Question

describe a client who initially presented as if she or he had a mental disorder but the final diagnosis was an organic or physical disorder.

Answer 1

Patients with underlying medical disease can present to the health care system with psychiatric symptoms predominating. Identification of an underlying medical condition masquerading as a psychiatric disorder can be challenging for clinicians, especially in patients with an existing psychiatric condition. The term medical mimic or secondary psychosis has been used to describe this clinical situation. Diagnostic categories from The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, that may encompass medical mimics include substance-induced disorders, which includes medications, and unspecified mental disorder due to another medical condition in situations where the clinician may lack needed information for a complete diagnosis. At this time, there is no single diagnostic test or procedure available to differentiate primary versus secondary psychosis on the basis of psychopathology presentation alone. When considering a diagnosis, clinicians should evaluate for the presence of atypical features uncharacteristic of the psychiatric symptoms observed; this may include changes in functionality and/or age of onset and symptom presentation severity. The purpose of this work is to provide a structured clinical framework for evaluation for medical mimics, identify groups considered to be at highest risk for medical mimics, and present common syndromic features suggestive of a medical mimic. Selected case scenarios are used to illustrate key concepts for evaluating and assessing a patient presenting with acute psychiatric symptomatology to improve judgment in ruling out potential medical causality

Myxedema Madness

Hypothyroidism is a clinical condition resulting from insufficient circulating thyroid hormone manifesting as a metabolic slowing. Commonly reported symptoms include fatigue, weakness, weight gain, cold intolerance, and dry, coarse hair, with corresponding dry, rough, pale skin. Psychiatric symptoms may include depression, irritability, memory loss or impairment, and myxedema coma. Much less frequently reported is a clinical condition referred to as myxedema madness, a severe psychosis related to significant hypothyroidism.1,20,21 Recent case reports highlighted the presentation of this change in cognition and onset of psychiatric symptoms.

In the first case, the patient had no prior psychiatric history but had a past medical history significant for hypothyroidism and was levothyroxine nonadherent for 4 months. On admission, delusions and visual hallucinations were reported. Admission lab work revealed a thyroid-stimulating hormone concentration of 60.29 mIU/L (normal range = 0.47-4.68 mIU/L), a total triiodothyronine concentration of 34 ng/dL (normal range = 97-169 ng/dL), and a thyroxine concentration of 1.3 μg/dL (normal range = 5.1-13.8 μg/dL). The patient's age and substance use history were not reported. Levothyroxine was resumed, and haloperidol was added. Clinicians were unable to evaluate whether the presenting psychotic features were due to the general medical condition or an unrelated change in mental status, leading to the plan to initiate low-dose haloperidol, discharge, and evaluate as an outpatient.20

In a separate case, the patient developed signs and symptoms of psychosis secondary to a thyroidectomy for thyroid cancer done prior to admission. Changes in mental status for this patient were characterized by psychomotor agitation, directives from an “inner voice,” and aggression (screaming and hitting family). Admission lab work was consistent with severe hypothyroidism: thyroid-stimulating hormone concentration of 62.9 mIU/L, a free thyroxine concentration less than 0.35 ng/dL (normal = 0.7-1.9 ng/dL), a triiodothyronine concentration of 70 ng/dL, and a total thyroxine concentration less than 1 μg/dL. Thyroid supplementation was initiated with levothyroxine, as were psychiatric agents (haloperidol, lorazepam, and levomepromazine—currently not available in the United States).

Following levothyroxine initiation, the severe hypothyroidism had almost completely resolved, and within 4 months of treatment, the psychopharmacologic medications were tapered to discontinuation with complete resolution of psychiatric symptoms.21 These case reports illustrate the presentation of an infrequently diagnosed medical condition masquerading as a psychosis in individuals with no prior history of mental illness. The sudden onset of psychosis with no prior history flagged the cases for additional follow-up. Following the comprehensive intake procedure, which consisted of a complete medical history, diagnostic lab work, and review of medication adherence, appropriate pharmacotherapy and follow-up were successfully initiated.

Delirium

To illustrate how delirium can be difficult to identify, the case of a 56-year-old white man diagnosed with bipolar I disorder (most recent episode manic), nicotine dependence, chronic kidney disease stage 3, and benign prostatic hypertrophy is described. The patient's history was significant for previous lithium toxicity and mood instability. At times the patient demonstrated neurocognitive deficits characterized by gait instability and balance problems. Social history was positive for tobacco (approximately 1 pack per day) and marijuana use (believed to be 2-3 times per week).

When the patient was evaluated in the psychiatric clinic, speech was fluent, rapid, and pressured. Thought processes were vague, tangential, and disorganized, with illogical content. He denied delusions or hallucinations. His medication regimen included aripiprazole 25 mg, olanzapine oral disintegrating tablet 15 mg daily, clonazepam 0.5 mg at bedtime, and hydroxyzine 50 mg at bedtime and 25 mg up to twice daily for anxiety. To monitor for divalproex adherence, a valproic acid level was ordered and found to be within normal limits. The attending physician did not order a serum ammonia level, although with the use of divalproex in this case (1500 mg), it may have been useful to rule out divalproex-associated encephalopathy. The patient was monitored for medication adherence, then returned home. Two weeks later, hospitalization was needed because of increasingly bizarre statements and behaviors. A urine drug screen and urinalysis were obtained. The urine drug screen was negative; however, the urinalysis revealed a urinary tract infection (UTI), which, when treated with appropriate antibiotics, led to a resolution of psychiatric symptoms. The admitting psychiatrist determined delirium was the primary cause for psychiatric decompensation based on patient presentation, time course of onset, and laboratory results. Following initiation of antibiotic therapy, the psychosis remitted, and he returned to his preadmission level of psychosocial functioning.

Delirium has been characterized as one of the most underrecognized and undertreated neuropsychiatric syndromes, with disturbances in cognition, psychomotor behaviors, and alertness.22 The origins are typically multifactorial. Risk factors include illicit drug use, medications (examples in Table 3), hydration status, and metabolic disorders.21 Appropriate and timely treatment are dependent on recognition. Common presentations include lethargy, disorientation, agitation, delusions, and hallucinations. Diagnostic criteria for delirium encompass disorganized thinking, disturbances in perception, and fluctuating clinical symptoms.4 Consistent with the components for a comprehensive evaluation, clinicians are encouraged to consider delirium (until proven otherwise) in cases of a sharp and sudden decline in cognitive function.

A systemic review of the published literature relative to UTIs and delirium reported UTIs as one of the most common bacterial infections in elderly patients, whose ages may include persons as young as 55 years. They are highly correlated with the onset or exacerbation of neuropsychiatric disorders. The mean weighted prevalence of UTI in individuals with delirium was 19.4% versus 12.8% in individuals without delirium. The 8 studies reviewed suggested that UTIs were an independent risk factor for developing delirium.23

Typical management of delirium includes completion of a validated, evidence-based delirium rating scale, pre-episode functioning (preexisting deficits in cognitive function), thorough medication history focusing on the use of psychoactive medications, and elimination of the possibility of metabolic imbalances and/or infection. In addition to routine laboratory studies, additional diagnostic tests may be performed to provide additional clinical information when indicated. Any abnormal findings, such as electrolyte imbalance, dehydration, hypercalcemia, and hypoxia, should be corrected, and potentially offending drugs discontinued or decreased.24 The sudden exacerbation of psychotic symptoms in the above delirium case was secondary to a UTI. As an example of the potential consequences of not performing a thorough medical workup in the evaluation schema outlined, a delay identifying the underlying correctable medical condition (UTI) occurred, along with lag time to appropriate treatment and associated increased morbidity.

Degenerative Neurologic Disorder

As the clinician gathers information, interprets diagnostic test results, and formulates a diagnosis, psychotic symptoms as features of degenerative neurologic disorders, such as Parkinson disease (PD), must also be considered.

Secondary psychosis or psychotic disorder due to another medical condition, arising from a degenerative neurologic disorder, such as PD, is relatively common. Features include visual hallucinations, progression over time, and emergence later in the disease course.25 The prevalence of hallucinations in this population has been reported to be up to 40%.26,27 Adverse medication effects have also been reported in persons with a diagnosis of PD, as illustrated by the following case.

A psychiatrically stable 56-year-old man with PD receiving a total daily dose of pramipexole 0.75 mg was titrated to 1.125 mg per day. Following this change, verbal and physical aggression increased. Psychotic symptoms presented. During the course of the next month, episodes of hallucinations and delusions tripled. Pramipexole was tapered to the previous total daily dose of 0.75 mg, and the behaviors returned to baseline levels by the second month. Anti-Parkinson pharmacotherapy and the corresponding increase in CNS dopamine are often implicated in causing or exacerbating psychosis.28

In this case, a thorough medication history, review of recent changes in a regimen (particularly the small dose change), and understanding of the patient's degenerative disease process contributed to a timely intervention and stabilization. Clinicians who may be new to neuropsychiatric patients are reminded that unintended behavioral and intended clinical response to medication may be impacted by a multidimensional set of variables, specifically age-related changes in drug metabolism and excretion (hepatic and/or renal insufficiency), multiple medications, and the use of CNS-active agents.

Conclusions

This work was developed to outline key elements in a clinical assessment construct that, when followed, should minimize the frequency of overlooking an underlying and potentially treatable medical illness that may be masquerading as a primary psychiatric illness, and thus avoiding delays in correct diagnosis and appropriate treatment. Formulation of a diagnosis conceptualizes the various possibilities in determining whether the clinical presentation is due to a primary psychiatric illness or a medical mimic and requires clinical vigilance as well as a structured process of evaluation. In addition to evaluating onset, duration, changes in medication use patterns, or metabolic abnormalities as part of a comprehensive assessment, clinicians are encouraged to consider (and obtain) information regarding change from the patient's baseline psychosocial functionality whenever possible. The diagnostic schema for ruling out medical mimics requires critical thinking, a multifactorial approach, clinical diligence, exclusion of infectious disease(s), metabolic disturbances, respiratory disorders, endocrine abnormalities, medications, trauma, and substance use when considering the potential for nonpsychiatric causes of the presenting symptoms, especially in the case of patients with a preexisting psychiatric illness.

The cases presented are designed to demonstrate the utility of application of a structured framework to aid patient evaluation. The case examples of myxedema demonstrate how a careful and comprehensive evaluation can aid in determining the medical etiology where psychiatric symptoms are the predominant initial presenting symptoms. In the case of delirium, the underlying cause was determined to be a UTI, and premorbid function resumed following antibiotic treatment. This case also illustrates how a potentially important lab test was not ordered, possibly leading to a delay in appropriate treatment. In the last case, a small medication change in a patient with a degenerative neurologic disorder resulted in the manifestation of psychiatric symptoms, whereby a dose reduction returned the patient to baseline psychosocial function. Improvements in diagnostic accuracy should aid in minimizing misdiagnosis and allow the patient's illness to be appropriately managed in a more timely manner