Water intoxication presenting as a suspected contaminated urine sample for drug testing.

Abstract: A patient was evaluated medically after submitting a urine sample for drug screening that was considered inappropriately dilute. Although it was thought that the dilute urine was the result of purposely adding water, the medical evaluation revealed that the patient had chronic water intoxication from a very strict weight loss regimen. The effect of dietary solute intake on water metabolism by the kidneys and the development of hyponatremia are discussed.

Key Words: hyponatremia, urinary dilution, water intoxication

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Urine drug testing is now commonplace in many industries. To avoid detection, subjects may provide altered or substituted urine samples. A sample is presumed adulterated when the urine specific gravity or creatinine concentration is exceedingly low, and can result in suspension or dismissal from employment. Reported in this article is a case of a 45-year-old asymptomatic woman suspected of providing an altered sample for drug testing after an industrial accident on the basis of a low urine specific gravity and creatinine concentration. Analysis of samples, including a witnessed urine collection, demonstrated hypotonic hyponatremia with maximally dilute urine consistent with water intoxication. Dietary history revealed the cause to be a marked decrease in solute intake combined with increased water ingestion as a result of an aggressive weight loss program. The effect of dietary solute intake on urinary dilution capacity is discussed. This case highlights the need for an understanding of free water metabolism by the kidneys when evaluating the reliability of a urine sample submitted for drug testing on the basis of its dilution and creatinine concentration, to avoid false accusations.

Case Report

A 45-year-old woman was referred for evaluation after the urine sample she submitted for drug testing was found to have a specific gravity of 1.001 and a creatinine concentration of 5 mg/dL. Her medical history was unremarkable. There were no medical diseases in her family. Her height was 157 cm and her weight was 50 kg. Four months before the evaluation, she had started a diet program when her weight was 73 kg. This diet consisted of several natural appetite suppressants and "fat-burning" pills available at health food outlets, avoidance of salt, conversion to an all-vegetarian diet, and large quantities of water intake. Her daily water consumption was estimated at 6 to 8 L/d. She carried water with her on the job site and had a water container with her during the evaluation. She awoke four to five times per night to urinate, and she kept a water container at her bedside. She denied increased thirst, and imbibed the water to suppress her appetite. Before starting the diet, she did not have polyuria, polydipsia, or nocturia. Her urine specific gravity, measured 10 years earlier, was 1.015. Physical examination revealed a thin woman with a blood pressure of 110/60 mm Hg, without postural change. Her heart and lung examination was normal. There was no peripheral edema, and her neurologic examination was normal.

The results of the laboratory evaluation are depicted in the Table. Collection of the urine sample, as requested by the patient, was witnessed. She had hyponatremia (124 mEq/L), with a low serum osmolality (249 mOsm/kg). Her urine was maximally dilute, with an osmolality of 26 mOsm/kg. Her urinalysis was normal except for the presence of ketones.

Discussion

Drug testing of urine samples is now commonplace in industry. (1) To avoid detection, subjects may submit substituted or altered specimens. Methods include adding adulterants to the specimen or imbibing large quantities of water before providing a urine sample. (2,3) Such maneuvers can result in false-negative drug screening. When the specific gravity or creatinine concentration is very low, the urine sample is considered contaminated. (4) The patient in this case had an unusual presentation of water intoxication in that its discovery was prompted by the suspicion that she had submitted an altered urine sample for drug testing, because of extreme dilution.

The ability of the kidneys to excrete free water is normally so great that it is difficult to develop hyponatremia from increased intake alone in the face of normal renal function (approximately 15-20 L/d). (5) Serum hypotonicity normally suppresses antidiuretic hormone (ADH) levels and allows the kidneys to produce maximally dilute urine. Typically, hyponatremia develops in circumstances where there is a persistent elevation in ADH levels, so that urine remains concentrated despite serum hypotonicity, as occurs in congestive heart failure or the syndrome of inappropriate ADH secretion. The patient in this case, in contrast, had maximally dilute urine consistent with suppression of ADH, yet still developed hyponatremia.

What often goes unappreciated is the kidneys' dependence on solute intake (mainly protein and sodium chloride) to excrete free water. The capacity to excrete free water becomes impaired if solute intake, and thus its excretion, is severely curtailed. Maximal free water clearance (c[H.sub.2]O) can be calculated with the following formula: (6)

c[H.sub.2]O = [Solute excretion/Uosm] X 1 - [Uosm/Posm] (1)

Therefore, on a typical diet containing 900 mOsm of solute, if the urine can be maximally diluted to 50 mOsm/kg, water intake would need to exceed 15 L/d to result in dilutional hyponatremia, according to the following formula:

c[H.sub.2]O = [900/50] X 1 - [50/300] = 15L (2)

Such is the case in patients with polydipsia associated with psychiatric disorders, such as so-called psychogenic polydipsia. (7,8) If, in contrast, dietary solute intake is severely limited, hyponatremia can occur with more modest amounts of water intake. On a diet containing only 300 mOsm/d, water intoxication will occur when water intake exceeds approximately 5 L/d despite maximally dilute urine, according to the following formula:

c[H.sub.2]O = [300/50] X 1 - [50/300] = 5L (3)

This mechanism has been postulated to explain the hyponatremia seen in beer drinkers (beer potomania) and lactoovo-vegetarians. (6,9)

The patient imbibed large quantities of water as part of a weight-loss program. Her estimated water intake of 6 to 8 L/d would not usually be associated with the development of hyponatremia. However, it was coupled with a severe restriction in solute intake by refraining from salt intake and conversion to a vegetarian diet. Thus, analogous to beer potomania, she developed hyponatremia due to the combination of excess water intake in the face of restricted solute intake. The maximally dilute urine confirms that ADH levels were appropriately suppressed by the low serum osmolality. The results are consistent with water intoxication from increased intake of free water rather than impaired excretion from persistent ADH effects. The lack of symptoms and neurologic findings is evidence for the chronicity of the disorder.

Water intoxication has been reported previously as a complication of urine drug testing. (10) The patient in that study differs from the one reported here in two aspects. First, the patient presented with symptoms of confusion, slurred speech, and unsteady gait resulting from acute water overload. Second, the patient had inappropriately concentrated urine consistent with the diagnosis of the syndrome of inappropriate ADH secretion, attributed to nausea and vomiting.

Conclusion

The patient was found to have dilutional hyponatremia after evaluation for submission of a dilute urine specimen for random drug screening. The case raises two important issues. One is the potential danger associated with extremely unconventional weight loss programs. Although the patient was asymptomatic, water intoxication can result in cerebral edema, with lethargy, confusion, and seizures. Finally, the patient's evaluation was prompted by the assumption that her dilute urine was indicative of deliberate tampering with the specimen submitted for drug testing and adds weight to objections raised with regard to such mandatory testing. (11)

Table. Results of the patient's laboratory evaluation

Serum
  [Na.sup.+]           124 mmol/L
  [K.sup.+]              4.7 mmol/L
  [Cl.sup.-]            88 mmol/L
  HCO[3.sup.-]          25 mmol/L
  Blood urea nitrogen    6 mg/dL
  Creatinine             0.7 mg/dL
  Osmolality           249 mOsm/kg
Urine
  Specific gravity       1.001
  Osmolality            26 mOsm/kg
  [Na.sup.+]             5 mmol/L
  Creatinine             7 mg/dL
  Trace ketones

Accepted July 24, 2003.

Copyright [c] 2004 by The Southern Medical Association

0038-4348/04/9706-0611

References

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5. Sterns RH, Ocdol H, Schrier RW, et al. Hyponatremia: Pathophysiology, diagnosis, and therapy, in Narins RG (ed): Maxwell & Kleeman's Clinical Disorders of Fluid and Electrolyte Metabolism. New York, McGraw-Hill Health Professions Division, 1994, ed 5, pp 590-599.

6. Thaler SM, Teitelbaum I, Berl T. "Beer potomania" in non-beer drinkers: effect of low dietary solute intake. Am J Kidney Dis 1998;31:1028-1031.

7. Langgard H, Smith WO. Self-induced water intoxication without predisposing illness. N Engl J Med 1964;266:378-381.

8. Rendell M, McGrane D, Cuesta M. Fatal compulsive water drinking. JAMA 1978;240:2557-2559.

9. Hilden T, Svendsen TL. Electrolyte disturbances in beer drinkers: a specific "hypo-osmolality syndrome." Lancet 1975;2:245-246.

10. Klonoff DC, Jurow AH. Acute water intoxication as a complication of urine drug testing in the workplace. JAMA 1991;265:84-85.

11. Rosenstock L, Cullen MR. Routine urine testing for evidence of drug abuse in workers: the scientific, ethical and legal reasons not to do it. J Gen Intern Med 1987;2:135-137.

RELATED ARTICLE: Key Points

* Water clearance by the kidneys is usually so efficient that water intoxication typically only occurs with compulsive water drinking associated with psychiatric illness.

* Water excretion by the kidneys is dependent on adequate dietary solute intake.

* A marked decrease in solute intake decreases the amount of water intake needed to cause water intoxication.

* Diet-induced water intoxication leading to cerebral edema and seizures has been reported in alcoholics and lacto-ovo-vegetarians.

Kevin W. Finkel, MD, FACP 

From the Division of Renal Diseases and Hypertension, University of Texas-Houston Medical School, Houston, TX.

The author has no financial or proprietary interests to disclose.

Reprint requests to Kevin W. Finkel, MD, FACP, Division of Renal Diseases and Hypertension, Department of Medicine, University of Texas-Houston Medical School, 6431 Fannin, MSB 4.148, Houston, TX 77030. Email: [e-mail]