Severe Hyponatremia: An Association with Lisinopril?

Abstract

A 63-year-old white woman with a history of hypertension and chronic obstructive pulmonary disease presented to the emergency room with worsening shortness of breath, anorexia, coughing, increased thirst, and leg edema of two weeks' duration. Medications included lisinopril 10 mg/d, which had been started six weeks earlier, sustained-release theophylline 300 mg q12h, and an albuterol inhaler. The lisinopril was discontinued on admission. Serum sodium concentration was 109 mmol/L; the osmolality of the blood and of the urine were 253 mOsmol and 438 mOsmol, respectively, with a specific gravity of 1.025 and a urine sodium of 17 mmol/L. The hyponatremia initially was considered to be the syndrome of inappropriate antidiuretic hormone secretion in response to the patient's suspected pneumonia. Due to worsening blood pressure, lisinopril was restarted and the serum sodium concentration dropped from 134 to 126 mmol/L. Evaluation of the patient's hyponatremia included assessment of thyroid, adrenal, hepatic, and cardiac function that were within normal limits. The patient was discharged on the following medications: sustained-release theophylline 300 mg tid, prednisone 10 mg/d, albuterol inhaler 2 puffs q6h, and sustained-release verapamil 240 mg/d for blood pressure control. Her serum sodium concentration has remained between 135 and 140 mmol/L during hospitalizations for exacerbations of chronic obstructive pulmonary disease and for pneumonias 10 and 12 months after discharge.

Effects of Antihypertensive Drugs on Thyroid Function in Type 2 Diabetes Patients With Euthyroidism

“…Renin-angiotensin-aldosterone system (RAAS) is activated by thyroid hormones in hyperthyroidism ( Silverstein et al, 1983 ). But no association between ACEI and ARB treatment with thyroid function change was found with euthyroid ones in this study, in accordance with other clinical studies ( Hume et al, 1990 ; Andjelkovic et al, 2016 ), conflicting with an animal study ( Vranckx et al, 1995 ). The increased intracellular availability of Ca 2+ plays an important role in the regulation and secretion of thyroid hormones ( Lalau et al, 1987 ).…”

“…However, the evidence for thyroid function-changing effect of second-and third-generation β 1 -adrenergic receptor blockers in euthyroid cases shows contrary outcomes (Kristensen and Weeke, 1977;Faber et al, 1979;Perret et al, 1984;Reeves et al, 1985;Kayser et al, 1991). The effect of ACEI, ARB (Hume et al, 1990;Vranckx et al, 1995;Andjelkovic et al, 2016) and CCB (Brabant et al, 1989;Jangid, 1993;Eidne et al, 1994;Roussel et al, 1995;Roussel et al, 1997;Pedemonte et al, 2005) on thyroid function were not consistent between animal study and clinical studies and the sample size was small (Isles et al, 1985;Haitas et al, 1986;Valensi et al, 1989;Andjelkovic et al, 2016).…”

An Unexpected Case of Lisinopril-Associated Severe Hyponatremia

“…The cessation of medication along with the initiation of fluid restriction typically resulted in the normalization of hyponatremia without significant adverse effects [ 3 ]. In one case, the re-initiation of lisinopril during the hospital stay corresponded with a decrease in serum sodium concentration [ 7 ]. In general, the outcome remains positive.…”

Prevalence of Hyponatremia and Association with Mortality: Results from NHANES

“…Specifically, we identified participants with evidence of hypertension, diabetes, congestive heart failure 30 , liver disease 19 , kidney disease 5 , stroke 35 , Chronic Obstructive Pulmonary Disease 36 , cancer 23 , HIV 37 , depression and other psychiatric disorders. We also identified subjects who were using medications with known or suspected associations with hyponatremia including diuretics, angiotensin-converting-enzyme (ACE) inhibitors 38, 39 , angiotensin receptor blockers (ARBs), nonsteroidal anti-inflammatory agents (NSAIDs), selective serotonin reuptake inhibitors (SSRIs), and tricyclic antidepressants (TCAs) 40 , carbamazepine, and lamotrigine. 6 Detailed description of methods used to identify comorbidities and medication usage is described in the Appendix.…”