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Year : 2015  |  Volume : 11  |  Issue : 4  |  Page : 1032

Inappropriate antidiuretic syndrome hypersecretion after a single dose of cisplatin

1 Department of Pediatric Oncology, Gulhane Military Medical Academy, Ankara, Turkey
2 Department of Pediatrics, Gulhane Military Medical Academy, Ankara, Turkey

Date of Web Publication15-Feb-2016

Correspondence Address:
Erman Atas
Department of Pediatric Oncology, Gulhane Military Medical Academy, Ankara
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0973-1482.146131

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 > Abstract 

Severe hyponatremia with seizure owing to the syndrome of inappropriate antidiuretic hormone secretion (SIADH) or cerebral/renal salt wasting syndrome related with high mortality. The correct diagnosis of the hyponatremia for each case is important because of the alteration of the treatment approach. SIADH is an important clinical manifestation that does not occur after all chemotherapy courses. We cannot estimate whether the disease will occur on, which course of the chemotherapy in this case.

Keywords: Antidiuretic hormone, cisplatin, inappropriate hypersecretion

How to cite this article:
Atas E, Kesik V, Karaoglu A, Kalkan G. Inappropriate antidiuretic syndrome hypersecretion after a single dose of cisplatin. J Can Res Ther 2015;11:1032

How to cite this URL:
Atas E, Kesik V, Karaoglu A, Kalkan G. Inappropriate antidiuretic syndrome hypersecretion after a single dose of cisplatin. J Can Res Ther [serial online] 2015 [cited 2021 Jan 27];11:1032. Available from: https://www.cancerjournal.net/text.asp?2015/11/4/1032/146131

 > Introduction Top

Syndrome of inappropriate antidiuretic hormone secretion (SIADH) and cerebral/renal salt wasting syndrome (C/RSWS) related with high mortality are two potential causes of severe hyponatremia with seizure. However, the clinical and laboratory findings overlap in most cases. As a result, controversy and delay in diagnosis and treatment of this clinical entity may be seen in these cases. Anticancer agents such as vincristine, melphalen and cyclophosphamide may induce SIADH.[1] However, we cannot estimate which course of the chemotherapy will cause. In this article, we reported hyponatremic seizure owing to SIADH after first dose of cisplatin treatment in this case with osteosarcoma.

 > Case Report Top

A 5-year-old boy was admitted with pain and swelling of right knee that was begun within 4 weeks. Magnetic resonance imaging of the right femur revealed an 8 cm mass in diaphyso-metaphyseal region of the distal femur with periosteal reaction. Pathological examination of the Tru-cut biopsy specimen from the right femur was consistent with classic osteosarcoma, osteoblastic variant instead of Ewing/primitive neurectodermal tumors. Chemotherapy protocol consisting high-dose methotrexate, doxorubicin and cisplatin was initiated.[2] Hyperhydration (3000 cc/m 2) was applied before receiving a single dose of cisplatin (60 mg/m 2/day during 2 days) with support of mannitol and magnesium sulfate on day 1. Generalized tonic-clonic seizure after 8 h from the first dose of cisplatin infusion was observed. The seizure lasted about 1 min without supporting of any antiepileptic medication. The blood pressure (BP) was 130/70 mmHg. Edema or respiratory distresses were not found. Serum sodium as 116 mEq/L, potassium as 2.48 mEq/L, urinary sodium as 200 mEq/L, urine osmolality as 335 mOsm/kg water, serum osmolality as 284 mOsm/kg water, FeNa as 2.7%, and urine beta 2 microglobuline as > 0.1 (0.02–0.25) were determined at time of convulsion. Plasma renin and aldosteron activity was found normal. BP was followed in normal level. Intravenous hidration was changed with 1/2 NaCl (70 mEq/L sodium) and 2 mEq/kg potassium. Control sodium and potassium levels were 114 and 2.68 mEq/L. Sodium level was planned to increase to the level of 130 mEq/L with 3% NaCl. However, the level of sodium was not increased from 116 mEq/L. We thought that these findings were more compatible with SIADH than C/RSWS. Fluid restriction (Input = Output + 400 cc/m 2) was started. 0.9% NaCl was used for insensible fluid replacement with 1/2 NaCl hidration. Despite fluid restriction and sodium replacement with 0.9% NaCl, the serum sodium level standard steady at 118 and 120 mEq/L in the 1st and 2nd days, respectively. Insensible fluid replacement was changed from 0.9% to 3% NaCl supplementation and serum sodium level increased slowly to normal and stand in same levels in 7 days. Nifedipine and amlodipine instead of furosemide were started for hypertension which was found 3 times high 140/80, 130/100, and 120/95 mmHg, respectively (BP = 112/72 mmHg; 95 p). After sodium level was reached 130–132 mEq/L, insensible replacement was changed from 3% to 0.9% NaCl first. Then, 0.9% NaCl was changed to 1/2 NaCl owing to steady state. Potassium level was also reached normal level and decreased to 1 mEq/kg. Nifedipine was stopped on day 2 and amlodipine on day 10 of the treatment parallel with the normalization of serum sodium level. The patient was discharged from hospital with 134 mEq/L sodium level and 0.2% FeNa. Oral salt tablet was prescribed to the patient. After steady state of sodium in normal level, this was also stopped. Cisplatin was changed with carboplatin on the following chemotherapy courses and no problem occurred. There was not any neurologic damage or physical finding due to hyponatremia confirmed with brain computed tomography and electroencephalography.

 > Discussion Top

Diagnostic criteria for SIADH are following: (1) Absence of adrenal, thyroid and renal insufficiency, heart failure, nephrotic sydrome, cirrhosis, diuretic intake, dehydratation, (2) urine osmolality >100 mOsm/kg (usually > plasma), (3) hypoosmolality; generally serum osmolality < 280 mOsm/kg, (4) serum sodium <135 mEq/L, (5) FeNa > 0,5 and (6) urine sodium >30 mEq/L.[3] Diagnosing of C/RSWS or SIADH is difficult. Hyponatremia owing to these causes is commonly misdiagnosed and treated with different ways. Because both conditions share similar laboratory values such as hypotonic hyponatremia and increased urine sodium. In this case, urine hyperosmolarity, plasma hypoosmolarity, severe hyponatremia, excessive urine sodium excretion, normal renal parameters and high BP were detected. Sodium loss was replaced with hyperosmolar sodium fluid first. However, we did not manage to increase sodium to the normal level. The patient may have been presumed to have SIADH. The high BP was thought as volume retention with body weight gain due to SIADH without sign of dehydratation. Furthermore, we thought that the extracellular volume and central venous pressure could be high in SIADH. Because of these reasons, we started fluid restriction and managed to keep stable sodium with hyperosmalar insensible support.

The exact mechanism on SIADH of cisplatin is unknown. A possible explanation may be cisplatin-induced hyponatremia with inappropriate antidiuresis.[4],[5] Before the seizure, this case was hydrated with 1/3 NaCl (50 mEq/L sodium) with the rate of 3000 cc/m 2. Also, we gave mannitol infusion concomitant with cisplatin infusion for prophylaxis, but SIADH occurred, which did not respond to hyperosmolar sodium replacement. Resolving of the symptoms could be improved slowly in a nearly 7 days with fluid restriction methods.

As in this case, hyponatremia due to inappropriate antidiuresis-induced by cisplatin appears to be rapid onset and transient.[4],[5] Increased sensitivity the patient's kidney to arginin vasopressin (AVP) or the presence of another antidiuretic substance immunologically distinct from AVP may be other possible causes.[5],[6],[7] High atrial natriuretic peptid (ANP) levels may probably be increased secretion by increased wall tension of atrial tissue owing to increased extracellular volume.[5] These two mechanisms about ANP and AVP were more suitable for this case after hyperhydration, but the mechanism of SIADH after cisplatin was unexplained.

In some studies, cisplatin was changed with carboplatin for following chemotherapy courses as we did.[8],[9] However, cisplatin administration without any change in plan of chemotherapy resulted with no complication in some reports. Recovery from glomerular toxicity owing to cisplatin is observed in most children if damage is not severe.[10] This was compatible with our patient's clinical course. The reason why cisplatin may not cause SIADH in the following courses is not clear whereas SIADH may be occurred by cisplatin again after the second cycle in some cases. After carboplatin is substituted for cisplatin, no further episodes of SIADH is observed.[11] Cisplatin was changed to carboplatin in our treatment schedule, and SIDH was not observed. Sodium level was stable and in normal range after treatment cycles of carboplatin. We recommend the changing.

Treatment of complications may be different from each other. Thus, the exact diagnosis of the disorder is very significant for patient's health and management of treatment. Although fluid restriction and sodium replacement are the major treatment options, the normalization of serum sodium level can be slower than expected as in this case. Another effective underlying pathway which cannot be clearly showed may cause this clinical course. The alterations in serum sodium, urine sodium, and volume status of the patient can cause a delay in diagnosis and exact treatment. In addition, the response time to sodium supplementation treatment is may be different and changed from person-to-person. Follow-up is important in treatment of these patients. Serum and urine sodium status should be checked closely for confidence in the diagnosis.

Syndrome of inappropriate antidiuretic hormone secretion is an important clinical manifestation that does not occur after all chemotherapy courses. We cannot estimate whether the disease will occur on which course of the chemotherapy. Thus, we should be alert for SIADH or other complications that need urgent diagnosis and treatment. A delay in diagnosis and treatment may cause severe morbidity and even mortality.

 > References Top

Verbalis JG, Goldsmith SR, Greenberg A, Schrier RW, Sterns RH. Hyponatremia treatment guidelines 2007: Expert panel recommendations. Am J Med 2007;120 11 Suppl 1:S1-21.  Back to cited text no. 1
Goorin AM, Schwartzentruber DJ, Devidas M, Gebhardt MC, Ayala AG, Harris MB, et al. Presurgical chemotherapy compared with immediate surgery and adjuvant chemotherapy for nonmetastatic osteosarcoma: Pediatric Oncology Group Study POG-8651. J Clin Oncol 2003;21:1574-80.  Back to cited text no. 2
Decaux G, Musch W. Clinical laboratory evaluation of the syndrome of inappropriate secretion of antidiuretic hormone. Clin J Am Soc Nephrol 2008;3:1175-84.  Back to cited text no. 3
Levin L, Sealy R, Barron J. Syndrome of inappropriate antidiuretic hormone secretion following dis-dichlorodiammineplatinum II in a patient with malignant thymoma. Cancer 1982;50:2279-82.  Back to cited text no. 4
Kamoi K, Ebe T, Hasegawa A, Sato F, Takato H, Iwamoto H, et al. Hyponatremia in small cell lung cancer. Mechanisms not involving inappropriate ADH secretion. Cancer 1987;60:1089-93.  Back to cited text no. 5
Zerbe R, Stropes L, Robertson G. Vasopressin function in the syndrome of inappropriate antidiuresis. Annu Rev Med 1980;31:315-27.  Back to cited text no. 6
Robertson GL. Cancer and inappropriate antidiuresis. In: Ruddon RW, editor. Biological Markers of Neoplasia. New York: Elsevier, North-Holland; 1978. p. 277-93.  Back to cited text no. 7
Stern JW, Bunin N. Prospective study of carboplatin-based chemotherapy for pediatric germ cell tumors. Med Pediatr Oncol 2002;39:163-7.  Back to cited text no. 8
Hamdi T, Latta S, Jallad B, Kheir F, Alhosaini MN, Patel A. Cisplatin-induced renal salt wasting syndrome. South Med J 2010;103:793-9.  Back to cited text no. 9
Brock PR, Koliouskas DE, Barratt TM, Yeomans E, Pritchard J. Partial reversibility of cisplatin nephrotoxicity in children. J Pediatr 1991;118:531-4.  Back to cited text no. 10
Brown KR, Leitao MM Jr Cisplatin-induced syndrome of inappropriate antidiuretic hormone (SIADH) in a patient with neuroendocrine tumor of the cervix: A case report and review of the literature. Eur J Gynaecol Oncol 2010;31:107-8.  Back to cited text no. 11


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