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Endocrinol. Japon. 1990, 37 (6), 787-796

A Case of Pseudo-Bartter's Syndrome Associated with Hypergastrinemia, Thrombocytosis and Increased Serum Thyroxine-Binding Globulin

KAZUTOSHI OKANO, KAZUKO SASAGAWA, HOZUMI ISOBE, NORIAKI SEKITA, SATOSHI SUZUKI, SATORU NAITOH, YUKIO YAMADA, MAKOTO SHIMIZU AND KAZUHIKO SOMEYA

Third Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki 216, Japan

Abstract

A housewife, 40 years of age, was admitted with dysesthesia of the extremities, muscle weakness, and attacks of adynamia and thirst. She had been taking a laxative for more than 20 years. On physical examination, pressure was 94/56 mmHg. Laboratory tests revealed thrombocytosis, low serum K and marked increases in both plasma renin activity and serum . Serum TBG was increased. Serum gastrin was also markedly increased and could not be enhanced by exogenous secretin. Both angiotensin 11 loading test and noradrenalin loading test failed to increase blood pressure. chloride loading to examine the disturbance of urinary acidification was abnormal in the short term test and borderline in the long term test. Following a diagnosis of pseudo-Bartter's syndrome induced by long term intake of laxative and repeated diarrhea, the administration of laxative was interrupted and , indomethacin and were administered. However, serum K remained low. Hypergastrinemia, thrombocytosis and a high serum TBG level also persisted, the causes of which remain unknown. This is the first reported case of pseudo-Bartter's syndrome associated with hypergastrinemia, thrombocytosis and increased serum TBG.

Bartter's syndrome is characterized by (Veldhuis et al., 1979), chronic diarrhea, long an increase in plasma refill activity, an term administration of laxative (Fleischer increase in serum aldosterone, , et al., 1969) or diuretics (Tajiri et al., 1981 metabolic , normo- to hypotension Jamison et al., 1982) and anorexia nervosa and decreased responsiveness of blood (Wolff et al., 1968) also induce a state pressure to exogenous angiotensin 11 similar to Bartter's syndrome, and such a (Bartter et al., 1962). Chronic vomiting syndrome is called pseudo-Bartter's syndrome (Meurer et al., 1968). Recently, cystic Received March 22, 1990 fibrosis (Davison and Snodgrass, 1983), Address correspondence: KAZUTOSHI OKANO, Third Department of Internal Medicine, St. cystinosis (Whyte et al., 1985), jejunoileal Marianna University School of Medicine, 2-16- bypass for obesity (Julkunen et al., 1982) 1, Sugao, Miyamae-ku, Kawasaki 216, Japan and chemotherapy (Lieber et al., 1984) also Endocrinol. Japon. 788 OKANO et al. December 1990

have been reported to induce so called platelets 59.7•~104 and WBC 14,500 (Band pseudo-Bartter's syndrome. 12, Seg 70, Eosino 0, Baso 0, Mono 5, In this paper, we report a case of Lymph 13%). ESR was 57 mm (1 h). pseudo-Bartter's syndrome induced by long Wasserman test, CRP, RA test, LE test, term intake of laxative and chronic diarrhea, antinuclear antibody and HBs antigen were with impaired urinary acidification and negative. HBs antibody was 64•~. IgG which was associated with hypergastrinemia, was 1,073 mg/dl, IgA 286 mg/dl and IgM thrombocytosis and an increase in serum 165 mg /dl. Urinalysis revealed a specific

TBG. gravity of 1.005, no sugar, traces of protein, a moderate degree of blood and normal urobilinogen. In sediment, RBC 8-10/svf Case Report and WBC 3-5/svf were observed. Fecal examination revealed no occult blood and History no parasitic ova. Coagulation tests were A 40-year-old housewife had been taking normal. Blood chemistry revealed TP 7.7 a laxative (Dokusogan) for constipation 3 g/dl (Alb 61.4, ƒ¿1-Gib 2.8, ƒ¿2-Glb 11.2,ƒÀ- times a week, since she suffered from Glb 11.4,ƒÁ-Glb 13.0%), Na 131 mEq/1, K peritonitis at 14 years of age. Stools were 2.0 mEq/l, Cl 91 mEq/1, Ca 9.1 mg/dl, P 2.9 passed every 3 to 10 days accompanied by mg/dl, Mg 2.7 mg/dl, creatinine 1.4 mg/dl, several episodes of diarrhea for one day. BUN 24 mg/dl, Osm 277 mOsm/kg, total In May, 1982, nausea, vomiting, cold sweat- bilirubin 0.6 mg/dl, GOT 10 mU/ml, GPT ing and spasms of the hands as well as 10 mU/ml, LDH 304 mU/ml, Al-P'ase 183 dull back pain appeared, then disappeared mU/ml, ƒÁ-GTP 11 mU/ml, LAP 31 mU/ml, within half a day. Since September, 1982, total cholesterol 336 mg/dl, triglyceride 311 attacks of adynamia appeared every 2-3 mg/di, phospholipid 379 mg/dl, chyromicron months, and her local doctor pointed out 10 mg/dl, VLDL-cholesterol 155 mg/ di, LDL- a renal stone. In March, 1985, hypokalemia, cholesterol 1049 mg/dl, HDL-cholesterol 75 hyperreninemia and hyperaldosteronemia mg/dl, amylase 200 SU/dl, CEA 1.1 ng/ml were pointed out at a hospital and she and AFP below 20 ng/ml. Urinary chemistry was admitted to this department for further revealed Na 44 mEq/day, K 18.7 mEq/day, examinations in July, 1985. Cl 57.9 mEq/day, Ca 110 mg/day and P 270 mg/day. Physical Examination. Among renal function tests, Fishberg's Body height was 149 cm and body test revealed a maximum specific gravity of weight 41 kg. Blood pressure was 94/56 1,012. PSP excretion was 7% (15 min.) mmHg. The right was palpable for and 45% (120 min.). Twenty-four h endo-

a half fingerbreadth. Tenderness and knock genous creatinine clearance was 13.21/day. pain were present in bilateral lumbar Serum BMG was 8.5 ƒÊg/1 and urinary BMG regions. Purpura was observed on the ex- 19, 950 ƒÊg/l. FENa was normal (1.9), FEK tremities. Neurological examination revealed increased (55.2) and FECl normal (4.3). Ex- slight decreases in deep tendon reflexes, cretion of was normal (0.11%). paresthesia and a decrease in muscle Intravenous pyelography revealed calcifica- power. tion of the bilateral . Reno- gram revealed bilateral renal dysfunction. Laboratory Tests Analysis of arterial blood gas revealed pH Peripheral blood examination revealed 7.46, PCO2 37.7 mmHg, PO2 104.2 mmHg, Hb 13.0 g/dl, RBC 418•~104, Hct 38.1%, HCO3-26.4 mEq/l, and SAT 97.6%. Culture Vol.37, No.6 PSEUDO-BARTTER'S SYNDROME WITH HYPERGASTRJNEMIA 789

Fi g . 1 .Ren a l b i o p s y s p e c i me n( P AS s t a i n ,4 0 0x ) . Endocrinol. Japon 790 OKANO et al. December 1990 of was negative. ECG showed a low did not reveal distinct hyperplasia of the T wave, U wave and depression of ST juxtaglomerular complexes, but interstitial segment. The circulating plasma volume was was suspected. marrow 44.3 ml/kg (normal 45 •}5) and circulating puncture revealed that megakariocytes blood volume 66.6 ml/kg (normal 80•}10). were increased in number and small in Roentgenological examination of the size. skull and hands were normal. Cranial CT In endocrinological tests, as shown in scan was normal. Chest X-ray film revealed Table 1, serum GH and serum PRL were an abnormal calcified density posterior to slightly increased. Serum T4 and TBG the heart. Plain abdominal X-ray film, were increased and resin uptake and %TRP abdominal CT scan and abdominal echogram were decreased. Serum cortisol was in- revealed atrophy and of bi- creased, while urinary 17-OHCS was normal. lateral kidneys. Fluoroscopy of the upper The dexamethasone suppression test revealed GI tract and opaque enema were negative. normal suppression of the serum cortisol Endoscopy of the upper GI tract revealed level. Both plasma renin activity and the hypertrophic gastritis, but biopsy of the serum aldosterone level showed marked increases. The angiotensin 11 level was gastric mucosa was normal. In the ex- amination of the gastric juice, BAO was high. Serum gastrin was markedly increased 7.30 mEq/h and MAO 17.56 mEq/h after and was not enhanced by exogenous se- cretin. 75 g OGTT exhibited impaired pentagastrin injection, indicating normal acidity. As shown in Fig. 1, renal biopsy glucose tolerance, while HbAIc was normal

Table 1. Endocrinological tests

Pituitary: serum GH 7.8 ng/ml (below 5.0), plasma ACTH 83 pg/ml (15-85), serum LH 3.3 mIU/ml (4-19), serum FSH 15.1 mIU/ml (10-17.3), serum PRL 27.6 ng/ml (2-20) Thyroid: serum TSH 2.6ƒÊU/ml (1-10), serum T4 14.0ƒÊg/dl (5.6-11.2), Resin uptake 22.0% (23.2-38.4), serum T3 1.0 ng/ml (0.9-2.0), TBG 43.4ƒÊg/ml (12-28) Parathyroid: serum PTH-C 0.78 ng/ml (0.20-1.00), %TRP 74.3% (85-98) Adrenal: plasma renin activity 50.8 ng/ml/h (0.5-2.0), serum aldosterone 1044.9 pg/ml (below 180), serum cortisol 24.7ƒÊg/dl (4-15), plasma angiotensin II 620 pg/ml (below 110), urinary 17-OHCS 5.0 mg/day (1.9-6.1), urinary total 17-KS 1.1 mg/day (3.1-8.8), plasma adrenalin below 10 pg/ml (below 120), urinary adrenalin 4.4 μg/day(below 12),plasma noradrenalin 556pg/ml(40-350),urinary noradrenalin 71.6ƒÊg/day (10-90), plasma dopamine below 200 pg/ml (below 700), urinary dopamine 40ƒÊg/day (100-700) Dexamethasone suppression test (23: 00) (8: 00) serum cortisol 23.6 5.0ƒÊg/dl GI Tract: serum gastrin 2362.3 pg/ml (42-200), serum secretin 94 pg/ml (60-120) Secretin loading test (before) (5 min) (10 min) (20 min) (40 min) serum gastrin 4123.8 3832.6 4463.4 3754.0 3049.6 pg/ml Pancreas: 75 g OGTT (before) (30 min) (60 min) (90 min) (120 min) (180min) serum insulin 5.5 31.1 41.3 167.1 164.1 167.8ƒÊU/ml plasma glucose 88 237 328 396 429 365 mg/dl HbAlc 5.1% (4.0-6.5), serum glucagon 227 pg/ml (70-160) Miscellaneous: plasma PGE 538 pg/ml (below 320), urinary PGE 120 ng/day (below 200), urinary kallikrein 1.08 U/day (below 1.4)

Normal values are indicated in parentheses. Vol.37, No.6 PSEUDO-BARTTER'S SYNDROME WITH HYPERGASTRINEMIA 791

Systolic BP Diastolic BP

Angiotensin II, ng/kg/min

Fig. 2. Angiotensin 11 loading test.

Systolic BP Diastolic BP

Noradrenalin, ng/kg/min

Fig.3. Noradrenalin loading test. Endocrinol. Japon. 792 OKANO et al. December 1990

NH4CI 0.1g/kgBW , per os Short term test Long term test

Fig. 4. Ammonium chloride loading test.

and glucose in 24 h urine was 0.24 g/day. Course The plasma PGE level was high, while This case was diagnosed as pseudo- urinary PGE and kallikrein levels were Bartter's syndrome induced by long-term within nomal limits. As shown in Fig. 2, administration of a laxative and chronic the angiotensin 11 loading test did not diarrhea. As shown in Fig. 5, the laxative cause an increase in blood pressure. As was withdrawn and potassium, indomethacin shown in Fig. 3, the noradrenalin loading and spironolactone were administered. How- test also did not increase blood pressure. ever, the serum K level remained low. The water loading chloride clearance test, Serum gastrin, the number of peripheral which indicates chloride by blood platelets and serum TBG also remained renal tubules, showed a slight decrease. In increased. Body weight was decreased by the ammonium chloride loading test, as 4 kg in 2 years and remained constant shown in Fig. 4, the 8-h method (left panel) thereafter. revealed a decrease in blood HCO3- from 24.8 mEq/1 to 18.8 mEq/l and disturbance of urinary acidification, while the 3-day Discussion method (right panel) revealed that urinary pH was decreased to the normal level (5.2) on Pseudo-Bartter's syndrome is described as the first day and second day but remained a syndrome which is caused by chronic above 5.5 on the third day. vomiting (Veldhuis et al., 1979), chronic diarrhea, long term administration of laxative (Fleischer et al., 1969) or diuretics 793 Vol.37, No.6 PSEUDO-BARTTER'S SYNDROME WITH HYPERGASTRINEMIA

Potassium aspartate

Fig. 5. Clinical course.

(Tajiri et ai., 1981; Jamison et al., 1982). 11 infusion (Bartter et al., 1962). 1 ne anorexia nervosa (Wolff et al., 1968), cystic present case was diagnosed as pseudo- flbrosis(DavisollalldSnodgrass,1983), Bartter's syndrome induced by the long cystinosis (Whyte et al., 1985), jejunoileal term administration of laxative and repeated bypass"for obesity (Julkunen et al., 1982) and diarrhea chemotherapy (Lieber et al., 1984), and With regard to the pathogenesis of displays the same findings as those of Bartter's syndrome, congenital hyporespon- Bartter's syndrome, namely an increase in siveness of peripheral arterioles to angio- plasma renin activity, an increase in serum tensin 11 (Bartter et al., 1962), over- aldosterone, hypokalemia, metabolic alka- production of prostaglandins in the kidney losis, normo- or hypotension and decreased (Fichman et al., -1976; Gill et al., 1976) response of blood pressure to angiotensin and disturbance of chloride reabsorption in Endocrinol. Japon. 794 OKANO et al. December 1990

Henle's loop (Gill and Bartter. 1978) have and chloride reabsorption by renal tubules been reported. However, details of the was slightly decreased, although the urinary pathogenesis remain unclear. In regard to the excretion rate of sodium bicarbonate and pathogenesis of pseudo-Bartter's syndrome, the serum Mg level were normal. The especially that caused by chronic laxative plasma PGE level was high, while urinary abuse (Oster et al., 1980), cyclic vomiting PGE and kallikrein levels were normal. The or diuretic abuse, these factors induce kind of tubular dysfunction observed in this sodium chloride and potassium depletion, case is thought to be due to functional leading to hypovolemia and hypokalemia, changes in renal tubules or tubular nephro- respectively. Hypovolemia causes hyper- pathy caused by long-standing hypokalemia reninemia, an increase in angiotensin 11 (Reiman and Schwartz, 1956). production and finally an increase in Hypergastrinemia has been reported tc aldosterone production. Hypokalemia caused be caused in Zollinger-Ellison's syndrome by these factors and hyperaldosteronemia (Zollinger and Ellison, 1955), pernicious induce an increase in vascular prostacyclin anemia, duodenal ulcer (Tam, 1988). production (Galveg et al., 1977), leading to carcinoid syndrome and chronic renal pressure insensitivity to angiotensin 11 and failure (Muto et al., 1988). In this case. noradrenalin. The suppressive effects on Zollinger-Ellison's syndrome was ruled out, blood pressure of hypovolemia and pressure because gastrin secretion was not enhanced insensitivity to angiotensin 11 and nor- by exogenous secretin, and upper gastro- adrenalin and the enhancing effects on intestinal endoscopy and abdominal CT scan blood pressure of increased blood angio- as well as the examination of gastric juice tensin 11 and aldosterone levels were revealed no abnormalities. Renal function counterbalanced, leading to the maintenance tests including Fishberg's tests, PSP excretion, of normal blood pressure. Hypovolemia urinary BMG and renogram revealed renal causes constipation, which in turn obligates dysfunction in this case, although serum the use of laxatives and invites a vicious creatinine and BUN levels showed slighi circle. increases. However, the hypergastrinemia It has been reported that renal tubular observed in this case could not be explained dysfunction leading to impaircd renal by such a degree of renal dysfunction. As acidification is present in Bartter's syndrome to the cause of hypergastrinemia in this (Stein, 1985). Bartter's syndrome happens case, further investigations are being per- to present features resembling renal tubular formed. There has been no report as- and vice versa (Rodriguez-Soriano et sociating Bartter's syndrome or pseudo- al., 1978 ; Takeda et al., 1973). Impaired Bartter's syndrome with hypergastrinemia. renal acidification has also been reported in The hyperlipemia (Fredrickson type IIb) pseuo-Bartter's syndrome induced by furose- observed in this case might be caused by mide abuse (Tajiri et al., 1981). It is known renal dysfunction or have occurred inci- that urine pH does not necessarily decrease dently, independently of pseudo-Bartter's in the ammonium chloride loading test in syndrome. Although hyperglycemia was a potassium deficient state because hypo- observed in 75g OGTT, HbAi, was normal kalemia enhances the production of am- and analysis of 24 h urine revealed a small monia, and that such an impaired renal amount of sugar, suggesting that such a acidification is normalized by potassium hyperglycemia is transient after meals and supplementation. In the present case, the secondary to hypokalemia in pseudo-Bartter's acidification of urine in the ammonium syndrome. chloride loading test was slightly disturbed In regard to the thrombocytosis observed Vol.37, No.6 PSEUDO-BARTTER'S SYNDROME WITH HYPERGASTRINEMIA 795 in this case, we could not detect any Fleischer, N., H. Brown, D. Y. Graham and S. definite cause inducing thrombocytosis, such Delena (1969). Chronic laxative-induced hy- as hematopoietic disorders, inflammatory peraldosteronism and hypokalemia simulating Bartter's syndrome. Ann. Intern. Med. 70, 791- diseases, neoplasma or essential thrombo- 798. cythemia (Murphy, 1983), although poly- Galuez, O. G., W. H. Bay, B. W. Roberts and cythemia vera and chronic myeloblastic T. F. Ferris (1977). The hemodynamic effects leukemia cannot be completely ruled out. of potassium deficiency in the dog. Circ. Res. There has been no report in which pseudo- 40 (Suppl 1), 1-11-1-16. Bartter's syndrome is associated with Gill, J. R., Jr., J. C. Frolich, R. Bowden, A. A. thrombocytosis. Taylor, H. R. Keiser, H. W. Seyberth, J. A. As to the causes of the increase in Oates and F. C. Bartter (1976). Bartter's syndrome-a disorder characterized by high serum TBG, pregnancy, estrogen adminis- urinary prostaglandins and a dependence of tration, acute intermittent porphyria, hypo- hyperreninemia on prostaglandin synthesis. gammaglobulinemia, acute hepatitis and Am. J. Med. 61, 43-51. hepatoma as well as familial increase in Gill, J. R., Jr. and F. C. Bartter (1978). Evidence serum TBG have been reported (Ross et al., for a prostaglandin-independent defect in 1983; Ramsden et al., 1983). In this case, chloride reabsorption in the loop of Henle as a proximal cause of Bartter's syndrome. Am. however, we could not detect any cause J. Med. 65, 766-772. of the increase in serum TBG except for a Jamison, R. L., J. C. Ross, R. L. Kempson, C. familial trait, which is now under investi- R. Sufit and T. E. Parker (1982). Surreptitious gation. There has been no report in which diuretic ingestion and pseudo-Bartter's syn- pseudo-Bartter's syndrome is associated drome. Am. J. Med. 73, 142-147 with an increase in serum TBG. Julkunen, R., J. Haapalahti, I. Torstila and T. A. Miettinen (1982). A Bartter like syndrome after jejunoileal bypass for obesity. Acta Med. Acknowledgements Scand. 211, 501-503. Lieber, I. H., S. D. Stoneburner, M. Floyd and W. L. McGuffin (1984). Potassium-wasting We are indebted to Dr. Y. Ogura, Toranomon nephropathy secondary to chemotherapy Hospital. and Assist. Prof. H. Nagoshi, St. simulating Bartter's syndrome. Cancer 54, 808- Marianna University, for their helpful advice 810. and to Assoc. Prof. J. P. Barron, St. Marianna Meurer, K. A., W. Kauffman, B. Steiner, J. University, for editing the manuscript. Schurholz, E. Streicher, H. Nieth, F. Durr, H. Held and R. Allner (1968). Zur Differential Diagnose des Bartter-Syndroms. Med. Welt 52, References 2886-2893. Murphy, S. (1983). Thrombocytosis and throm- Bartter, F. C., P. Pronove, J. R. Gill, Jr. and bocythemia. Clin. 1ematol. 12, 89-106. R. C. MacCardle (1962). Hyperplasia of the Muto, S., Y. Asano, S. Hosoda and M. Miyata juxtaglomelular complex with hyperaldos- (1988). Hypochlorhydria and hypergastrinemia teronism and hypokalemic alkalosis. Am. J. and their association with gastrointestinal Med. 33, 811-828. bleeding in young patients with chronic renal Davison, A. G. and G. I. A. I. Snodgrass failure. 50, 5-9. (1983). Cystic fibrosis mimicking Bartter's Oster, J. R., B. J. Materson and A. I. Roggers syndrome. Acta. Paediatr. Scand. 72, 781- (1980). Laxative abuse syndrome. Am. J. 783. Gastroent. 74, 451-458. Fichman, M. P., N. Telfer, P. Zia, P. Speckart, Ramsden, D. B., M. C. Sheppard, R. S. Sawers, M. Golub and R. Rude (1976). Role of S. C. H. Smith and R. Hoffenberg (1983). prostaglandins in the pathogenesis of Bartter's Serum free thyroxine concentrations in normal syndrome. Am. J. Med. 60, 785-797. euthyroid subjects and ones with high serum Endocrinol. Japon. 796 OKANO et al. December 1990

thyroxine binding globulin concentration. presenting as a syndrome resembling Bartter's Clin. Chim. Acta 130, 211-217. syndrome, in a patient with arachnodactyly. Relman, A. S. and W. B. Schwartz (1956). The Acta Endocrinol. 73, 531-542. nephropathy of potassium depletion: a Tam, P. K. H. (1988). Hypergastrinemia in clinical and pathological entity. N. Engl. J. children with duodenal ulcer. J. Pediatr. Med. 255, 195-203. Surg. 23, 331-334. Rodriguez-Soriano, J., A. Vallo and R. Oliveros Veldhuis, J. D., C. W. Bardin and L. M. (1978). Bartter's syndrome presenting with Dembers (1979). Metabolic mimicry of features resembling renal tubular acidosis. Bartter's syndrome by covert vomiting. Am. Helve. Paediat. Acta 33, 141-151. J. Med. 66, 361-363. Ross, D. S., G. H. Daniels, J. L. Dienstag and Whyte, P. M., S. Shaheb and H. W. Schnaper E. C. Ridgway (1983). Elevated thyroxine (1985). Cystinosis presenting with features levels due to increased thyroxine-binding suggesting Bartter's syndrome. Clin. Pediatr. globulin in acute hepatitis. Am. J. Med. 74, 24, 447-451. 564-569. Wolff, H. P., P. Vecsei, F. Kruck, S. Roscher, Stein, J. H. (1985). The pathogenetic spectrum J. J. Brown, G. O. Dusterdieck, A. F. Lever of Bartter's syndrome. Kidney Mt. 28, 85- and J. I. S. Robertson (1968). Psychiatric 93. disturbance leading to potassium depletion, Tajiri, J., M. Nakayama, T. Sato, S. Isozaki sodium depletion, raised plasma renin con- and K. Uchino (1981). Pseudo-Bartter's centration, and secondary hyperaldosteronism. syndrome due to furosemide abuse: report of Lancet 1, 257-261. a case and an analytical review of Japanese Zollinger, R. M. and E. M. Ellison (1955). literature. Jap. J. Med. 20, 216-221. Primary peptic ulcerations of the jejunum as- Takeda, R., S. Morimoto, M. Kuroda and M. sociated with islet tumors of the pancreas. Murakami (1973). Renal tubular acidosis, Ann. Surg. 197, 594-607.