Primary hypodipsia in a cat with severe hypernatremia

Abstract

Clinical summary:

A 4.5-year-old male castrated domestic shorthair cat presented with a 2-month history of muscle tremors progressing to weakness, pelvic limb ataxia, mild facial twitching, poor appetite and polyuria. Primary hypodipsia and resultant hypernatremia was diagnosed. Intensive fluid therapy and monitoring were initially required for stabilization, and the cat’s condition was successfully managed long-term using canned food supplemented with additional water.

Practical relevance:

Primary hypodipsia is rare in clinical practice, but experience with this case suggests that associated hypernatremia can be successfully managed using a water-enriched diet to provide maintenance hydration.

Case history

A 4.5-year-old male castrated domestic shorthair cat presented with a 2-month history of muscle tremors progressing to weakness, pelvic limb ataxia, mild facial twitching, poor appetite and polyuria.

Clinical investigation prior to referral

One month prior to presentation the cat had been examined, hospitalized, and treated for 3 days at another facility. Diagnostics had included an unremarkable complete blood count (CBC). A chemistry panel revealed azotemia (creatinine 282.9 µmol/l; reference interval [RI] 50–110 µmol/l, urea 33.6 nmol/l; RI 3.6–7.1 nmol/l) and hyperphosphatemia (2.62 mmol/l; RI 0.8–0.16 mmol/l). Marked hypernatremia and hyperchloridemia were reported as greater than the level of detection (>180 mmol/l and >160 mmol/l, respectively). Feline leukemia and feline immunodeficiency virus tests were negative. Urine specific gravity (USG) was 1.035, with pyuria observed; aerobic culture was negative. Mild hyperaldosteronemia was present (488 pmol/l; RI 194–388 pmol/l).

The cat was hospitalized for 3 days and treated with intravenous fluids (Normosol-R; Abbott Laboratories) at 5.2 ml/kg/h. The patient was discharged with hypernatremia (170 mmol/l), but was clinically improved and eating. While hospitalized, drinking was not observed. Discharge instructions included monitoring of water consumption, administration of subcutaneous fluids (42.7 ml/kg q48h), and feeding of water-enriched canned food. At the time of discharge, the cat’s appetite was normal and muscle tremors had resolved; however, personality and activity level had not normalized.

Patient evaluation on presentation

Initial examination on presentation to the authors revealed quadriparesis, with the pelvic limbs being more affected. The cat was unable to rise but could maintain sternal recumbency. Mental dullness was present, and the cat was dehydrated. It became fractious when handled or restrained. Except for a grade 2/6 left parasternal systolic heart murmur, physical examination was unremarkable.

Initial laboratory testing included a CBC and serum chemistry panel. Key pertinent findings were a leukocytosis (32 × 10⁹/l; RI 3.4–13.5 × 10⁹/l) with a mature neutrophilia (30 × 10⁹/l; RI 1.5–9.6 × 10⁹/l), hematocrit of 38% (RI 31–51%), total protein of 100.0 g/l (RI 67.0–89.0 g/l), azotemia (creatinine 397.8 µmol/l; RI 79.6–203.3 µmol/l, urea 42.5 nmol/l; RI 5.4–12.5 nmol/l), hyperphosphatemia (3.97 mmol/l; RI 0.84–2.84 mmol/l), hyperglycemia (14.76 mmol/l; RI 4.16–7.43 mmol/l), hyperproteinemia (total protein 85 g/l; RI 55–71 g/l), severe hypernatremia (219 mmol/l; RI 148–157 mmol/l), hyperchloremia (>175 mmol/l; RI 115–128 mmol/l) and normokalemia. Urine was not initially available.

Therapy

Initial therapy included administration of intravenous fluids at 10.4 ml/kg/h (Plasmalyte-A; Abbott Laboratories) to correct hypernatremia and dehydration. Free water deficit was estimated to be 1189 ml based on the equation: (weight in kg) (0.6) [(patient sodium – 155) ÷ 155]. Initially, a conservative approach was taken using solely isotonic crystalloid, with a planned recheck of the patient’s sodium. Because the cat was fractious, a sedative combination of butorphanol (0.2 mg/kg) and dexmedetomidine (5.2 µg/kg) was administered intravenously to allow recheck of electrolytes, urine collection via cystocentesis, and completion of an abdominal ultrasound exam.

After 2 h of fluid therapy the sodium had decreased to 215 mmol/l. Serum osmolality via freezing point depression revealed severe hyperosmolality (496 mOsm/kg; RI 290–330 mOsm/kg). Urinalysis revealed a USG of 1.020, 2+ proteinuria, rare granular and hyaline casts, rare calcium oxalate crystals, and 10–25 white blood cells per high power field. Urine culture was negative. Measured urine osmolality was 802 mOsm/kg. Abdominal ultrasound revealed mild bilateral adrenal enlargement (left: 1.1 × 0.52 cm; right: 1.26 × 0.58 cm) and mild bilateral chronic degenerative changes within the renal cortices.

The cat was hospitalized for intravenous fluid therapy for a total of 3 days, and electrolytes were monitored twice daily. The target decrement in serum sodium concentration was 10–12 mmol/day. ¹ Adjustments to choice of fluids and fluid rate were made according to changes in electrolytes. Two days after admission the cat ate readily and was able to stand. Muscle fasciculations were only noted when the patient was approached. During hospitalization the cat drank minimal water once and, when questioned, the owner reported similar observations. On day 3 of hospitalization, plasma sodium was 188.0 mmol/l and an esophagostomy tube was placed to facilitate water administration. Financial constraints necessitated discharge prior to normalizing serum sodium concentrations, which remained quite elevated at 180.5 mmol/l.

Initial follow-up

The working diagnosis at discharge was primary hypodipsia with severe hypernatremia. Feeding instructions included slowly increasing kilocalories fed to achieve resting energy requirements after 3 days. Initially, supplementation of water via the esophagostomy tube was conservative to avoid rapid sodium correction and potential neurologic complications from cerebral edema including stupor, coma, seizures or death. Water was available in the home environment and intake was closely monitored.

Over the ensuing 14 days the patient was observed drinking a small amount on one occasion only, with no measurable water intake detected by the owner. The patient and sodium levels were rechecked frequently. The cat began eating canned food about 10 days after discharge, to which water was added. As hypernatremia persisted but slowly improved the volume of supplemental water provided via the esophagostomy tube was gradually increased to 225 ml a day. Two weeks after discharge plasma sodium was 161.0 mmol/l. At this time the patient was consuming approximately an additional 176 ml water by mouth with food per day, representing a total daily water intake of 401 ml (83 ml/kg/ day).

In the following weeks increasing amounts of water were added to the cat’s canned food and the water provided via the esophagostomy tube was reduced. Throughout this period the cat rarely drank water. The esophagostomy tube was dislodged 5 weeks after placement. Four days later sodium concentration was 163.0 mmol/l and the cat was consuming approximately 217 ml water per day via water-enriched food. Serum creatinine was normal (185.6 µmol/l; RI 79.6–203.3 µmol/l) and there was a mildly elevated urea nitrogen (13.6 nmol/l; RI 5.4–12.5 nmol/l). USG was low (1.012), indicating dilute urine.

Long-term follow-up

Detailed follow-up examination was performed 10 months after discharge, at which point the cat was reported to be active and behaving normally. The owner observed spontaneous water drinking from 6 months post-discharge, averaging 1–2 ounces per day (6.3–12.6 ml/kg/day). Canned food mixed with water was being fed, providing an estimated total daily water intake of 266 ml (56 ml/kg/day).

General physical examination was unremarkable. Neurologic examination revealed normal cranial nerve function, and normal proprioception and hopping responses in the thoracic limbs. The pelvic limbs had absent proprioception and reduced hopping responses. A serum chemistry panel revealed hypernatremia (sodium 163 mmol/l; RI 148–157 mmol/l), and elevated creatinine (229.8 µmol/l; RI 79.6–203.3 µmol/l) and urea (20.2 nmol/l; RI 5.4–12.5 nmol/l). Urinalysis revealed a USG of 1.024.

To help exclude pituitary dysfunction, which could affect release of antidiuretic hormone and result in hypernatremia, resting cortisol was measured and was normal (85.5 nmol/l; RI 27.6–137.9 nmol/l). Thyroid function testing revealed a total T₄ of 19.3 nmol/l (RI 24.5–61.8 nmol/l), which was interpreted as likely euthyroid sick syndrome, although additional testing would be needed to definitively rule out hypothyroidism. Aldosterone concentration was suppressed (9 pmol/l; RI 194–388 pmol/l), excluding hyperaldosteronism; patients with hyperalosteronism typically are not hypernatremic.

At the time of writing, 18 months after diagnosis, the cat was continuing to consume a water-enriched canned food diet, and exhibit normal behavior and activity levels.

Discussion

This report describes a cat with primary hypodipsia and resultant hypernatremia. Hypodipsia is rare in clinical practice, and the degree of hypernatremia was remarkable in this case. The cat’s thirst was disproportionately low relative to the presence of persistent hypernatremia. At the time of initial evaluation, spontaneous water consumption was rare, and 6 months later the fluid intake remained inadequate.

Hypernatremia typically results from hypotonic fluid losses (eg, vomiting/diarrhea, diabetes mellitus). Hypernatremia secondary to impermeant solute gain (eg, salt poisoning, hyperaldosteronism) or pure water loss (eg, primary hypodipsia, diabetes insipidus, fever, inadequate access to water) are both uncommon. ¹ Primary hypodipsia has been previously described in two cats^2,3 and several dogs.^1,4–7

In fully conscious animals without polyuria and with access to water, the cause of hypernatremia is most often abnormal osmoregulation of antidiuretic hormone and hypodipsia from hypothalamic lesions. Hypernatremia does not typically result in clinical signs unless the increase occurs rapidly and/or sodium exceeds 180 mmol/l. Clinical signs of hypernatremia are associated with central nervous system dysfunction and may include lethargy, weakness, mental dullness, seizures, coma and even death. ¹

An antidiuretic assay was unavailable for this patient. The cat’s urine concentration suggests diabetes insipidus was highly unlikely as those patients typically have USG <1.006 and/or only occasionally achieve isosthenuria. ⁸ The cat’s urine osmolarity likewise did not support the presence of diabetes insipidus. Pets with diabetes insipidus also have an intact thirst mechanism and display an avid thirst.

Commencing from 6 months after discharge the cat was reported to consistently drink 1–2 ounces of water daily. This equates to 6.3–12.6 ml/kg/day, which is well below a normal water intake of 20–70 ml/kg/day. ⁸ Advanced brain imaging was not possible but might have revealed malformations of the corpus callosum and prosencephalon. ¹ Osmoreceptors that stimulate thirst are located in this region, just rostral to the hypothalamus, and a lesion in this region could have resulted in an abnormal thirst response. ³

Conclusions

Cases of hypernatremia and hypodipsia can be successfully managed by feeding water-enriched diets to provide maintenance hydration. ¹ This cat was managed successfully for more than 20 months with this approach.