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