the prognostic significance of thyroid function in mania

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  • J. psychiat. Res., Vol. 25, No. 1/2, pp. 1-6, 1991. 0022-3956/91 $3.00 + .00 Printed in Great Britain. 1991 Pergamon Press plc




    University Department of Psychological Medicine, Christchurch School of Medicine, P.O. Box 4345, Christchurch, New Zealand

    (Received 21 February 1990; revised 5 September 1990)

    Summary--Free thyroxine index (FT4I) and thyroxine (T4) levels were measured in 31 manic patients shortly after admission to a psychiatric hospital. Over one-third had elevated thyroid hormone levels, and this was largely due to increases in FT4I. Increased FT4I levels were associated with greater sleep disturbance and with being male, and were negatively associated with having had hospital admissions in the past six months. More interestingly, however, low FT4I levels prospectively predicted more hospital admissions in the 12 months from index admission, and this was not due to past admissions predicting future admissions. This adds to the growing literature on important relationships between thyroid hormones and treatment outcome in patients with affective disorders.


    A RE~ATIONSI-In" between thyroid disease and mood disturbance has long been recognized, and both hypothyroidism and hyperthyroidism are part of the differential diagnosis of depression and mania. This has resulted in the frequent evaluation of thyroid function in acutely disturbed psychiatric patients, and to the realization that many acute psychiatric patients have elevated thyroid function tests but do not have thyroid disease. This so-called euthyroid hyperthyroxinaemia occurs not only in acute psychiatric illness but also in a variety of other acute medical disorders (Borst, Eil, & Burman, 1983). A number of studies (Cohen & Swigar, 1979; Levy, Jensen, Laus, Agle & Engel, 1981; Spratt et al., 1982) have documented that an elevated free thyroxine index (FT4I) and/or thyroxine (T4) occurs in 9-3370 of acute psychiatric admissions. These abnormalities seldom reflect thyroid disease and usually return to normal over a period of a few weeks. However, the psychiatric correlates of these abnormalities have seldom been looked at in detail, and where diagnostic information was available, all affective disorders were lumped together (e.g. Spratt et al., 1982). Very little information appears to be available on the prevalence of hyperthyroxinaemia in manic patients and whether thyroid status is related to any clinical features in manic patients.

    At the opposite end of the spectrum of thyroid activity is the hypothyroid state, and there has been recent interest in the observations that sub-clinical hypothyroidism may be especially associated with rapid-cycling bipolar affective disorder (Extein, Pottash, & Gold, 1982; Cowdry, Wehr, Zis, & Goodwin, 1983; Alarcon, 1985; Roy-Byrne, Joffe, Uhde, & Post, 1985; Tapp, 1988). Furthermore, it has been suggested that hypermetabolic doses of thyroxine may be of benefit in treating rapid-cycling bipolar affective disorder (Stancer & Persad, 1982; Extein & Gold, 1988).


    We were therefore interested in measuring thyroid activity in acutely admitted manic patients and documenting the prevalence of hyperthyroxinaemia, with a view to seeing whether this condition is related to certain symptoms of mania, to past history of illness, or to prospective history of readmission.


    Patients aged 16-65 inclusive who were admitted from the community to an acute ward in a psychiatric hospital, with a diagnosis of mania using DSM-III criteria, were included in this study. During the first four days of hospitalization, blood was drawn for thyroid function tests; thyroxine (T4) was measured by radioimmunoassay and the free thyroxine index (FT4I) was calculated. Patients' mania was assessed on admission using the Bech- Rafaelsen mania scale (Bech, Bolwig, Kramp, & Rafaelsen, 1979). Data were also collected on the duration of the manic episode prior to admission and the number of hospital admissions in the past six months, two years, five years and lifetime.

    A year later, each patient's notes were checked for further admissions to this hospital. If there were any grounds for suspecting patients had been admitted to the one other hospital with an acute in-patient psychiatric ward within the region, then this was checked. In two instances, we became aware and were able to confirm that patients had been admitted to hospitals outside the region.

    Results are expressed as mean 4-SD. Statistical analyses were performed using SYSTAT on an IBM PC compatible computer.

    Results Prevalence of hyperthyroxinaemia

    During the course of this study, complete data were collected on 31 manic patients (17 males and 14 females). The mean thyroxine (T4) level was 116 4- 23 nmol/L, and only two patients had T4 levels above the normal upper limit of 140 nmol/L" the mean free thyroxine index (FT4I) was 145 4- 40, and nine patients had FT4I levels above the normal upper limit of 160. Of the nine patients with an elevated FT4I level, six were males. FT4I levels were significantly higher in males (158 4- 42) than females (128 4- 31) (t = 2.22, p < .05). Altogether, 10 manic patients (327o) had an elevated T4 and/or FT4I level. No manic patients had T4 or FT4I levels even approaching the lower limit of the normal range.

    Relationship between thyroid activity and manic symptoms The majority of manic patients had been unwell in the present episode for less than one

    month, and only three had had manic symptoms for over two months. The mean rating on the mania scale was 19 (4-8). T4 and FT4I levels were each correlated with 13 variables, namely duration of illness, the 11 manic symptoms, which are assessed in the mania scale, and total mania score. Only one correlation even reached a .05 level of significance, which was that FT4I did correlate with the item assessing sleep disturbance (r = 0.47, p < .01).

    Effect of lithium on thyroid activity Of the 31 manic patients, none of the seven first admissions, and 20 of the 24

    readmissions, had ever been prescribed lithium. Sixteen had been taking lithium in the six


    months prior to admission, but ten of these patients had discontinued lithium at least one month prior to admission, leaving only six who had been on lithium regularly prior to admission, all of whom were still taking it when their thyroid function was assessed shortly after admission. Neither the six currently on lithium, nor the 16 who had been on lithium in the past six months, had significantly different T4 or FT4I levels to those patients not on lithium.

    Relationship between thyroid activity and past admissions In this sample of manic patients, seven were having their first admission to hospital for

    an affective disorder. Three had one past admission, five had two, nine had 3-10 past admissions and seven had over 10, with the greatest number being 26 past admissions.

    As FT4I is calculated from T4, and as FT4I was more often elevated and was associated with sleep disturbance in mania, only FT4I was looked at in relationship to past history of admissions for affective disorder. From Table 1, which shows the Pearson correlation between FT4I and number of past admissions in the past six months, two years, five years and lifetime, it will be seen that FT4I was significantly inversely correlated with number of admissions in the past six months (r= .38, p < .05). Furthermore, the FT4I was significantly lower in those who had been admitted in the past six months (120.7 24.7) than in those who had not been admitted (154.6 41.0; t= 2.82, p < .01). Although the observation did not quite reach statistical significance, none of the nine patients who had had an admission within the past six months had an elevated FT4I, while nine of the patients without an elevated FT4I had been admitted within the past six months (X2= 2.85, p


    As both FT4I and numbers of past admissions were correlated with the likelihood of readmission, and as sex influenced FT4I levels, a multiple linear regression was performed, with number of readmissions as the dependent variable and FT4I, the number of admissions in the past five years, and sex as independent variables. From Table 3, it will be seen that both a low FT4I (t = -2.23, p < .034), and number of admissions in the past five years (t = 2.07, p < .048) significantly contribute to the prediction of readmissions.

    Table 3 Multiple linear regression of number of prospective readmissions against FT41, number of past admissions over the past five years, and sex

    Variable Standard Coefficient t p

    FT4I -.40 -2.23 .034 Past admissions .35 2.07 .048 Sex .12 .66 .513

    Multiple R = .54, R2 = .29, F (3,27 dO = 3.67, p < .024.


    The first finding from this study is that about one-third of acutely manic patients have elevated thyroid function tests, largely consisting of an elevated FT4I rather than T4. This finding is consistent with earlier reports (summarized in the Introduction) that up to one- third of acutely admitted psychiatric patients may have a euthyroid hyperthyroxinaemia.

    FT4I values in these manic patients were correlated with the manic symptom of sleep disturbance but with no other individual symptom, to total manic severity or to duration of manic episode. Given that more than 20 correlations were carried out, it is possible that this is only a chance finding although, as this correlation was at the .01 level, such an interpretation on balance, is unlikely. Assuming that this is not a chance finding, it is of interest that a recent study of