Reset Osmostat in a Healthy Patient

Case Report

The 60-year-old man was generally healthy, had an advanced engineering degree, and was a full-time supervisor until he recently retired. His serum sodium levels, documented on multiple occasions at our institution during a 13-year period, ranged from 125 to 130 mmol/L. He denied using cigarettes (since 1968), diuretic agents, and laxatives. He also denied having polydipsia, polyuria, nausea, and emesis. His past medical history was notable for a grenade explosion to the face, in 1951, that resulted in a chronic, low-grade, superficial infection of the orbital area, which persisted until definitive reconstructive surgery was done in 1974. No neurologic sequelae were noted. He also had mild hypertension, treated with a β-blocker, since 1988.

On physical examination, his blood pressure was 140/80 mm Hg with no orthostatic changes. The left eye had been enucleated, and the area was well-healed. The patient was clinically euvolemic with no evidence of edema. The level of serum sodium was 129 mmol/L, of potassium was 4.8 mmol/L, of glucose was 6.05 mmol/L, of blood urea nitrogen was 5.71 mmol/L, and of creatinine was 97.2 µmol/L. The creatinine clearance was 1.70 mL/s with “less than 60 mg” of protein noted after a 12-hour urine collection. Results of cosyntropin stimulation, thyroid function, thyrotropin-releasing hormone stimulation, and liver function tests were all within normal limits. His cholesterol level was slightly increased to 6.67 mmol/L with normal levels of triglycerides and total protein. Computed tomography of the head showed no damage to the hypothalamic–pituitary area, although some superficial metallic fragments were noted around the left orbit. A magnetic resonance imaging scan (with gadolinium enhancement) and a positron emission tomographic scan (using fluorine-18 deoxyglucose and 1-cm slices) showed no evidence of structural hypothalamic-pituitary damage.

Results

Water Loading Test

After an overnight fast, a standard water load of 20 mL/kg was ingested by the patient during a 10-minute period. Serum sodium, urinary and serum osmolality, and plasma arginine vasopressin levels (radioimmunoassay, INCSTAR, Stillwater, Minnesota) were measured at 0, 30, 60, 120, 180, and 240 minutes. After water loading, the urinary osmolality decreased to 76 mmol/kg, and the plasma arginine vasopressin level was not detectable. The serum osmolality decreased from 269 to 260 mmol/kg and the serum sodium level decreased from 127 to 123 mmol/L (Figure 1, top left). The entire water load was excreted in 3.5 hours. The minimum urinary osmolality was 76 mmol/kg, the maximal free water clearance was 0.187 mL/s, and the osmolal clearance was 0.077 mL/s.

Hypertonic Saline Load

After completing the water load, 345 mL of 3% saline was administered intravenously during a 3-hour period. The serum osmolality increased from 265 to 270 mmol/kg, the serum sodium level from 128 to 131 mmol/L, and the urinary osmolality from 411 to 597 mmol/kg Figure 1, top right). Arginine vasopressin levels were not measured during this portion of the test.

Water Deprivation

The patient achieved sodium balance using a 87 mmol/d diet, confirmed by serial 24-hour urine collections. After water deprivation, the serum sodium level increased from 126 to 127 mmol/L and the serum osmolality increased from 263 to 270 mmol/kg. The arginine vasopressin level increased from 0.32 to 1.19 pmol/L, and the urinary osmolality increased from 348 to 538 mmol/kg Figure 1, bottom left). At this time the test was stopped because the patient had lost 2% of his body weight.

During a total period of 6 days, precise evaluation of the patient's urine output was made in our metabolic unit using serial 24-hour urine collections. Urine output averaged 2223 mL/d (range, 1670 to 2500 mL/d). Input was also recorded and averaged 2270 mL/d (range, 2180 to 2480 mL/d). No evidence was noted of polydipsia or polyuria, and he remained hyponatremic.

Discussion

When hyponatremia occurs in a euvolemic person, there are many possible causes [6]. Some of the more important causes include inappropriate antidiuretic hormone secretion in the setting of some tumors, various pharmacologic agents, polydipsia, the postoperative state, and an abnormal resetting of the hypothalamic osmoreceptor. The term “osmoreceptor” is used for those neuronal cells in the anterior hypothalamus that initiate the antidiuretic response [7]. As with other neurons, these cells most likely do not regenerate and, therefore, any damage may be permanent.

We reviewed the database of the National Library of Medicine using a MEDLINE search and found only one report [8] of reset osmostat in a “healthy” person, an 8-month-old infant born with a cleft palate and lip. Our adult patient had chronic stable hyponatremia of the reset osmostat variety but was otherwise healthy.

Comprehensive water concentrating and diluting studies were done. Before the water load, the patient's urinary osmolality was 663 mmol/kg, which was well within 1 SD of the maximum urinary concentration attainable for his age group [9]. The minimum urinary osmolality, the maximal free water clearance, and the osmolal clearance in our patient did not differ from observations in previous studies [5, 10] of healthy persons. A complete neuroradiologic examination and an endocrine evaluation of the adrenal, thyroid, and hypothalamic-pituitary axis could not identify any structural or functional cause to account for the reset osmostat. It is possible that the grenade explosion that the patient had 41 years ago contributed to this reset osmostat variant of hyponatremia, perhaps by specific permanent damage to the hypothalamus.