoration can be found. It should rather be considered as a case of “dehydration hyperglycemia" and be
treated as such

Fukui, Hiroshi

Izumi, Yukiko

Kamata, Osamu

Matsumoto, Masami

Nishiyama, Toshimasa

Okamoto, Shingo

Sakaki, Toshisuke

Tsujii, Tadasu

English

Global Institutional repository of Nara Medical University

奈医誌. (]. Nara M巴d.As.) 4， 185~191 ， 1993 A CASE OF DIABETES INSIPIDUS ACCOMPANYING THIRST DISORDER ASSOCIATED WITH HYPEROSMOLAR DIABETIC COMA SHINGO OKAMOTO， OSAMU KAMA T A， MASAMI MA TSUMOTO， (185) YUKIKO IZUMI， TOSHIMASA NISHIYAMA， HIROSHI FUKUI and T ADASU TSUJII The Third Dゆart削 ent01 Internal Medicine， Nara Medical University TOSHISUKE SAKAKI The Second nψartment 01 Surgery， Nara Medical University Received May 31， 1993 Summary: The case of a 14-year-old female who suffered from hyperosmolar diabetic coma (HODC) after resection of craniopharyngioma and during treatment for hypopituitar-ism and diabetes insipidus is presented. In Aug. 1989， craniopharyngioma was diagnosed and she underwent resection surgery and radiotherapy. Since then， she had been on supplemental therapy with hydrocortisone and thyroxin and desmopressin (DDAVP). On Jan. 17， 1992， she fel into HODC upon ingesting a large amount of soft drink to supplement water due to persistent polyur匂 Sheimproved quickly when supplementary fluids and insulin were administered. She had demonstrated no abnormality in glucose tolerance prior to this manifestation_ Insulin therapy was. deemed unnecessary after her recovery from HODC. Because of a disorder in the central nervous thirst mechaninm， she lacked the sense of thirst and concomitantly the thirst-mediated waterintake in spite of elevated plasma osmolarity due to' dehydration and hyperglycemia. This seemed to be the cause of her accelerating dehydration. The resulting insulin resistance then brought about her HODC. Thus， it is difficult to consider such a case of HODC as symptomatic of diabetes when no abnorma1ity in glucose tolerance either before manifestation or after restoration can be found. It should rather be considered as a case of “dehydration hyperglycemia" and be treated as such. Index Terms hyperosmolar diabetic coma， dehydration INTRODUCTION HODC is a pathological state peculiar to diabetes， resulting from the disturbance of glucose and water metabolism. At present， the fatality rate remains high (1) (2) (3)， so that early and proper treatment is essential at the time of diagnosis. Most HODC cases have demonstrated diabetes before manifestation. It is said that the patients frequently fal into HODC triggered by infection or cerebrovascular disease. The following mechanism may be speculated: dehydration promotes the secretion of hormones which are antagonistic to insulin such as glucagon， cortisol and epinephrine， dehydration Increases insulin resistance in the periphery (4) (5) or dehydration inhibits insulin secretion from (186) s. Okamoto， etal. the islets of Langerhans¥ However， the fact that ketoacidosis does not occur concomitantly has not yet been clarified. We report a case which may provide some suggestion for clarifying the mechanism of HODC with specific attention to the relation between dehydration and HODC. CASE REPORT: The patient was a 14-year-old female who demonstrated weakness of sight and walking difficulty in April1988. In July 1989， craniopharyngioma was diagnosed. The tumor was about 3 cm in diameter with accompanying calcification which extended from supura sellar to third ventricle (Fig. 1). The tumor could not be extirpated completely， so radiotherapy by lineac， with a total radiation of 30 GY was applied. N 0 cognitive or intellectual disorder resulted. However， she was almost blind， being able to sense only light. Postoperative examination of pituitary function (Table 1) revealed that she had panhypopituitarism. Subse-quently， supplemental therapy of 20 mg/ day of hydrocortisone and 75μg/ day of thyroxin was prescribed. In addition， an injection of gonadotropin (HMG/HCG) every 3 weeks was adminis-tered. The DDA VP dose was controlled on the basis of the urine and water intake per day， as diabetes insipidus and her thirst disorder were concomitant. Because of her thirst disorder， she did not feel thirsty even when her plasma osmolarity was as high as 320 mOsm/L. Daily water intake was calculated on the basis of urine volume and given by her mother. Her weidght was 53.9 kg with a height of 146 cm， with a normal height increase (4.0 cm/year) in spite of her growth hormone secretion disorder. She showed 15 % obesity but no abnormality in glucose Fig. 1. MRI scan demonstrating a larg巴 tumor巴xtendingto third venricle accompanying hydroce phalus Cenhanced by Gd-DTPA). A case of diabet巴sinsipidus accompanying thirst disorder associated with hyp巴rosmolardiabetic coma (187) tolerance. On J an. 17， 1992， she showed polyuria and weight reduction triggered by a respiratory infection. Her family then gave her a large amount of soft drink containing glucose for supplement of water， which brought about gradual clouding of consciousness. She was hospita1ized on an emergency basis on J an. 19. At the time of admission， she was drowsy and did not respond when called. Her blood pressure was 120/70 mmHg， pulse rate 86/ min. and respiration rate 20/min. Her skin was s1ightly dry. Neurologically， no paralysis or abnormal movement of extremities were found. She was ableptic and demonstrated lateral nystagmus. The results of urine and blood chemical examination (Table 2) showed high glucose in urine and keton body trace positive. The blood glucose levels were as high as 600 mg/dl or higher. GPT， LDH， CPK and the electrolytes， Na and Cl were elevated. The plasma osmolarity (427 mOsm/L) was remarkably high. The urine osmolarity was 634 mOsm/L. HbA1c was 10.0 %. On the basis of these results， she was diagnosed as having fallen into HODC， for which administration of supplemental fluids and insu1in was started. As shown in Fig. 2， these treatments quickly norma1ized the blood glucose levels. She recovered consciousness， but s1ightly degraded on the 4 th day， when she demonstrated hyponatremia and low. plasma osmolarity. We judged it transitional to water overload state and controlled the dose of DDA VP and supplemental fluids， which successfully ameliorated the symptoms. Insu1in administration could be suspended by the 5 th day and the blood glucose maintained normallevels thereafter. The elevation of LDH and CPK seen at the time of initiation rapidly Table 1. Pituitary function t巴stsaft巴rremoval of craniopharyngioma 1. Basal hormone values ACTH 19.9 pg/ml Cortisol 0.4μg/dl GH 0.5 ng/ml T3 51.3 ng/dl PRL 12.6 ng/ml T4 3.8μg/dl LH < 0.5 mlU/ml freeT4 0.6 ng/dl FSH < 0.5mlU/ml TSH 1.2μU/ml PRA 23.9 ng/ml/h ADH 0.2 pg/ml Aldost巴ron巴 127.6pg/ml 11. 1nsulin tolerance test (4U R巴gularinsulin i. v.) 0' 10' 20' 30' 40' B. gl ucose (mg/ dl) 98 95 6 NE 40 GH (ng/ml) 0.4 0.4 0.5 0.5 0.5 Cortisolμg/dl) 2.6 NE NE NE 2.5 * NE : noexamin巴dII. G RF test c1 0 0μg i. v.) 。， 15' 30' 60' 120' GH (ng/ml) 0.5 0.6 0.5 0.6 0.6 Table 2. Labolatory data ; urinary， blood chemical and blood gas analysis on admission (J an 19th 1992) Urine pH 6.0 Ch-E 6711U/L Protein (-) T. Chol 210 mg/dl glucose 〔十十十〉 BUN 19m9/dl ketone body (土〕 Cr 0.8mg/dl bilirubin (-) N日 151mEq/l urobilinogen 〈土〉 K 3.6mEq/l ocult blood (ー〉 Cl 114mEq/l glucose >600 mg/dl P巴ripheralblood RBC 381 x 10' /mm3 CRP 3.6mg/dl Hb 10.6g/dl HbA1C 10目。%Ht 33.7% Fructosamine 440μmol/dl WBC 6，60 /mm3 Pl 12.3X10' /mm3 Blood gas analysis Blood Chemistry pH 7.41 T. Bil 2.0 mg/dl PO， 73mmHg D. Bil 0.7mg/dl PCO， 32. 2 mmHg 1. Bil 1. 3 mg/ dl HC03 20.5 mmol/l GOT 47IU/L B. E. -2.8mmol/l GPT 19 IU/L LDH 162 IU/L Plasma and Urinaly Osmolarity CPK 785 IU/L P-Osm 427 mOsm/l U -Osm 634 mOsm/l 立liJness協劾~吻』BS Na P-Osm (mg/d.Q) (mEq/~) (mOsm/~) (18) 600 160~ 350 500 150 400 140 300 130~ 300 200 120 1 00 ~ 1 0 { 250 S.Okamoto，巴tal DDAVP 15μg/ day 。一ーや:BS __:Na 品 一 ー 唱 :P-Osm PD 2gub}』申阿国主凋“-FD由戸』コ一O〉口:oral int鵬図:drip 仙 slonqL 由U4白HC一nU唱l内J(』国刀、占)由E20〉FhJV 。c℃コ1 2 3 4 5 6 7 8 9 1 0 1 12 13 14 15 16 17 18 19 20 day Fig. 2. Th巴bloodglucose， Na， plasma osmolarity and water balanc巴afteradmission. improved. This seemed to have been caused by rhabdomyolysis associated with HODC. One month later， 75 g OGTT showed CTable 3) a slight abnormality in glucose tolerance. However， insulin secretion was high both in basic levels and peak. Although the peak lagged， itdid not reach the level of the diagnostic criteria for diabetes. Subsequently， the glucose levels maintained normal and the response to 75 gOGTT showed normal 10 months later. A case of diabetes insipidus accompanying thirst disorder associated with hyperosmolar diabetic coma (189) Table 3. 75 g Oral glucose tolerance test after resto日ration from hyperosmolar diabetic coma (日ODC)I. 1 month aft巴rHODC (Feb. 7th 192) 。30' 60' 90' 120' B. g!ucose(mg/dl) 90 13 178 193 194 IRIμU/ml) 23.3 7l.8 14.8 129.4 159.8 I. 10 months after HODC (N ov. 19th 192) 。 30' 60' 90' 120' B. g!ucose (mg/ d]) 9 157 195 17l 15 IRI (，ug/dl) 30.1 84.6 9l.3 90.8 106.3 DISCUSSION HODC is a state of metabolic failure unaccompanied by ketoacidosis in spite of marked hyperglycemia， and is basically different in its pathogenetic mechanism from diabetic ketoacidosis. Specifically， HODC can be found in subjects without any history of diabetes prior to manifestation (6). Moreover， not a few of those cases show necessitating without any treatment for diabetes or demonstrating no abnormality in glucose tolerance after restoration. The present patient also had no previous history of diabetes before the occurrence of HODC. It started during treatment for hypopituitarism and diabetes insipidus and diabetes was not found after the recovery. The pathogenesis of HODC in the present case is considered to be as follows CFig. 3) : Due to her thirst disorder， she did not feel thirsty even under water deficiency. For water supplement， the necessary amount of fluid was calculated on the basis of urine volume. Under these circumstances， she demonstrated polyuria due to insufficient dosage of DDA VP. As a result of giving water by a large amount of soft drink which contained glucose， she fel into HODC. According to the mechanism shown in Fig. 3， the plasma osmolarity elevated due to the lack of DDA VP supplement and the lack of water intake， which resulted in insulin resistance in the periphery. Because of the glucose rich soft drink， hyperglycemia also accelerated dehydration and then increased insulin resistance so as to induce HODC. Two cases of diabetes insipidus associated with HODC reported by MITSUKA W A et al. (6) also did not have any history of diabetes before their manifestation. They fel intoHODC upon interruption of DDA VP. It is problematic whether these cases ought to be classified according to the criteria of HODC， because they presented a transient hyperglycemia due to dehydration. We believe that HODC which accompanies transient abnormality in glucose tolerance due to dehydration should be considered as an independent entity. Among reported cases of HODC， cases without diabetes are not few. In most of them， dehydration plays the initial role of instigator， e. g. high-calorie transfusion triggering HODC in cerebrovascular disease， burns (7) (8)， or surgery， and vomiting and diarrhea sometimes producing HODC in infants (9) (10). Let us consider the pathogenic mechanisms wherein dehydration triggers HODC: I. induction of insulin resistance in the peripheral t (190) S. Okamoto， etal. DDAVP supplement water intake 「Dehyd凶 ion1-ご乏をご-i Hyperosmolarity i /~-ア一一一Insulin resistance impaired in peripheral tissue insulin secretion ¥〉Lmt担glycem出<4--由---田ingestion of t glucose-rich soft drink Diabetes mellitus would accelerate this vicious circle Fig. 3. Schematic presentaion of a mechanism by which this case could have falen into hyperosmolar diabetic coma osmolarity (5) I. reduction of insulin secretion due to dehydration. II. acceleration of secretion of antagonistic hormones to insulin such as glucagon and cortisol (1). IV. elevation of arginine vasopressin (A VP) due to dehydration and dehydration itself play a role of resistance to transition to ketoacidosis (8). If HODC occurs by the above mechanisms， diabetes is not an indispensable factor. Rather it is easier to accept the view that diabetic cases might easily shift to become a distinct pathological entity， HODC. If diabetes may be regarded as one of the factors causing dehydra-tion， as shown in Fig. 3， we can recognize the HODC resulting inmarked hyperglycemia due to dehydration as “dehydration hyperglycemia". Then cases with diabetes prior to HODC manifestation would be treated as“dehydration hyperglycemia with diabetes" within the same concept as HODC has heretofore been consid目ered， while those without pre-existing diabetes would be treated simply as“dehydration hyperglycemia without diabetes" It has been considered that the reason for ketoacidosis not occurring even with severe hyperglycema is that dehydration inhibits lipolysis (4) or that A VP inhibits production of keton bodies (12). It is c1ear that diabetic ketoacidosis (DKA) and dehydration hyperglycemia (DHG) A case of diabetes insipidus accompanying thirst disorder associated with hyp巴rosmolardiab巴ticcoma (191) are totally different. The basic cause for DKA is an absolute deficiency of insulin. On the other hand， in DHG， there is sudden dehydration for some reason， bringing about hyperglycemia. Thus， starting from initiation， their respective pathologies are totally different. If the HODC cases are studied based on the broad concept of “dehydration hype町rg剖lycemi泊a"the mechan凶1討ismof its manifestation is very easy to recognize. Considering the above factors， if HODC would be viewed as DHG and not as a pathology peculiar to diabetes， cases of dehydration would then be treated with an awareness of the possibility of HODC occurring REFERENCES 1) Hamblin， P. S.， Topliss， D. J.， Chosich， N.， Lording， D. W. and Stockigt， J.R. : Deaths associated with diabetic ketoacidosis and hyperosmolar coma， 1973-1988. Med. ]. Aust. 151・438-444，1989 2) Wachtel， T. J. : The diabetic hyperosmolar state. Clin. Geriatr. Med. 6 : 797-806， 1990目3) Ellis， E. N. F. : Conc巴ptsof fluid therapy in diabetic ketoacidosis and hyperosmolar hyp巴rglycemicnonketotic coma目 Pediatr.Clin. North. Am. 37 : 313-321， 1990. 4) Gerich， J.， Penhos， J.， Gutman， R. and Recant， L.: Effect of dehydration and hyperosmolarity on glucos久fr巴巴 fattyacid and keton body metabolism in the rat. Diabetes 22 : 264← 27l， 1973. 5) Brautusch・Marrain，P. R. and DeFronzo， R. A. : Impairment of insulin mediated glucose metabolism by hyp巴rosmolarityin man. Diabetes 32・1028-1034，1983. 6) Mitsukawa， T.， Toshimori， H.， Yamaguchi， H.， Enoki， S.， Nakatsuru， O. and Matsukura， S.: Two cas巴Sof secondary central diabetes insipidus associated with hyperosmolar diabetic coma. ]. Japan Diabetic Society 35 : 31-35， 1992. 7) Rosenberg， S. A.， Brief， D. K.， Kinney， J.M.， Herrera， M. G.， Wilson， R. E. and Moor， F. D. : The syndrome of dehydration， coma， and severe hyperglycemi丘 withoutketosis in patient convalescing from burns目 New Eng. ]. Med. 272 : 931← 938， 1965 8) Aruey， G. K.， Pearson， E. and Sutherland， A. B.目 Burnstress ps巴udodiabetes目 Ann.Surg. 152 : 77-90， 1960. 9) Mandell， F. and Fellers， F.: Hyperglycemia in hypernatremic dehydration. Clin. Pediatr.13 : 367-369，1974. 10) Stevenson， R. and Bowyer， F.: Hyperglycemia with hyperosmolar dehydration in nondiabetic infant. ]. Pediatr. 77 : 818-823， 1970. 11) Tasaka， Y.， Matsumoto， H.， Inoue， Y.， Mochizuki， N. and Hirata， Y. : Plasma insulin and glucagon and their releas巴 frompancreatic islet in hyperosmolar diabetic rat. Endocrinol. Jap. 38 : 53-59， 1991 12) Hirano， A.， Hidaka， H.， Kojima， H.， Harano， Y. and Shigeta， Y. : Supprssive effect of vasopressin on ketosis in diabetic rats.日orm目 Metab目 Res.24 : 5-9， 1992. 

A CASE OF DIABETES INSIPIDUS ACCOMPANYING THIRST DISORDER ASSOCIATED WITH HYPEROSMOLAR DIABETIC COMA

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A CASE OF DIABETES INSIPIDUS ACCOMPANYING THIRST DISORDER ASSOCIATED WITH HYPEROSMOLAR DIABETIC COMA

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