Psychosomatics 46:259-261, June 2005
© 2005 The Academy of Psychosomatic Medicine
Acute Mania in the Setting of Severe Hypothyroidism
Charles P. Stowell, M.D., and
John W. Barnhill, M.D.
Received May 10, 2004; revision received Oct. 20, 2004; accepted Nov. 15, 2004. From the Department of Psychiatry, New York-Presbyterian Hospital, Weill-Cornell Medical Center. Address correspondence and reprint requests to Dr. Stowell, Department of Psychiatry, New York Presbyterian Hospital, Weill-Cornell Medical Center, 525 East 68th St., New York, NY 10021; chs9017{at}nyp.org (e-mail).
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ABSTRACT
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Although the associations between depression and hypothyroidism and between mania and hyperthyroidism are well described, mania in the setting of hypothyroidism is unusual. The authors present the case of a patient whose acute mania appears to have been precipitated by hypothyroidism secondary to postpartum thyroiditis. This case underscores the importance of thyroid screening in patients with mood and psychotic disorders, including patients who lack the classical psychiatric features of thyroid dysfunction. Further investigation is required on the nature of the relationship between thyroid function and bipolar disorder and any implications it may have for the diagnosis and treatment of this illness.
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INTRODUCTION
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Thyroid hormone abnormalities have been associated with a variety of affective and psychotic disorders. Advanced hypothyroidism has been implicated, for example, in acute psychosis, termed "myxedema madness" by Asher in 1949 in his classic article on the subject.1 Rapid administration of levothyroxine has been reported to precipitate manic symptom profiles,2 and depressive symptoms are thought to be more likely to emerge in the presence of diminished thyroid function.3 Although the links between depression and hypothyroidism and between mania and hyperthyroidism are well described, mania in the setting of hypothyroidism is unusual.4–6 Here we present the case of a patient whose acute mania appears to have been precipitated by hypothyroidism secondary to postpartum thyroiditis, an autoimmune disorder of the thyroid gland that affects 5–7% of women in the first postpartum year.7
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Case Report
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Ms. A was a 35-year-old woman who came to the emergency room with a 2-week history of manic and psychotic symptoms. She had no psychiatric or substance abuse history and was a highly successful professional. She had given birth to twins 7 months earlier.
Ms. A had been in her usual state of good mental health throughout this first pregnancy and for several months afterward. She returned to work part-time 3 months after delivery. She began to feel increasingly fatigued and, despite much effort, was unable to lose the weight she had gained during her pregnancy. About 2 weeks before admission, she began to experience an increased overall level of energy and described greatly increased activity at work and at the gym. She began sleeping only a few hours per night and eating less. She endorsed having "racing thoughts" during this period. She became religiously preoccupied, and, in what she and her husband later described as highly uncharacteristic behavior, she began regularly to read the Bible, pray, and attend church, to which she made a large donation. She told her husband that she believed that God was the father of their babies and that he had been sending her messages. She later reported that certain words in the Bible "jumped out" at her as having special meaning. On the day of admission, Ms. A was found collapsed in the bathroom by her children’s nanny. Her husband brought her to her internist, who ordered a computerized tomographic scan of her head, which was read as normal. She was referred to a private psychiatrist, who sent her to the emergency room. Additional history gathered from Ms. A’s family in the emergency room indicated that she had an aunt who "gets very religious when she’s jetlagged" and who takes psychiatric medication.
A mental status examination in the emergency room revealed a well-groomed, well-nourished woman. She was lethargic, difficult to engage, and spoke to the interviewer with her eyes closed. Her speech was not pressured or rapid. Her mood was dysphoric and her affect constricted. Her thought process was disorganized. Initially, she denied believing that God had fathered her babies or had been sending her messages. Later, she became delusional and agitated, screaming "God" repeatedly. Although she reported no auditory or visual hallucinations, she appeared to be distracted by internal stimuli. Initially, she was fully oriented but later was oriented to person only. Her physical examination was notable for nonpitting edema in her lower extremities and dry, flaky skin.
In the emergency room, Ms. A developed a fever of 38.5°C. A lumbar puncture was performed to rule out meningitis, and a CSF analysis was within normal limits. Her laboratory results were significant for a thyroid-stimulating hormone level >150 µU/ml (reference range=0.34–4.25 µU/ml), a free levothyroxine level of 0.2 ng/dl (reference range=0.8–1.8 ng/dl), a total cholesterol level of 352 mg/dl (high=>239 mg/dl), and a creatinine phosphokinase level of 988 units/liter (reference range=46–295 units/liter), all of which were consistent with severe hypothyroidism. On the basis of her physical examination, her history of recent weight gain and fatigue, and her laboratory data, a presumptive diagnosis of postpartum thyroiditis with neuropsychiatric symptoms of delirium, affect dysregulation, and psychosis secondary to severe hypothyroidism was made. Ms. A was admitted to the medical service for treatment. Thyroid peroxidase antibody titers, drawn at the time of admission, later came back as significantly elevated, confirming the diagnosis of postpartum thyroiditis.
Ms. A was started on levothyroxine replacement therapy at 100 µg intravenously b.i.d., and daily levothyroxine levels were measured. She was given oral risperidone, 0.5 mg b.i.d., for psychosis. Over the first 3 days of hospitalization, her mental status was notable for periods of remission of her psychotic symptoms alternating with periods of psychosis, during which, for example, she believed that staff members’ identification badges were signs that "God is king." On the third day, her free levothyroxine level was almost within normal range (0.8 ng/dl), and her levothyroxine dosage was changed to 150 µg orally b.i.d. On day four, her risperidone was increased to 1 mg b.i.d. for persistent psychosis and thoughts of self-harm stemming from a belief that she had "failed God." Her free levothyroxine level had reached 1.7 ng/dl, and her levothyroxine dose was changed to 150 µg/day. Concurrent with the normalization of her free levothyroxine level, her mental status improved. For all of the fourth and fifth days of hospitalization, Ms. A was without symptoms of mania, depression, psychosis, or delirium. On the sixth day, risperidone was discontinued, and she was discharged home with oral levothyroxine, 150 µg/day, with appropriate psychiatric and endocrinological follow-up.
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Discussion
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"Myxedema madness" is often described as delirium with auditory hallucinations and paranoid delusions. Less often, it takes the form of psychotic depression or pure psychosis without evidence of cognitive impairment or disorientation.8 Uncharacteristically, our patient had a 2-week history of decreased sleep and appetite, increased energy and goal-directed activity, hyperreligiosity, and grandiose delusions, all consistent with a manic episode. By the time of her presentation, she had become lethargic, dysphoric, and intermittently disoriented, resembling more closely the classic picture of affective psychosis associated with myxedema. The concurrence of the resolution of her psychiatric symptoms with the normalization of her free levothyroxine level and her lack of a previous psychiatric history support a causal link between her hypothyroidism and her manic and psychotic symptoms.
Only a few other cases of mania or hypomania associated with hypothyroidism have been reported. Balldin et al.4 reported the case of a woman with schizoaffective disorder and treatment-resistant mania whose manic symptoms resolved rapidly with levothyroxine treatment of her primary hypothyroidism. Levitte5 described the case of a man with bipolar disorder whose symptoms of hypomania resolved with the initiation of thyroid-replacement therapy. Mahendran6 published a report about a woman with congenital familial hypothyroidism whose first episode of hypomania occurred in the setting of severe hypothyroidism, which had resulted from stopping levothyroxine therapy.
In the context of these cases and our patient’s case, it is interesting to consider the evidence regarding the relationship between bipolar disorder, thyroid dysfunction, and thyroid autoimmunity. Kupka et al.9 found a significantly higher rate of thyroperoxidase antibodies in patients with bipolar disorder than in the general population, which was not associated with lithium treatment. Several studies have shown a higher incidence of hypothyroidism in patients with rapid-cycling bipolar disorder than in nonrapid cyclers.10,11 Levothyroxine treatment of hypothyroidism in rapid cyclers has been shown to decrease the severity and frequency of manic and depressive episodes, and high-dose levothyroxine therapy has been used successfully to treat refractory rapid cycling in the absence of measurable thyroid deficiency.12,13 Thus, it has been suggested that hypothyroidism may induce or contribute to the induction of rapid cycling in bipolar illness.14
Although the mechanism underlying the relationship between thyroid dysfunction and bipolar disorder is unclear, it has been hypothesized that it hinges on thyroid hormones’ regulation of CNS catecholamine receptor sensitivity.3 Evidence from human and animal studies indicates that thyroid hormones increase ß-adrenergic receptor sensitivity. It has been postulated that a surplus of thyroid hormone could lead to mania by promoting the action of catecholamines at central receptor sites, and, conversely, low thyroid levels could diminish the use of norepinephrine in times of stress, leading to depression.3 Although this would not explain mania in the setting of hypothyroidism, perhaps the explanation lies in a relationship between thyroid states and catecholamine receptor sensitivity that is more complex than currently understood. Another possibility is that our patient’s hypothyroid state was preceded by a period of thyrotoxicosis, as postpartum thyroiditis classically presents itself7, and that it was actually a hyperthyroid state that induced her mania. This seems unlikely, however, given the amount of time generally required for thyroid-stimulating hormone to rise in reaction to low levels of circulating thyroid hormone.15
Alternatively, the association may depend on the role that thyroid hormone plays in regulating biological rhythms, a possibility supported by the observation of cyclical behavior in thyroidectomized animals.11,13 One could speculate that a disruption in the regulation of her circadian rhythms caused by hypothyroidism was involved in inducing our patient’s mania.
Further investigation is required to understand better the nature of the relationship between thyroid function and bipolar disorder and any implications it may have for the diagnosis and treatment of this illness. Nevertheless, this case underscores the importance of thyroid screening in patients with mood and psychotic disorders, including patients who lack the classical psychiatric features of thyroid dysfunction.
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REFERENCES
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- Asher R: Myxedematous madness. Br Med J 1949; 2:555[Free Full Text]
- Josephson AM, Mackenzie TB: Thyroid-induced mania in hypothyroid patients. Br J Psychiatry 1980; 137:222–228[Abstract/Free Full Text]
- Whybrow PC, Prange AJ: A hypothesis of thyroid-catecholamine-receptor interaction. Arch Gen Psychiatry 1981; 38:106–113[Abstract/Free Full Text]
- Balldin J, Berggren U, Rybo E, Kjellbo H, Lindstedt G: Treatment-resistant mania with primary hypothyroidism: a case of recovery after levothyroxine. J Clin Psychiatry 1987; 48:490–491[Medline]
- Levitte SS: Coexistent hypomania and severe hypothyroidism. Psychosomatics 1993; 34:96–97[Free Full Text]
- Mahendran R: Hypomania in a patient with congenital familial hypothyroidism and mild mental retardation. Singapore Med J 1999; 40:425–427[Medline]
- Muller AF, Drexhage HA, Berghout A: Post-partum thyroiditis and autoimmune thyroiditis in women of childbearing age: recent insights and consequences for antenatal and postnatal care. Endocr Rev 2001; 22:605–630[Abstract/Free Full Text]
- Lishman WA (Ed): Organic Psychiatry: The Psychological Consequences of Cerebral Disorder. Boston, Blackwell Scientific Science Ltd, 1980, pp 508–515
- Kupka RW, Nolen WA, Post RM, McElroy SL, Altchuler LL, Denicoff KD, Frye MA, Keck PE, Leverich GS, Rush AJ, Suppes T, Pollio C, Drexhage HA: High rate of autoimmune thyroiditis in bipolar disorder: lack of association with lithium exposure. Biol Psychiatry 2002; 51:305–311[CrossRef][Medline]
- Bauer MS, Whybrow PC, Winokur A: Rapid cycling bipolar affective disorder. I. association with grade I hypothyroidism. Arch Gen Psychiatry 1990; 47:427–432[Abstract/Free Full Text]
- Cowdry RW, Wehr TA, Zis AP, Goodwin FK: Thyroid abnormalities associated with rapid cycling bipolar illness. Arch Gen Psychiatry 1983; 40:414–420[Abstract/Free Full Text]
- Bauer MS, Whybrow PC: Rapid cycling bipolar affective disorder. II. treatment of refractory rapid cycling with high-dose levothyroxine: a preliminary study. Arch Gen Psychiatry 1990; 47:435–440[Abstract/Free Full Text]
- Stancer HC, Persad E: Treatment of intractable rapid cycling manic-depressive disorder with levothyroxine. clinical observations. Arch Gen Psychiatry 1982; 39:311–312[Abstract/Free Full Text]
- Kusalic M: Grade II and grade III hypothyroidism in rapid-cycling bipolar patients. Neuropsychobiology 1992; 25:177–181[Medline]
- Martini L (ed): TSH, in Encyclopedia of Endocrine Diseases. New York, Elsevier, 2004, pp 303–313
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ABSTRACT
INTRODUCTION
