An unusual case of hyponatraemia Natasha Porcu Southampton General Hospital

Mrs M 30 yr old Portuguese female pc: presented in A&E (13/12/04)- abdominal pain and frequent vomiting On examination: abdomen soft and tender, BP 162/94 Pregnancy test (+) ectopic pregnancy? - plasma β-HCG: 682 IU/L (500-10, weeks pregnant) - normal ultrasound

dh: not on any prescribed medication sh: 10 cigarettes/day, ½ bottle of wine/night regular cannabis user pmh: admitted 8 months earlier with abdominal pain Gastritis? pain resolved after 2 days.

Blood Test requested ResultReference range Sodium134 mmol/L mmol/L Potassium4.8 mmol/L mmol/L Urea5.7 mmol/L mmol/L Creatinine85 mmol/L mmol/L Corrected calcium2.29 mmol/L mmol/L Total protein75 g/L63-80 g/L Haemoglobin133 g/L g/L White blood count6.7x10 9 /L x10 9 /L Platelet count182x10 9 /L x10 9 /L Red blood count4.8x10 12 /L x10 12 /L

High blood pressure/tachycardia throughout her hospital stay Free T4= 48.9 pmol/L ( ) TSH= <0.01 mIU/L ( ) TFT’s (21/12/04)

Abdominal pain Gastritis, constipation, appendicitis ruled out Porphyria? Random urine porphyrin screen (24/12/04) Porphobilinogen - detected Urine porphyrin 1800 nmol/L (0-320) Porphyrin/creatinine ratio (0-35) Acute Intermittent Porphyria

Trend in measured plasma sodium during her hospital stay

Day 14: plasma Na 103 mmol/L ( ) plasma osmolality=225 mOsmol/kg ( ) urine osmolality= 735 mOsmol/kg urine sodium= 57 mmol/L Syndrome of inappropriate ADH secretion (SIADH)? Summary: acute porphyria, pregnant, thyrotoxic with SIADH

SIADH: A diagnosis of exclusion Criteria: low plasma sodium and osmolality urine sodium >20 mmol/L urine osmolality inappropriately high (>200 mOsm/kg) patient should be clinically euvolaemic exclude renal, adrenal, hypopituitary and cardiac disease exclude drugs that may affect water balance clinical and biochemical improvement to water restriction

Acute Intermittent Porphyria Haem Biosynthetic Pathway Marshall WJ, Bangert SK. Clinical Chemistry. 5th ed. 2004

rare autosomal dominant disorder (1-2 cases:100,000 in UK) build-up of neurotoxic porphyrin precursors during an acute attack Precipitating factors: alcohol physical/emotional stress weight loss hormonal changes many drugs - AIP

Symptoms of acute intermittent porphyria (AIP ) Abdominal pain Nausea and vomiting Tachycardia Hypertension Hyponatraemia (SIADH) Psychological disturbances Muscle weakness Thyrotoxicosis? neurological

Brodie et al (1978), 17 patients with AIP: 13 in remission (normal thyroid function) 4 in acute attack- had significantly elevated thyroid hormones (increase related to severity of attack) ‘‘AIP may represent a reversible cause of hyperthyroidism in man…… increased thyroidal sympathetic neural stimulation may be responsible’’ Brodie et al. Thyroid function in acute intermittent porphyria: A neurogenic cause of hyperthyroidism? Horm Metab Res 1978; 10:

Recovery of Mrs M IV haem-arginate to suppress the pathway (26/12/04) Propanolol and propylthiouracil for thyrotoxicosis (24/12/04) Random urine sample: porphobilinogen (not detected) urine porphyrin 78 nmol/L (0-320) Free T4= 19.3 pmol/L ( ) TSH= 0.02 mIU/L ( ) Na = 137 mmol/L on discharge