Abstract
Thunderclap headaches (TCHs) are severe and hyperacute headaches with maximal intensity at onset, not unlike a clap of thunder. The term TCH was first used to describe headaches caused by unruptured intracerebral aneurysms (1). However, TCH was recently discovered to be a presentation of many other diseases. Although primary TCH usually has a benign prognosis, it is important to note that primary TCH is a diagnosis of exclusion (2). Urgent assessment of TCH is important in order to avoid the potentially catastrophic consequences of secondary TCH.
Phaeochromocytomas are rare, catecholamine-producing tumours of chromaffin cells of the adrenal medulla or of the paraganglia. The typical clinical manifestations of a phaeochromocytoma include sustained or paroxysmal hypertension, severe headache, palpitation and sweating, which result from the direct action of catecholamines. However, its presentations are highly variable and can mimic many other disorders. If left unrecognized and untreated, it can cause life-threatening conditions (3).
Many clinicians are unaware that a phaeochromocytoma can be manifested as a TCH. Here, we report our experience of a patient with a phaeochromocytoma whose initial presentation was a TCH.
Case report
A 45-year-old woman presented with severe recurrent headaches of abrupt onset, lasting a week. She experienced an explosive and pulsatile headache in bilateral frontal areas, which spread to her entire crania, instantaneously reaching its maximal intensity. She described her headache as being the worst of her life. There were no other accompanying symptoms such as nausea, vomiting, photophobia, phonophobia, aura or dizziness. There was no conjunctival injection, lacrimation, nasal obstruction, facial sweating, ptosis or miosis. She denied sweating, palpitation, flushing, pallor or anxiety. The headache attacks recurred every day. Once an attack developed, the intensity gradually decreased and it usually disappeared within 3 h.
She had been treated with non-steroidal anti-inflammatory drugs in a local hospital with suspected common migraine, but the headache was getting worse each day in severity and duration. She had no history of head trauma or surgery or of headache and hypertension, and she did not smoke or drink. She was referred to our emergency room 7 days after onset of the headaches. She had no headache at the time of visit. Initial physical and neurological examinations were normal. Her blood pressure was 114/79 mmHg and the pulse rate was 77 beats/min. Brain computed tomography (CT) and magnetic resonance imaging were normal. On cerebrospinal fluid tapping, nothing abnormal was found, with normal opening pressure and physiological Q-test. Conventional cerebral angiography, performed to confirm cerebral venous sinus thrombosis or cerebral vasoconstriction, showed no notable irregularities. On admission, the headaches occurred once or twice a day with no provoking factors. There were no abnormalities on physical and neurological examinations during attacks except for elevated blood pressure. Her systolic pressure was not elevated during attacks at first, but with repeated check-ups it was sometimes found elevated up to 190 mmHg. Increased blood pressure was well controlled with intermittent intravenous labetalol. As the blood pressure was lowered, her headache gradually subsided. We started work-ups for the phaeochromocytoma after several days to wait for the wash-out of the labetalol effect. Vanillylmandelic acid and metanephrine in 24-h urine samples were elevated to 12.2 mg/day (normal range 0∼8.0 mg/day) and 2.9 mg/day (normal range 0∼1.2 mg/day), respectively. Her abdominal and pelvic CTs revealed a 5-cm well-enhancing solid mass in the retroperitoneum. Under tentative diagnosis of phaeochromocytoma, she was operated and the diagnosis was confirmed pathologically. She has subsequently been headache free for 6 months.
Discussion
According to International Classification of Headache Disorders, 2nd edn, diagnostic criteria, primary TCH is defined as a severe headache of sudden onset with maximal intensity within 1 min. It may last from 1 h to 10 days and it does not recur regularly over subsequent weeks or months. Primary TCH should be diagnosed only after all other potential causes have been excluded. Table 1 shows the diagnoses that must be excluded in the diagnosis of primary TCH. As TCH could be a presentation of exceedingly lethal disorders, the underlying cause of the TCH must be identified as soon as possible. Our patient presented with symptoms similar to those of TCH, and we made a final diagnosis of phaeochromocytoma, which can also have catastrophic results without an accurate diagnosis.
Causes of secondary thunderclap headache
The number in parentheses is the reference number.
Despite recent advances in the diagnosis of phaeochromocytoma, there remains a delay of 3 years between the onset of symptoms and final diagnosis (3). Thus, it is important to commence diagnostic work-ups based on strong suspicions of this rare disorder. Since paroxysmal symptoms and signs of phaeochromocytomas are a consequence of episodic secretion of catecholamines, certain clues can assist in diagnosis. Tumour manipulation, food, micturition (in case of urinary bladder phaeochromocytomas) and various chemical compounds and drugs are known to be stimuli of the induction of paroxysms (3). Without these clues, the diagnosis might be more difficult because most patients present with non-specific individual symptoms such as headache, palpitation and sweating. Hypertension often accompanies a phaeochromocytoma, since it produces catecholamines. However, < 60% of patients suffer from sustained hypertension, 30% of whom have the paroxysmal form with normotension between paroxysms (9). In our case, there were no preceding or associated symptoms and signs except for the headaches. Moreover, even during the headache attacks, hypertension was not always evident at first. However, repeated blood pressure checks with a high degree of suspicion led to the correct diagnosis. A recent report has demonstrated that bladder phaeochromocytoma could present as TCH. The author stated that the headache attacks and paroxysmal hypertension following micturition led them to suspect this extremely rare disorder (10).
Angiographically, reversible cerebral vasoconstriction has been proven in several cases of phaeochromocytoma (11, 12). They presented with paroxysmal symptoms including severe headache, although it is not certain whether the headaches met the criteria of TCH or not. In those cases, multifocal arterial narrowing resembling vasculitis or vasospasm has been reported. Furthermore, follow-up angiography revealed a normal appearance after the resection of the phaeochromocytoma (11). Unfortunately, we could not prove reversible vasoconstriction in our case. Considering that cerebral vasoconstriction is reversible and is mediated by paroxysmal secretion of catecholamines, normal angiography is not unusual during the period without headache attacks.
This case demonstrates that a phaeochromocytoma can present with a recurrent isolated TCH. Without comprehensive evaluation, it can be easily misdiagnosed as primary TCH. Clinicians should suspect the possibility of a phaeochromocytoma in patients with recurrent isolated TCH with or without episodic blood pressure elevation. Urgent investigation of the potential underlying causes of the TCH is the only way to rescue patients from this life-threatening condition.