Endocrine Abstracts

A 17 year old woman attended the Emergency Department following an episode of chest pain and pre-syncope, coinciding with high blood pressure readings taken at home. Her blood pressure was recorded as 170/101 with no signs of end organ damage on clinical examination. She had no clinical features of Cushing’s disease or Neurofibromatosis and her BMI was 22.4. She had been seen at a Cardiology clinic 18 months previously for hypertension and chest pains. A 24 hour blood pressure monitor had recorded an average BP of 140/97 mmHg. She was recommended a 6 month trial of lifestyle changes with weight loss and low salt diet. When this was ineffective she was commenced on Ramipril 1.25 mg and Indapamide 2.5 mg. She was on no other regular medications and had no significant family history. Initial investigations in the Emergency Department showed a troponin of 25 ng/l (ref<14), creatinine 96 umol/l and potassium 4.8 mmol/l (3.5–5.3). An ECG showed sinus tachycardia with no evidence of left ventricular hypertrophy and 24 hour urine protein was normal at 0.1 g/24 hrs. Her chest x-ray showed clear lung fields. A transthoracic echocardiogram showed good left ventricular function with a structurally normal heart. 24 hour urinary metadrenalines were performed in primary care and showed elevated Normetadrenaline at 23.4 umol/24 hours (05–3) with 3-Methoxytyramine 2.39 umol/24 hours (05–2.8) and Metadrenaline 0.7 umol/24 hours (05–1.8). A 24 hour urine free cortisol was normal at 45 nmol/24 hours (<120). A CT scan of her adrenal glands showed an 8.9−5.6 cm left adrenal lesion with central necrosis and avid enhancement. The right adrenal gland and other abdominal viscera appeared normal. She was commenced on doxazosin and went on to have a laparoscopic left adrenalectomy. Her procedure and stay in hospital were uncomplicated. Histology confirmed a non-invasive pheochromocytoma with Ki67 0%, PASS score 0 and clear margins. Large areas of the lesion showed SDHB staining positivity. Genetic screening was undertaken which identified a heterozygous Fumarate Hydratase gene missense mutation (NM_000143.3:c.908T>c p.Leu303Ser). This is a rare cause of Hereditary Phaeochromocytoma and Paraganglioma Syndrome which results in intracellular accumulation in fumarate. In common with SDH mutations this results in activation of Hypoxia Inducible Factor alpha (HIFα), resulting in an increased lifetime risk of phaeochromocytomas, paragangliomas, uterine myofibromas and renal cell carcinoma. Her specific mutation (L303S) has previously been reported in one patient who presented similarly with phaeochromocytoma, and whose family history was notable for renal cell carcinoma. Her family now await genetic testing.