There is a significant dilemma when underlying medical disorders present as psychiatric conditions. It is important to identify the medical condition because treatment and management strategies need to be directed to the presenting symptoms and also to the underlying medical condition for successful treatment of the patient. Some systemic disorders present with psychiatric manifestations more often than others. The pattern of psychiatric disturbance seen may be specific for a particular medical disorder but may also be varied. Many drug formulations and medications also may produce psychiatric presentations. This article considers the management of nonpsychiatric medical conditions presenting with psychiatric manifestations.
One of the most significant dilemmas arise when there is an underlying medical disorder presenting as a psychiatric presentation. It is important to identify the medical condition because treatment and management strategies need to be directed not only to the presenting symptoms but also to the underlying medical condition for appropriate success in the treatment of the patient. Some systemic disorders are known to present with psychiatric manifestations more often than others. The pattern of psychiatric disturbance seen may be specific for a particular medical disorder but also may be varied. Many drug formulations and medications also may produce well-recognized psychiatric presentations. The spectrum of medical disorders that may present with psychiatric clinical presentations is listed in Box 1 . Many endocrine system disorders may present with a wide range of psychiatric symptoms. This article discusses the overlapping of psychiatric clinical features in these endocrine disorders and addresses appropriate management strategies in these scenarios.
Endocrine disorders a
- •
Thyroid
Hypothyroidism
Hyperthyroidism
- •
Parathyroid disorders
Hypoparathyroidism
Hyperparathyroidism
- •
Adrenal disorders
Hypoadrenocorticism/adrenal insufficiency
Hypercorticism/Cushing syndrome
Pheochromocytoma
- •
Disorders of glycemic control
Hyperglycemia/diabetes mellitus
Hypoglycemia
- •
Genetic syndromes
Klinefelter syndrome
Turner syndrome
- •
Metabolic disorders
- •
Porphyrias
- •
Vitamin deficiencies
B 1 deficiency
- •
Hepatic disorders
Hepatic encephalopathy
Wilson disease
- •
Immunologic disorders
- •
Systemic lupus erythematosus
- •
Multiple sclerosis
- •
Fibromyalgia
- •
Central nervous system disorders
Infectious diseases
- •
Rheumatic fever
- •
Human immunodeficiency virus infections
- •
Syphilis
- •
Malaria
- •
Typhoid
- •
a These disorders are discussed in this article.
Thyroid disorders
Hypothyroidism and hyperthyroidism may present with signs and symptoms that closely overlap a variety of psychiatric features. The presence of coexistent neuropsychiatric manifestations may cause a more serious and insidious functional decline. At times, psychiatric symptoms may be the only, or the most prominent, presenting symptoms of thyroid disequilibrium and these are the patients who may be misdiagnosed with a primary psychiatric illness. Cognitive dysfunction with slowing of the mental processes, difficulties in short-term memory, decreased concentration, inattention, and attention deficit hyperactivity disorder (ADHD), are some of the clinical features that may mislead the diagnosis. Table 1 lists some of the common psychiatric presentations seen in various thyroid disorders.
| Thyroid Disorders | Depression | Mania | Anxiety Spectrum | Psychosis | ADHD | Delirium | Cognitive Dysfunction |
|---|---|---|---|---|---|---|---|
| Hypothyroidism | +++ | + | ++ | ++ | + | + | +++ |
| Hyperthyroidisms | ++ | ++ | +++ | ++ | + | + | ++ |
| Subclinical hypothyroidism | + | + | + | ± | + | ± | + |
Hypothyroidism
Clinical features
Clinical presentation varies greatly based on severity of hypothyroidism and on whether the hypothyroidism develops acutely or is more chronic in onset. The chronic, slow-developing hypothyroidism presents with vague, nonspecific features and has the potential for a delayed diagnosis. Children and adolescents may be asymptomatic but, on routine physical examination, may be noted to show evidence of suboptimal growth. They may complain of being lethargic with low energy levels, fatigue, loss of appetite, weight gain, sallow complexion, memory loss, menstrual disturbances generally with increased and prolonged bleeding, dry skin, temperature intolerance, and hair loss.
Psychiatric features
Depression as the hallmark of hypothyroidism has been well documented in literature. However, manic presentation is uncommon, even in patients with established bipolar disorder, but there are reports of mania induced by thyroxine treatment in hypothyroid patients. Myxedema madness was once a common initial presentation of hypothyroidism but now accounts for only about 5% to 15% of cases. A wide variety of symptoms have been reported with myxedema madness, including depression and restlessness, perceptual disturbances in the form of auditory and visual hallucinations, delusions of a persecutory nature, paranoia, and loosening of associations. The presence of psychosis usually signifies chronic hypothyroidism. The severity of illness does not always correlate with the occurrence of psychotic symptoms and therefore cannot be used as a predicting factor. Two types of encephalopathy have been reported in hypothyroidism. Hashimoto encephalopathy in children and adolescents 9 to 17 years of age is reported to present with dysphoric mood, hallucinations, decreased alertness, decline in cognition, anxiety, hyperactivity, and various neurologic symptoms including myoclonus, hemiperesis/hemiplegia, and focal and generalized seizure activity. Acute exhaustion psychosis or delirium has been reported in older studies citing mortality rate as high as 70%. The incidence of hypothyroidism in patients being treated with lithium is reported to be around 2% to 10%. Clinicians must counsel their patients regarding the possibility of hypothyroidism when starting on this treatment. It is also prudent to do baseline thyroid function tests, including antithyroid antibodies, before initiation of lithium therapy. The risk of rapid-cycling bipolar disorder (4 or more manic, hypomanic, or depressive episodes occurring in 1 year) is seen in 10% to 12% of patients with bipolar disorder. Bauer and colleagues reported that grade 1 hypothyroidism in bipolar patients is a risk factor for development of rapid cycling.
Medical work-up
Thyroid function tests, including free thyroxine (FT 4 ) and thyroid stimulating hormone (TSH) levels, are the main diagnostic laboratory studies used to diagnose thyroid disorders ( Table 2 ). If thyroid dysfunction is noted, further testing, including antithyroperoxidase and antithyroglobulin antibodies, may be done to establish any underlying autoimmune cause. Imaging studies, including thyroid ultrasound, may be done only if needed. This further work-up is best addressed in coordination with a pediatric endocrinologist.
| Free Thyroxine | Thyroid Stimulating Hormone | |
|---|---|---|
| Subclinical/compensated hypothyroidism | Normal | Increased |
| Overt hypothyroidism | Low | Increased |
| Central hypothyroidism | Low | Low/normal |
Psychiatric work-up
Diagnosis of depression poses a diagnostic dilemma in the presence of hypothyroidism because many of the clinical features of hypothyroidism mimic the neurovegetative symptoms of depression. The high association of the 2 disorders should alert any clinician to do a mandatory screen for depression. Use of psychiatric testing measures for the identification of psychiatric illness and for the ongoing monitoring of these disorders is gaining some popularity in primary care settings.
Medical treatment
It is recommended that overt hypothyroidism be treated adequately; however, the consensus about treatment of subclinical or compensated hypothyroidism is not as clear. Initial presentation with borderline, mild, or subclinical hypothyroidism should be followed with a repeat of FT 4 and TSH testing in several weeks for confirmation and to watch for a trend. Treatment decisions need to be individualized and may depend on multiple factors including growth pattern, symptoms, thyroid enlargement, antibody status, and the laboratory values. Thyroid hormone preparations recommended for use are the recombinant levothyroxine (LT 4 ) preparations. FT 4 and TSH levels are repeated in 4 weeks after initiating treatment to make appropriate dose titrations.
Psychiatric treatment
Selective serotonin reuptake inhibitors (SSRIs) have now become the first-line treatment of depression and anxiety in adults because of their efficacy. The relative safety of SSRIs versus their predecessors, the tricyclic antidepressants (TCAs), has revolutionized the way patients with medical comorbidities can be treated for their psychiatric illness. The SSRIs have equal clinical efficacy but only few are approved for use in pediatric populations ( Table 3 ). The selection of a particular agent depends on multiple factors including age, previous response to any particular SSRI, any contraindications, side effects, possible drug interactions, and previous good response to a particular SSRI in the patient or in another family member. The other factors affecting the choice of SSRI include ease of dosing (eg, availability of different formulations, ie, suspensions and tablets) and daily dosing options (ie, once daily vs 2 to 3 times a day). The most important factor can be the cost of the particular SSRI, insurance coverage, and the availability of generic versus brand name formulations. Hashimoto encephalopathy is a steroid-responsive encephalopathy associated with Hashimoto thyroiditis and usually responds well to high-dose glucocorticoid therapy. Treatment usually starts with intravenous therapy followed by prednisone 1 to 2 mg/kg/d for 6 to 8 weeks. Relapses have been reported in spite of initial good response. Cognitive deficits may persist even after successful treatment.
| Psychotropic | Indication | Age (y) | |
|---|---|---|---|
| SSRIs | Fluoxetine | Depression | ≥8 |
| OCD | ≥7 | ||
| Fluvoxamine | OCD | ≥8 | |
| Sertraline | OCD | ≥6 | |
| Escitalopram | Depression | ≥12 | |
| Tricyclic antidepressants | Imipramine | Depression | ≥12 |
| Clomipramine | OCD | ≥10 | |
| Doxepin | Depression | ≥12 | |
| Mood stabilizers | Carbamazepine | Epilepsy monotherapy/adjunctive | All ages |
| Oxcarbazepine | Epilepsy monotherapy | ≥4 | |
| Lamotrigine | Epilepsy monotherapy | ≥16 | |
| Gabapentin | Epilepsy adjunctive therapy | ≥3 | |
| Topiramate | Epilepsy monotherapy | ≥10 | |
| Typical antipsychotics | Chlorpromazine | Severe behavior problems | 0.5–12 |
| Haloperidol | Severe behavior problems | ≥3 | |
| Pimozide | Tourette disorder | ≥12 | |
| Atypical antipsychotics | Risperidone | Schizophrenia | ≥13 |
| Bipolar disorder type I | ≥10 | ||
| Irritability in autistic disorder | 5–16 | ||
| Apiprazole | Schizophrenia | ≥13 | |
| Bipolar disorder type I | ≥10 | ||
| Irritability in autistic disorder | 6–17 |
Hyperthyroidism
Clinical features
Patients with hyperthyroidism may present with a wide spectrum of symptoms depending on severity and acuity of onset, including weight loss with increased appetite, heat intolerance, menstrual disturbances generally with menorrhagia/metorrhagia, palpitations, warm and flushed skin, diaphoresis, exophthalmos, proptosis, and lid lag.
Psychiatric features
The debate about the role of thyroid dysfunction in children and adolescents with ADHD continues, with strong arguments on both sides without any clear conclusion. Children with hyperthyroidism may display deterioration in school performance, hyperactivity, and inattention. The onset of neuropsychological symptoms generally precedes the diagnosis of abnormality of thyroid function. The spectrum of anxiety disorders has a strong correlation with hyperthyroidism. Neuropsychiatric symptoms, including anxious dysphoria and irritability, may predate the diagnosis of thyrotoxicosis by up to a year. Studies have also found a strong correlation between depression and anxiety among hyperthyroid patients. A survey of 137 patients with Graves disease found irritability in 78%, shakiness in 77%, and anxiety in 72% of patients. Specific phobias have also been reported as a presenting symptom in hyperthyroidism. Panic disorder with agoraphobia (fear of having a panic attack in a situation from which escape is difficult, which can make the patient housebound) is a debilitating disorder and at times is the presenting symptom of hyperthyroidism. Psychotic symptoms with mania and hypomania have been associated with more morbidity and loss of functioning than a hyperthyroid state without mania, and are associated with a higher lifetime risk of hospitalization for psychiatric reasons.
Medical work-up
FT 4 and TSH are primary laboratory tests for diagnosis of hyperthyroidism. Further testing if needed may include free T 3 levels, antithyroperoxidase and antithyroglobulin antibodies, and thyroid-stimulating immunoglobulin levels ( Table 4 ).
| Thyroid Disorder | FT 4 | TSH | Free Triiodothyronine |
|---|---|---|---|
| Overt hyperthyroidism | Increased high | Low | Not needed |
| Subclinical hyperthyroidism | Normal | Low | Not needed |
| Triiodothyronine toxicosis | Normal | Low | High |
Psychiatric work-up
It is prudent to complete a thorough initial psychiatric evaluation. The focus should be on developmental psychology to differentiate between the concerns and fears normally associated with a given developmental stage versus an anxiety disorder. Separation anxiety, situational anxiety related to school, gender and sexual identity, and so forth are age-appropriate developmental responses with features of anxiety but usually are transient and resolve on their own. Several screening tests can be used in children more than 8 years of age for the diagnosis of anxiety disorders, for example the Multidimensional Anxiety Scale for Children or the Screen for Child Anxiety-related Emotional Disorders ( Table 5 ).
| Presentation | Psychological Tests | Ages (y) | Time (min) |
|---|---|---|---|
| Depression | Weinberg Depression Scale for Children and Adolescents | 5–17 | 3–5 |
| Children’s Depression Rating Scale-Revised | 6–12 and adolescent | 15–20 | |
| Beck Depression Inventory for Youth | 7–14 | 3–5 | |
| Reynolds Child/Adolescent Depression Scales: Child Adolescent | 8–12 11–20 | 10 10 | |
| Center for Epidemiologic Studies Depression Scale for Children | 6–17 | 5 | |
| Children Depression Inventory | 7–17 | 10–15 | |
| Bipolar disorder | Young Mania Rating Scale Parent version of the Young Mania Rating Scale | 5–17 5–17 | 15–30 5 |
| Mood Disorder Questionnaire | ≥12 | 5–10 | |
| Weinberg Affective Scale | 7–17 | 5 | |
| Suicide risk assessment | Suicidal Ideation Questionnaire | 13–18 | 10 |
| Anxiety spectrum disorders | Depression and Anxiety in Youth Scale | 6–19 | 15–20 |
| Beck Anxiety Inventory for Youth | 7–14 | 10 | |
| Self-report for Childhood Anxiety-related Emotional Disorders | ≥8 | 5 | |
| How I Feel Questionnaire | 7–17 | 5–10 | |
| Children’s Yale-Brown Obsessive Compulsive Scale | 6–14 | 40 | |
| ADHD | Conners Rating Scale Scales Revised short form | 3–17 | 5–10 |
| Vanderbilt ADHD Diagnostic Parent Rating Scale | 6–12 | 10 | |
| Conners-Wells Self-report | 12–17 | 5–10 | |
| Psychotic disorders | Kiddie Schedule for Affective Disorders and Schizophrenia | 6–18 | 90–120 |
| Delirium/encephalopathy | Pediatric Anesthesia Emergence Scale Delirium Rating Scale in Children and Adolescents | 19 mo to 6 y 6 mo to 19 y | 1 |
| Achievement/development/learning | Wide Range Assessment of Visual Motor Abilities Test of language Development-Primary, 4th edition Test of Visual Perceptual Skills,3rd edition Test of Nonverbal Intelligence 4th edition | 3–17 4–8 4–18 6–11 onward | 4–10 per subset 60 30–40 20 |
Medical treatment
Hyperthyroidism may be treated with medications, surgery, or radioactive iodine (RAI). Medical therapy includes 2 main groups of medications: methimazole/tapazole or thionamides such as propyl thiouracil. RAI therapy for Graves disease is becoming increasingly popular in the adolescent age group, whereas it is the treatment of choice in adults. Total or partial thyroidectomy may have to be undertaken in younger children in situations in which RAI may be contraindicated, or if the thyroid gland is very large. Propranolol or atenolol may be used initially to control some of the sympathomimetic effects of hyperthyroidism.
Psychiatric treatment
The ADHD-like symptoms respond well to antithyroid treatment if the treatment is initiated early. However, a delay in diagnosis and treatment may result in persistence of the neuropsychiatric and cognitive issues. The anxiety symptoms of hyperparathyroidism generally respond well to medical treatment. However, if a comorbid anxiety disorder is present, psychiatric intervention may be indicated. The initial treatment of anxiety spectrum disorders is psychotherapy, with some data to support the efficacy of psychodynamic therapy, cognitive behavioral therapy (CBT), and parent-child and family therapy. SSRIs offer efficacious therapeutic options in anxiety disorders if psychotherapy alone is unsuccessful. Other anxiolytics approved for adults, but not clearly approved in the pediatric population, such as benzodiazepines, buspar, venlafaxine, bupropion, and TCAs, have also been used alone or in combination for treatment of childhood anxiety disorders. Psychotic symptoms usually resolve spontaneously when TSH levels normalize. However, atypical antipsychotics may be useful in the short-term.
Parathyroid disorders
Disturbances in parathyroid hormone metabolism comprise mainly hypoparathyroidism and hyperparathyroidism. The main clinical presentation is caused by features of hypocalcemia or hypercalcemia respectively.
Hypoparathyroidism
Clinical features
Children and adolescents with hypoparathyroidism may present with generalized weakness, fatigue, and listlessness; signs of muscle irritability, twitching, tetany, or frank seizures; and slow cognition or severe cognitive impairment. Chevostek and Trousseau signs may be present. Abnormalities of cardiac rhythm may be present. These patients may also present for attention with psychiatric symptoms even before the physical features described.
Psychiatric features
Psychiatric symptoms are usually associated with long-standing hypoparathyroidism. Velasco and colleagues studied the frequency of occurrence of psychiatric symptoms and noted that cognitive impairment (39%) is the commonest followed by nonspecific psychiatric symptoms (21%), neurotic symptoms (12%), and psychosis (11%). Electrolyte studies should be done in these patients before the start of therapy because hypocalcaemia and hypomagnesemia may cause treatment resistance to psychotropics.
Medical work-up
Laboratory findings for hypoparathyroidism are noted in Table 6 . Serum magnesium levels may also be low.
| Parathyroid Disorder | Ca | P | Parathyroid Hormone |
|---|---|---|---|
| Hypoparathyroidism | Decreased | Increased | Decreased |
| Hyperparathyroidism | Increased | Decreased | Increased |
| Pseudohypoparathyroidism | Decreased | Increased | Increased |
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