thyroid dysfunction has been associated with numerous neuropsychiatric manifestations of which depression , apathy , disturbances in cognition , psychosis , and affective disorders are common . although depressive and manic symptoms have been well described with hypo- and hyperthyroidism , respectively , mania in the setting of hypothyroidism is unusual .
we present the case of a patient whose acute mania is probably due to the administration of levothyroxine in hypothyroid state .
a right - handed 27-year - old unmarried indian male nondiabetic , normotensive , vegetarian was diagnosed with hyperthyroidism 7 months earlier [ antithyroid peroxidase antibody : 16.1 ( reference range : 065 ) iu / ml , t3 : 5.59 ( reference range : 0.922.33 ) nmol / l , t4 : 207.30 ( reference range : 60120 ) nmol / l , thyroid stimulating hormone ( tsh ) : 0.05 ( reference range : 0.355.5 ) iu/ ml , 99mtc - pertechnetate thyroid scan suggestive of thyroiditis ] and started on medications ( neomercozole 30 mg / day ) by an endocrinologist .
three months later he started complaining of weakness and lethargy and upon investigating his tsh levels were raised significantly [ tsh : 32.7 iu / ml , t4 : 8.6 ( reference range : 1222 )
pm / l , ultrasonography thyroid  both lobes mildly hyperechoic and heterogenous in pattern with no definite nodule or calcification seen ] and he was shifted to thyroxine 25 g per day in view of hypothyroidism .
subsequently , after about a week of treatment , he developed manic symptoms ( euphoria , increased talkativeness , over familiarity , over religiosity , increased energy levels , reduced need for sleep , abusive and violent behavior with socio - occupational dysfunction ) .
he presented to psychiatry department with 2 months history of such symptoms and was admitted . upon investigating ,
tsh levels were found to be within normal limits with increased t3 [ t3 : 5.48 ( reference range : 24 ) pg / dl , t4 : 1.30 ( reference range : 0.62 ) ng / dl , tsh : 3.74 iu/ ml ] .
his manic symptoms remitted within 5 days of stopping thyroxine and initiating valproate 800 mg/ day and olanzapine 20 mg / day .
his young mania rating scale scores ( to assess improvement in mood symptoms ) reduced from 28 to 11 in 5 days and thyroid hormone levels normalized within 20 days .
patient was euthymic with normal thyroid hormone levels after 2 months of followup wherein his medications were tapered off and did not show mood symptoms when seen 2 months later .
our case reports that manic symptoms were precipitated during hypothyroid state when the patient was treated with thyroxine .
only a few cases of mania or hypomania associated with hypothyroidism have been reported in the literature . while most of these cases have reported improvement in manic symptoms after initiating thyroid replacement therapy , occurrence of mania with psychotic features
has also been reported following abrupt normalization of thyroid status , both in grave 's disease and in hypothyroid states .
josephson and mackenzie reviewed 18 case reports of patients with hypothyroidism developing mania soon after the initiation of replacement therapy , but concluded that 15 of them had psychosis prior to the treatment , attributing symptom production to past history of personal or familial psychiatric disorder and high normal dosage initiation of levothyroxine ( 150 g / day ) , which could abruptly augment catecholamine receptor sensitivity , thereby precipitating a hypercatecholaminergic state and subsequent manic symptoms .
our case neither had a past personal or family history of any psychiatric illness , nor was not exposed to abrupt high initial dosage of thyroxine .
it has been speculated that thyroid hormone  catecholamine receptor interactions might underlie these t3-associated clinical manifestations as well . with previous literature reports ,
rapidity and concurrent initiation as well as resolution of manic symptoms with thyroxine , supported by serum thyroid hormone levels , lack of previous or family psychiatric history and , naranjo adverse drug reaction probability scale score of 5 , led to our conclusion that the manic symptoms were probably secondary to thyroxine supplementation .
whybrow and prange proposed the hypothesis that interactions between thyroid and neurotransmitter systems may have a causal role in the pathophysiology of mood disorders .
they suggested that the antidepressant properties of t3 could be explained by its augmentation of postsynaptic beta - adrenergic activity .
hypothyroidism was , thus , believed to cause depression by producing a functional decrease in noradrenergic transmission .
the obverse of this would be mania caused by a hyperadrenergic state , which may be the case in our patient .
with literature supporting thyroxine induction as well as attenuation of manic symptoms , we suggest that a subset of thyroid dysfunction patients exists with a potential for producing manic - like symptom after thyroid replacement in hypothyroid state .
 the current literature variedly ascribes depressive and manic symptoms to hypo- and hyperthyroid state , respectively , reporting mania in hypothyroidism as an unusual entity . 
 more unusual is precipitation of manic state in hypothyroid subjects after thyroxine supplementation for which studies report otherwise treating manic symptoms in hypothyroid state with thyroxine . 
 we report a case of a patient whose acute mania appears to have been precipitated by thyroxine supplementation in hypothyroidism state . 
 this case underscores the importance of thyroid screening in patients with mood and psychotic disorders , as well as the potency of thyroxine in producing manic symptoms . 
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