Hypothyroidism: An Important Diagnostic Consideration for the Psychiatrist

Published on Psychiatric Times
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Hypothyroidism: An Important Diagnostic Consideration for the
Psychiatrist
News [1] | July 11, 2013 | Bipolar Disorder [2], Metabolic Disorders [3], Mood Disorders [4],
Psychopharmacology [5], Schizophrenia Psychotic Features [6], Special Reports [7]By Kristi R.
Estabrook, MD [8] and Thomas W. Heinrich, MD [9]
Hypothyroidism is a common clinical disorder that psychiatrists frequently encounter. However,
symptoms of thyroid dysfunction are often vague and nonspecific, which can lead to delayed or
missed diagnosis.
Source:
Hypothyroidism is a clinical state of thyroid hormone deficiency that may have a primary or
secondary (central) cause. Primary hypothyroidism, which is more common than secondary
hypothyroidism, is defined as failure of the thyroid gland to respond appropriately to
thyroid-stimulating hormone (TSH) produced in the anterior pituitary gland. Primary hypothyroidism
can be caused by autoimmune disease (Hashimoto disease), iodine deficiency, or infiltrative
diseases, or it can be caused iatrogenically by surgery or irradiation of the gland. Subclinical
hypothyroidism refers to mildly increased TSH levels in the setting of normal thyroxine (T
4
) and
triiodothyronine (T
3
) levels. Secondary hypothyroidism is defined as insufficient thyroid gland
stimulation by the hypothalamus or pituitary gland.
What new information does this article provide?
This article provides a simple and concise review of the varied physical and neuropsychiatric
presentations of hypothyroidism and important diagnostic and treatment information.
What are the implications for psychiatric practice?
Hypothyroidism presents with a myriad of neuropsychiatric signs and symptoms. It is therefore
imperative that psychiatrists are aware of the varied presentations of hypothyroidism and the
appropriate assessment of laboratory tests of thyroid function and the basic treatment options.
Drugs commonly associated with thyroid dysfunction include lithium and amiodarone. Lithium has an
antithyroid effect that can cause hypothyroidism at any point in treatment, which may not reverse
with discontinuation of the lithium. Valproate and carbamazepine have also been found to decrease
T
4
levels in patients treated long-term.
1
The prevalence of hypothyroidism in the US general population is estimated to be 1 in 300 persons;
however, rates of hypothyroidism are higher in certain populations.
2
Hypothyroidism is 10 times
more common in women than in men, but with increasing age, it becomes more common in persons
of both sexes. Higher rates of hypothyroidism have been found in hospitalized patients in both
medical and psychiatric settings than in the general public.
3-5
Subclinical hypothyroid-ism is even
more common and occurs in 4.3% to 8.5% of the general US population.
2,6
Populations with a higher risk of hypothyroidism include postpartum women and persons with a
family history, previous head or neck surgeries, endocrine conditions such as diabetes, and
nonendocrine autoimmune disorders such as multiple sclerosis.
Signs and symptoms
The somatic signs and symptoms of hypothyroidism are varied and nonspecific (Table 1). A majority
of these signs and symptoms may be linked to a decreased rate of metabolism and the accumulation
of glucosaminoglycans associated with low levels of circulating thyroid hormones. Although the signs
and symptoms of hypothyroidism are nonspecific, certain symptoms, such as cold intolerance, dry
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Hypothyroidism: An Important Diagnostic Consideration for the Psychiatrist
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skin, constipation, muscle cramps, and fatigue, may have increased specificity for the disease.
The severity of the presenting complaints and physical findings usually reflects the degree of
hypothyroidism. However, the presenting signs and symptoms of thyroid deficiency may vary with
patient age and acuity of onset. Since the symptoms of hypothyroidism are nonspecific, many other
illnesses can present with similar symptoms. The differential is broad, depending on the specific
symptoms (Table 2).
CASE VIGNETTE
Sandra is a 37-year-old woman with well-controlled type 1 diabetes mellitus who presents with
depressed mood. In addition to her affective complaint, the patient endorses worsening fatigue and
impaired concentration. A comprehensive review of symptoms reveals constipation, dry skin, cold
intolerance, and weight gain. Routine vital signs indicate a mild asymptomatic bradycardia. A TSH
test and a complete blood cell count are ordered. No pharmacotherapy is initiated.
Laboratory evaluation shows mild normocytic anemia and an abnormally elevated TSH level. A
second serum TSH test and a free T
4
measurement are ordered. The serum TSH level remains
elevated, and the free T
4
level is abnormally low. Clinical primary hypothyroidism is diagnosed.
Levothyroxine supplementation is initiated and the patient’s affective and somatic signs and
symptoms slowly resolve along with the patient’s hypothyroid state.
Thyroid dysfunction is known to cause a variety of neuropsychiatric symptoms, including mood
disorders, psychosis, and cognitive dysfunction. However, the mechanism by which thyroid hormone
causes psychiatric disturbance is not fully understood. In the brain, the active form of thyroid
hormone, T
3
, binds to nuclear receptors, which are widely distributed, and alters gene transcription.
Thyroid receptors located in the limbic system are theorized to cause the psychiatric manifestations
of hypothyroidism.
7
Affective disorders. Depressed mood is a well-known and accepted symptom of hypothyroidism.
Clinical symptoms such as poor concentration, weight changes, memory issues, and poor energy are
common overlapping symptoms of depression and hypothyroidism, so routine screening in
depressed patients is prudent. In fact, approximately 40% of patients with clinical hypothyroidism
have significant depressive symptoms.
8
The connection between subclinical hypothyroidism and depressed mood is more controversial.
Some studies have found higher frequency and severity of depression in patients who have
subclinical hypothyroidism than in euthyroid individuals.
9
There is also evidence that subclinical
hypothyroidism can negatively affect the treatment of depression by interfering with antidepressant
response.
10
Hypothyroidism can also present with mania. While mania is an uncommon presentation for
hypothyroidism, several cases have been described.
11,12
In these cases, the mania has resolved with
thyroid replacement. There are also case reports of aggressive titration of levothyroxine causing
secondary mania.
13
There appears to be a relationship between bipolar disease and hypothyroidism. Antithyroid
peroxidase antibodies have been found at higher rates in patients who have bipolar disorder than in
the general public.
14
Treatment of hypothyroidism in patients with rapid cycling bipolar disorder has
been found to decrease the severity and frequency of manic episodes.
15
Psychosis. Classic myxedema madness was first described by Asher
16
in 1949 in a case series of
patients with severe hypothyroidism and psychosis. While myxedema madness most typically
presents as delirium, psychotic symptoms secondary to hypothyroidism may present in a patient
who does not have altered consciousness or cognitive impairment. In fact, an array of psychotic
symptoms, including delusions, visual and auditory hallucinations, paranoia, and thought disorders,
have been reported secondary to hypothyroidism.
17
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Hypothyroidism: An Important Diagnostic Consideration for the Psychiatrist
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Psychosis does not necessarily appear to be related to the severity of the thyroid dysfunction
because psychosis has been reported in both clinical and subclinical hypothyroidism.
18
While
psychosis can be the presenting symptom that brings a patient to clinical attention, it typically
occurs late in the disease course.
Cognitive dysfunction. Cognitive impairment is common in hypothyroidism and can range from mild
to severe. Deficits vary from impaired concentration and slowed processing speed to general
declines in intelligence, psychomotor speed, visual-spatial skills, and memory. Cognitive deficits
associated with hypothyroidism tend to be more pronounced in the elderly. In fact, hypothyroidism is
thought to be one of the reversible causes of dementia, and therefore a screening TSH test is
indicated in all dementia workups. However, severe hypothyroidism that has progressed to dementia
is not always fully reversible, even after appropriate treatment.
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If thyroid dysfunction is suspected clinically, the preferred initial test is serum TSH. If the serum TSH
level is abnormal, the TSH should be rechecked along with a free T
4
level. The results of these
laboratory tests will allow the classification of the patient’s thyroid condition (Table 3). Primary
hypothyroidism is diagnosed when the TSH level is elevated and the free T
4
level is low. Subclinical
hypothyroidism is the diagnosis when the TSH level remains high on repeated testing and the free T
4
level is found to be in the normal range. A low serum free T
4
level combined with a low, or
inappropriately normal, TSH level likely represents second-ary hypothyroidism.
If the laboratory evaluation reveals primary hypothyroidism and the thyroid gland is normal on
physical examination, additional laboratory testing or imaging is usually unnecessary. However, in
the case of subclinical hypothyroidism, repeated testing of TSH and free T
4
levels in 4 to 6 months is
appropriate, because TSH levels may either spontaneously normalize or progress to those indicative
of clinical hypothyroidism. The risk of progression of subclinical hypothyroidism may be greatest for
those patients with serum TSH levels higher than 10 mIU/L. In addition, measurement of antithyroid
peroxidase antibodies may prove useful in the context of subclinical hypothyroidism, because
elevated levels of antithyroid peroxidase antibodies predict an increased risk of progression to
primary hypothyroidism at a later date. In patients with evidence of secondary hypothyroidism,
measurement of additional pituitary hormones, MRI of the sellar region, and referral to endocrinology
are appropriate.
Treatment
The initial treatment of neuropsychiatric symptoms of hypothyroidism should be directed at
correcting the underlying thyroid deficiency. Thyroxine replacement is usually effective for resolving
all the signs and symptoms of hypothyroidism, although the time course to resolution is very
individual.
However, if the neuropsychiatric symptoms are significant, symptomatic treatment may be
appropriate. For example, antipsychotics are often used in an attempt to acutely manage psychotic
symptoms secondary to hypothyroidism until the underlying hypothyroid state is corrected. Patients
with hypothyroidism complicated by affective or cognitive disturbance should have their
hypothyroidism treated before starting psychotropic medications. If after appropriate levothyroxine
treatment the patient remains symptomatic, appropriate pharmacotherapy may be initiated.
Psychiatric medications should be dosed low and titrated slowly when used in patients with
hypothyroidism.
Primary hypothyroidism. The goal of treatment is to resolve the signs and symptoms of
hypothyroidism by returning the patient to the euthyroid state. This most frequently necessitates
lifelong thyroid hormone replacement. There are many thyroid hormone preparations available for
treatment of hypothyroidism. Levothyroxine is identical to the T
4
produced by the thyroid. It is the
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Hypothyroidism: An Important Diagnostic Consideration for the Psychiatrist
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preferred medication for thyroid replacement because it has a long half-life, thereby allowing
once-a-day dosing and minimal fluctuations in serum levels.
The starting dosage of levothyroxine in healthy adults younger than 60 years with primary
hypothyroidism is 1.6 μg/kg of ideal body weight daily. In older patients and patients with coronary
artery disease, the starting dosage of T
4
should be lower (25 to 50 μg/d)—the dose should be titrated
slowly to avoid cardiac complications. The average replacement dosage ranges from 100 to 150 μg/d
in women and from 125 to 200 μg/d in men. After initiation of appropriate therapy, the
manifestations of hypothyroidism usually resolve over weeks to months.
L-triiodothyronine is a synthetic form of the T
3
hormone. Its use is complicated by a short half-life that
requires multiple daily doses and results in peak concentrations that are often supraphysiologic,
which may lead to adverse effects.
Levothyroxine and L-triiodothyronine combination treatment has been tried, but a meta-analysis of
combined therapy versus levothyroxine monotherapy for treatment of clinical hypothyroidism failed
to find any additional benefit of combined treatment in improving quality of life and depressive
symptoms.
19
Subclinical hypothyroidism. Treatment of patients with subclinical hypothyroidism is a controversial
clinical issue and deserves consultation with the patient’s primary care physician or endocrinologist.
Treatment should be considered for patients with a TSH level greater than 10 mIU/L (given
associated adverse physiological effects and risk of progression to primary hypothyroidism) and for
patients with elevated antithyroid peroxidase antibody titers (given an increased rate of conversion
to primary hypothyroidism). In addition, patients with TSH levels of 5 to 10 mIU/L coupled with
symptoms suggestive of hypothyroidism may benefit from levothyroxine therapy. Patients with
subclinical hypothyroidism may require only 25 to 50 μg/d of levothyroxine supplementation, given
the mild nature of the associated thyroxine deficiency.
Monitoring treatment
After initiating treatment with hormone replacement, the effectiveness of treatment should be
monitored by measuring the serum TSH level in 8 to 12 weeks. This allows time for the
pituitary-thyroid axis to reset and reflects the current state of circulating thyroid hormones. The
biochemical goal of treatment is to keep the patient’s TSH level within the lower half of the normal
range.
If, on follow-up testing, the TSH level is found to be high or low, the dosage of levothyroxine will
need to be increased or decreased. The TSH level should be rechecked 2 months after any dose
adjustment. Once the patient is euthyroid, the serum TSH should be checked in 6 months because
metabolism of levothyroxine may be increased compared with the hypothyroid state. Thus, the initial
dose of levothyroxine may be inadequate to maintain a euthyroid state.
Summary
Hypothyroidism is a common clinical disorder that psychiatrists frequently encounter. However,
symptoms of thyroid dysfunction are often vague and nonspecific, which can lead to delayed or
missed diagnosis. Thyroid dysfunction can cause an array of physical and neuropsychiatric
disturbances and, thus, early diagnosis and treatment are important for reducing morbidity.
Psychiatric symptoms can be the initial presentation of thyroid dysfunction. Psychiatrists must have
a high degree of suspicion for potential underlying, exacerbating, or treatment-related thyroid
disorders.
DISCLOSURES:
Dr Estabrook is a Psychosomatic Medicine Fellow in the department of psychiatry and behavioral
medicine, and Dr Heinrich is Associate Professor in the department of psychiatry and behavioral
medicine and the department of family and community medicine at the Medical College of Wisconsin
in Milwaukee. The authors report no conflicts of interest concerning the subject matter of this article.
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