Saudi Journal of Kidney Diseases and Transplantation

CASE REPORT
Year
: 2017  |  Volume : 28  |  Issue : 3  |  Page : 625--628

Recurrent syndrome of inappropriate antidiuretic hormone secretion due to tolterodine in an elderly male patient


Abdullah K Alhwiesh1, Husain Alsharani2, Eman Fathi Ibrahim2, Zaid Alanazi2, Bushra Ahmed AlGhamdi2, Nadia Alaudah3, Feras Alzahrani2, Adnan Alsarawi2, Ashwaqu Almohaws2, Ibraheem Saeed Abdurrahman1,  
1 Department of Internal Medicine, Division of Nephrology, King Fahd Hospital of the University, Imam Abdulrahman Bin Faisal University, Al-Khobar, Saudi Arabia
2 Department of Internal Medicine, Division of Nephrology, Security Force Hospital, Eastern Province, Dammam, Saudi Arabia
3 Department of Pathology, Dammam Medical Complex, Dammam, Saudi Arabia

Correspondence Address:
Abdullah K Alhwiesh
Department of Internal Medicine, Division of Nephrology, King Fahd Hospital of the University, Imam Abdulrahman Bin Faisal University, Al-Khobar
Saudi Arabia

Abstract

Hyponatremia is defined as serum sodium of <135 mmol/L and equates with a low serum osmolality once translocational hyponatremia and pseudohyponatremia are ruled out. True hyponatremia develops when normal urine-diluting mechanisms are disturbed. In elderly patients, this complication is not uncommon, especially in nursing homes and assisted living facilities. Medications are often the most common cause of hyponatremia in these patients. Herewith, we reported a 65-year-old Saudi male, a known case of benign prostatic hypertrophy and hypertension, who developed recurrent hyponatremia secondary to tolterodine. To our knowledge, this is the fifth case reported in literature of such association.



How to cite this article:
Alhwiesh AK, Alsharani H, Ibrahim EF, Alanazi Z, AlGhamdi BA, Alaudah N, Alzahrani F, Alsarawi A, Almohaws A, Abdurrahman IS. Recurrent syndrome of inappropriate antidiuretic hormone secretion due to tolterodine in an elderly male patient.Saudi J Kidney Dis Transpl 2017;28:625-628


How to cite this URL:
Alhwiesh AK, Alsharani H, Ibrahim EF, Alanazi Z, AlGhamdi BA, Alaudah N, Alzahrani F, Alsarawi A, Almohaws A, Abdurrahman IS. Recurrent syndrome of inappropriate antidiuretic hormone secretion due to tolterodine in an elderly male patient. Saudi J Kidney Dis Transpl [serial online] 2017 [cited 2019 Nov 15 ];28:625-628
Available from: http://www.sjkdt.org/text.asp?2017/28/3/625/206471


Full Text

 Introduction



Drug-induced hyponatremia is becoming the most common cause of hyponatremia.[1],[2] Thiazide diuretics are the most common culprits, followed probably by selective serotonin reuptake inhibitors. Hyponatremia can be mediated by vasopressin analogs such as desmopressin (brand name DDAVP, 1-desamino-D- arginine vasopressin), drugs that enhance vasopressin release, and agents that potentiate the action of vasopressin. In other cases, the mechanism is unknown. Increasing use of desmopressin for nocturia in elderly patients and enuresis in young persons has resulted in a marked increase in the number of reported cases of hyponatremia. Most patients with a serum sodium above 125 mmol/L are asymptomatic. Below 125 mmol/L, the patients start to develop headache, lethargy, nausea, reversible ataxia, psychosis, seizures, and coma may occur as a result of cerebral edema. Rarely, hypotonicity leads to cerebral edema so severe that there is increased intra-cerebral pressure, tentorial herniation, respiratory depression, and death. Hyponatremia-induced cerebral edema usually occurs with the rapid development of hyponatremia, typically in hospitalized postoperative patients receiving diuretics or hypotonic fluids. In patients with untreated severe hyponatremia, mortality is as high as 50%.[3] We herewith report a 65-year-old Saudi male, a known case of benign prostatic hypertrophy and hypertension, who developed recurrent episodes of hyponatremia secondary to tolterodine. To our knowledge, this is the fifth case in literature of such association.

 Case Report



A 65-year-old Saudi male, known case of hypertension and benign prostatic hypertrophy since five years was maintained on the following medications: amlodipine 10 mg once daily, bisoprolol 5 mg once daily, lisinopril 10 mg once daily, simvastatin 10 mg once daily, aspirin 81 mg once daily, and tolterodine tartrate 2 mg once daily. He was referred to the emergency department at the Security Forces Hospital for a complaint of cough for the past three days. The cough was dry in the beginning but became productive with white sputum. There was no history of chest pain, hemoptysis, breathlessness, or fever. He gave a history of frequent admissions due to hyponatremia, three times during the past two years, with the last one being four months before the present admission.

On examination, the patient was conscious, oriented to time, place, and person. Vital signs including blood pressure of 140/80 mm Hg, pulse rate of 72/min, and respiratory rate of 18/min were normal and he was afebrile. Head and neck examination and jugular venous pressure were normal and the chest was clear.

Cardiovascular system was normal, abdomen was soft, nontender with no organomegaly, there was no edema, and the peripheral pulses were intact. Central nervous system examination was normal. The patient was admitted to the hospital with a provisional diagnosis of tracheobronchitis.

Investigations performed included the following: hemoglobin 11.5 g/dL, platelet 440, white blood cell count 8.3, blood urea nitrogen 22 mg/dL, creatinine 0.5 mg/dL, serum sodium 121 mmol/L, potassium 4.3 mmol/L, chloride 98 mmol/L, urine sodium 30 mmol/L and serum osmolality 260, urine osmolality 300, random blood sugar 150 mg/dL, serum triglyceride 150 mg/dL, total cholesterol 140 mg/ dL, total protein 6.5 g/L, and serum uric acid 6 mg/dL. Thyroid function tests and serum cortisol were within normal limits. Chest X- ray and abdominal ultrasound were normal. Patient was treated initially with fluid restriction to <1 L/day but without improvement; after three days, the serum sodium dropped to 118 mg/dL and the urine osmolality increased to 320; tolterodine was discontinued on the 3rd day as a possible inducer of syndrome of inappropriate antidiuretic hormone (SIADH) secretion. On the 4th day, serum sodium increased to 123 and urine osmolality dropped to 250, and on the 5th day, the serum sodium was 128 and urine osmolality was 213. After one week, the serum sodium rose to 135 and urine osmolality was 200 [Table 1].{Table 1}

 Discussion



Hyponatremia, defined as a serum sodium level <135 mmol/L, is the most common electrolyte abnormality in hospitalized patients. Certain drugs (e.g., diuretics, antidepressants, and antiepileptics) have been implicated as causes of either asymptomatic or symptomatic hyponatremia.

However, hyponatremia occasionally may develop in the course of treatment with drugs used in everyday clinical practice (e.g., newer antihypertensive agents, antibiotics, and proton- pump inhibitors).[4] Diuretics make up one of the most common causes of hyponatremia, with an estimated incidence of 11% in one series of 114 geriatric patients.[5],[6],[7] Interestingly, diuretics are the most common cause of community-developed hyponatremia.[1] Diuretic- induced hyponatremia is caused almost exclusively by thiazide or thiazide-like agents.[1],[5] Loop diuretics, by inhibiting sodium chloride reabsorption in the thick ascending limb of the loop of Henle, reduce the osmolality of the renal medullary interstitium. Consequently, loop diuretics are rarely associated with hyponatre- mia because they impair both the renal concentrating and diluting mechanisms. Conversely, thiazide diuretics act solely in the distal tubules and do not interfere with urinary concentration and the ability of antidiuretic hormone (ADH) to promote water retention, which is the critical point for the development of hyponatremia.

Tolterodine is commonly used to treat patients with overactive urinary bladder. The usual dose is 2 mg twice per day (extended release 4 mg once daily) and has a half-life up to 24 h.[8],[9],[10] The most common adverse reactions are dry mouth, dizziness, constipation, urinary retention, dry skin, and postural hypotension; hyponatremia has been reported in a few cases in the literature. Juss et al reported a case of a 78-year-old female hospitalized with increased confusion and worsening of urinary retention. Tolterodine had been initiated during hospital admission two months earlier. During the second admission, the patient was treated with norfloxacin for urinary tract infection and developed antibiotic-associated diarrhea. The patient’s serum sodium dropped to 125 mmol/L and hyponatremia persisted after diarrhea resolved. After tolterodine was discontinued, the serum sodium increased to 135 mmol/L, and when the patient was re- challenged with tolterodine, her serum sodium decreased to 117 mmol/L and the hyponatre- mia resolved again to 137 mmol/L when tolterodine was discontinued. Our case was similar to the reports of Juss et al[11] and Ustun et al[12] whose patients rapidly responded to the discontinuation of tolterodine within 48 h. The fact that urine osmolality exponentially decreased with the improvement of serum sodium [Table 2], raised important questions about tolterodine-induced SIADH secretion that could be due to increased central production of the ADH or potentiating its action on renal collecting duct, which causes SIADH secretion. Further investigations are needed to evaluate the mechanism of tolterodine-induced hyponatremia.

 Acknowledgment



The authors express their sincere thanks and appreciation to all nursing staff at male medical word and the technical staff at the Security Forces Hospital, Dammam.

Conflict of interest: None declared.

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