Case Report of Vasopressin-Responsive Diabetes Insipidus Associated With Chronic Myelogenous Leukemia

DAVID JUAN, MD,' SHU-DEAN HSU, MD,t AND JAMES HUNTER, MDt

A sixth case in the world literature is reported of a 59-year-old male with diabetes insipidus (DI) associated with chronic myelogenous leukemia (CML). The patient is unique in that his CML was diagnosed 10 years before he presented with vasopressin-responsive DI. Radiation to the central nervous system failed to reduce the daily requirement of his need for vasopressin.

Cancer 56:1468-1469, 1985.

IABETES INSIPIDUS (DI) is a rare complication of D leukemia. In 197 1, Miller and Campbell reviewed the world literature and found a total of 20 reported cases of leukemia associated with DI.' The association of DI and chronic myelogenous leukemia (CML) has been reported in only five cases in the world literature. In most patients this complication developed during or shortly preceding the onset of acute blastic transforma- tion.2"

The following patient is unique in that he had CML 10 years before he presented with vasopressin-responsive DI and continued in chronic phase of CML for more than 18 months after the development of D1.

Case Report

A 59-year-old white man was admitted to the Veterans Administration Medical Center in February 1982 with a I - month history of polyuria and polydipsia. The patient was well until March 1972 when he was hospitalized with a history of weight loss, hepatosplenomegaly, and hernotologic findings compatible with CML. He underwent splenectomy in 1976. He was initially treated with Myleran (busulfan) and from 1975 to 1981 he was given hydroxyurea. Before 1982, his serum electrolyte level and urinalysis results were normal. Significant medical history included chronic obstructive lung disease. The only pertinent finding on physical examination was hepatomegaly of 15 cm.

Laboratory data on admission included serum sodium level of 148 meq/l, potassium level of 4.5 meq/l, chloride level of 104 meq/l, carbon dioxide level of 30 meq/l, glucose level of

Department of Medicine, Northwestern University Medical School, Chicago. Illinois.

t Department of Medicine, University of Arkansas for Medical Sciences, Little Rock, Arkansas.

Address for reprints: David Juan, MD, Northwestern University Medical School, Department of Medicine, 303 E. Superior Street, Chicago, IL 606 I I.

The authors thank Debbie Muse for preparing the manuscript. Accepted for publication November 12, 1984.

97 mg/dl, calcium level of 9.1 mg/dl, cholesterol level of 269 mg/dl, triglyceride level of 552 mg/dl, creatinine value of 1.0 mg/dl. urea nitrogen level of 9 mg/dl. albumin level of 4.0 g/ dl, globulin level of 2.7 g/dl, alkaline phosphatase level of 72 U/L, and lactic dehydrogenase level of 224 U/L. Hematologic findings included hematocrit, 40%; leukocyte count, 2 1,400; myeloblasts, 2.0%; promyelocytes, 2.0%; myelocytes, 4.090: metamyelocytes, 1 .O%; bands, 3.0%; segmented neutrophils. 56%; basophils. 12%; monocytes, 6.0%; lymphocytes, 14%; and platelet count, 3 19,000. Bone marrow aspirate showed myeloid hyperplasia without evidence of blastic transformation. Uri- nalysis was unremarkable except for a specific gravity of I .004. Daily urine output averaged 9 I, with urine osmolarity below I 10 mosmol/kg H20. Skull roentogenogram, lumbar puncture, computerized tomogram of the head, and sella tomograms were all normal.

Results of the 12-hour dehydration test plus response to 5 units of subcutaneous vasopressin are summarized in Table I . A clinical trial of 1 desamino-8-D-arginine vasopressin (DDAVP) 0.1 ml twice a day significantly controlled his symptoms and reduced his urine volume to 2 I/day. A course of radiotherapy to the central nervous system failed to bring about any amelioration of his symptoms or change his require- ment for DDAVP.

Discussion

Diabetes insipidus is a rare complication of leukemia. In the leukemic child, DI may occur alone or as part of the hypothalamic obesity syndrome.' In the 20 cases reputed by Miller and Campbell,' 12 cases were classified as myelocytic, three as lymphocytic, three as monocytic, one as stem cell, and one as hemocytoblastic. The acute form accounted for over 50% in both the myelocytic and the lymphocytic leukemias. DI was the presenting complaint in CML in only five cases and was associated with terminal phase of the disease. The current report is the sixth case in the world literature of CML associated with D1.2-6

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No. 6 VASOPRESSIN-RESPONSIVE DIABETES - Juan et al. 1469

The exact cause of our patient's DI cannot be ascer- tained. Two types of pathologic findings have been described in the pituitary gland in leukemic patients: diffuse leukemic infiltration of the posterior pituitary gland and/or thrombosis of the small vessels in the hypothalamic nuclei and posterior lobe of the pituitary.' Masse and co-workers examined the pituitary glands in adult leukemic patients who came to autopsy and re- ported periglandular infiltration in 46%, none of whom had symptoms of DI.' Leukostasis syndrome associated with leukocyte count greater than 100,000/mm3 and small arteriolar thrombi from leukemic cell aggregation with perivascular bleeding and necrosis has been invoked as an important pathogenetic factor in some leukemic patients with DI.8

Cytologic and radiologic investigations of the central nervous system in these patients are usually disappoint- ing. In the series of Miller and Campbell series, only three of five patients had positive cytologic findings in the cerebrospinal fluid.' Several cases of DI with leukemia occurred before any effective treatment for this disease was available. Nonetheless, recent reports failed to show efficacy of antineoplastic therapy in reducing symptoms of DI in any leukemic patients. Radiation therapy of the central nervous system failed to bring about amelio- ration of our patient's symptoms of DI or reduce the need for DDAVP.

Although our patient responded well to D D A V P , it has been reported that up to 15% of leukemic patients with DI are vasopressin-re~istant.~ Shurygin has reported two cases of vasopressin-resistant DI where leukemic cells had infiltrated the renal tubules."

As more effective antineoplastic therapy appear on the horizon, leukemic patients are expected to live longer than the usual 3 years. One important reason why DI developed in our patient may be because he

TABLE I . Dehydration Test and Response to Vasopressin*

Time Weight Usp Uosm Serum osm

0 90.5 1.004 83 290 4 1.003 105 6 1.004 158 8 I .004 I44

10 1.003 144 12 88.4 1.003 1 I6 305 13 1.006 239 14 1.012 448 15 1.01 I 425

* Five units of vasopressin given subcutaneously at I2 hours.

(hr) (kg) gravity (mosmol/kg H20) (mosmol/kg H20)

survived 10 years after the diagnosis of CMI. Thus, the DI syndrome may become an increasingly prevalent problem in the management of leukemic patients.

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diabetes insipidus. Rev Ass& Med Argent I96 I ; 75:G 1-408. 4. Kovacs K. Manus ZB. Diabetes insipidus syndrome developed

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