A 31-year-old man with no notable medical history was brought to the psychiatric emergency department by his mother and sister for new-onset aggression, paranoid behavior, and hallucinations for 4 days. He was married with 2 young children and worked as a taxi driver. 

After the patient was triaged in the psychiatric emergency department, his blood and urine were sent to the laboratory for medical clearance before he could be admitted to the inpatient psychiatric unit. A computed tomographic scan of his head showed no abnormality, and initial urine toxicologic findings were negative. Rapid plasma reagin results and electrolyte levels were within normal limits. His thyroid-stimulating hormone (TSH) level was markedly elevated at 306 mIU/L, and his free thyroxine level was 0.24 ng/dL. He was immediately transferred to the general emergency department, where urgent endocrinology and medical intensive care unit (ICU) consultations were requested. Suspecting myxedema psychosis due to suspected Hashimoto thyroiditis, the endocrinologist ordered 100 mg of intravenous (IV) hydrocortisone to be administered followed by 150 µg of IV levothyroxine. He was admitted to the ICU, where he received 100 µg of IV hydrocortisone every 8 hours for 1 day, followed by tapering doses, because adrenal insufficiency was of low clinical suspicion. He was also given 100 mg of IV levothyroxine daily for 2 days, followed by 125 µg orally. His cortisol level was also checked from the initial sample obtained in the psychiatric emergency department to evaluate for adrenal insufficiency, and it was found to be normal. 

While in the medical ICU on hospital day 2, the patient had worsening and evolving psychosis, consisting of religious delusions, disorganized thoughts with flight of ideas, paranoid behavior, and aggression toward staff. He began walking around the unit praying and experiencing delusions of deceased family members being treated throughout the ICU. At one point, the patient’s aggression toward staff escalated to violence, which required a psychiatric crisis prevention team response. This response protocol involved hospital police and chemical sedation with haloperidol. 

On hospital day 3, the patient continued to have confusion, but he began to question his delusional perceptions. His agitation and aggression began to improve. A thyroid peroxidase antibody test taken earlier in his hospital course came back as 4871 IU/mL, confirming the diagnosis of previously suspected Hashimoto thyroiditis. His TSH level showed daily improvement throughout the hospital course, decreasing from 306.0 mIU/L on admission to the psychiatric emergency department to 74.0 mIU/L on hospital day 3. He was transferred from the ICU to the medical floor. 

While on the medical floor, the patient returned to his baseline mental status, with recollection of all the events that took place throughout his hospital course. His myxedema psychosis did not cause any lapses in memory. The remainder of his hospital course was uncomplicated. He was discharged from the hospital on hospital day 4, with close follow-up in the endocrine clinic. On discharge, his TSH level had improved to 15.35 mIU/L. 

About a week after being discharged, the patient returned to the medical ICU for follow-up. He was nearly unrecognizable. The former disheveled and delusional man was replaced by a well-dressed, well-groomed, clean-shaven, and apologetic man. He shed light on his thought progression while in the hospital, with what seemed to be an internal struggle with determining right from wrong and reality vs delusion. He said that he knew that things could not be as they appeared to him, but he was still not able to control his compulsions and actions in the moment. The patient continued to follow up at the endocrine clinic with excellent compliance. 

An extensive literature search revealed that myxedema psychosis is a rare yet well-established entity.⁵ A presentation of myxedema psychosis is often seen in patients with longstanding Hashimoto thyroiditis, after thyroidectomy, or with medication noncompliance.^1,2 Progressively worsening symptoms of hypothyroidism can include fatigue, cold intolerance, decreased concentration, weight gain, hoarse voice, and constipation (Figure). Severe symptoms can include hypotension, hyponatremia, or hypoglycemia. This myriad of symptoms, if left untreated, can ultimately lead to hallucinations, myxedema psychosis, or myxedema coma.⁶ The patient in the current case report not only had myxedema psychosis as his initial and only symptom and an unremarkable medical history, but he had the highest level of TSH noted in the literature for patients presenting with hypothyroid-induced psychosis. Reported levels have ranged from 21.9 mIU/L to 122.2 mIU/L.^1-8 

Hypothyroidism can be found in 0.3% to 0.4% of people, and subclinical hypothyroidism in 4.30% to 8.5%.9 Despite the high incidence of hypothyroidism, psychiatric disturbances as a presenting symptom of hypothyroidism are extremely rare, with an unknown incidence.^7,8 Forty percent of patients with hypothyroidism have superimposed signs and symptoms of depression.^1,9 A meta-analysis performed by Howland⁹ found that approximately 50% of patients with refractory depression had evidence of subclinical hypothyroidism. 

Management of myxedema psychosis is similar to that of myxedema coma, with the ideal therapy remaining controversial, owing to the lack of clinical trials. Treatment in an ICU is recommended, with cardiac monitoring and monitoring for hyponatremia, hypoglycemia, hypoventilation, hypothermia, and hypotension, which can be severe and life threatening in some cases.⁶ The American Thyroid Association recommends combination levothyroxine and liothyronine.¹⁰ Intravenous loading doses of 300 to 600 µg of levothyroxine, followed by daily doses of 50 to 100 µg, have been successfully used, with higher doses conferring the possibility of cardiac complications such as myocardial infarction and arrhythmias but without providing any additional benefit.^6,9,12 With decreased conversion of thyroxine to triiodothyronine in patients with severe thyroid hormone abnormalities, replacement with liothyronine with initial 5 to 20 µg, followed by 2.5 to 10 µg every 8 hours, can be given. Symptomatic and clinical improvement is expected to take place over 7 days with continued thyroid hormone replacement medication. Conversion to oral medication should be made as soon as patients are able to tolerate medications by mouth. 

Concerns for concomitant primary adrenal insufficiency and increased metabolism of cortisol after sudden correction of thyroid levels should be addressed with steroid replacement. Stress-dose steroids should be administered in any patients with these concerns until further testing with random cortisol or adrenocorticotropic hormone stimulation testing can rule out adrenal insufficiency. Fifty to 100 mg of hydrocortisone every 8 hours or 2 to 4 mg of dexamethasone every 12 hours can be given, with the latter having the advantage of not interfering with the results of a cortisol or adrenocorticotropic hormone stimulation test. 

The use of antipsychotics during thyroid replacement therapy remains a controversial issue.^4,13 A review of the literature¹³ found that antipsychotics are best reserved for patients who have received thyroid replacement therapy, achieved a euthyroid state, and have not had improvement in their psychosis.⁴ In the current case, haloperidol was used for severe agitation before the patient could achieve a euthyroid state. 

It is essential to rule out Hashimoto encephalopathy as a cause of psychosis, which can be a common mimicker of myxedema psychosis and is not responsive to thyroid replacement therapy. In the current case, a computed tomographic scan of the patient’s head and an electroencephalograph were negative for intracranial abnormalities, which made myxedema psychosis a more likely diagnosis. Although Hashimoto encephalopathy can present with similar psychiatric disturbances, it is also often accompanied by ataxia, myoclonus, aphasia, tremors, and seizures. Electroencephalogram studies are found to be abnormal in 98% of patients with Hashimoto encephalopathy,¹¹ which was not seen in the current case. Differentiation of these 2 clinically separate entities is of paramount importance, as the management of Hashimoto encephalopathy requires corticosteroids and does not respond to thyroid hormone replacement therapy. Undiagnosed and untreated myxedema psychosis has a 20% mortality rate.⁶ 

The osteopathic manipulative treatment (OMT)approach to a patient with hypothyroidism is centered around increasing fluid flow and nerve conduction to the thyroid gland. After initial viscerosomatic responses initiated by the thyroid gland, left untreated, the dysfunction perpetuates itself, leading to a vicious cycle of autonomic imbalance. Although directed OMT to the thyroid was not possible in our acutely agitated patient, ideally, treatment should be initiated at the first sign of thyroid abnormalities to maintain homeostasis. Because myxedema psychosis was the presenting symptom, implementation of OMT was not possible. Management should be focused on somatic dysfunctions in the cervical, upper thoracic, and shoulder soft tissue reflected by hypertonicity of the musculature. Myofascial trigger points found at C2, C3, and C4 dermatomes respond well to OMT techniques applied to the sternocleidomastoid (C2-3), trapezius (CN 12, C3-4), and splenius capitus (C4-5) muscles.¹⁴ 

Left untreated, hypothyroidism can lead to many cognitive disturbances, including psychosis or coma. Myxedema psychosis is an uncommon consequence of a common medical condition. Homeostasis of the dysregulated thyroid gland can be accomplished through OMT of the musculoskeletal and visceral changes in the cranial, cervical, and thoracic regions and the upper extremities. Thyroid abnormalities should be considered in all patients presenting with altered mental status and changes in cognition, as these changes can take place acutely or have an insidious onset. This case helps to illustrate the importance of promptly recognizing and implementing treatment for reversible causes of psychosis in an atypical presentation of a common medical condition.