An interesting case of Hyponatremia
Dr Siva Sankar MDNB Resident
Department of Internal MedicineMallige Medical Centre
Bangalore
Dr Ravindra TSHead of the Department
Department of Internal MedicineMallige Medical Centre
Bangalore
History
• Mrs. S, aged 48 years, house wife from Bangalore was brought to ER at 10 pm.
• Complaints• Altered sensorium for past 4 hours.
• One episode of loose stool in the morning.
• Also had pain in the epigastrium with sour belching.
• No history of cough, breathlessness, fever.
• No history of weight loss.
• No history of any diuretic use.
Past History
• Similar complaints of altered sensorium twice in the past 10 months with low serum sodium levels and received treatment for same in another hospital.
• Seizure disorder since 2004. Initially on 2 AEDs (Phenytoin, Clobazam) and later tapered to one AED (Phenytoin) for past 2 years. Currently seizure free for past 2 years.
• Left eye sub macular hemorrhage in the year 2014 due to choroidal neo-vascular membrane. Received Intra-vitreal Injection Bevacizumab.
• Abdominal wall pedunculated tumor which was excised in 2016, and HPE confirmed as Fibro-epithelial tumor.
Menstrual and Obstetric History
• Menopause at the age of 26 years.
• Prior to that excessive bleeding during cycles, with frequency of 1 month ± 1 week.
• One male child full term normal vaginal delivery without any post-partum complications at the age of 19 years.
• No history of any abortions.
Clinical Examination
• HR - 86/min, RR - 18/min, SpO2 - 96% on room air, BP - 136/78 mm Hg in Right upper limb supine position.
• CVS – Normal S1 S2, No S3 or S4, No added sounds or murmurs.
• RS - Bilateral Vesicular breath sounds heard, No adventitious sounds.
• PA – Soft, No tenderness, No organomegaly, Bowel sounds heard.
• CNS – Drowsy and arousable, Pupils equally reacting, Moves all limbs, No neck rigidity, No papilledema, Bilateral plantar flexor.
Investigations
• Blood urea – 16 mg/dL
• Serum creatinine – 0.48 mg/dL
• Serum Sodium – 113 mEq/L
• Serum Potassium - 3.8 mEq/L
• Bicarbonate – 20.10 mEq/L
• eGFR – 116 mL/min/m2
• Serum osmolality – 245 mOsm/kg
• Urine osmolality – 691 mOsm/kg
• Urine Sodium - 271 mOsm/kg
• Uric Acid – 2.9 mg/dL
• Blood glucose – 109 mg/dL
Suggestive of SIADH
(Syndrome of Inappropriate secretion of Anti Diuretic
Hormone)
Investigations
• Hemoglobin – 11.9 g/dL
• Total WBC count - 5600/mm3
• Neutrophils – 62%, Lymphocytes – 31%,Eosinophils – 6%, Monocytes – 1%
• ESR – 65 mm at the end of first hour.
• Total/Direct/Indirect Bilirubin – 0.6/0.2/0.4 mg/dL
• AST – 49, ALT - 18, ALP - 72, GGT - 44
• Total Protein/Albumin/Globulin - 7.2/4.3/2.9 g/dL
Next...
• Patient was started on 3% NaCl and Tolvaptan.
• Her Sodium improved to 130 mEq/L over next 2 days.
• Her sensorium improved.
Further investigations
• CT Brain plain – Mild cerebral edema (done at the time of admission).
• Chest X ray – Superior mediastinal widening with infiltrates in both lungs.
• Ultrasound Abdomen – Multiple enlarged abdominal lymph nodes.
• CECT Abdomen – Multiple enlarged abdominal lymph nodes in the retroperitoneum, peripancreatic regions.
• HRCT Chest – Multiple mediastinal enlarged lymph nodes with nodular thickening with in bilateral upper lobes and ground glass appearance.
• HIV, HBsAg, HCV – Negative.
Thyroid Profile
• T3 – 0.42 ng/mL (0.70 - 2.00)
• fT3 – 0.50 pg/mL (0.82 - 2.00)
• T4 – 1.40 mcg/mL (4.50 - 11.0)
• fT4 – 0.14 ng/dL (0.82 - 2.00)
• TSH – 0.07 μIU/mL (0.40 - 4.20)
Suggestive of Central hypothyroidism
Adrenal function
• Cortisol (8 AM) – 0.82 μg/dL (7-28)
• Cortisol (4PM) – 0.74 μg/dL (2-18)
• ACTH (8 AM) – 3.6 pg/mL (5-27)
Suggestive of Secondary Adrenal
Insufficiency
Other Pituitary hormones
• FSH – 0.6 mIU/mL (36.6 - 168.8)
• LH – 0.1 mIU/mL (14.4 - 62.2)
• Prolactin – 5.1 ng/mL (4.79-23.3)
MRI for Pituitary gland
• Partial empty sella.
Differential Diagnosis
• Tuberculosis
• In favor:Her PPD test was 14 mm at 48 hours. Her ESR is 65 mm.
• Against:Long standing history, No typical symptoms of tuberculosis.
Differential Diagnosis
• Sarcoidosis
• In favor:She had generalized lymph node enlargement (Cervical, Mediastinal and Abdominal) and infiltrates in both lungs on Chest X-ray and also HRCT chest.
• Against:Her Serum ACE levels – 38 μmol/L (12-68)
NOTE: Elevated ACE levels are reported only in 60% of patients with acute disease and only 20% of patients with chronic disease
Differential Diagnosis
• Methylene Tetra hydro folate Reductase (MTHFR) deficiency.
• Homozygous MTHFR deficiency was reported in a 20 year old male patient who presented with Choroidal Neovascular Membrane formation and Hypo-pituitarism from Turkey in the year 2014.
(Aydogan Aydogdu, et al - Combined choroidal neovascularization and hypopituitarism in a patient with homozygous mutation in methylenetetrahydrofolate reductase gene. J Res Med Sci. 2014 Jan; 19(1): 75–79.)
• These patients have elevated homocysteine levels and are at risk of thromboembolic events.
Differential Diagnosis
• Methylene Tetra hydro folate Reductase (MTHFR) deficiency.
• In favor:She had Left eye Choroidal neo-vascular membrane with sub macular hemorrhage.
• Against:Her Homocysteine levels – 12.89 mmol/L (< 15 mmol/L)
Treatment
We started the patient on• Anti-Tubercular Treatment.
• Prednisolone.
• Thyroxine.
• By the third day her Sodium reached to normal levels and she is without any Sodium supplements or Tolvaptan.
Follow up
• No more symptoms of altered sensorium.
• Her Serum Sodium levels were consistently in the normal range.
What literature says???
• Harrison Principles of Internal Medicine says "Hyponatremia can occur in patients with adrenal insufficiency due to diminished inhibition of ADH release by Cortisol resulting in mild SIADH.
• Nelson Textbook of Pediatrics says"Patients with adrenal insufficiency may present resembling SIADH""In patients with pan-hypopituitarism, treating cortisol deficiency can increase free water excretion, thus unmasking central diabetes insipidus"
Take home points...
• Always a good history will give a clue to the diagnosis.
• Never miss menstrual and obstetric history in females.
• Before labelling as SIADH• Always rule out Renal, adrenal, thyroid insufficiency, Heart failure, Nephrotic
syndrome, Cirrhosis of liver.
• Rule out diuretic ingestion.
Thank you
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