Rogers et al examined the prevalence and characteristics of medical illness in 711 patients who were enrolled in the Harvard-Brown Anxiety Disorders Research Program (HARP), a multi-center, longitudinal study of anxiety disorders. They noted that patients with panic disorder and co-morbid major depressive disorder had significantly higher rates of reported medical illnesses than anxiety disordered patients who did not suffer with concurrent depression. When they compared the rates of medical illness for their subjects to those of the Rand Health Insurance experiment, they found the prevalence of peptic ulcer disease, angina and thyroid disease to be disproportionately increased.
They noted that 2% of the males in the study and 9% of the females in the study had thyroid disease, while 1.3% of the men and 4.1% of the women suffered from diabetes mellitus. The prevalence of thyroid disease in women was higher than expected in the general population. It was not increased in men. The study noted that patients who also suffered from panic disorder were more likely to have an underlying medical illness causing their anxiety, particularly thyroid disease in women.
Psychiatric presentations are often the first sign of hypothyroidism, occurring as the initial symptoms in approximately 2% to 12% of reported cases, with organic mental deficits being the most frequently reported initial symptoms. Anxiety and progressive mental slowing associated with diminished recent memory, speech deficits and diminished learning ability are the characteristic initial progression of symptoms.
Spontaneous hypothyroidism occurs predominantly in women between the ages of 40 and 60. Physical symptoms generally seen include weakness, fatigue, cold intolerance, diminished libido, lethargy, dry skin, headaches, and menorrhagia. Physical signs include brittle nails, thin, course hair; slowed pulse, and pallor. Delayed return of deep tendon reflexes is also commonly encountered. Later symptoms include perceptual changes in taste, smell, vision and hearing; reduced or absent perspiration, weight gain, pallor, hoarseness, peripheral edema, muscle cramps, dyspnea and angina. Amenorrhea or menorrhagia and galactorrhea may also be seen.
The development of severe anxiety disorders in hypothyroid states are as much or more related to the rapidity of change of thyroid hormone levels as they are to the absolute levels encountered. Whether the cause of hypothyroidism is auto-immune or follows thyroidectomy, oblation of the gland by radioactive iodine, the ingestion of medicines such as lithium carbonate, or is associated with thyroid cancer, the neuropsychiatric symptoms are similar.
The incidence of myxedema madness as an initial presentation of hypothyroidism has diminished dramatically since the late 1880s when it occurred in almost 50% of cases. Today psychosis is reported to occur in between one to fifteen percent of patients. Anxiety disorders, on the other hand, occur in between 30% and 40% of patients developing acute hypothyroidism.
The most characteristic picture of patients with rapidly developing myxedema is one of progressive anxiety with generalized agitation. Patients may experience a progressive disorientation, persecutory delusions, hallucinations, and bouts of lethargy alternating with periods of extreme restlessness. They are often extremely irritable, delusional, and paranoid and may complain of auditory and visual hallucinations. Hypersexuality, irritability, suspicion, delusions, inability to concentrate, and failing memory are all conspicuous signs of rapidly developing thyroid disease.
Slowly progressive changes in thyroid hormone levels are more likely to be associated with a picture of chronic anxiety, increased fatiguability and psychomotor slowing. The severity of mental symptoms are greater in elderly patients and, as noted, in patients with rapidly changing thyroid hormone levels. In a study of patients with Hashimoto's thyroiditis, anxiety was a prominent initial symptom at the time that the condition was diagnosed. It was often associated with a lability of mood, withdrawal from normal duties due to perplexity, and in severe cases, generalized agitation, disorientation, and persecutory delusions as well as extreme restlessness.
The anxiety associated with significant hypothyroidism usually resolves within days to months following the initiation of treatment. The clinician must remember that the central nervous system effects of profound hypothyroidism may not fully clear for two to twelve months after successful treatment. Sleep and growth hormone production during sleep have been shown to be disturbed for weeks to months following the replacement of thyroid hormone. Return of these functions to normal seems to be related to the cessation of the anxiety states that these patients experience. Kales et al have shown that patients' improvement parallels restoration of their normal sleep patterns, and, in fact, note that the return of a normal sleep pattern is an excellent predictor of treatment outcome.
Anxiety and Hyperthyroidism Hyperthyroidism is one of the most frequently encountered endocrine diseases. It most commonly occurs in women between the ages of 20 and 40. Graves' disease usually presents with a diffuse goiter and ocular disturbances. The most frequent symptoms seen at onset include anxiety, fatigue, irritability, cold intolerance, fine tremor, a sensation of somatic restlessness, insomnia, excitability, lability of mood, nervousness, weight loss, increased sweating, palpitations, impaired coordination, doubts, and persistent fear. Weight loss is unusual as most of these patients have a ravenous appetite. Patients also complain of difficulty focusing their eyes, pressure symptoms related to goiter, diarrhea, and irregular rapid heart rate.
Other causes of hyperthyroidism include toxic adenoma, iodine-induced hyperthyroidism in patients with multinodular goiters, exogenous thyroid hormone ingestion, struma ovarii, iatrogenic hyperthyroidism, hydadidiform mole, and TSH secreting tumors of the pituitary.
Between 1% and 20% of hyperthyroid patients have been reported to present with psychosis. Current best estimates suggest about 5% present initially with psychotic symptoms.34 Between 30% and 40% present with conspicuous complaints of anxiety, nervousness, apprehension, dread, depression, restlessness, diminished concentration, forced thinking, emotional lability, and hyperkinesia.
Trepacz et al report a high prevalence of general anxiety disorder in a series of patients with untreated Graves' disease. Ettigi and Brown note that hyperthyroidism is almost inevitably associated with mental changes, the most common including nervousness, apprehension, restlessness, inability to concentrate, marked emotional lability and hyperkinesia. These patients often present as hyperactive individuals with specific complaints of anxiety and "nervousness." A fine generalized tremor may be present, and the patient reports an internal sensation of feeling shaky or jittery. Family members often remark about personality changes and increases in both irritability and emotional lability. Jefferson and Marshall point out that the nervousness of the hyperthyroid patient is dissimilar to that seen in the patient with a primary anxiety neurosis in that it is characterized by "restlessness, shortness of attention span, and a need to move about."
Popkin and MacKenzie note that the behavioral changes of hyperthyroidism are numerous and useful in differentiating it from a primary anxiety neurosis or a neurasthenia. Patients with hyperthyroidism are differentiated from primary anxiety states as "in thyroid dysfunction, sleeping pulse will remain accelerated; sedated pulse will exceed 80; palms will be dry and warm, not cold and clammy; fatigue will be accomplished by a desire to be active; and cognitive dysfunction is more prominent than in neurasthenia."
Cognitive effects clear rapidly with restoration of normal thyroid levels, in contradistinction to the slow return to normal function often seen in patients with significant hypothyroidism.34 Whybrow et al note the elevation of schizophrenia and paranoid scales on the MMPI when patients are hyperthyroid and psychotic. They report that these changes clear quickly following treatment and note that the behavioral manifestations of hyperthyroidism clear rapidly with treatment. They are toxic phenomenon related to elevated levels of circulating thyroid hormone.
Paschke et al studied 15 female patients with Graves' disease, administering psychological tests at the time that their hyperthyroidism was first diagnosed and then following them through their course of antithyroid treatment. Psychological testing was obtained when the patients achieved a biochemically euthyroid state. Patients were subsequently followed while being treated with antithyroid drugs or surgery. The investigators noted that patients' psychological parameters showed considerable change as their thyroid status improved. The psychiatric symptoms most prevalent while patients were hyperthyroid included anxiety, depression, irritability and exhaustion. Patients often described themselves as anxious, nervous, irritable, tired, without energy, exhausted, and fatigued. 75.5% complained of significant anxiety when first evaluated. The authors felt that the most consistent psychological pattern seen in these patients consisted of a mixture of severe anxiety with depression, exhaustion, a decreased ability to concentrate, irritability and extroversion. The investigators noted the cessation of anxiety and irritability at the time that the patients achieved a euthyroid state. Depression took one month following the development of a euthyroid state before normalizing, whereas the personality changes took three months to subside after the patient became euthyroid. It was noteworthy that the type of thyroid therapy made no difference in the course of the patient's psychological symptoms, i.e., patients who became euthyroid from drug treatment vs. those who became euthyroid from surgery responded similarly. The authors noted that there was no relationship between the severity of disruption of thyroid hormone level and symptoms, but there was significant correlation between a return to normal thyroid function and a return to normal psychological function. There was no correlation noted between psychological test scores and the degree of autoimmune dysfunction seen in these patients. The authors concluded that patients with Graves' disease developed significant anxiety manifested as a constant personality trait when compared to the control group.
If the estimated 60% to 75% incidence of severe anxiety in patients with hyperthyroidism is correct, one could conclude that with the 300,000 new cases estimated to occur in the United States this year, that a significant number of these patients will be initially seen by psychiatrists. They are likely to evidence other signs and symptoms of hyperthyroidism when seen, specifically, nervousness, weight loss, heat intolerance, warm skin, excessive perspiration, easy fatiguability, muscular weakness, diarrhea, fine tremor, and a wide-eyed stare with possible protrusion of the eyes.
Hall notes that the most frequent initial presentation of hyperthyroidism centers on complaints of anxiety and nervousness. The most frequent misdiagnoses of hyperthyroidism is that of generalized anxiety disorder. This diagnosis is particularly likely in the early stages of the disease when patients present with anxiety, increasing irritability, emotional lability and personality change. Kathol and Dalahunt report that when DSM-III criteria are used, the incidence of depression and generalized anxiety disorder is three to four times higher in hyperthyroid patients than that expected in the general population.
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