Metastatic paraganglioma: management of orthostatic hypotension – a case report
A 40 year old lady with malignant metastatic paraganglioma was admitted electively to a medical ward for management of severe and incapacitating orthostatic hypotension.\nShe had been diagnosed at the age of 10 following unsuccessful treatment of suspected migraines. She had had symptoms of severe headaches and visual disturbances associated with sweating and vomiting, and had been treated with clonidine therapy. During a visit to her general practitioner, her blood pressure was noted to be unreadably high, and she was therefore immediately sent to hospital. In hospital, chest x-ray demonstrated a right-sided paravertebral opacity, and 24 hour urine collection revealed increased catecholamine levels. She underwent thoracotomy and tumour excision, and a diagnosis of extra-adrenal phaeochromocytoma was made. She was discharged from follow-up 3 years later.\nAt the age of 23, she became pregnant and had debilitating morning sickness and regular urinary tract infections. At 32 weeks' gestation, a 24 hour urine collection was performed and revealed increased catecholamines once again, at which point she was admitted to hospital. Investigations, including MIBG scanning, revealed recurrence of the paravertebral mass in her chest, and a deposit in the left scapula was also noted. She was started on oral labetalol at this point. She remained in hospital until the onset of labour at 38 weeks, at which point she underwent elective Caesarean section under general anaesthesia. 3 months post-partum, she commenced the first of five cycles of intravenous MIBG therapy, the duration of treatment lasting 2 ½ years in total.\nFollowing this treatment she remained well for the next 8 years, during which time she underwent premature menopause at age 25. At age 29, with the assistance of in-vitro fertilization, she gave birth to twins, this pregnancy being eventful only by the need for Caesarean section due to breech position and hysterectomy being necessary intra-operatively due to intra-partum haemorrhage. She was subsequently commenced on hormone replacement therapy.\nShe remained under regular follow-up, and another 24 hour urine collection 5 years following her second pregnancy revealed increased catecholamines once again. MIBG imaging demonstrated the known lesions in the shoulder and chest, and she underwent 2 cycles of MIBG therapy, which was complicated by thrombocytopenia. Following this she underwent repeat resection of the right thoracic mass which was adherent to the lung.\nAfter this she remained under regular follow-up and was well, with normal urinary catecholamine secretion, until three years later when 24 hour urinary cathecholamines increased again. She underwent four further cycles of MIBG therapy, however on this occasion the catecholamine response was poor and she had also developed pain in the thoracic spine, which on further investigation (including MIBG and magnetic resonance imaging) proved to be caused by spread into the vertebral column at T3. She underwent debulking surgery including vertebral reconstruction, which led to a reduction in urinary catecholamine level; however, over the course of several months her pain increased, and further investigation revealed re-growth of the debulked tumour along with multiple new lesions throughout the spine. She underwent radiotherapy to the spinal lesions and was commenced on CVD chemotherapy.\nManagement of blood pressure in this patient has been extremely complex, with the need to control severe blood pressure surges whilst at the same time to avoid postural drops both from the anti-hypertensive medications used and from the disease process itself.\nFollowing the completion of her first cycle of CVD she developed profoundly symptomatic orthostatic hypotension requiring admission, with postural drops of 40–90mmHg in systolic BP, leaving the patient virtually bed-bound and causing severe distress. Her BP prior to this had been managed successfully with labetalol 200mg twice daily and amlodipine 5mg once daily. In hospital, she was found to be clinically dehydrated and management was initially with aggressive intravenous fluid replacement, which caused a transient improvement in both symptoms and postural BP drop. Relief of symptoms with intravenous hydration was very short-lived however, and although clinically euvolaemic following this, her orthostatic symptoms persisted. The amlodipine dosage was reduced to 2.5mg daily and sertraline (which she had been taking for depression) was stopped. Her BP having stabilized to some degree, she was discharged, but then readmitted for recurrence of severe orthostatic hypotension associated with paroxysms of severe hypertension; on this occasion, she was liberally intravenously hydrated, amlodipine was stopped and phenoxybenzamine was commenced, titrating up to a final dose of 20mg twice daily whilst continuing labetalol 200 mg twice daily. On this regimen she improved. Although her BP surges settled, she continued to have symptomatic orthostatic hypotension. Therefore labetalol was reduced to 50mg twice daily and phenoxybenzamine to 10mg twice daily. This resulted in an improvement both in symptoms and in BP profile, with only occasional (and short-lived) paroxysms of hypertension and, although she continues to have orthostatic hypotension, this is reduced in severity and causing very little in the way of symptoms.