Endocrine Abstracts

Introduction: Syndrome of inappropriate antidiuretic hormone secretion(SIADH) is frequently encountered in clinical settings. Hyponatraemia is often seen in cancer and correlates with poor prognosis. It can rarely precede cancer diagnosis. We present a case series of two patients with idiopathic SIADH, who developed terminal malignancy later in life.

Case 1: A 59-year-old female presented in 2016 with seizure due to severe euvolemic hyponatraemia Na103 moml/l (135-145 mmol/l). She received hypertonic solution followed by fluid restriction. Biochemistry showed plasma osmolality 267 mOsmol/kg, urine osmolality 304 mOsmol/kg, urine sodium 55 mmol/l, 9am cortisol 414 nmol/l, TSH 2.1 mU/l. CXR showed small left pleural effusion. MRI brain/CT Chest/abdomen/pelvis were unremarkable. Citalopram was ceased. A diagnosis of idiopathic SIADH was made with advice on long term fluid restriction. Mild hyponatraemia (Na 126-135) persisted until presentation in 2023 with severe hyponatraemia 113 mmol/l requiring hospital admission. CT chest/abdomen/pelvis showed a pulmonary nodule 23×15 mm in the left upper lobe confirming small-cell lung cancer.

Case 2: A 51-year-old female presented in 2014 with severe euvolemic hyponatraemia Na110 mmol/l. She had a history of anorexia nervosa. Biochemistry showed plasma osmolality 260 mOsmol/kg, urine osmolality 342 mOsmol/kg, urine sodium 62 mmol/l, 9 am Cortisol 280 nmol/l, TSH 3.0 mU/l and unremarkable CT head/chest/abdomen and pelvis. No regular medications that could lead to hyponatraemia were identified. Following a diagnosis of idiopathic SIADH, patient was commenced on tolvaptan due to difficulty maintaining stable sodium by fluid restriction. In 2018, she developed dysphagia and was diagnosed with metastatic squamous cell carcinoma of the oesophagus.

Discussion: Although hyponatraemia was observed in several types of cancer, the aetiology of cancer-associated hyponatremia (CAHN) remains poorly understood. About 14% of inpatients hyponatraemia is due to underlying cancer-related-condition. The most common cause of hyponatremia in cancer is thought to be SIADH. There is, however, an increasing evidence for functional involvement of Na⁺-transporting-proteins in malignancy. It is hypothesised that various sodium transporting proteins are expressed during early cancer development which gradually deplete sodium. Therefore, hyponatremia can predate cancer diagnosis; however, the evidence overall is not completely clear. As most studies of cancer-related hyponatraemia are carried out in oncology, these patients have multiple confounding variables making it difficult to discern whether hyponatraemia predates or follows malignancy. In the cases presented, hyponatraemia preceded the diagnosis of cancer by a few years further strengthening the role of sodium-transporting proteins in CAHN.

Conclusion: Meticulous follow up in patients with previously diagnosed idiopathic SIADH appear to be the key to early cancer diagnosis and better patients’ outcomes.