Anxiety Secondary to General Medical Conditions

By | March 12, 2015

Many medical problems have been reported to cause anxiety, but their significance is in some cases uncertain due to reporting bias and lack of controlled studies. Nonetheless, it is important for the psychosomatic medicine physician to consider medical causes of anxiety when evaluating an anxious patient. It is particularly important to evaluate medical causes when the history is not typical for a primary anxiety disorder (e.g., lack of personal or family history, lack of psychosocial stressors) and when the onset of anxiety is at a later age. In addition, it is important to evaluate medical causes when the anxiety is accompanied by disproportionate physical symptoms (e.g., marked dyspnea, tachycardia, or tremor) or atypical physical symptoms (e.g., syncope, confusion, or focal neurological symptoms).

It is important for the clinician to keep in mind the distinction between anxiety that is physiologically secondary to a general medical condition and anxiety that is comorbid with, or a psychological reaction to, a general medical condition. (For example, hyperthyroidism appears to biologically cause anxiety, whereas diabetes mellitus usually does not.) The DSM-IV-TR diagnosis of anxiety due to a general medical condition refers to the former, not the latter. This difference has not been clearly articulated in some reviews in this area, and it can also be confusing for patients. One source of confusion results from the assumption of causality when there is an epidemiological association between anxiety and a specific medical condition. For example, in one young adult cohort, the odds ratio of any anxiety disorder among individuals with migraine was 2.7, but the onset of anxiety disorders generally precedes that of migraine.

Components of the medical evaluation of the anxious patient should be determined by the patient’s specific medical symptoms. For example, it may be necessary to obtain electroencephalograms and a neurological consultation for a patient with seizure-like episodes. The general evaluation of all anxious patients should include the following elements:

1.History and physical examination, including neurological examination

2.Evaluation of the potential role of medications and substances ()

3.Screening diagnostic studies (e.g., routine blood chemistries, complete blood cell count, calcium concentration, thyroid hormone levels, electrocardiogram)

In the following subsections, we discuss common medical conditions that are associated with anxiety for which data are strongly supportive of a causal relationship.

Thyroid Disease

Anxiety symptoms commonly occur among individuals with thyroid disease. Trzepacz et al. () found that 7 of 13 patients with untreated Graves’ disease met research diagnostic criteria for GAD and major depression. In another study, 15 of 32 hyperthyroid patients reported increased anxiety symptoms compared with baseline levels (“Endocrine and Metabolic Disorders”).

Hyperthyroidism may be difficult to distinguish from a primary anxiety disorder. Signs that may be suggestive of thyrotoxicosis include persistent tachycardia, palms that are warm and dry (not cold and clammy), and fatigue accompanied by the desire to be active. However, data differentiating the two are not definitive in this regard, and much of the research in this area is not current. Some individuals with hyperthyroidism may also have cognitive impairment. Improvement in anxiety usually parallels successful treatment of the hyperthyroidism. Therefore, specific antianxiety treatment may not be necessary. Nonetheless, antianxiety treatment should be considered during normalization of thyroid hormone levels, particularly for individuals with moderate to severe symptoms. Beta-blockers, which are used routinely for acute treatment of hyperthyroidism, will relieve peripheral manifestations of anxiety.

Because thyroid dysfunction is so common among individuals with anxiety, a screening thyroid-stimulating hormone (TSH) assay should be considered for patients with new-onset anxiety disorders and treatment-resistant anxiety, particularly when the anxiety is generalized and accompanied by prominent physical symptoms. If the TSH level is abnormal, further evaluation of the thyroid axis is recommended (e.g., free thyroxine index or free thyroxine measurement).

There are a number of putative mechanisms for the association between abnormalities of the thyroid axis and mood or anxiety symptoms. A blunted TSH response to thyrotropin-releasing hormone stimulation occurs in up to one-third of depressed patients, many of whom may have concomitant anxiety symptoms. The adrenergic overreactivity that accompanies hyperthyroidism provides a ready explanation for its association with anxiety. Finally, thyroid hormones interact with brain neurotransmitters (e.g., the serotonergic and noradrenergic systems). Nonetheless, the association between the thyroid axis and anxiety is not well understood.

Anxiety has been reported to be a symptom of hypothyroidism, but data are minimal. Its association may be better explained by the association between depression and hypothyroidism, in which anxiety is conceptualized as a symptom of depression as opposed to a direct biological result of a hypothyroid state.

Pulmonary Disease

Patients with pulmonary disease often experience symptoms of anxiety. Rates of panic disorder among individuals with asthma and chronic obstructive pulmonary disease are higher than among the general population. The psychological stress and uncertainty of living with asthma certainly make important contributions to this association. In addition, it is essential to consider physiological factors intrinsic to asthma. For example, both hypercapnia and hyperventilation may lead to symptoms of a panic attack; in one model, hypercapnia may lead to increased locus coeruleus activity, which could cause panic and hyperventilation. Furthermore, carbon dioxide inhalation has been shown to precipitate panic attacks among individuals with panic disorder. Asthma may also be associated with panic attacks through a process of classical conditioning. In this paradigm, because a severe asthma attack is so terrifying, a future sensation of mild dyspnea might precipitate a full-blown panic episode. In addition, anxiety may worsen asthma, thereby contributing to a vicious circle in which pulmonary and anxiety symptoms exacerbate each other. Several asthma medications may cause anxiety (). Pulmonary emboli may also lead to symptoms of anxiety; this diagnosis is more easily missed when the emboli are small (“Lung Disease”).

Parkinson’s Disease

Anxiety is often seen in individuals with Parkinson’s disease. Most studies of the prevalence of anxiety disorders among patients with Parkinson’s disease involve small samples, but they indicate that these disorders are much more common among Parkinson’s disease patients than in the general population. Anxiety often appears after the manifestations of symptoms of Parkinson’s disease. For example, some individuals may develop social anxiety disorder symptoms because they are embarrassed about manifestations of the Parkinson’s disease (e.g., tremor) (American Psychiatric Association 2000). Anxiety may also be due to the uncertainty associated with Parkinson’s disease, with respect to both day-to-day functioning and long-term prognosis. Some authors have found that anxiety may be worse during “off periods compared with “on” periods, but findings are not definitive.

Depression and anxiety symptoms often coexist among individuals with Parkinson’s disease. In one study of 42 patients with Parkinson’s disease, of the 12 patients with an anxiety disorder (5 of whom had panic disorder and 5 of whom had GAD), 11 had a depressive disorder. In the same study, of the 18 patients with a depressive disorder, 12 also had an anxiety disorder.

The neurobiology of anxiety in Parkinson’s disease has not been clearly delineated, but there is limited evidence supporting the roles of neurotransmitter abnormalities, particularly in central noradrenergic systems. The dopaminergic neural circuits implicated in Parkinson’s disease have intimate connections with systems involved with anxiety (e.g., serotonin). Anxiety may also be due to medications used to treat Parkinson’s disease, such as levodopa and pergolide (see Table 2). Anxiety may also occur with declining dopamine levels.

Poststroke Anxiety

Poststroke anxiety may occur as a symptom of the more widely described syndrome of poststroke depression. Less commonly, anxiety may appear alone. When they appear after a stroke, anxiety symptoms have been shown to persist in many individuals. For example, in one study, 31% of patients had GAD at 3 months, and 19% had it at 3 years. Anxiety has been associated with right-hemisphere lesions, whereas depression and mixed depression and anxiety are more commonly associated with left-hemisphere lesions.

Seizures

Anxiety symptoms may be caused by seizures. For example, complex partial seizures may be accompanied by symptoms of panic disorder, including fear, depersonalization, derealization, dizziness, and paresthesias. One group used ambulatory electroencephalographic monitoring with sphenoidal electrodes to study patients with atypical panic attacks (i.e., panic attacks with concomitant neurological symptoms such as change in level of consciousness, aphasia, and focal paresthesias). Focal paroxysmal electroencephalographic changes were found in 5 of 11 patients who had panic attacks during monitoring. Animal models provide some support for the hypothesis that limbic kindling might lead to interictal anxiety.

For further discussion of neurophysiological and neuroanatomic aspects of anxiety disorders, the reader is referred to “Neurology and Neurosurgery”.

Other Conditions

In addition to the disorders discussed above, anxiety has reportedly been caused by many other medical conditions. For example, anxiety may be associated with hypocalcemia and hypomagnesemia. Relatively rare conditions for which there are only limited data supporting a causal relationship include carcinoid syndrome, hyperparathyroidism, and pheochromocytoma. In the absence of other findings suggestive of one of these rare disorders, it is not advisable to screen for them (e.g., serotonin metabolites to rule out carcinoid, parathyroid hormone levels to rule out hyperparathyroidism, or catecholamine metabolites to rule out pheochromocytoma).

 

Selections from the book: “Textbook of Psychosomatic Medicine”, 2005.