Depression masked as paroxysmal hypertension episodes

Abstract

This paper describes a clinical picture frequently seen in specialty hypertension clinics, a patient with paroxysmal or intermittent hypertension not related to pheochromocytoma. A variety of diagnostic labels given to these patients is reviewed, including pseudopheochromocytoma and panic attacks. The clinical features, pathophysiology, diagnosis and treatment of these syndromes are outlined. It is proposed that successful management of these patients may be best achieved by collaborative care between a hypertension specialist and a psychiatrist, or clinical psychologist with expertise in cognitive-behavioral panic disorder management, stress-reduction techniques including controlled breathing, and effective treatment of anxiety. The use of drugs effective for treatment of panic disorder can also be helpful in managing those patients.

Key Words::

• Depression
• hypertension crisis
• hypertension
• panic attacks
• pseudopheochromocytoma

Introduction

Patients with paroxysmal hypertension frequently undergo extensive work up to rule out secondary causes, primarily catecholamine-secreting tumors. However, only 2% of patients with paroxysmal hypertension actually have pheochromocytoma (1). The cause and management of paroxysmal hypertension remain unclear and few papers have addressed this issue (1–5). The term pseudopheochromocytoma is used to describe an often disabling syndrome characterized by episodes of paroxysmal severe hypertension and symptoms of catecholamine excess, including feelings of anxiety, tremor, sweating and palpitations. Other features might also be present such as chest pain, headache, nausea, dizziness and pseudoseizures (6). Patients with this disorder often remain undiagnosed and ineffectively treated. This paper presents a case report of a patient who presented with paroxysmal hypertension with typical characteristics of pheochromocytoma but the disorder proved to have a psychological basis.

Case report

The patient was a 20-year-old white man referred for evaluation of paroxysmal hypertension. He never had a history of hypertension or any other cardiovascular disease. In addition, he was not exposed to any cardiovascular or other risk factor including smoking, dyslipidemia, family history, diabetes, renal disease, metabolic syndrome or cocaine use.

The episodes of paroxysmal hypertension began 2 months prior to presentation, described as starting with flushing in his face, palpitations, light-headedness, and a feeling of warmth and anxiety. His blood pressure was typically high (190 mmHg systolic) during these episodes. The duration of the episodes was approximately 60 min and terminated rather suddenly. No obvious causal factors could be detected. The patient denied recent use of illicit drugs, amphetamines, monoamine oxidase inhibitors or clonidine. Drug screening, when performed for these drugs, was negative. Patients with this syndrome are afraid for their lives and for this reason are unlikely to be using illicit drugs. He was currently having about one episode every 2–3 days, mainly during the afternoon. During the episodes, he was referred to the emergencies of different hospitals receiving treatment for hypertensive crisis and dismissed, until he was referred to our clinic, where he was hospitalized for 1 week. At this time, he had an extensive workup for secondary causes of hypertension including pheochromocytoma.

The patient was first subjected to standard laboratory testing. A normal electrocardiogram and chest X-ray were obtained and transthoracic echocardiography was normal. Based on the physical examination and echocardiographic examination, the possibility of aortic coarctation was ruled out. Measurements of catecholamine metabolites in 24-h urine collection were performed in order to investigate the possibility of pheochromocytoma. Levels of 5-HIAA, VMA, metanephrines and HVA were all normal. Furthermore, VMA levels in urine sample during an episode of paroxysmal hypertension were also normal; 24-h ambulatory blood pressure monitoring revealed a mild elevation in mean systolic blood pressure (Table I). Other causes of secondary hypertension such as hyperthyroidism, hyperaldosteronism or hyperreninemia were also explored (Table II). Thyroid hormone, calcitonin and cortisol levels were found to be within the normal range, whereas a mild increase was observed in both resting and exercise levels of renin and aldosterone. This increase could be related to either renal artery stenosis or a tumor of the juxtaglomerular apparatus. Thus, the patient was subjected to angiography of the renal arteries and to magnetic resonance tomography of the kidneys, both of which were proved normal.

Table I. Hormones profile.

Examination	Units	Value	Normal reference range
T3	nmol/l	1.64	1.23–3.08
T4	nmol/l	126	58–154
TSH	mU/l	0.47	0.3–4.0
Renin (rest)	ng/ml/h	5.56	0.2–2.8
Renin (stress)	ng/ml/h	8.94	1.5–5.7
Aldosterone (rest)	pg/ml	334	10–160
Aldosterone (stress)	pg/ml	642	35–300
Calcitonin	pg/ml	2.0	1.9–9.6
Cortisol	μg/dl	19.0	0.2–2.8

Table II. Causes of paroxysmal hypertension

•	Pheochromocytoma
•	Labile hypertension
•	Panic disorder
•	Hyperthyroidism
•	Anxiety
•	Cluster or migraine headaches
•	Hypertensive encephalopathy
•	Coronary insufficiency
•	Renovascular hypertension
•	Central nervous system lesions, such as stroke, tumor, hemorrhage, compression of lateral medulla, and trauma
•	Seizure disorder
•	Carcinoid
•	Drugs (cocaine, lysergic acid diethylamide, amphetamine)
•	Tyrosine ingestion combined with monoamine oxidase inhibitors
•	Baroreflex failure
•	Factitious hypertension

The patient was referred to the neurologist in order to exclude an organic cause of the attacks, such as epilepsy, but neurological examination revealed no pathology and no further examination of the CNS was suggested. The patient reported no stressors other than his illness. Because of the paroxysmal nature of his hypertension and the prior unrevealing medical investigation, the patient's psychosocial history was carefully explored. When the hospital psychiatrist evaluated the patient, a diagnosis of severe psychological stress was made based of his family status and he was prescribed Escitalopram (Cipralex) once daily. Two-month, 6-month and 1-year follow-up appointments were scheduled, and the patient was instructed to call the office if he encountered problems or had further questions. When he was seen for follow-up, he was symptom-free.

Discussion

The diagnoses most likely to be considered in patients with this disorder are pheochromocytoma, labile hypertension and panic disorder. The diagnosis of pheochromocytoma should be excluded in all patients with unprovoked paroxysmal hypertension. Usually, plasma or urinary catecholamine studies are sufficient to serve this purpose.

In most patients with pheochromocytoma, plasma and urinary catecholamine levels are persistently and markedly elevated. Normal levels, particularly when obtained during an episode, virtually exclude a pheochromocytoma (7). In contrast, in patients with paroxysmal hypertension who do not have a pheochromocytoma, catecholamine levels are normal between episodes and are either normal or only mildly elevated during the hypertensive crisis (8,9). If elevated, further efforts to exclude the possibility of a pheochromocytoma may be indicated. Furthermore, the possibility of renal artery stenosis or a tumor of the juxtaglomerular apparatus should be explored in cases of elevated rennin and aldosterone levels. However, it must be pointed out that paroxysmal hypertension of different causes can result in mild elevation of rennin and aldosterone levels mainly because of activation of the adrenergic system.

Labile hypertension differs starkly from paroxysmal hypertension in the clear relationship between blood pressure elevation and stress or emotional distress. Patients know they are upset and readily blame the blood pressure elevation on their distress. In strong contrast, patients with paroxysmal hypertension insist that the disorder is not related to stress or emotional distress. Kaplan described a relationship between symptomatic hypertension and anxiety-induced hyperventilation, but the patients he described had refractory, sustained hypertension, and most had symptoms of anxiety. Paroxysmal hypertension differs from arterial hypertension during panic attacks in that it is characterized by extreme blood pressure elevation that is not triggered by fear or panic. Some patients may experience fear but only in reaction to the worrisome physical symptoms. In simple panic disorder, blood pressure elevation is generally mild and fear or panic is prominent (10–14).

Despite these differences, these two conditions do resemble each other. The physical symptoms are similar. In addition, in one report (15), panic disorder presented as arterial hypertension during the episodes. Both disorders appear to share an origin in emotions that are repressed from conscious awareness and both respond to treatment with antidepressant drugs. It is thus likely that these disorders are related, with paroxysmal hypertension dominated by autonomic manifestations and arterial hypertension related to panic disorder by emotional ones (16,17).

The most critical clinical difference between the two disorders is that, in the absence of panic or emotional distress, paroxysmal hypertension is viewed as an unexplained medical disorder. Physicians and patients rarely consider the possibility of an emotion-based cause or treatment because patients do not report emotional distress. Kuchel and colleagues (18) considered this disorder a form of “hyperadrenergic-essential hypertension,” but could not explain why it occurs. Many entities, such as anxiety, hyperthyroidism, hyperdynamic–adrenergic circulatory state, cluster or migraine headaches, hypertensive encephalopathy, coronary insufficiency, renovascular hypertension, central nervous system lesions (stroke, tumor, hemorrhage, compression of lateral medulla, trauma), seizure disorder, carcinoid, drugs (cocaine, lysergic acid diethylamide, amphetamine), tyrosine ingestion combined with monoamine oxidase inhibitors, baroflex failure, and factitious hypertension, can occasionally manifest as paroxysmal hypertension and should be considered where clinically appropriate. Other entities can on rare occasion manifest as paroxysmal hypertension, but are rare in the absence of any other signs or symptoms suggestive of them.(16,17)

It is unlikely that baroreceptor failure, a cause of blood pressure fluctuation with both hypertension and hypotension, underlies this disorder, particularly in the absence of a predisposing condition (e.g. neck surgery or irradiation) (17,18). The absence of blood pressure fluctuations between episodes and the elimination of attacks with psychotherapeutic or psychopharmacological intervention also argue strongly against baroreceptor failure as a cause.

The rapid and permanent cessation of attacks observed in patients who had suffered for months or years strongly suggests that the improvement was a result of the treatment. This case indicates that successful treatment is usually possible and involves the use of three modalities, either alone or in combination: antihypertensive agents, psychopharmacological agents and psychotherapy.

The paroxysmal nature of this hypertensive disorder, its association with tachycardia in some patients, evidence of sympathetic activation, and response to alpha and beta-blockade all suggest involvement of the sympathoadrenal system (10,18,19). Preventive treatment with adrenergic blockade seems more logical and appears far more effective than treatment with agents such as angiotensin-converting enzyme inhibitors and diuretics, which are directed more at nephrogenic mechanisms of essential hypertension. Central agonists (e.g. clonidine) can be effective, but fatigue and somnolence usually preclude adequate dosing.

Even with these agents, treatment can be difficult, because of the severity of blood pressure elevation during the hypertensive crisis and the lower or even normal blood pressure level at other times, which often limits the prescribed dose. If severe the hypertensive crisis recur despite antihypertensive treatment, acute intervention may also be necessary, administered either intravenously (labetolol) or orally (labetolol, prazosin, terazosin, clonidine). An extra dose of a blocker might be useful if attacks are accompanied by tachycardia.

If alpha- and beta-blockade does not control the disorder, adding a psychopharmacological agent can be dramatically effective in eliminating the hypertensive crisis and restoring a normal quality of life.

Even when patients reject the possibility of an emotional basis, treatment with antidepressant agents, possibly combined with an anxiolytic agent, can eliminate attacks. Treatment may have to be initiated by the primary care physician if the patient is unwilling to consult a psychiatrist. Tricyclic antidepressants, such as desipramine, and selective serotonin-reuptake inhibitors, such as paroxetine, used at their usual recommended doses, have been effective. There is inadequate data to suggest that one type of agent is more effective than any other. The efficacy of these agents in the absence of concomitant administration of adrenergic-blocking agents has not been evaluated.

Antihypertensive and psychopharmacological agents can control the disorder but cannot cure it. The responses indicate that in some cases psychotherapeutic intervention can provide a cure, and an alternative to unending pharmacological treatment. Further studies are needed to determine the type or types of psychotherapy best suited for this disorder.

Conclusions

Paroxysmal hypertension that is not attributable to a curable secondary cause such as pheochromocytoma is not uncommon, and it is possibly becoming more frequently identified with the increased use of self-monitoring. It is unclear at what point the normal variability of blood pressure becomes paroxysmal, but it is a source of anxiety to patients and, in some cases, may become a vicious cycle. An evaluation of stress, anxiety, and panic attacks in such patients may be very rewarding and enable treatment to be directed not only at lowering the blood pressure but also at relieving the associated psychological problems.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.