Introduction:
This case highlights a complex case of severe double-digit hyponatremia which turns out to be pseudohyponatremia due to paraproteinemia associated with multiple myeloma.
The patient's clinical course, diagnostic challenges with respect to evaluation of hyponatremia, and successful management with plasmapheresis and chemotherapy are discussed.
Methods:
Case Presentation:
69-year-old male with a medical history of well-controlled type 2 diabetes of 5 years duration (on glimepiride and metformin) and hypertension of 5 years duration (on telmisartan 40 mg/day). Patient has also been an ex-smoker and was recently, 2 months back, labelled chronic obstructive airway disease (COAD) and started on inhalers (containing bronchodilators and inhalational steroids). The patient also gave a year long history of pain in lower back and paresthesia all four limbs for which he has been taking pregabalin on and off. Patient presented to outpatient department of SMHS Hospital medical wing with one and a half months history of generalized weakness, dyspnea on exertion, and low back pain.
Investigations:
Investigations done in the out-patient setting showed high MCV (108-114) anemia (hb 8.5-9.4 mg/dl) with thrombocytopenia (21000/µl to 69000/µl), with progressively falling platelet count. He had fluctuating renal function with creatinine as low as 0.99 to highest 1.82 g/dl. Serum calcium was high (albumin corrected calcium ranged between 10.6mg/dl-12.16mg/dl) and PTH was low normal (16.9 pg/mL). Both CPK (119 µ/L) and LDH (314 U/L) were normal. He had elevated liver enzymes (AST: 856 U/L and ALT : 844 U/L) but both bilirubin (0.5 mg/dL) and alkaline phosphatase (84 IU/L) were normal.
He was found to have profound hyponatremia (Serum Na < 100 mEq/L) and hypokalemia (Serum K varied between 2.3 mEq/L to 3.0 mEq/L). Severe hyponatremia and hypokalemia prompted hospitalization of the patient as otherwise he had no specific symptoms pertaining to severe double digit hyponatremia. Urine osmolality (freezing point depression) was 598 mOsm/kgH2O but plasma osmolality by same method could not be done.
Spot urinary Na was 130 mEq/L and Spot urinary K was 43 mEq/l. Serum uric acid was 6.6 mg/dL. With urinary biochemical parameters suggestive of syndrome of inappropriate antidiuretic hormone secretion, both thyroid-stimulating hormone (TSH) (4.3 µU/mL) and morning cortisol (11.9 µg/dL) sent were normal and ruled out endocrine etiology.
Results:
Course in hospital
Thought to be chronic hyponatremia, drug history was reviewed and it was attributed to pregabalin use which patient was taking for back pain and paresthesias. Pregabalin was stopped and patient was advised fluid restriction during hospital stay. Patient was advised to restrict all kinds of oral fluids and take liberal salt.
After 24hrs of hospital stay, Instead of getting better, patient worsened and developed neurological symptoms and oral mucosal bleeding. Patient who had no neurological symptoms previously began to start feeling dizzy on standing up and unsteady upon walking. He developed increased somnolence and drowsiness. Repeat labs showed neither worsening nor improvement in hyponatremia. At this point 3% saline was also given as per protocol but with no benefit. With high plasma protein concentration (non-albumin: wide gamma gap of around 10 g/dL (Total serum Protein: 12 g/dL, serum Albumin: 2.0 g/dL)), development of neurological symptoms and oral bleeding with restriction of oral fluids, paraprotein related hyperviscosity was thought and pseudohyponatremia was suspected.
Blood myeloma workup was initially unprocessable due to high viscosity. The laboratory technician reported that even after redrawing the sample and applying higher centrifugal forces (g/min), proper separation of the cells and serum did not occur upon centrifugation. Due to the high viscosity of the blood, processing for paraproteins was not feasible initially. Consequently, urine studies were conducted. The urine test for Bence Jones protein was negative, and urine protein electrophoresis revealed no M band, showing only an albumin peak. Low-dose CT whole spine showed an evidence of fracture of L5 vertebral body involving inferior endplate and surrounded by sclerotic margins suggestive of an old healed fracture, which was probably the cause of chronic back pain in this patients. There were no lytic or blastic lesions seen.
Plasma sodium levels were measured by direct potentiometry by doing analysis on venous blood gas (VBG) machine, which returned normal. Blood viscosity could not be done in any of the labs. Bone marrow aspiration and biopsy showed a hypercellular marrow (80%) with plasmacytosis (51%) in diffuse pattern of infiltration and consisting of immature, binucleate forms and plasmablasts. Both erythropoiesis (with normoblastic maturation) and myelopoiesis (with all stages of maturation) were suppressed.
Patient was given two sessions of plasmapheresis with albumin replacement. His symptoms got better. Meanwhile , immediately after the first plasmapheresis blood sample was again sent for myeloma proteins. Serum Protein Electrophoresis showed huge M-band at gamma region (M protein: 5.4g/dl). Serum Protein Immunofixation typified Monoclonal protein as IgG Lambda. Immunoglobulin Assay showed high IgG : 71 g/l with depressed IgM (0.24 g/L) and IgA (0.19 g/L). Serum free light chain assay showed normal kappa concentration (15.24 mg/l) and high lambda concentration (188.9 mg/l). Echo done as an evaluation of dyspnea showed moderate concentric left ventricular hypertrophy with global LV hypokinesia and reduced LV ejection fraction (40%). Both total cholesterol (55 mg/dL) and total triglycerides (32 mg/dL) were very low likely dilutional effect by paraproteins.
Treatment and Outcome:
Worsening of symptoms during hospital course was attributed to iatrogenic dehydration aimed to correct hyponatremia which increased the blood viscosity further therefore causing encephalopathy and oral mucosal bleeding. After a decrease in sensorium, the patient was administered IV fluids. Once the sensorium improved, liberal intake of oral fluids was recommended.
Plasmapheresis was initiated to remove serum paraproteins and decrease blood visvocity with twofold goals: one, alleviate patients symptoms and other decrease blood viscosity so that blood sample could be processed. The patient exhibited improvement with plasmapheresis and was initiated on CyBorD chemotherapy.
The patient's neurological symptoms, oral bleeding, and hyponatremia responded positively.
Conclusions:
This case underscores the importance of suspecting and separating pseudohyponatremia cases from true hyponatremia, the latter being more common. Timely plasmapheresis and chemotherapy led to a favorable clinical response in this case of multiple myeloma with atypical presentation as hyperviscosity syndrome and pseudohyponatremia. Some lessons to learn from the above case report are:
Pseudohyponatremia is always asymptomatic vis a vis symptoms pertaining to true hyponatremia, although patient may have symptoms of underlying disease which has resulted in pseudohyponatremia at the first place.
Severe hyponatremia if asymptomatic should raise suspicion of pseudohyponatremia, such patients should get their plasma sodium levels repeated by direct potentionmetry methods like blood gas analysers.
Difficult to correct hyponatremia, using fluid restriction and 3% saline, should raise suspicion of pseudohyponatremia because no matter how we change the plasma and water ratio, the non-water artifact will persist.
If upon fluid restriction plasma sodium levels do not improve and instead patients clinical condition worsens it should raise suspicion of hyperviscosity and pseudohyponatremia
I have no potential conflict of interest to disclose.
I did not use generative AI and AI-assisted technologies in the writing process.