History
A 24-year-old woman attended her GP surgery complaining of severe bouts of headaches that have come and gone over several months. She describes the headaches as pound-ing. During an attack she feels anxious with palpitations and sweatiness. These episodes can last up to 20 minutes. There is no vomiting, visual disturbance or other neurological symptoms. She feels well between episodes and has no other medical problems. She has tried taking paracetamol and ibuprofen for the headaches but these did not seem to work.
She does not drink alcohol nor smoke. There are no significant illnesses in her family history.
Examination
A urinalysis did not show any abnormalities. She appeared sweaty and pale but there was no tremor or evidence of weight loss. Fundoscopy did not show papilloedema or other hypertensive changes. Her heart rate was 120/min and regular, blood pressure 220/110 mmHg and respiratory rate 22/min.
On arrival in the ward her blood pressure is now 190/98 mmHg, heart rate 98/min in sinus rhythm. She appears anxious and her headache is still present. Her cardiorespira-tory, abdominal and neurological examinations are all unremarkable. An ECG shows evidence of left ventricular hypertrophy. A chest X-ray is normal.
INVESTIGATIONS
Normal range
White cells 6.1 4–11 ¥ 109/L
Haemoglobin 12.1 13–18 g/dL
Platelets 260 150–400 ¥ 109/L
Sodium 148 135–145 mmol/L
Potassium 4.8 3.5–5.0 mmol/L
Urea 5.4 3.0–7.0 mmol/L
Creatinine 78 60–110 mmol/L
Thyroid-stimulating hormone 2.4 nmol/L 0.4–4.0 mIU/L
Questions
• What is the likely diagnosis and how could it be confirmed?
• What would be appropriate management?
This patient describes intermittent episodes of palpitations, sweating and headache asso-ciated with hypertension. These features raise the possibility of an underlying phaeochro-mocytoma. Other diagnoses to consider are hyperthyroidism (may present with tremor and weight loss but her TSH is normal), carcinoid syndrome (also episodic but presents with intense flushing, associated diarrhoea and wheeze may be present), anxiety attacks (diagnosis of exclusion), recreational drugs (amphetamines and cocaine can mimic the features of an episode).
In phaeochromocytoma these symptoms are due to the episodic release of catecholamines from the tumour. Phaeochromocytomas arise predominantly in the chromaffin cells of the adrenal medulla. They produce adrenaline and noradrenaline. Other sites of tumours include chromaffin cells of the autonomic nervous system (paragangliomas). The surge in catecholamines released by these tumours gives rise to the episodic symptoms and signs (headache, sweating, palipitations and pallor). Tumours are most often benign;
malignancy is more likely to occur in paragangliomas. Most cases are sporadic but up to a quarter of cases are hereditary and occur in multiple endocrine neoplasia (MEN) types 2A and 2B, von Hippel–Lindau disease and neurofibromatosis type 1.
Diagnosis is best made with a 24-hour urine collection for catecholamines and meta-nephrines (the breakdown products of catecholamines), preferably just after an episode.
Serum metanephrines and normetanephrines can also be measured. If the urine or blood test is positive, further investigation is required to identify the source. Imaging by MRI or CT of the abdomen and pelvis will identify most phaeochromocytomas. However if very small they can be missed. If the suspicion is high despite a negative CT or MRI, iodine-131 MIGB (metaiodobenzylguanidine) scintigraphy can be performed. This will detect a phaeochromocytoma anywhere and is 99 per cent specific.
She presents with hypertension and a headache. Initial assessment should begin with determining any organ involvement that would necessitate immediate action to lower the blood pressure. In cases of suspected phaeochromocytoma who are not in a hyper-tensive emergency there are specific management considerations that differ from other causes of severe or malignant hypertension. The treatment aim is to block the effects of catecholamines on the heart and peripheral vasculature by blocking alpha- and receptors. The safest method is administering alpha-blockers first. The reason why beta-blockers cannot be administered right away is that the alpha-receptors in the peripheral vasculature will be completely unopposed. This will lead to vasoconstriction and trigger or worsen a hypertensive crisis. It is important to ensure that patients are adequately hydrated, as a sudden drop in peripheral vascular resistance with alpha-blockade will cause severe hypotension! Normal saline or Hartmann’s solution can be used. Adequate hydration is determined by assessment of the central venous pressure (CVP), mucous membranes, skin turgor and urine output. Choice of alpha-blocker is either phenoxy-benzamine or doxazosin. Once an alpha-blocker is commenced a beta-blocker such as metoprolol can be administered. The beta-blocker will also reduce the tachycardic effect of catecholamines. If hypertension is not controlled with alpha- and beta-blockade a calcium-channel antagonist can be added. In a hypertensive emergency the first-line treatment of choice should be intravenous phentolamine (alpha-blocker). Nitroprusside infusion is an alternative.
Once blood pressure is controlled surgery should be considered. Recurrence is more likely in those with a hereditary cause. If the tumour is benign then surgery has a high cure
127 rate. Malignant tumours have a variable course depending on timing of diagnosis and treatment modalities.
KEY POINTS
• Hypertension secondary to phaeochromocytomas should be controlled with the initiation of an alpha-blocker followed by a beta-blocker.
• Hypertension secondary to phaeochromocytomas is rare. However, in young people presenting with hypertension it should be considered as a cause.
History
A 58-year-old man has been brought by ambulance to the emergency department. He returned home three days ago from visiting family members abroad. He started to feel unwell on the flight and was aware of several cases of people with similar symptoms in the city he had been visiting. An outbreak of severe acute respiratory syndrome (SARS) was rumoured, so he moved to stay elsewhere in the country. He returned home a week after moving from the city. He is now unwell with increasing difficulty in breathing and drowsiness. Symptoms started two days ago with myalgia, shortness of breath, cough, headache and chills. He has no existing medical problems and is not on regular medica-tions. He does not smoke or drink alcohol.
Examination
This man appears unwell with shallow respiratory effort. He has reduced chest wall expansion bilaterally. On auscultation there is reduced air entry bilaterally and inspira-tory crackles. The jugular venous pulse (JVP) is not elevated and heart sounds are normal.
His pulse is thready and rapid and he has cool hands and feet. Abdominal examination is normal. His score on the Glasgow Coma Scale is 14/15 (opens eyes in response to voice, orientated, obeying commands). A chest X-ray is obtained (Fig. 58.1). An ECG reveals sinus tachycardia. Observations: temperature 38.5°C, heart rate 105/min, blood pressure 85/51 mmHg, respiratory rate 28/min, SaO2 89 per cent on room air.
INVESTIGATIONS
Normal range
White cells 12.0 4–11 ¥ 109/L
Haemoglobin 11.5 13–18 g/dL
Platelets 376 150–400 ¥ 109/L
Sodium 139 135–145 mmol/L
Potassium 3.9 3.5–5.0 mmol/L
Urea 6.0 3.0–7.0 mmol/L
Creatinine 82 60–110 mmol/L
C-reactive protein 98 <5 mg/L Arterial blood gas on room air:
pH 7.34 7.35–7.45
PO2 7.2 9.3–13.3 kPa
PCO2 3.8 4.7–6.0 kPa
Lactate 2.8 <2 mmol/L
HCO3 21 22–26 mmol/L
129 Figure 58.1
Questions
• Give a differential diagnosis for this presentation.
• What should be the immediate management?
This returning traveller has presented with sudden onset of respiratory symptoms and signs, having had recent contact with suspected SARS cases. So SARS is indeed a top differential diagnosis. However, other conditions can present in this way. A severe community- acquired pneumonia, atypical pneumonia (Legionella, Chlamydia, myco-plasma or Coxiella), influenza (including the recent pandemic-causing influenza strain influenza A (H1N1), swine influenza, or potentially the H5N1 subtype, avian influenza) can all present in this way and are difficult to tell apart without further investigations.
However, the history of preceding events will narrow down the likely causes. His chest X-ray shows bilateral diffuse airspace shadowing.
Severe acute respiratory syndrome was first identified in China in November 2002. In February 2003, SARS was identified as the cause of a sudden outbreak of a respiratory illness that caused high fever, dry cough, myalgia and a sore throat. It started in South East Asia and spread to several countries around the world due to global transmission via travel. It was rapidly progressive with many cases requiring ventilatory support within a week of symptoms first developing. Mortality rate was high, around 10 per cent. The epidemic came to an end in July 2003. The causative organism was a coronavirus. It is suspected to have originated in animals, but the natural reservoir is not known. Sporadic outbreaks have occurred since then but none has developed into an epidemic.
The SARS-coronavirus causes an inflammatory pneumonitis followed by pulmonary fibrosis. Confirmatory tests rely on polymerase chain reaction (PCR) of the viral DNA taken from aspirates or swabs of the nasopharynx. PCR can also be performed on blood and stool specimens. PCR can also rule out other viral causes of an acute respira-tory distress syndrome. Changes in blood tests that can occur (leucopenia, elevation of transaminases) also occur in atypical pneumonias and other viral causes. Blood and spu-tum cultures, serological tests on urine and blood will help to exclude other diagnoses.
High-resolution CT of the thorax can show ground-glass opacities and interlobular septal thickening in the majority of SARS cases even with a normal chest X-ray. However, these changes can occur with influenza pneumonitis.
Immediate management of any critically ill patient is the rapid assessment and manage-ment of the airway, breathing and circulation (the ABCDE approach to the critically ill person). Regardless of cause, the initial management is the same for anyone presenting in acute respiratory distress. An assessment of airway and breathing indicate he has respira-tory failure. He will require intubation and mechanical ventilation as he is at high risk of respiratory arrest. An anaesthetist should be called to assist in airway maintenance. The intensive-care unit should also be notified. In previous outbreaks of SARS about a quarter required ventilation, either non-invasive or invasive. Assessment of his circulation and presence of lactaemia indicate he is shocked. This may be a combination of sepsis and hypovolaemia (a fluid challenge should be administered).
The target should be to preserve organ function. Generally several parameters can help indicate adequate provision of tissue perfusion: CVP 8–12 cmH2O, mean arterial pressure 65 mmHg or more, urine output 0.5 mL/kg per hour, central venous oxygen saturations of 70 per cent or more. Vasopressors are indicated if blood pressure response is refrac-tory after initial fluid resuscitation. Additional supportive care consists of stress ulcer and deep vein thrombosis prophylaxis, blood sugar control, nutritional support, maintaining optimal haemoglobin levels and electrolyte balance.
131 Current advice from the World Health Organization is that there is no proven treatment for SARS in addition to supportive therapies. However, there may be a role for ribavirin or protease inhibitors (lopinavir or ritonavir) with steroids in severe cases, but there is no formal recommendation for the use of antivirals.
KEY POINTS
• Acute respiratory distress, regardless of infective cause, is managed in the same way initially (support of airway and breathing).
• There is no proven treatment for SARS.
• Suspected cases should be isolated and notified to the Health Protection Agency.
133